1 4994706266967244834 PDF

Donald School
Textbook of
Transvaginal
Sonography
Donald School
Textbook of
Transvaginal
Sonography
Second Edition
Editors
Asim Kurjak MD PhD
Department of Obstetrics and Gynecology
Medical School University of Zagreb
Sveti Duh Hospital
Zagreb, Croatia
Faculty of Health Science
Dubrovnik International University
Dubrovnik, Croatia
Jose Bajo Arenas MD PhD

University Hospital Sta Cristina
Madrid, Spain
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Donald School Textbook of Transvaginal Sonography
First Edition: 2005
Second Edition: 2013
ISBN 978-93-5090-473-2
Printed at
Dedicated to
Biserka, Igor and Alan
—Asim Kurjak
Marina, Marinita and Juan

—Jose Bajo Arenas
Contributors
Alenka Aksamija Santiago Bau

Department of Obstetrics and Gynecology International Ruber Hospital
Medical School University of Zagreb Madrid, Spain
Sveti Duh Hospital Zoran Belics
Zagreb, Croatia Department of Obstetrics and Gynecology
Muna T Al-Abdulla Jahn Ferenc Teaching Hospital
Al-Amal Maternity Hospital Budapest, Hungary
Amman, Jordan Branko Breyer
Breyer Laboratory
Omar A Al-Omari
Zagreb, Croatia
Al-Amal Matenity Hospital
Amman, Jordan Yesin Bulbul Baytur
Wiku Andonotopo Celal Bayar University School of Medicine
Fetomaternal Unit Manisa, Turkey
Raydeen Busse
Eka Hospital, Bumi
Serpong Damai, Serpong
John A Burns School of Medicine
Fetomaternal Unit
University of Hawaii
Department of Obstetrics and Gynecology Kapiolani Medical Center for Women and Children
Tangerang General Hospital Honolulu, Hawaii, USA
Banten, Indonesia
PS Casas
Aris Antsaklis Ultrasound Division and Fetal Medicine
1st Department of Obstetrics and Gynecology University Hospital of Canary Islands
University of Athens Sta Cruz de Tenerife, Spain
Athens, Greece
MT Clavijo
Panos Antsaklis Ultrasound Division and Fetal Medicine
1st Department of Obstetrics and Gynecology University Hospital of Canary Islands
University of Athens Sta Cruz de Tenerife, Spain
Athens, Greece Carmina Comas
Guillermo Azumendi Pérez Fetal Medicine Unit
Clinica Gutenberg Department of Obstetrics and Gynecology
Malaga, Spain Institut Universitari Dexeus
Barcelona, Spain
Kazunori Baba
G Daskalakis
Center for Maternal
1st Department of Obstetrics and Gynecology
Fetal and Neonatal Medicine
Fetal Medicine Unit
Saitama Medical Center
Athens University
Saitama Medical School Athens, Greece
Kamoda, Kawagoe, Saitama, Japan
Deepika Deka
Jose Bajo Arenas Department of Obstetrics and Gynecology
Department of Obstetrics and Gynecology All India Instiute of Medical Sciences
University Hospital Sta Cristina New Delhi, India
Madrid, Spain
Tibor Fekete
Maria J Barco 1st Department of Obstetrics and Gynecology
University Clinic “Lozano Blesa” Semmelweis University
Zaragoza, Spain Budapest, Hungary
viii Donald School Textbook of Transvaginal Sonography
Biserka Funduk Kurjak L Martínez-Cortés

Faculty of Health Science Ultrasound Division and Fetal Medicine
Dubrovnik International University University Hospital of Canary Islands
Dubrovnik, Croatia Sta Cruz de Tenerife, Spain
P Hernández-Ponz I Martínez-Wallin
Ultrasound Division and Fetal Medicine Ultrasound Division and Fetal Medicine
University Hospital of Canary Islands University Hospital of Canary Islands
Sta Cruz de Tenerife, Spain Sta Cruz de Tenerife, Spain
Ulrich Honemeyer Anita Matai
Department of Mother and Child Department of Obstetrics and Gynecology
Welcare Hospital EHL Garhood All India Institute of Medical Sciences
Dubai, UAE New Delhi, India
Takashi Ito Takashi Murakami
Department of Obstetrics and Gynecology Department of Obstetrics and Gynecology
Hakuai Hospital Tohoku University Graduate School of Medicine
Yonago, Japan Sendai, Japan
Ashok Khurana CB Nagori
The Ultrasound Lab Dr Nagori’s Institute for Infertility and IVF
New Delhi, India Ahmedabad, Gujarat, India
Sanja Kupesic Plavsic Tomoko Ogura
Paul L Foster School of Medicine Taijukao-Kaisei General Hospital
Texas Tech University Health Science Center Kagawa, Japan
El Paso, Texas, USA
Kunihiro Okamura
Asim Kurjak Department of Obstetrics and Gynecology
Department of Obstetrics and Gynecology Tohoku University Graduate School of Medicine
Medical School University of Zagreb Sendai, Japan
Sveti Duh Hospital
Zagreb, Croatia Sonal Panchal
Faculty of Health Science Dr Nagori’s Institute for Infertility and IVF
Dubrovnik International University Ahmedabad, Gujarat, India
Dubrovnik, Croatia Zoltan Papp
Maria Larrazaleta Maternity Private Department of Obstetrics
Department of Obstetrics and Gynecology Gynecology and Clinical Genetics
Paul L Foster School of Medicine Semmelweis University
Texas Tech University Health Science Center Budapest, Hungary
El Paso, Texas, USA Ma Angela Pascual
Kazuo Maeda Gynecological Ultrasound Unit
Department of Obstetrics and Gynecology (Emeritus) Obstetrical and Gynecological Department
Tottori University School of Medicine Institut Universitari Dexeus
Yonago, Japan Barcelona, Spain
W Mahtani T Pérez-Medina
Unit of Ultrasound and Fetal Medicine Department of Obstetrics and Gynecology
University Hospital of Canary Islands University Hospital Sta Cristina
Tenerife, Spain Madrid, Spain
Narendra Malhotra KyongHon Pooh
Malhotra Nursing and Maternity Home Pvt Ltd Department of Neurosurgery
Agra, Uttar Pradesh, India Kagawa National Children’s Hospital
Zentsuji, Japan
OY Marco
Ultrasound Division and Fetal Medicine Ritsuko K Pooh
University Hospital of Canary Islands CRIFM, Clinical Research Institute of Fetal Medicine PMC
Sta Cruz de Tenerife, Spain Osaka, Japan
Contributors ix
Pilar Prats Kuldeep Singh
Fetal Medicine Unit Dr Kuldeep’s Ultrasound and Color Doppler Clinic
Department of Obstetrics and Gynecology New Delhi, India
Institut Universitari Dexeus A Souka
Barcelona, Spain 1st Department of Obstetrics and Gynecology
University of Athens
Mladen Predanic
Athens, Greece
Maternal-Fetal Medicine Division
Department of Obstetrics and Gynecology Juan M Troyano Luque
Weill Medical College of Cornell University Unit of Ultrasound and Fetal Medicine
University Hospital of Canary Islands
New York, USA
Tenerife, Spain
Matija Prka
Masaji Utsu
Medical School University of Zagreb Seirei Mikatahara Hospital
Sveti Duh Hospital Hamamatsu, Japan
Zagreb, Croatia
Vaneesha Vallabh-Patel
Rosa Sabatel Department of Obstetrics and Gynecology
Department of Obstetrics and Gynecology Paul L Foster School of Medicine
Texas Tech University Health Science Center
University of Granada
El Paso, Texas, USA
Granada, Spain
Gino Varga
Maher G Sarraf Department of Obstetrics and Gynecology
Department of Ultrasound and Fetal Well-Being Medical School University of Zagreb
Al-Amal Maternity Hospital Sveti Duh Hospital
Amman, Jordan Zagreb, Croatia
Cihat Sen Nobuhiro Yamamoto

Department of Perinatology, Obstetrics and Gynecology Department of Obstetrics and Gynecology
Seirei Mikatahara Hospital
University of Istanbul
Hamamatsu, Japan
Cerrahpasa Medical School
Istanbul, Turkey Ivica Zalud
Mariko Serizawa John A Burns School of Medicine
Department of Obstetrics and Gynecology University of Hawaii
West Shizouka Medical Center Kapiolani Medical Center for Women and Children
Hamamatsu, Japan Honolulu, Hawaii, USA
Preface to the Second Edition
In recent years, there have been dramatic technical advances in diagnostic ultrasound. The advent of color Doppler, power
Doppler and, more recently, three-dimensional imaging has very dramatically developed into a revolution of new ways of
doing and seeing things. These developments now occur at such a rapid pace that unless we keep up with the developing
technology, we will inevitably and inexorably fall behind. In order to stay with the leading edge of diagnostic ultrasound,
one has to keep pace with what colleagues are doing around the world. This book, written by the lecturers of the Ian Donald
Inter-University School of Medical Ultrasound, represents the current knowledge on one of the newest achievements in
obstetric and gynecologic ultrasonography, transvaginal sonography.
In recent years, the sophisticated ultrasound imaging technique of transvaginal ultrasound has become available for both
obstetricians and gynecologists. Today, many types of transvaginal probe exist which are designed with adequate shape
and high frequency of ultrasound, such as 5.0, 6.0, 6.5 or 7.5 MHz. Accordingly high quality of two-dimensional (2D)
and three-dimensional (3D) images of the uterus, ovaries or the early conceptus in the uterus can be obtained through the
vaginal fornix, even though with some limitations like a narrow view field of the image.
The most exciting recent developments are color Doppler and transvaginal sonography. The combination of these two
modalities in the same vaginal probe provides for superb simultaneous visualization of structural and flow information
and offers new insight into dynamic studies of blood flow within the female pelvis. Most of these exciting developments
are illustrated in this book.
The authors contributing to Donald School Textbook of Transvaginal Sonography have all been selected for their special
expertise in their own chosen fields, their access to outstanding visual material and their ability to explain the significance
of it in an effective and lucid way. Finally, particular emphasis is being placed on achieving a very high quality reproduction
in the printing process itself in order to do full justice to the wide variety of visual images presented.
The textbook contains more than 600 original (black & white and color) ultrasound pictures, as well as diagrams and
photographs of babies after delivery. The book is divided into 5 sections with total of 42 chapters covering General Aspects,
Obstetrics, Gynecology and Infertility, Doppler Sonography, and 3D and 4D Transvaginal Sonography. This major new work
in ultrasound diagnosis also comprises an outstanding collection of images produced by the most sophisticated techniques
and equipment currently available. We do believe that this book will be of great value to gynecologists, obstetricians and
specialists in infertility as well as to diagnostic radiologists.
We are grateful to all contributors, to the publisher and to secretary Mrs Jadranka Cerovec with whom we have worked
so pleasantly.
Asim Kurjak
Jose Bajo Arenas
Preface to the First Edition
In recent years, there have been dramatic technical advances in diagnostic ultrasound. The advent of color Doppler, power
Doppler and, more recently, three-dimensional imaging has very dramatically developed into a revolution of new ways of
doing and seeing things. These developments now occur at such a rapid pace that unless we keep up with the developing
technology, we will inevitably and inexorably fall behind. In order to stay with the leading edge of diagnostic ultrasound,
one has to keep pace with what colleagues are doing around the world. This book, written by the lecturers of the Ian Donald
Inter-University School of Medical Ultrasound, represents the current knowledge on one of the newest achievements in
obstetric and gynecologic ultrasonography, transvaginal sonography.
In recent years, the sophisticated ultrasound imaging technique of transvaginal ultrasound has become available for both
obstetricians and gynecologists. Today, many types of transvaginal probe exist which are designed with adequate shape
and high frequency of ultrasound, such as 5.0, 6.0, 6.5 or 7.5 MHz. Accordingly high quality of two-dimensional (2D)
and three-dimensional (3D) images of the uterus, ovaries or the early conceptus in the uterus can be obtained through the
vaginal fornix, even though with some limitations like a narrow view field of the image.
The most exciting recent developments are color Doppler and transvaginal sonography. The combination of these two
modalities in the same vaginal probe provides for superb simultaneous visualization of structural and flow information
and offers new insight into dynamic studies of blood flow within the female pelvis. Most of these exciting developments
are illustrated in this book.
The authors contributing to Donald School Textbook of Transvaginal Sonography have all been selected for their special
expertise in their own chosen fields, their access to outstanding visual material and their ability to explain the significance
of it in an effective and lucid way. Finally, particular emphasis is being placed on achieving a very high quality reproduction
in the printing process itself in order to do full justice to the wide variety of visual images presented.
The textbook contains 550 original (black & white and color) ultrasound pictures, as well as diagrams and photographs
of babies after delivery. The book is divided into 5 sections with total of 40 chapters covering General Aspects, Obstetrics,
Gynecology and Infertility, Doppler Sonography, and 3D and 4D Transvaginal Sonography. This major new work in
ultrasound diagnosis also comprises an outstanding collection of images produced by the most sophisticated techniques
and equipment currently available. We do believe that this book will be of great value to gynecologists, obstetricians and
specialists in infertility as well as to diagnostic radiologists.
We are grateful to all contributors and to the publisher and secretary Mrs Jadranka Cerovec with whom we have worked
so pleasantly.
Asim Kurjak
Jose Bajo Arenas
Contents
Section 1: General Aspects

1. Transvaginal Probe: Technical Aspect 3
Kazunori Baba
Convex Probes 3
Mechanical Sector Probes 3
Three-dimensional Transvaginal Probes 4
Accessories of a Transvaginal Probe 5
2. Basis of Transvaginal Scanning 7

Kazunori Baba
Preparing the Patient and the Probe 7
Probe Insertion and Rotation 7
Basic Techniques in Transvaginal Scanning 8
3. Ultrasound Safety in Transvaginal Scan 13

Kazuo Maeda
Ultrasonic Bioeffect 13
Ultrasound Safety in B-Mode 14
Safety of Doppler Ultrasound (Wfumb Safety Statement on Doppler Ultrasound in Pregnancy) 15
Safety of 3D Transvaginal Ultrasound 15
Safety of 4D Transvaginal Ultrasound 15
Nonmedical Use of Diagnostic Ultrasound 15
4. Ultrasonic Tissue Characterization with Gray Level Histogram Width 17

Kazuo Maeda, Masaji Utsu, Nobuhiro Yamamoto, Mariko Serizawa, Takashi Ito
Methods 17
Technical Results 18
Clinical Results 18
5. Transrectal Sonography 21
Maher G Sarraf, Muna T Al-Abdulla, Omar A Al-Omari
Probes, Planes, and Orientation 21
Indications of Transrectal Sonography 22
Safety and Contraindications 26
Technique and Preparation 26
Section 2: Obstetrics
6. Fetal Anatomy on the First Trimester of Pregnancy 31
Aris Antsaklis, A Souka
Normal First Trimester Fetus 31
Fetal Anatomy at 11–14 Weeks 33
Studies Screening for Structural Defects by First Trimester Ultrasound 36
Structural Defects at 11–14 Weeks 37
7. Ultrasound Imaging of Early Extraembryonic Structures 46

Tibor Fekete, Zoltan Papp
Gestational Sac 46
Blighted Ovum 46
Chorionic Plate 47
Yolk Sac 48
xvi Donald School Textbook of Transvaginal Sonography
8. Ultrasound Markers of Aneuploidy in the First Trimester 52

Zoran Belics, Zoltan Papp
Nuchal Translucency 52
Cystic Hygromas 54
Fetal Growth Disorders 54
Nasal Bone 54
Megacystis 56
Ductus Venosus Velocimetry 56
Pulsatility Index of the Umbilical Artery 57
Fetal Heart Rate 57
Umbilical Cord 57
Omphalocele 57
Other Abnormalities 57
Future Possibilities 58
9. Early Detection of Fetal Abnormality 61

Ritsuko K Pooh
Abnormal Yolk Sac 61
Fetal Structural Anomaly 61
10. Echocardiography in Early Pregnancy 71

Carmina Comas, Pilar Prats
Technical Issues 72
Ultrasound Anatomy of the Normal Heart 72
Diagnosis of Congenital Heart Defects 74
Advantages and Limitations 79
Pathological Confirmation 80
Indications of Early Fetal Echocardiography 81
11. Assessment of Fetal Central Nervous System 85

Ritsuko K Pooh, KyongHon Pooh
Transvaginal Approach to the Fetal Brain 85
Three-dimensional Transvaginal Sonography 86
Hydrocephalus and Ventriculomegaly 87
Transvaginal Assessment of Congenital Central Nervous System Anomalies 91
12. Ultrasonographic Signs of Poor Pregnancy Outcome 102

Jose Bajo Arenas, T Perez-Medina
Spontaneous Interruptions of the Development of the Conceptus, Frequency of the Spontaneous Abortion,
Causes of the Abortion 102
Normal Development in the First Trimester of Pregnancy 103
Sonographic Findings to Diagnose an Interrupted Pregnancy 105
Poor Prognosis of Pregnancy: Sonographic Findings 107
13. Placenta and Transvaginal Sonography 116

Ashok Khurana
Safety and Accuracy of Trasvaginal Ultrasound 116
Placenta Previa 116
Placenta Accreta 118
14. Assessment of Placental Vascularization by Three-dimensional Power Doppler Ultrasound:

Placental Biopsy in Normal Pregnancies 125
Luis T Mercé, María J Barco, Santiago Bau, Jose Bajo Arenas
Three-dimensional Power Doppler “Placental Vascular Biopsy” 125
Three-dimensional Doppler Indices During Normal Gestation 128
Placental Biopsy in Fetal Growth 131
15. Cervical Measurements and Preterm Labor 134

Aris Antsaklis, G Daskalakis
Technique 134
Interventions for Cervical Incompetence Based on Ultrasonographic Findings 139
Contents xvii
16. Transvaginal Assessment of the Cervix 144
Cihat Sen, Yesin Bulbul Baytur
Measurement, Assessment, and the Pitfalls 144
Prediction of the Preterm Delivery by Transvaginal Measurement of the Cervix 146
Therapeutic Cervical Cerclage for Prevention of Preterm Delivery 150
Transvaginal Cervical Length Measurement in Predicting Successful Labor Induction 151
17. Cervix in the First Trimester of Pregnancy 154

Panos Antsaklis, Aris Antsaklis
Cervical Length Measurement During the First Trimester of Pregnancy 154
Cervicometry in the First Trimester: Newer Data 156
Cervicometry in the First and Second Trimesters 157
18. Transvaginal Sonography in Multiple Pregnancy 160

Ulrich Honemeyer, Asim Kurjak, Jose Bajo Arenas
Two-dimensional Sonography in Diagnosing Multiple Pregnancy 160
Three-dimensional Sonography in Diagnosing Multiple Pregnancy 163
Four-dimensional Sonography in Multiple Pregnancy 172
Section 3: Gynecology and Infertility

19. Uterine Lesions 179
Sanja Kupesic Plavsic, Asim Kurjak, Jose Bajo Arenas
Normal Uterus 179
Endometrial Polyps 180
Intrauterine Synechiae (Adhesions) 181
Adenomyosis 182
Endometrial Hyperplasia 183
Endometrial Carcinoma 184
Leiomyoma 186
Leiomyosarcoma 187
20. 2D and 3D Power Doppler Ultrasound Study of Endometrium as Implantation Marker 191
Two-dimensional Ultrasound and Doppler of the Endometrium 191
Three-dimensional Ultrasound and Power Doppler of the Endometrium 193
21. Follicular Monitoring 202

Sonal Panchal, CB Nagori
Follicular Assessment 202
B-Mode Features of a Mature Follicle 202
Doppler Features of a Good Pre-hcg Follicle 203
Implications of Flow Parameters on Ovum Quality 203
Our Data 203
Volume Ultrasound for Follicular Assessment 204
Volume Ultrasound Parameters of Good Pre-hCG Follicle: Follicular Volume 204
Cumulus 205
3D Pd for Follicular Assessment 206
3D Pd Indices and Follicular Quality 208
Doppler Parameters of Follicle and Time of Intrauterine Insemination 209
Endometrial Evaluation 209
B-Mode Features of Endometrium with Good Receptivity 210
Doppler Features of Endometrium with Good Receptivity 211
Uterine Artery Doppler 211
Volume Ultrasound Assessment of Endometrium 212
3D and 3D pd Features of Good Endometrial Receptivity 213
Contractions and Maximum Implantation Point 215
xviii Donald School Textbook of Transvaginal Sonography
22. Asymptomatic Simple Ovarian Cyst in Postmenopausal Women:

Syndrome of “Visible Ovary“ 218
Ivica Zalud, Raydeen Busse, Biserka Funduk Kurjak
Natural History of the Postmenopausal Ovary 218
Pathology of Simple Cysts 219
Sonography 219
Role of CA-125 221
Management 221
23. Transvaginal Sonography in Evaluation of Functional Ovarian Cysts 223
Ma Angela Pascual
Barcelona Experience 223
Illustrative Examples 224
Some Conclusions from Author’s Experience 227
24. Baseline Scan and Ultrasound Diagnosis of PCOS 232

Baseline Scan 232
Techniques for Baseline Scan of Ovaries 232
Normal Ovaries 234
Low Reserve Ovaries 235
Poorly Responding Ovaries 235
Polycystic Ovaries 237
Antral Follicle Count 238
Pathophysiology 238
Antral Follicle Count in Pco and its Hormonal Implications 238
Arrangement of Follicles 238
Stromal Abundance 239
Assessment of Stromal Abundance 239
Stromal Abundance in Pco and its Hormonal Implications 240
Stromal Vascularity 241
Stromal Vascularity in Pco and its Hormonal Implications 241
Deciding Stimulation Protocol 242
25. Hormone Replacement Therapy: Ultrasound Role 245
Ivica Zalud, Deepika Deka, Anita Matai
Physiology of Menopause and Postmenopausal Symptoms 245
Hormone Replacement Therapy 245
Ultrasound Role in “Pretreatment Assessment” 247
Progesterone Challenge Test and Ultrasonography 248
Color Doppler Ultrasound 248
Sonohysterography 249
Role of Ultrasound for “On Hormone Replacement Therapy Assessment” 249
Effect of Hormone Replacement Therapy on Morphology of Uterus and Ovaries 249
Role of Ultrasound in Special Conditions 250
Internal Carotid Artery and Cerebrovascular System 251
26. Ectopic Pregnancy 255

Sanja Kupesic Plavsic, Alenka Aksamija, Jose Bajo Arenas, Asim Kurjak
Role of Biochemical Markers in Ectopic Pregnancy 255
Role of Ultrasound in the Diagnosis of Ectopic Pregnancy 256
Other Sites of Implantation 261
Therapy 264
27. Female Pelvic Floor: Descriptive Anatomy and Clinical Exploration by

Transvaginal Ultrasound Echography 269
Juan M Troyano Luque, MT Clavijo, P Hernández-Ponz, I Martinez-Wallin, OY Marco, PS Casas,
L Martinez-Cortés, Luis T Mercé, Jose Bajo Arenas, Biserka Funduk Kurjak
Echography Use in Pelvic Diagnosis 269
Pathologies of the Posterior Pelvic Region 275
Pathologies of the Anterior Pelvic Region 281
Contents xix
28. Sonography of the Pelvic Infection 289
Endometritis 294
Hydrosalpinx 296
Hysterosalpingosonography 297
Sonographic Drainage as a Guide to Pelvic Abscess Perforation 298
29. Sonohysterography 300

Takashi Murakami, Kunihiro Okamura
Indications 300
Technique 301
Findings 302
Complications 304
30. Transvaginal Sonography in Postmenopausal Women 307

Kuldeep Singh, Narendra Malhotra
Normal Endometrium in Menopause 307
Postmenopausal Bleeding 308
Endometrial Fluid Collections 310
Myometrium in Menopause 310
Normal Atrophic Ovary 310
Ovary and Ovarian Cancer Screening 310
31. Use of Different Ultrasound Techniques in the Field of Urogynecology 315

Vaneesha Vallabh-Patel, Sanja Kupesic Plavsic
Pelvic Organ Prolapse 315
Pelvic Anatomy 315
Section 4: Doppler Sonography

32. Physical Principles of the Doppler Effect and its Application in Medicine 333
Branko Breyer
Doppler Effect 333
Doppler Indices 335
Instrumentation for Doppler Measurements 336
Data Acquisition 337
Signal Processing 337
Flow versus Velocity 337
Two-dimensional Flow Measurement: Two-dimensional Color Doppler Display 338
Power Doppler Ultrasound 338
Basic Limitations of Doppler Examinations 339
Contrast Media 340
Artifacts 340
33. Use of Ultrasound in the Field of Infertility 343

Sanja Kupesic Plavsic, Maria Larrazaleta
Cyclic Changes 343
Transvaginal Sonography of the Uterus and Ovaries During the Menstrual Cycle 343
Transvaginal Color Doppler Assessment of Ovarian and Uterine Blood Flow 347
Uterine Perfusion in Infertile Patients 351
Endometrial Thickness and Vascularity 352
Three-dimensional and 3D Power Doppler Ultrasound Markers of Implantation 352
Ovarian Causes of Infertility 353
Uterine Causes of Infertility 359
Tubal Causes of Infertility 361
34. Chorionic Volume and Intervillous Blood Flow in Normal First Trimester Pregnancies
Assessed by 3D Power Doppler Ultrasound 367
Maria J Barco, Luis T Mercé, Rosa Sabatel, Jose Bajo Arenas
Current Knowledge about Early Placental Circulation 367
Intervillous Blood Flow and Chorionic Volume During the First Trimester Normal Pregnancies by 3D PDA 369
xx Donald School Textbook of Transvaginal Sonography
35. Doppler Evaluation of the Ovary: Clinical Applications and Challenges 376
Ivica Zalud
Technique of Doppler Study 376
Future Challenges 382
Section 5: 3D and 4D Transvaginal Sonography

36. Three-dimensional Sonoembryology 385
Guillermo Azumendi Pérez, Asim Kurjak, Wiku Andonotopo, Jose Bajo Arenas
Three-dimensional Ultrasound Findings from Ovulation to Implantation 386
Events Following Implantation 388
Three-dimensional Ultrasound in Multiple Pregnancy 400
Three-dimensional Ultrasound as a Tool for Measurement of the Nuchal Translucency 400
Three-dimensional Ultrasound in Early Detection of Fetal Anomalies 402
Dynamic Real-time 3D Ultrasound (4D Technique) as a Tool for Assessment of Fetal Behavior in Early Pregnancy 403
37. Cesarean Scar Hysterotomy: Assessment by 3D Transvaginal Echography 410

Juan M Troyano Luque, MT Clavijo, I Martinez-Wallin, OY Marco, W Mahtani, PS Casas,
Jose Bajo Areans, Ulrich Honemeyer
Background 410
Echography Survey of Hysterotomy-Made Scars 410
Material and Methods 411
Results 412
38. Assessment of Normal and Abnormal Ovaries by Transvaginal Sonography 415

Asim Kurjak, Matija Prka, Ma Angela Pascual, Jose Bajo Arenas, Biserka Funduk Kurjak
Sonographic Parameters 415
Sonographic Differential Diagnosis of Pelvic Masses 417
Evaluation of an Ovarian Mass 424
39. Screening for Ovarian Cancer by Different Modes of Transvaginal Sonography 431
Asim Kurjak, Matija Prka, Jose Bajo Arenas
Difficulties in Ovarian Cancer Screening 431
Attempts to Screen—Some Lessons Learned 431
Screening Tests 433
Target Populations 434
Ovarian Cancer Screening Trials 435
Ovarian Cancer: The Role of 3D Ultrasound and 3D Power Doppler Imaging 436
Zagreb Ovarian Cancer Screening Trial 438
40. Four-dimensional Technical Aspects 443

Gino Varga, Asim Kurjak, Ulrich Honemeyer
Technicalities 444
41. Fetal Upper Limb Movement in the First Half of Pregnancy Detected by
Transvaginal 4D Ultrasound 453
Ritsuko K Pooh, Tomoko Ogura
Ultrasound Approach to Fetal Movement 453
Normal Fetal Hand and Finger Positioning and Movement in Early Pregnancy by 3D/4D Technology 454
Abnormal Positioning and Contracture of Fetal Hand/Fingers 454
42. Advanced Sonographic Assessment of Benign Endometrial Disease 459

Mladen Predanic
Endometrial Hyperplasia 459
Endometrial Polyps 460
Endometrial Changes in Tamoxifen Patients 463
Index.................................................................................................................................................................... 467
Section 1
GENERAL ASPECTS
¯¯ Transvaginal Probe: Technical Aspect
¯¯ Basis of Transvaginal Scanning
¯¯ Ultrasound Safety in Transvaginal Scan
¯¯ Ultrasonic Tissue Characterization with Gray Level Histogram Width
¯¯ Transrectal Sonography
CHAPTER
1 Transvaginal Probe:
Technical Aspect
Kazunori Baba
Introduction
Transvaginal sonography gives more accurate and more
detailed information on pelvic organs and masses than
vaginal examination. It is preferable to set an ultrasound
scanner with a transvaginal probe by each gynecological
examination table (Fig. 1.1).
A transvaginal probe consists of a head, shaft and a
grip (Figs 1.2A to C). A straight-type probe (Figs 1.2A
and B) may be easier to manipulate for obtaining a
desirable tomographic image than a bending-type probe
(Fig. 1.2C). A bending-type probe may be favorable to
vaginosonographical-guided aspiration.
The head of the probe houses transducers and its shape
is determined mainly by the scanning method, scanning
angle and scanning direction (forward, obliquely forward
or lateral). A mechanical sector probe (Fig. 1.3A) or a
convex (curved-array) probe (Figs 1.3B and C) is used as
a transvaginal probe. A phased-array probe is not used for
the transvaginal approach because a transvaginal probe
should have a wide scanning angle and the shape of the tip is
preferable to be either hemispherical-shaped or arc-shaped.
Convex Probes Figure 1.1 An ultrasound scanner with a transvaginal probe by a

gynecological examination table
Many small transducers are aligned on the convex surface
of the probe head. The principle of scanning is the same in a
transabdominal convex probe.1 But the radius of the convex
Mechanical Sector Probes
surface of the transvaginal probe is much smaller than that Figure 1.6 illustrates the principle of a mechanical sector
of a transabdominal probe, since a transvaginal probe must probe. Two transducers are rotated in the head of the
have a wide scanning angle in the narrow vagina. probe constantly by an ordinary motor in the grip of the
A convex probe performs electronic beam focusing1 probe or a small direct-driving motor attached directly to
and dynamic focusing,1 and the depth of the focal zone is the transducers. Each transducer has its proper frequency
selectable (Fig. 1.4). There are many grating lobes2 on both and ultrasound frequency can be selected by switching the
sides of the main lobe from a convex probe. These grating active transducer.
lobes as well as side lobes cause artifacts (Fig. 1.4). A The tip of a mechanical sector probe is a small
convex probe has the capability of color, power and pulsed hemisphere, and thus a mechanical sector probe can be
Doppler as well as B-mode imaging (Fig. 1.5). easily inserted into the vagina. This is especially preferable
4 Section 1  General Aspects
A
A
B
B
C
Figures 1.2A to C Transvaginal probes: (A) A straight-type mechanical Figures 1.3A to C Probe heads: (A) A mechanical sector probe; (B)
sector probe; (B) A straight-type convex probe; (C) A bending-type convex A convex probe; (C) A convex probe for obliquely forward scanning
probe (Abbreviations: G, grip; H, head; S, shaft;)
Figure 1.4 An image of a simple cyst obtained with a convex probe. Figure 1.5 Images of an ovary obtained with a convex probe. Left,
The focal zone (depth) is indicated by a semicircle (arrow) on the a B-mode image. Right, a power Doppler image of the same section
left side. Grating and side lobes from the probe make many artifacts showing blood flows surrounding the corpus luteum
(triangles) and the inner outline of the cyst is not shown clearly
for examining virgins and old women with atrophic vaginae. of color, power or pulsed Doppler which requires that
The scan angle can be easily widened to more than 200°. the ultrasonic beams be transmitted to the same direction
The focal zone is fixed at a constant depth determined several times successively.
by the shape of the transducer and there appears no mark
indicating the focal zone (Fig. 1.7). A mechanical sector Three-dimensional
probe is superior to a convex probe in B-mode image
quality, mainly because there is no grating lobe (compare
Transvaginal Probes
Figs 1.4 and 1.7). A three-dimensional (3D) transvaginal probe is used in 3D
The transducer is always in motion in a mechanical ultrasound (Figs 1.8A to C). The head of the probe houses
sector probe and consequently it has not the capability either a convex probe or a mechanical sector probe which
Chapter 1  Transvaginal Probe: Technical Aspect 5
Figure 1.6 Principle of the scanning of a mechanical sector probe.3 The

head is filled with acoustically transparent liquid and two transducers
rotate in it at high speed. One transducer is for a low-frequency and
Figure 1.7 An image of a simple cyst obtained with a mechanical
the other for a high-frequency. The ultrasonic frequency is changeable
sector probe (the same cyst in Figure 1.4). The focal zone is not
by switching the active transducer
indicated on the image because it is fixed. The inner outline of the cyst
is clearer than in Figure 1.4, because a mechanical sector probe has
no grating lobe and causes less artifacts
Figures 1.8A to C Three-dimensional transvaginal probes. (A) A Figure 1.9 Principle of three-dimensional (3D) scanning. A mechanical
mechanical sector probe is housed in the head; (B and C) A convex sector probe or a convex probe housed in the probe head swings and
probe is housed in the head a bunch of tomographic images is acquired automatically for 3D data
set construction4
swings to acquire 3D data4 as a large number of consecutive which cannot be obtained by a conventional transvaginal
tomograms (Fig. 1.9). A 3D probe can also be used for probe, can be obtained easily.5
B-mode imaging when 3D scanning is not activated.
A 3D image and any arbitrary section can be seen by
Accessories of a Transvaginal Probe
3D ultrasound.4 In obstetrics, a 3D image of a fetus and the
standard section for crown-rump length measurement can Both the head and the shaft of the transvaginal probe should
be easily obtained regardless the position and orientation be covered with a condom to prevent any possible infection
of the fetus.5 In gynecology, a coronal section of the uterus, from other patients. Ultrasonic jelly is appropriately applied
A B
Figures 1.10A and B (A) A needle guide and a transvaginal probe; (B) The transvaginal probe prepared with a condom, the needle guide and
a long needle for aspiration
to the probe head prior to the tight-fit placement of the 2. American Institute of Ultrasound in Medicine. Recommended
condom, thus avoiding the presence of air that would ultrasound terminology. AIUM. 1997.
prevent ultrasound transmission. 3. Baba K. Leaps of Obstetrics and Gynecology by
A needle guide is attached to a transvaginal probe in Ultrasonography. Osaka, Japan: Nagai Shoten; 1992.
transvaginal ultrasound-guided follicular/cyst aspiration 4. Baba K, Okai T. Basis and principles of three-dimensional
for ease and safety (Figs 1.10A and B). ultrasound. In: Baba K, Jurkovic D (Eds). Three-dimensional
Ultrasound in Obstetrics and Gynecology. Carnforth,
England: Parthenon; 1997. pp 1-19.
References
5. Baba K, Io Y. Ultra-sonografia Tridimensional em
1. Baba K, Kinoshita K. Video: physics and equipment of Ginecologia e Obstetricia. In: Sao Paulo, Brazil: Roca Ltda;
ultrasound imaging. Medical View (Tokyo, Japan), 1991. 2003.
CHAPTER
2 Basis of
Transvaginal Scanning
Kazunori Baba
Introduction ÀÀ Let the patient urinate to vacate the bladder to bring the
uterine body closer to the vaginal fornix (Figs 2.1A and B).
The transvaginal approach gives clearer images with higher À See the position and direction of the uterus and
resolution than the transabdominal approach, because there intrapelvic masses by vaginal examination or by
is no tissue, such as the abdominal wall causing distortion transabdominal sonography before the transvaginal
and reverberation of the ultrasonic waves between the scanning. This preparation is important, especially for
probe and the pelvic organs, and because high-frequency beginners.
ultrasound can be used in the transvaginal approach. À Wipe the head of the probe. Put a clean condom or a
However, improper usage of a transvaginal probe cannot probe cover on the probe after putting ultrasonic jelly
give clear images and consequently leading to an inaccurate on the head or into the condom. Make sure that there is
interpretation of the anatomy and misdiagnosis. Some no bubble between the head and the condom.
techniques for obtaining clear images with a transvaginal
probe are described in this chapter.
Probe Insertion and Rotation
Preparing the Patient and the Probe À Wet the tip of the condom with clean water or put some
cream on it to insert the probe into the vagina smoothly
À Explain transvaginal sonography to the patient, without causing any pain to the patient.
especially when she has not undergone transvaginal À Insert the probe into the vagina slowly and obtain a
sonography to ease her fear. sagittal (longitudinal) section of the uterus (Fig. 2.2).
A B
Figures 2.1A and B (A) Transabdominal sonography requires a full-bladder to see a normal size uterus and ovaries; (B)
An empty-bladder is preferable for transvaginal sonography1
Figure 2.2 A display of a sagittal section of an anteverted uterus by

the transvaginal approach, a patient’s abdomen is shown on the left
side of the image and the back is on the right side1
Figure 2.3 Rotating the probe from 12 o’clock to 9 o’clock and going
It is a landmark for gynecological examination. Come back to 12 o’clock is an easy way for not loosing the orientation1
back to this section when the orientation is lost during
the examination. If the vagina is too narrow for the
transvaginal probe, insert the probe into the rectum and
scan the pelvic organs through the rectal wall becomes worse as the distance from the probe gets longer
ÀÀ Make sure that the direction of the image is always fixed because ultrasound is emitted radially over a wide angle
not to lose or confuse the orientation. For example, the from a small head in transvaginal sonography.
abdominal side of the patient is displayed on the left side Figure 2.4A shows a sagittal section of a retroverted
of the image and the back side of the patient is displayed uterus, when the probe head is inserted into the anterior
on the right side of the image as shown in Figure 2.2. vaginal fornix. The cervix prevents the uterine body from
When the probe is rotated counterclockwise from 12 being seen satisfactorily. When the probe head is moved
o’clock to 9 o’clock (Fig. 2.3), a transverse section of the into the posterior vaginal fornix, the uterine body comes
uterus (parallel to the abdominal wall), is displayed such closer to the probe head and its clear image is obtained
that the right side of the patient is displayed on the left (Fig. 2.4B).
side of the image and the left side of the patient on the When an ovary is far from the vaginal fornix, the ovary
right side of the image. To keep the orientation correctly, is not depicted clearly (Figs 2.5A and B). In this case,
it is important to rotate the probe always from 12 o’clock the probe should be inserted further more to push the
to 9 o’clock to go from a sagittal section to a transverse vaginal fornix. The ovary comes closer to the probe head
section of the uterus and 9 o’clock to 12 o’clock to go and a clear image can be obtained (Fig. 2.5C). When an
back to a sagittal section. ovary is in the cul-de-sac (the pouch of Douglas), the
probe head must be put in the posterior vaginal fornix
Basic Techniques in to obtain a clear ovarian image (Figs 2.6A and B)
Transvaginal Scanning À Select the ultrasound frequency appropriately when
using a frequency-selectable probe. A clear image can
ÀÀ Bring the probe head as close as possible to the object be obtained with a high-frequency when the object
to ensure a clear image. It is hard to obtain a clear image is near the vaginal fornix. But an object far from the
of the object remote from the probe head, because a vaginal fornix is depicted obscurely due to poor tissue
transvaginal probe uses high-frequency ultrasound penetration of the high-frequency ultrasound (Fig.
having poor tissue penetration. And because ultrasonic 2.5B). An object should be initially searched with low-
beam density becomes lower and the lateral resolution frequency ultrasound (Fig. 2.5A), followed by getting
Chapter 2  Basis of Transvaginal Scanning 9
A A
B B
Figures 2.4A and B A sagittal section of a retroverted uterus. (A) The
uterine body and the endometrium cannot be seen clearly because the
cervix prevents them from being seen satisfactorily; (B) A clear image
can be obtained by putting the probe head in the posterior vaginal
fornix.1 (Abbreviations: C, cervix; EM, endometrium)
the probe as near as possible. And then observe it with

high-frequency ultrasound (Fig. 2.5C).
Figure 2.7A shows a dermoid cyst imaged with low-
frequency ultrasound. A solid-type dermoid cyst tends to
be overlooked with high-frequency ultrasound because
of its low tissue penetration (Fig. 2.7B)
À Adjust the depth of the focal zone properly to obtain a
clear image when a convex probe is used (Figs 2.8A and
B). Reduce the number of focal zones, when seeing fetal C
cardiac activity in the early first trimester. Because the Figures 2.5A to C (A) An ovary (triangle) with a follicle is barely seen
frame rate is reduced and critical, fetal cardiac activity with low-frequency ultrasound; (B) The ovary cannot be seen with
may be overlooked when the focal zones are too many. high-frequency ultrasound due to its poor penetration; (C) When the
probe is pressed against the vaginal fornix, the ovary comes closer to
À Consider the pressure to the object by the probe head. the probe head and a clear ovarian image can be obtained with high-
The pressure by the probe head is easily transmitted frequency ultrasound1
A B
Figures 6A and B (A) An ovary in the cul-de-sac should not be scanned through the anterior vaginal fornix and the cervix;
(B) The probe head should be placed in the posterior vaginal fornix1
A B
Figures 2.7A and B (A) With low-frequency ultrasound, a dermoid cyst (triangle) attenuating ultrasound strongly can be outlined; (B) The dermoid
cyst cannot be outlined clearly with high-frequency ultrasound (Abbreviations: C, cervix; F, fetus)
to the object, because there is no hard tissue like the or a touch of two organs or masses may be distinguished
abdominal wall in transabdominal sonography. Soft by moving them around with the probe head (Figs 2.10A
objects, such as an ovarian cyst or the uterine cervix and B)
in pregnancy, are temporarily deformed by pressing À Use a negative contrast medium (saline) for outlining
excessively with the probe (Figs 2.9A and B). The the uterine cavity clearly (Figs 2.11A and B). This
probe head should be maintained in a short but adequate technique is called sonohysterography (see the Chapter
distance from soft objects being viewed. 29: Sonohysterography).
ÀÀ Palpate the uterus or ovaries with the probe head, when
the patient complains of a lower abdominal pain. The When a Clear Image Cannot be Obtained
causing organ may be identified by palpating each organ When the object is far from the vaginal fornix, put your
with the probe head and recreating the pain. An adhesion hand on the abdomen and push the object toward the vaginal
Chapter 2  Basis of Transvaginal Scanning 11
A B
Figures 2.8A and B (A) Fetus (arrow) is depicted clearly when the focal zone (left triangle) is adjusted to it; (B) The fetus is depicted obscurely
when the focal zone is not adjusted to it
A B
Figures 2.9A and B (A) A simple ovarian cyst; (B) The cyst is deformed when it is pushed excessively with the probe head
A B
Figures 2.10A and B (A) A solid mass seems a pedunculated myoma because it seems to rise from the uterine fundus (triangle); (B) The uterus
and the mass separate from each other and the uterine contour (triangles) is clearly depicted by pressing between the two with the probe, leading
a conclusion that the mass is not a myoma of the uterus (Abbreviations: B, bladder; M, solid mass; U, uterus)
A B
Figures 2.11A and B (A) A sagittal section of a uterus shows thick hyperechoic endometrium; (B) Multiple polyps are clearly visualized after
infusion of saline into the uterine cavity
fornix. If it does not work satisfactorily or the object is too Reference

big, use transabdominal sonography or other modalities
like CT and MRI. Transvaginal sonography is powerful in 1. Baba K, Kinoshita K. Video: basic knowledge and technique
of endovaginal ultrasound imaging. Medical View (Tokyo,
gynecologic examination but not universal.
Japan), 1991.
CHAPTER
3 Ultrasound Safety in
Transvaginal Scan
Kazuo Maeda
Abstract the embryo and fetus more clearly in TVS than the
transabdominal scan due to the shortened distance between
Simple diagnostic B-mode ultrasound including simple the probe and the subjects. Recently, it is common to screen
transvaginal scan (TVS) is safe when the thermal index (TI) the embryo and fetus, and detect fetal abnormality or signs
and mechanical index (MI) are 1.0 or less in diagnostic use, to suspect congenital anomalies in the first trimester of
and simple B-mode machine was not concerned from the pregnancy, e.g. correct diagnosis of fetal ages by the crown-
thermal reason due to its extremely low output ultrasound rump length (CRL) and diagnosis of fetal life by heart
intensity. Diagnostic ultrasound safety was established beats with 2D real-time B-mode, 3D ultrasound imaging
after no suppression was found on the growth of cultured for the early stage diagnosis of fetal anomalies, trisomies
cells by the exposure to less than spatial peak temporal and fetal central nervous system anomalies, the 2D B-mode
average (SPTA) 240 mW/cm2 pulse wave ultrasound and for nuchal translucency (NT) in the assessment of trisomy,
the Japan Industrial Standard (JIS) regulated B-mode or the pulsed Doppler flow studies of fetal ductus venosus.
ultrasound output to less than SPTA 10 mW/cm2. As the The diagnosis of fetal intracranial structure through fetal
TVS is unique in the location of its probe and close to fontanelle or sutures in TVS contributed the fetal neurology.
the pelvic organs, the surface temperature of TVS prove In gynecology, uterine anomaly, fibroids, endometrial
should be lower than 41ºC. Simple 3D and 4D ultrasound hypertrophy, polyp, malignancy, trophoblastic diseases,
without Doppler technology will be safe because they are fallopian tube patency, hydrosalpinx, polycystic ovary,
composed of simple B-mode, while the exposure time is benign ovarian cysts and malignant masses, endometriosis,
recommended to be within 30 minutes. The pulsed Doppler ovarian follicle, ovulation, hyperstimulation syndrome,
flow velocity measurement as well as color and power and others are diagnosed by 2D, 3D, and Doppler TVS
Doppler imaging should follow the World Federation for ultrasound. No hazardous effect of ultrasound has therefore
Ultrasound in Medicine and Biology (WFUMB) statement been studied from these wide utility of TVS ultrasound.
in early pregnancy, because the TVS studies embryo and
early fetus of which tissue may be potentially sensitive to
excessive energies. TVS machine should be used under
Ultrasonic Bioeffect
obstetrical setting where TI and MI are 1.0 or less. The Heating Effect (Thermal Effect) of Ultrasound
use of diagnostic ultrasound should be limited for medical
Direct heating of animal fetus produced head and neck
purposes, but not for the entertainment or keepsake of
anomalies with long exposure of low temperature and
pregnancy.
short heating by high temperature of 43ºC (Fig. 3.1). 9
Since ultrasound exposure to biological tissue produced
Introduction temperature rise due to ultrasound absorption, medical
Although no adverse effect of diagnostic ultrasound has ultrasound exposure was indirectly regulated by the
been reported, ultrasound bioeffect and the safety of temperature rise, where 1ºC or less temperature rise did
ultrasound diagnosis have been concerned because the not produce fetal anomaly.
embryo and early fetus is diagnosed by ultrasound in the The 1ºC temperature rise exposure of ultrasound in a
sensitive stages of their tissues to external energies, 1-8 standard tissue was defined as 1.0 of TI. Since temperature
and the ultrasound probe is close to the embryo and early rise is high in the bone and low in the soft tissue, TI was
pregnancy fetuses in the TVS, which is able to visualize classified into the bone TI (TIB), soft tissue TI (TIS), and
Figure 3.1 Tolerable exposure time of animal fetuses to the temperature rise, TI and actual temperature based on the report
of NCRP9 and the calculation with the equation of AIUM; T (°C) = 6 – {(log10 t)/0.6}, where T is temperature rise (= TI) and
t is nonhazardous time (minutes)4
cranial TI (TIC), where bone TI was applied to the fetus is several 10 W/cm2. Hence, the mechanical effect is higher
after bone production in 10 weeks of pregnancy, soft tissue than the continuous wave ultrasound, and its mechanical
TI in the embryo before 10 weeks, and cranial TI to the brain effect is expressed by the MI that is rarefactional sound
examination within the skull. TI should be one or less in pressure (Pr) in Mega-Pascal (MPa) divided by square root
daily clinical practice, screening of the fetus and scientific of ultrasound frequency (MHz), e.g. MI is 1.0 when Pr is 1
study. TI should be also 1.0 or lower in obstetrical setting. MPa and the US frequency is 1 MHz.
In clinical use of ultrasound devices, output ultrasound TI The MI indicates nonthermal effect of ultrasound
higher than 1.0 should be controlled by the user until the particularly for the cavitation in the presence of gas bubbles
TI shown on the monitor screen indicates 1.0 or less. in the liquids, because the cavitation may produce local high
temperature and strong pressure. The cavitation, however,
Other Thermal Issues does not occur in the cell due to high viscosity of cell plasma,
The surface of TVS probe should not be heated to 41ºC or and the free radical produced by cavitation in the liquid does
more because of hazardous effect on the vaginal mucosa or not reach the cell due to its short life span. It is, however,
the subjects in the pelvis. Caution should be paid on febrile recommended that the MI should be less than 1.0 in the
patient whose temperature is higher than 37ºC, i.e. actual fetus and neonate. Adverse mechanical effects caused by the
TI is higher than nonfebrile condition, and therefore, the standing wave or acoustic streaming have not been reported.
exposure time should be shorter in the occasion.
Ultrasound Safety in B-Mode
Mechanical Effect of Ultrasound In our experience,10 cultured cells of amniotic origin floated
Most diagnostic ultrasound, except for the continuous wave in culture medium and held in ultrasound lucent container
of fetal monitor, is pulse wave with short μsec duration were exposed to pulsed ultrasound for 20−30 minutes
containing few ultrasound waves and high peak intensity, insulating the heat of the transducer by the thermostatic
i.e. average intensity is milli-W/cm2 while the peak intensity water, where the cell growth curve showed no difference to
Chapter 3  Ultrasound Safety in Transvaginal Scan 15
the sham by the pulse wave ultrasound of which intensity information on safety and bioeffects (e.g. TI, exposure
was below SPTA 240 mW/cm 2. Afterward since JIS times, and how to reduce the output power)
regulated the output intensity of ultrasound B-mode below ÀÀ When scanning maternal uterine arteries are in the
SPTA 10 mW/cm2, ultrasound safety was established in first trimester, there are unlikely to be any fetal safety
Japan.11 According to WFUMB safety committee, there was implications as long as the embryo/fetus lies outside the
no thermal reason to concern simple B-mode ultrasound Doppler ultrasound beam.
because of its very low output intensity.
Since TVS sonography is simple B-mode unless the Safety of 3D Transvaginal Ultrasound
association of Doppler technology, there is no reason to
concern its use by thermal reason. Transvaginal as well as The 3D ultrasound images are obtained by computer
abdominal scan B-mode without Doppler ultrasound user processing of repeated simple B-mode scans in a few
would follow the suggestion of ultrasound organizations seconds where a part of fetus will not be repeatedly exposed
that the exposure time would be less than 30 minutes from to the ultrasound. Since the use of simple B-mode without
the concern on the report on the disturbed neuron migration Doppler ultrasound is not concerned by the thermal effect
of animal fetus after exposure to common B-mode because of its very low output power,1 its use is safe if its TI
ultrasound for more than 30 minutes.12 and MI are 1.0 or less. The combination of pulsed Doppler
flow velocity measurement, color or power Doppler flow
Safety of Doppler Ultrasound imaging, however, should follow the 2011 WFUMB
statement listed in this chapter.13
(WFUMB Safety Statement on
Doppler Ultrasound in Pregnancy) Safety of 4D Transvaginal Ultrasound
The pulsed Doppler flow velocity measurement requires higher
Since the 3D ultrasound is repeated with the 10−20/second
intensity of ultrasound than simple B-mode. The ultrasound
frame rate in simple 4D ultrasound to analyze the motion
intensity of color or power flow imaging was less than pulsed
of subjects on the screen, the basic imaging is simple
Doppler due to scanning of ultrasound beam but needed higher
B-mode technique and therefore basically safe from the
output intensity than simple B-mode. Therefore, Doppler
thermal effect of ultrasound due to low output intensity of
ultrasound TI is requested to be one or less in the obstetrical
ultrasound probe, and the examination is safe if the TI and
setting.
MI are 1.0 or less. The 4D study duration is recommended
On January 27, 2011, the WFUMB Administrative Council13 to be less than 30 minutes according to the opinion of
approved the following statement on the safe use of Doppler ultrasound organizations on the report of disturbed neuron
ultrasound during 11−14 weeks scan (or earlier in pregnancy): migration of animal fetus.12 The combination of pulsed
ÀÀ Pulsed Doppler (spectral, power and color flow imaging) Doppler flow velocity measurement, color or power
ultrasound should not be used routinely Doppler flow mapping should follow the 20011 WFUMB
ÀÀ Pulsed Doppler ultrasound may be used for clinical statement listed in this chapter.13
indications, such as to refine risks for trisomies
ÀÀ When performing Doppler ultrasound, the displayed TI
should be less than or equal to 1.0, and exposure time
Nonmedical Use of
should be kept as short as possible (usually no longer Diagnostic Ultrasound
than 5−10 minutes) and not exceed 60 minutes Although the use of diagnostic ultrasound should be limited
ÀÀ When using Doppler ultrasound for research, teaching for medical purposes and users should be responsible to the
and training purposes, the displayed TI should be less safety of ultrasound, i.e. users must keep the knowledge on
than or equal to 1.0, and exposure time should be kept as possible ultrasound bioeffect and use the ultrasound under
short as possible (usually no longer than 5−10 minutes) the ALARA (as low as reasonably achievable) principle,
and not exceed 60 minutes. Informed consent should nonmedical ultrasound in entertainment or keepsake
be obtained ultrasound, fetal portrait studies or prenatal boutiques which
ÀÀ In educational settings, discussion of first-trimester record intrauterine fetal 3D/4D ultrasound on DVD are
pulsed or color Doppler should be accompanied by recent problems concerning ultrasound safety.14-17
The WFUMB14 disapproves the use of ultrasound for 7. The safety group of the British medical ultrasound society.
the sole purpose of providing souvenir images of the fetus. Guidelines for the safe use of diagnostic ultrasound
Because the safety of an ultrasound examination cannot equipment. BMUS Bulletin. 2000;3:29-33.
be assured, the use of ultrasound without medical benefit 8. Maeda K. Safety of ultrasound in obstetrics and gynecology.
should be avoided. Furthermore, ultrasound should be In: Kurjak A, Chervenak FA (Eds). Donald School Textbook
employed only by health professionals who are well trained of Ultrasound in Obstetrics and Gynecology, 3rd edition.
New Delhi: Jaypee; 2011.pp.3-9.
and updated in ultrasound clinical usage and bioeffects. The
use of ultrasound to provide keepsake images or video of 9. National Council on radiation protection and measurements;
exposure criteria for medical diagnostic ultrasound: I.
the fetus may be acceptable if it is undertaken as part of
Criteria based on thermal mechanisms. NCRP report No.
normal diagnostic ultrasound examination, provided that it
113, 1992.
does not increase exposure to the fetus. Ultrasound imaging
10. Maeda K, Murao F, Yoshiga T, et al. Experimental
for nonmedical reasons is not recommended unless carried studies on the suppression of cultured cell growth curves
out for education, training or demonstration purposes. Live after irradiation with CW and pulsed ultrasound. IEEE
scanning of pregnant models for equipment exhibition at Trans Ultrasonics Ferroelectrics and Frequency Control.
ultrasound congresses is considered a nonmedical practice 1986;33:186-93.
that should be prohibited since it provides no medical 11. Maeda K, Ide M. The limitation of ultrasound intensity for
benefit and affords potential risk to the fetus. diagnostic devices in the Japanese industrial standards. IEEE
Trans Ultrasonics Ferroelectrics and Frequency control,
References 1986;33:241-4.
12. Ang ESB Jr, Gluncic V, Duque A, et al. Prenatal exposure
1. Barnett SB, Kossoff G. WFUMB symposium on safety to ultrasound waves impacts neuronal migration in mice.
and standardization in medical ultrasound. Issues and PNAS. 2006;103(34):12909-10.
recommendations regarding thermal mechanisms for
13. WFUMB administrative council (January 2011). Safe use of
biological effects of ultrasound. Ultrasound in Med Biol.
Doppler ultrasound during 11 to 14 weeks scan (or earlier in
1992;18:731-810.
pregnancy). AIUM Sound Waves Weekly. March 10, 2011.
2. American Institute of Ultrasound in Medicine/National
Electrical Manufacturers Association: Standard for real time 14. Barnett SB, Abramowicz JS, Ziskin MC, et al. WFUMB
display of thermal and mechanical acoustic output indices symposium on safety of nonmedical use of ultrasound.
on diagnostic ultrasound equipment; 1992. Ultrasound in Med Biol. 2010;36:1209-12.
3. Barnett SB, ter Haar GR, Ziskin MC, et al. Current status 15. Abramowicz JS. Nonmedical use of ultrasound: bioeffects
of research on biophysical effects of ultrasound. Ultrasound and safety risk. Ultrasound in Med Biol. 2010;36(8):1213-
in Med Biol. 1994;20:205-18. 20.
4. AIUM official statement changes; revised statements; 16. Phillips RA, Stratmeyer ME, Harris GR. Safety and US
clinical safety, AIUM Reporter. 1998;154(Issue 1): 6-7. regulatory considerations in the nonclinical use of medical
5. Barnett SB, Rott HD, ter Haar GR, et al. The sensitivity ultrasound devices. Ultrasound in Med Biol. 2010;36:
of biological tissue to ultrasound. Ultrasound in Med Biol. 1224-8.
1997;23:805-12. 17. Brezinka C. Nonmedical use of ultrasound in pregnancy:
6. ISUOG bioeffects and safety committee; safety statement: 2000 ethical issues, patients’ rights and potential misuse.
(reconfirmed 2002). Ultrasound Obstet Gynecol. 2002;19:105. Ultrasound in Med Biol. 2010;36:1233-6.
CHAPTER
4 Ultrasonic Tissue Characterization

with Gray Level Histogram Width
Kazuo Maeda, Masaji Utsu, Nobuhiro Yamamoto, Mariko Serizawa, Takashi Ito
Abstract characterizations were reported.3-5 The results are excellent,

but most of the methods require particular analyzing
Tissue character is estimated by the B-mode image system and skillful investigators. The facilities and staffs
brightness with gray level histogram width (GLHW), are, however, hardly prepared in the common hospitals
which is reproducible among commercial real-time and clinics. The authors tried the analysis of gray level
scanners that incorporate histogram menu. Gray level histograms which were incorporated in many ultrasound
histogram width value is not influenced by the changes scanners, and it is possible to quantitatively analyze B-mode
of device gain, sensitive time control (STC), depth of the images. The authors studied mean gray levels of the pixels
region of interest (ROI), and standardized by the tests in the ROI in various tissues. However, the data changed
with ultrasound phantom. High scanner contrast increases by the gain control of the scanner. Fortunately, the authors
GLHW value, but it is easily calibrated with small factor. found the stable nature of the histogram base width, and
Tissues are characterized in obstetrics by the high GLHW analyzed placental GLHW every 2 weeks of pregnancy,
values in differentiation of Grannum grade III placenta, and normal ranges of placental GLHW were obtained. Gray
periventricular echodensity (PVE) of fetal brain, and level histogram width value of Grannum grade III placenta
meconium-stained amniotic fluid. Fetal lung immaturity is was higher than normal placenta.1
estimated by the lower GLHW of fetal lung than fetal liver
and normal fetal lung. In gynecology, GLHW of connecting
Methods
multiple ROIs are characteristic in ovarian masses.
Endometrial hyperplasia is separated from malignancy by The gray level histogram menu is found in ultrasound
the GLHW, and significantly higher GLHW is determined scanners, which are Aloka UIP-100 computer system, Aloka
in malignancy. Tissue characterization with GLHW can be SSD-650, SSD-680 and SSD-1000 and 2000, Toshiba SSA-
further applied in general medicine, including the diagnosis 270A, Yokogawa RT-8000 and Kretz-530D in this study.
of adult organs. The GLHW nature is checked among the devices by using
RMI-412 ultrasound phantom before the clinical application.
The transducer is attached to the phantom via ultrasound
Introduction jelly, gray level histograms are displayed on the screen and
It is another application of ultrasound images in medicine then mean gray level and other parameters are measured
quantitatively to analyze its echogenicity of real-time on the screen. The percentage of histogram base to the full
ultrasound composed of multiple echogenic pixels. Although gray scale is GLHW (Fig. 4.1) that is compared among the
the nature of B-mode subject is estimated usually by visual ultrasound machines.6 As device contrast influences the
observation, visual impression insufficiently recognizes histogram width, the devices are set at the lowest contrast
exact tissue character. Consequently, investigations and compared to the values obtained by UIP-100 system.
have been focused on the quantified objective tissue Gray level histogram width is a clinical tissue
characterization, including changes of ultrasonic frequency, characterization that is useful in various fields of obstetrics
velocity, attenuation, nonlinearity, back scatter, echodensity and gynecology. Three categories are reported in this paper
and texture analysis. In our past studies, excellent results in the assessment of fetal lung maturity, analysis of PVE
were obtained in the frequency-dependent attenuation by of fetal brain and the diagnosis of endometrial malignancy,
Akaiwa.1 Placenta was visually evaluated by four Grannum because fetal brain and uterine tissue are familiar subjects
grades2 in ultrasonic image, and various placental tissue in transvaginal scan ultrasound.
In clinical application, contrast is recommended to be

the lowest, but the device gain is voluntarily set up by the
user in order to obtain the best image. Therefore, GLHW
is calibrated in high contrast with the regression equation
obtained by the phantom test. After the ROI is set and
histogram is recorded, its width is measured by precise ruler
in manual processing, and standardized GLHW is obtained
by the percentage to full gray scale length (Fig. 4.1). Its
reproducibility was confirmed among the ultrasound
scanners produced in different periods.6
As the histogram base width is the difference between
the maximum gray level and not-zero minimum in the ROI
(Fig. 4.1), the GLHW is automatically determined by using
the algorithm. The program is incorporated in Aloka devices
Figure 4.1 Measurement of gray level histogram width as an option. There is no difference between manual and
automatic determinations.6
Technical Results
Clinical Results
Gray level histogram width of the homogeneous part of
RMI-412 ultrasound phantom is measured and compared Assessment of Fetal Lung Maturity
in various ultrasound scanners. Gray level histogram Fetal lung maturity is usually estimated by the tests of
width values of UIP-100, Aloka SSD-680 and Toshiba amniotic fluid obtained by amniocentesis. Although
SSA-270A show no significant difference. Aloka SSD-650 noninvasive ultrasonic analyses have been reported,8-11 visual
and Yokogawa show mild difference that is corrected by image evaluation is subjective, and in objective method
small factor to the level of UIP-100. Aloka SSD-2000 has mean gray levels are influenced by the device gain and other
identical GLHW to these machines at the scale 2 of contrast controls. Objective and quantitative assessments are based
control.7 Kretz Voluson 530D has the menu of 2D histogram on the GLHW of fetal lung and its comparison to fetal liver
that shows identical GLHW after a mild calibration. Aloka in this study. Fetal lung GLHW before 30 weeks of normal
and Toshiba machines are practically used in the GLHW pregnancy is lower than the values in later stage of pregnancy,
determination of clinical subjects. and also it is lower than the liver GLHW.7 Fetal liver GLHW
The influence of various controls of ultrasound devices is stable throughout the pregnancy. Therefore, premature fetal
including the gain, contrast, STC (depth compensation) and lung is suspected if the fetal lung GLHW is less than the value
the change due to image depth is tested by using RMI 412 of 30 or more weeks of pregnancy and lower than fetal liver.
phantom. The gain control and STC change do not influence Serizawa classified fetal lungs into nonrespiratory
GLHW within clinical ranges. Gray level histogram width distress syndrome (non-RDS) and respiratory distress
obtained in the ROI of various depths shows no significant syndrome (RDS) groups by the stable microbubbles (SMB)
difference within 10 cm from the surface. of amniotic fluid, and studied fetal lung GLHW of each
The only factor that influences on GLHW value is image group. The SMB with the diameter less than 15 µm are
contrast. Almost linear GLHW enlargement is shown by the counted in 1 mm2 area under microscope after pipetting
increase of contrast scale. Gray level histogram width value the amniotic fluid on the slide glass. Non-RDS group is
is measured at the lowest contrast except for SSD-2000 in classified when the SMB is five or more and no neonatal
this paper. As the contrast of Toshiba and Kretz devices is RDS exists, while RDS group is determined when the SMB
controlled by the dynamic range, they are adjusted to have is less than five and/or neonatal RDS is present.
high dynamic range, e.g. Kretz machine is adjusted at 75 dB. Gray level histogram width of non-RDS group is identical
Gray level histogram width is stable when the pixel number to those of normal late stage of pregnancy and often higher
is 1,000 or more in the ROI. No significant difference than that of liver of the fetus. Pulmonary GLHW of the fetus
is noted between GLHW values of transabdominal and in RDS group is significantly lower than that of non-RDS
transvaginal transducers tested by RMI phantom. group and it is lower than the GLHW of fetal liver (Fig. 4.2).
Chapter 4  Ultrasonic Tissue Characterization with Gray Level Histogram Width 19
Noninvasive prediction rate of neonatal RDS was studied Periventricular Echodensity of Fetal Brain
in preterm infants by the product of fetal lung to liver GLHW As cerebral palsy was frequently caused by neonatal
ratio multiplied by gestational weeks. The AUC of ROC curve periventricular leukomalacia (PVL), Yamamoto et al.13
was 0.91, where 96 % of immature fetal lung was detected with ultrasonically studied fetal brain by transvaginal scan
72 % of specificity (Fig. 4.3). New cases were prospectively and looked for fetal PVL in many high-risk pregnancies,
and correctly diagnosed12 Since noninvasive GLHW tissue but no fetal PVL was found, instead, PVE was frequent.
characterization predicts immature fetal lung with as high The fetal PVE was often followed by neonatal PVL if the
sensitivity as invasive amniocentesis methods, invasive one PVE persisted until delivery particularly in preterm births,
will not be mandatory for the diagnosis of fetal lung immaturity. whereas no neonatal PVL was found in case of no fetal PVE
or its disappearance before the birth.
Therefore, fetal PVE was a clinically significant
abnormality, but it was visually diagnosed when ultrasonic
echogenicity was as high as choroid plexus in fetal brain.
Further objective method for the PVE detection was needed,
and GLHW of fetal brain was studied, where significantly
larger GLHW values were found in fetal PVE than normal
fetal brain, i.e. the GLHW is 21.49 ± 3.55% in 7 normal
fetal brains and 36.86 ± 4.53% in 12 fetal PVE (Fig. 4.4).
Therefore, GLHW plays important diagnostic role in the
fetal PVE, and it is clinically useful in the prediction of the
neonates who may possibly develop PVL.
Figure 4.2 Fetal lung maturity is studied by gray level histogram
width (GLHW) levels where the GLHW in respiratory distress
syndrome (RDS) group (stable bubbles <5) is significantly smaller Endometrial Hyperplasia and Malignancy
than that of nonrespiratory distress syndrome (non-RDS) group
Thick endometrium of uterine image is suspected to be
(stable bubbles ≥5) and smaller than the fetal liver. No difference is
found between GLHW values of livers in RDS and non-RDS groups pathological in ultrasonic diagnosis. In addition, Ito reports
Source: M Serizawa in this paper that the comparison of GLHW values obtained
in normal endometrium, hyperplastic endometrium
and invasive endometrial carcinoma show significant
results. The GLHW is significantly larger in hyperplastic
endometrium than normal one. Myometrial invasion of
endometrial cancer shows significantly larger GLHW
Figure 4.3 The ROC analysis of fetal lung to liver GLHW ratio Figure 4.4 Upper photos show the change of periventricular echodensity
multiplied by gestational weeks. The sensitivity and specificity to (PVE) of fetal brain to neonatal periventricular leukomalacia after the
detect immature fetal lung were 96 and 72% respectively,12 i.e. 96% sustained fetal PVE until the birth. Lower figure shows significantly higher
of RDS was noninvasively predicted by GLHW and gestational weeks gray level histogram width value in fetal PVE than normal fetal brain
before births Source: Yamamoto et al
References
1. Akaiwa A. Ultrasonic attenuation character estimated from
backscattered radiofrequency signals in obstetrics and
gynecology. Yonago Acta Med. 1989;32:1-10.
2. Grannum PA, Berkowitz TH, Hobbins JC. The ultrasonic
changes in maturing placenta and the relation to fetal
pulmonic maturity. Am J Obstet Gynecol. 1979;133:915-22.
3. Almond DC, Pryce WIJ. Characterization of in vivo
placental ultrasonic images, using digital techniques: a
preliminary report. Ultrasound Med Biol. 1982;8:29-39.
Figure 4.5 Gray level histogram width (GLHW) of endometria is 4. Crawford DC, Fenton DW, Price WI. Ultrasonic tissue
larger in hyperplastic endometrium than normal. The hyperplasia characterization of the placenta: is it of clinical value? J
includes one simple hyperplasia, an atypical one and two of tamoxifen
therapy. Myometrial invasion of endometrial malignancy shows
Clin Ultrasound. 1985;13:533-7.
significantly higher GLHW than normal and hyperplastic endometria 5. Morris DT. An evaluation of the use of texture measurement
Source: T Ito for the tissue characterization of ultrasonic images of in vivo
than normal and hyperplastic endometria where the cut-off placenta. Ultrasound Med Biol. 1988;14:387-95.
GLHW value seems about 50 (Fig. 4.5). 6. Maeda K, Utsu M, Kihaile PE. Quantification of sonographic
echogenicity with grey level histogram width: a clinical tissue
Other Application of characterization. Ultrasound Med Biol. 1998;24:225-34.
Gray Level Histogram Width 7. Maeda K, Utsu M, Yamamoto N, et al. Echogenicity of fetal
lung and liver quantified by the grey-level histogram width.
Connected multiple scans of ovarian malignancy showed
Ultrasound Med Biol. 1999;25:201-8.
higher mean value and lower coefficient of variation
(CV) of GLHW than benign ovarian masses (Kihaile).14 8. Reeves GS, Garrett WJ, Waren PS, et al. Observation of
fetal lung reflectivity using real-time ultrasound. Aust NZ
Meconium-stained amniotic fluid revealed larger GLHW
J Obstet Gynaecol. 1984;249:91-4.
value than normal fluid, which was identical to that of fetal
colon (Yamamoto). Other general application may include 9. Cayea PD, Grant DC, Doubilet PM, et al. Prediction of
fetal lung maturity: inaccuracy of study using conventional
adult liver that will be appropriated in the GLHW studies
ultrasound instruments. Radiology. 1985;155:473-5.
because CV of normal liver GLHW is small,1 and therefore,
liver GLHW will be useful in clinical medicine. Gray level 10. Feingold M, Scollins J, Cetrulo CL, et al. Fetal lung to
liver reflectivity ratio and lung maturity. J Clin Ultrasound.
histogram width of other fetal and adult tissues and organs
1987;15:384-7.
are expected to be useful in the ultrasonic assessment.
11. Fried AM, Loh FK, Umer MA, et al. Echogenicity of
Conclusion fetal lung: relation to fetal age and maturity. AJR Am J
Gray level histogram width is reproducible in commercial real- Roentgenol. 1985;145:591-4.
time scanners that incorporate histogram function. Gray level 12. Serizawa M, Maeda K. Noninvasive fetal lung maturity
histogram width is not influenced by the device gain, STC and
depth of images. Gray level histogram width is a standardized
prediction based on ultrasonic gray level histogram width.
and reproducible index in the tissue characterization. The scanner Ultrasound in Med and Biol. 2010;36:1998-2033.
contrast influences GLHW value, but it is easily calibrated. Gray 13. Yamamoto N, Utsu M, Serizawa M, et al. Neonatal
level histogram width are studied in obstetrics on the placenta,
fetal brain, meconium-stained fluid with significant results, and periventricular leukomalacia preceded by fetal periventricular
the fetal lung maturity is estimated by the GLHW of fetal lung and echodensity. Fetal Diagn Ther. 2000;15:198-208.
liver. Ovarian masses, endometrial hyperplasia and malignancy are 14. Kihaile PE. Ultrasonic tissue characterization of ovarian
studied in gynecology with GLHW, and significantly larger GLHW is
obtained in malignancy. Gray level histogram width can be further tumors by the scanning of grey-level histograms. Yonago
applied in general medicine including the diagnosis of adult liver. Acta Med. 1989;32:251-60.
CHAPTER
5
Transrectal Sonography
Maher G Sarraf, Muna T Al-Abdulla, Omar A Al-Omari
Introduction Both TRS and TVS probes are designed as elongated

finger-like instruments that fit their respected hollow
The rectum is a hollow viscous connecting the sigmoid organs, with diameters less than other older instruments
colon to the anal canal. It lies posterior to the female such as the vaginal speculum or the rectoscope (Fig. 5.2).
genital organs, that include the vagina, cervix, and uterus. The classical transrectal linear probe, introduced a few
It is situated anatomically more or less parallel to the decades ago, was designed originally for the sole aim of
vagina; hence, the uterus will be in most cases, anteverted examining the prostate. It included a linear array transducer
anteflexed on the rectum (Fig. 5.1). with a wave direction of 90° angle to the axis of the probe
Transrectal sonography (TRS) was first performed to itself. This design had limited its usefulness in examining
examine the male prostate, and then its use was extended the female pelvic organs.
to examine other pelvic organs in both males and females. The convex probe that was introduced in the late 1980s
In this chapter, the authors have presented a basic and offered a better image of the female pelvis. It projects sound
general overview on the topic of “transrectal sonography”: waves frontally in 90–240° sectors, which divide the pelvis
its indications, contraindications, techniques, and their own into fan-shaped planes. With such a probe, the pelvis can be
experience with TRS. adequately assessed transrectally or transvaginally, in both
sagittal and coronal planes.
Probes, Planes, and Orientation From the authors’ experience, they prefer to use the offset
The anatomical proximity and similarity of the rectum to or stearable probes in order to decrease the intracavitary
the vagina imposes much of the similarities between TRS probe movements while examining lateral structures or
and transvaginal sonography (TVS) in relation to their severely anteverted or retroverted uteri.
probe designs, basic probe movements, scanning planes, The radial probe is a recently developed rectal probe,
and orientation difficulties. which gives an axial image of the rectal canal and greatly
helps assess the perirectal space as well as the integrity and
pathology of the anal sphincter. Its axial image demonstrates
the rectum as a multilayered circle. However, this probe is
expensive and its use is better saved for cases of suspected
anal sphincter trauma or anorectal canal pathologies.
A biplanar probe was introduced and used by some
authors1 to assess the pelvic structures in two planes at the
same time.
Both TRS and TVS share the five basic probe movements,
which include sliding, rocking, tilting, rotating and
compressing.
Using the transabdominal sonography (TAS) approach,
we can obtain an infinite number of sagittal, coronal, and
transverse planes of the examined structures. On the other
Figure 5.1 Relation of transrectal sonography probe to the pelvic hand, using TVS or TRS can only yield a midsagittal and
anatomy coronal planes, but no transverse planes. Any attempt
Figure 5.2 Transrectal sonography probes
A A
B B
Figures 5.3A and B Planes of sonographic examination Figures 5.4A and B Orientation problem of transcavitary sonography
to obtain parasagittal planes will ultimately cause some an articulating monitoring system to allow rotation of the
discomfort to the patient and only yield oblique views (Figs monitor according to the anatomical position of the patient.
5.3A and B). Meanwhile, it leaves the operator with the responsibility to
Whether the ultrasound examination is done in the supine correct the image direction in this mind.
or the lateral decubitus positions, a problem of orientation
will be faced since the sonographic waves are sent in a
direction different from that of the displayed image on the
Indications of Transrectal Sonography
monitor (Figs 5.4A and B). The need for eye-hand movement Transrectal sonography was first introduced in the field
synchronization adds to the orientation difficulty. Yee et al.2 of gynecology as an alternative to TVS in cases where
suggested that the ultrasound manufactures should develop TVS was impossible to perform, or when it produced
Chapter 5  Transrectal Sonography 23
unsatisfactory results. Transrectal sonography thereafter
became a complementary investigation that provides
additional information to TVS or TAS examination. Many
clinicians are now using TRS during some interventions in
order to ease the procedure or in some instances to obtain
more accurate results.
Transrectal sonography is indicated instead of TVS in
cases of virginity, especially in conservative communities
where virgins do not accept any interference, which may
lead to hymen injury (Table 5.1).
Children and young adolescents are also candidates of
TRS rather than TVS due to the psychological trauma that
may occur due to the vaginal examination and due to the
anatomical limitations imposed by narrow and short vagina.
Anatomical characteristics of that age group like the higher
ovarian level and the higher ratio of cervical to uterine sizes
should be kept in mind (Fig. 5.5). Figure 5.5 Vagina, cervix and uterus in an 8-year-old adolescent
Some congenital genital tract abnormalities may also
make TVS impossible. These include vaginal atresia,
transverse vaginal septum, Rokitansky-Küster-Hauser
syndrome, hematocolpometrium, etc. (Fig. 5.6).
Table 5.1 Indications of transrectal sonography

Instead of TVS
• Virginity
• Children and young adolescents
• Congenital genital tract abnormalities: vaginal atresia, trans
verse vaginal septum, Rokitansky-Küster-Hauser syndrome,
hematocolpometrium, etc.
• Vulvovaginal atrophy: senile, postirradiation, etc.
• Postoperative vaginal shortening
• Cervical cancer staging
Figure 5.6 Enlarged cervix may draw attention to possible cervical
• Vulvovaginal lesions carcinoma
• Anorectal pathologies: fistulas, trauma, neoplasia, etc.
• Preterm premature rupture of membranes Transrectal sonography can be considered as the diagnostic
In addition to TVS
method of choice in the assessment of canalization defects of
the vagina. This was supported by many authors. Fedel et al.3
• Retroverted uteri
compared TRS, TAS and MRI with surgical findings in nine
• Distant ovarian lesions
cases of Rokitansky-Küster-Hauser syndrome and transverse
• Ectopic pregnancy
vaginal septa. They reported that TRS was superior to TAS
Interventional
and MRI in predicting the surgical findings. Several other
• Dilatation and curettage
authors like Kushnir et al.4 and Anguenot et al.5 reported
• Intrauterine contraceptive device and radiotherapy tandem that TRS is the diagnostic method of choice for transverse
insertion or removal
vaginal septa and imperforate hymen.
• Cervical cerclage
Gerald Lopez-Rasner et al.1 assessed the value of TRS
Emergencies
in the diagnosis of vaginal abnormalities using a biplanar
• Bleeding
probe equipped with 5 MHz axial sector and longitudinal
• Ascites linear transducers. Their TRS findings were confirmed later
• Appendicitis by surgical findings.
Postmenopausal vulvovaginal atrophy, atrophy following

radiotherapy and postoperative short vaginal cuffs are
other gynecologic contraindications of TVS, thus, TRS is
indicated.
Transrectal sonography was found to be effective in
cervical carcinoma staging, detection of vulvovaginal
lesions, and in the examination of rectoanal canal
pathologies, such as fistulas, sphincter trauma and
neoplastic lesions (Fig. 5.7).
Transrectal sonography can also demonstrate bladder,
ureteral, vaginal, and rectal involvement in cases of cervical
carcinoma. Areas of increased echogenicity or hypoechoic
areas with an irregular outline signify changes compatible
with cervical carcinoma.6
Rifkin and Marks 7 showed that TRS can detect Figure 5.7 Hematocolpometrium evident by transrectal sonography
masses situated within 12 cm of the anus. They also

demonstrated that TRS can detect perirectal fat infiltration
by malignancies, and perirectal lymph node infiltration at
least as accurate as CT scanning.
St. Ville et al.8 stated that TRS is very effective in
identifying and localizing rectal wall lesions, although these
findings are usually nonspecific.
Pretlove et al.9 studied the use of TRS immediately
postpartum to detect sphincter injuries (Fig. 5.8) and the
adequacy of primary repair. They found that TRS was an
acceptable, noninvasive and reliable method even in cases
of epidural anesthesia.
Erbay et al. 10 reported the diagnosis of rectal
hydrocystoma by TRS. Anorectal canal was described to
be best examined using a radial 7–10 MHz probe.
Figure 5.8 A radial transrectal sonography showing postpartum
Transrectal sonography is seen to be favorable for pelvic sphincter injury about the position of 6 o’clock
examination in cases of preterm premature rupture of
membranes, where chorioamnionitis is a major concern.
Transrectal sonography is also found to be of value in
addition to TVS in some cases such as retroverted uteri,
ovarian lesions distant from vagina (Fig. 5.9), fundal uterine
pathologies (Figs 5.10A and B), and suspected ectopic
pregnancies.
In cases of retroverted uteri, TRS may give a better view
as it is sometimes difficult to depict the endometrium and
measure its thickness using TVS. This is due to the fact
that sonographic waves are aligned with the endometrium
in case of TVS, while they are perpendicular to the
endometrium in case of TRS (Figs 5.11A and B).
Furthermore, TRS is frequently used as a monitoring
tool during interventions, such as dilatation and curettage
(Fig. 5.12), intrauterine contraceptive device insertion and Figure 5.9 Transrectal sonography advantage of detecting distant
removal (Fig. 5.13), cervical cerclage to localize the level ovarian pathologies
A B
Figures 5.10A and B Fundal uterine fibroid displayed by (A) transrectal sonography better than (B) transvaginal sonography
A B
Figures 5.11A and B The transrectal sonography advantage of examining endometrium in retroverted uteri
Figure 5.12 Endometrium polypectomy under transrectal sonography Figure 5.13 The intrauterine device removal guided by transrectal
guidance sonography
of internal os, and in intrauterine radiotherapy tandem communities such as ours. It has to be clearly stated that
insertion. this procedure does not interfere with the hymen, especially
Fleischer et al.11 studied the effect of TRS in dilation if this mode of examination is chosen for the main aim of
and curettage, and intrauterine tandem insertion. They “preserving” virginity.
found that it clearly helped in providing guidance for those To undergo the examination, the patient is usually
procedures and helped to avoid uterine perforations. Similar undressed only from waist downward. A gown or suitable
results were found with cervical cerclage placement. cover is offered. The patient is recovered after introducing
Kuligowska et al.12 studied and proved the efficacy of the probe. The authors do prefer the presence of an
TRS in pelvic abscess drainage using an ultrasound-guided accompanying colleague, especially when examining patients
needle aspiration and lavage. Savader et al.13 preferred the who are supposed to be virgins.
use of biplanar probes TRS for this purpose due to the The authors did find the supine position to be less
accurate localization of pelvic masses. embarrassing, less uncomfortable and easier for the
Moreover, TRS is seen to be helpful in some emergencies as sonographer. However, some authors, like Wachsberg,15
in cases of intra-abdominal bleeding, appendicitis and ascites. advocate the left lateral decubitus position.
A cushion placed under the lower back of the patient
Safety and Contraindications may ease the examination.
When examining virgins, the authors perform the
The safety of introducing TRS probes into the rectum has procedure in the presence of another physician, and in the
been questioned. We can advocate its safe use depending supine position. The supine position helps in demonstrating
on our own experience and on our extensive literature both the vulva and anus when you separate the buttocks.
review about trauma of similar older procedures. To date, The examiner has to make sure that the fourchette lies
there has not been any reported case of rectal trauma during anterior to the probe before its introduction into the anal
rectoscopy in the English literature. canal. It is preferable to show the patient that the probe is
Anderson et al.14 reported that in 10,486 colonoscopies contaminated with stool but not blood after its withdrawal.
over a period of 10 years, only 0.19% perforations were In cases of interventional TRS, the authors found it more
noted, and most of them were due to the use of cautery. practical for the operator to hold the probe in his left hand.
The TVS probe penetrates only 10–12 cm into the The authors use disposable plastic speculums with
rectum, and it is highly unlikely to cause any trauma even the blades directed sideways rather than the usual
if it is advanced further. anteroposterior position. This helps obtain a better view
The contraindications of TRS, which are usually relative, (Fig. 5.14).
are similar to those of a rectal examination. This includes
acute anal fissure, severe or thrombosed piles, or severe
inflammatory bowel disease with rectal ulceration.
Technique and Preparation

The authors have been practicing TRS for almost 5 years
now. During this period, the main concerns that were voiced
and seen among our patients were embarrassment, fear of
pain and anxiety about their virginity.
Extensive explanation of the procedure and its potentially
added efficacy in diagnosis was relayed to the patients
to put them at ease. We made sure that the patients were
well informed about the aim of the procedure. They were
informed that TRS is an uncomfortable examination but not
painful. Showing the patient the probe proved to be helpful.
As mentioned previously, the issue of conserving
virginity is a main concern, especially in conservative Figure 5.14 Shadow of metal speculum
The procedure is equally tolerated by elderly and young
patients. The authors did not find any significant advantages
of using local anesthesia or an enema, although some
authors had advocated the use of local anesthesia.7
Authors’ Results
The authors have carried out a study in their center
comparing the reliability of TAS with that of TRS (these
results have not been published yet).
They examined 74 patients using TAS and TRS. Their
findings were confirmed either by laboratory investigations,
other radiological assays or surgical findings.
The findings included polycystic ovaries (Fig. 5.15),
ovarian cysts (Figs 5.16A and B), myomas, hematocolpometra, Figure 5.15 Polycystic ovary as seen by transrectal sonography in a
Rokitansky-Küster-Hauser syndrome, streak ovaries and 19-year-old virgin female
endometrial polyps (Figs 5.17A and B).
They found that TRS was superior to TAS in 72 cases and
similar to TAS in one case. Furthermore, TAS was superior
to TRS in one case only due to the large size of an ovarian
cyst that was obstructing the pouch of Douglas.
Their results were comparable to other studies published
on the same topic, especially Timor-Tritsch et al.16 who
performed their study on 42 patients and found a superior
value of TRS in 41 of them (Table 5.2).
Summary
It is of great importance to appreciate and recognize that TRS is
another modality of ultrasonic examinations that is not merely an
alternative but rather a complementary one, one which can add
crucial clinical information to the standard ways of examination. A
It is through this concept that the authors want to highlight the
importance and usefulness of TRS in the field of obstetrics and
gynecology.
Throughout this chapter, authors have provided the reader with
a general but comprehensive picture regarding TRS. They have
described various scenarios and indications where TRS is the
only acceptable modality of examination and instances where
TRS completes the clinical picture at hand. In conclusion, they
have explained their experience and extent of future possibilities
of TRS, which will hopefully open the doors for further research
and clinical trials into this novel and exciting dimension of
ultrasonography.
Acknowledgment
The authors of this chapter would like to thank Dr. Khaled B
Sarraf, BSc. (Hons.) MBBS (London) for his contributions Figures 5.16A and B Ovarian cyst seen by (A) tranrectal sonography
to this chapter. much better than (B) transabdominal sonography
Table 5.2 Results of the study References

Normal findings No. of cases
1. López-Rasines G, Abascal F, Calabia A, et al. Transrectal
Polycystic ovaries 57
sonography in the assessment of vaginal pathology: a
Ovarian cysts 6 preliminary study. J Clin Ultrasound. 1998;7:353-6.
Uterine fibroids 5 2. Yee B, Rosen GF, Cassidenti DL. Transvaginal sonography
in infertility. Lippincott-Raven Publishers;1995.pp.1-25.
Rokitansky-Küster syndrome 2
3. Fedel L, Portuese A, Bianchi S, et al. Transrectal
Hematocolpometrium 1 ultrasonography in the assessment of congenital canalization
Streak ovaries 1 defects. Hum Reprod. 1999;14:359-62.
4. Kushniro O, Garde K, Blankstein J. Rectal sonography for
Endometrial polyp 1
diagnosing hematocolpometra: a case report. J Reprod Med.
Diagnosis 1 1997;42:519-20.
5. Anguenot JL, Ibecheole V, Salvat J, et al. Hematocolpos
secondary to imperforate hymen, contribution of transrectal
echography. Acta Obstet Gynecol Scand. 2000;79:614-5.
6. Innocenti P, Pulli F, Savino L, et al. Staging of cervical cancer:
reliability of transrectal US. Radiology. 1992;185:201-5.
7. Rifkin MD, Marks GJ. Transrectal US as an adjunct in
the diagnosis of rectal and extrarectal tumors. Radiology.
1985;157(2):499-502.
8. St. Ville EW, Jafri SZ, Madrazo BL, et al. Endorectal
sonography in the evaluation of rectal anal perirectal disease.
AJR Am J Roentgenol. 1991;157:503-8.
9. Pretlove SJ, Thompson PJ, Guest P, et al. Detecting anal
sphincter injury: acceptability and feasibility of endoanal
ultrasound immediately postpartum. Ultrasound Obstet
Gynecol. 2003;22:215-7.
10. Erbay N, Kruskal JB, Kane RA. Rectal hydrocystoma. J
Ultrasound Med. 2002;21:933-5.
A 11. Fleischer AC, Burnett LS, Jones HW, et al. Transrectal
and transperineal sonography during guided intrauterine
procedures. J Ultrasound Med. 1995;14(2):135-8.
12. Kuligowska E, Keller E, Ferrucci JT. Treatment of pelvic
abscesses: value of one-step sonographically guided
transrectal needle aspiration and lavage. AJR Am J
Roentgenol. 1995;164:201-6.
13. Savader BL, Hamper UM, Sheth S, et al. Pelvic masses:
aspiration biopsy with transrectal US guidance. Radiology.
1990;176:351-3.
14. Anderson ML, Pasha TM, Leighton JA. Endoscopic
perforation of the colon: lessons from a 10-year study. Am
J Gastroenterol. 2000;95:3418-22.
15. Wachsberg RH. Transrectal ultrasonography for problem
solving after transvaginal ultrasonography of the female internal
reproductive tract. J Ultrasound Med. 2003;22:1349-56.
B 16. Timor-Tritsch IE, Monteagudo A, Rebarber A, et al. Transrectal
Figures 5.17A and B Endometrium polyp can be displayed by (A) scanning: an alternative when transvaginal scanning is not
transrectal sonography much better than (B) transabdominal sonography feasible. Ultrasound Obstet Gynecol. 2001;21:473-9.
Section 2
OBSTETRICS
¯¯ Fetal Anatomy on the First Trimester of Pregnancy
¯¯ Ultrasound Imaging of Early Extraembryonic Structures
¯¯ Ultrasound Markers of Aneuploidy in the First Trimester
¯¯ Early Detection of Fetal Abnormality
¯¯ Echocardiography in Early Pregnancy
¯¯ Assessment of Fetal Central Nervous System
¯¯ Ultrasonographic Signs of Poor Pregnancy Outcome
¯¯ Placenta and Transvaginal Sonography
¯¯ Assessment of Placental Vascularization by Three-dimensional Power Doppler Ultrasound: Placental
Biopsy in Normal Pregnancies
¯¯ Cervical Measurements and Preterm Labour
¯¯ Transvaginal Assessment of the Cervix
¯¯ Cervix in the First Trimester of Pregnancy
¯¯ Transvaginal Sonography in Multiple Pregnancy
CHAPTER
6 Fetal Anatomy on
the First Trimester of Pregnancy
Aris Antsaklis, A Souka
Introduction of the neck, abnormal collagen biosynthesis, fetal anemia

and congenital infections.
First trimester ultrasound scan was initially used to date the The majority of the fetal organs can be visualized in
pregnancy. In the last 15 years, technological progress and the first trimester, and transvaginal scanning has greatly
in particular the introduction of the transvaginal approach increased our ability to examine the first trimester fetus.
made possible the detailed examination of fetal anatomy Using ultrasound scanning in the first trimester, we can
in the first trimester, the diagnosis of structural defects. accurately date the pregnancy, establish fetal viability and
In the decade, a number of studies have shown that ascertain chorionicity in multiple pregnancies. At 11–14
nuchal translucency (NT) (the accumulation of fluid in weeks, we can estimate the risk of chromosomal defect by
the nuchal area) can be measured by ultrasound at 11−14 NT measurement and examine fetal anatomy.
weeks (Fig. 6.1). Nuchal translucency measurement is a
sensitive and accurate screening test for the diagnosis of
chromosomal abnormalities yielding a sensitivity of about
Normal First Trimester Fetus
75% for a 5% screen positive rate.1 The introduction of first Several ultrasound studies4-28 using mainly the transvaginal
trimester biochemical markers free beta-human chorionic approach at 4–12 weeks of gestation describe the
gonadotropin and pregnancy associated plasma protein-A development of the normal fetus as follows:
has increased the sensitivity to about 90% for the same
screen positive rate.2 4th Week
Increased NT at 11–14 weeks has been associated with The gestational sac is visible from about 4 weeks and 3 days
structural defects and, in particular cardiac defects and a wide as a hypoechoic, ring-like 2–3 mm structure surrounded by
range of genetic syndromes.3 Possible pathophysiological a hyperechoic rim. Further details within the sac cannot
mechanisms include cardiac dysfunction, venous stasis, yet be defined. The sac represents the chorionic cavity and
anomalous or delayed development of the lymphatic vessels is typically located in the upper part of the decidualized
endometrium in an eccentric position.
5th Week
The yolk sac becomes visible as the first structure within the
sac at about 5 weeks and is always present at 5 weeks and
4 days. At the end of the 5th week, the fetal pole measuring
2–3 mm can be seen by the yolk sac, and heart motion may
be identified. At this stage, the fetal heart rate is about 100
beats per minute.
6th Week
At 6 weeks, the embryo measures crown-rump length
(CRL) 4–8 mm. The fetal pole, yolk sac and heart motion
Figure 6.1 A 7-week fetus. The arrow points to the cavity of the are always visible. Heart activity should always be seen
rhombencephalon in embryos of 5 mm (6 weeks and 4 days) or more.
32 Section 2  Obstetrics
The gestational sac contains two fluid-filled cavities: The limbs appear as short echogenic outgrowths and the
(i) the celomic (chorionic) cavity with the yolk sac and first body movements become visible during the 8th week.
(ii) considerably smaller amniotic cavity with the fetal
pole. The two cavities are separated by a thin membrane 9th Week
surrounding the embryo, “the amniotic membrane”. At the At 9 weeks, the CRL is 23–31 mm. The amniotic cavity
end of 6th week, the cavity of rhombencephalon becomes is now larger than the celomic cavity and occupies most
visible as a small hypoechogenic area at the cephalic part of the sac volume. The fetal body becomes ellipsoid with
of the fetal pole. the head being disproportionally big, and soles of the feet
touch in the midline. The choroid plexuses are obvious
7th Week and occupy almost fully the lateral ventricles. The cortex
At 7 weeks, the CRL is 9–14 mm and the mean heart rate is thin and hypoechoic. The cerebral hemispheres become
is about 130 beats per minute. The amniotic cavity starts visible and are clearly separated. The connection between
expanding rapidly. The head can be distinguished from the the mesencephalon and third ventricle becomes narrower.
body, and hypoechogenic areas (brain vesicles) (Fig. 6.1) The fetal heart rate reaches a peak of about 175 beats per
appear in developing brain at the cephalic end of the minute. Bowel herniation is visible in all fetuses. The first
embryo. The cavity of rhombencephalon that will eventually ossification centers can be seen at the mandible and clavicle.
form the pons and cerebellum can always be identified at Limb movements can be identified.
7 weeks as a rhomboid, hypoechoic area at the cranial
pole of the embryo. At this stage, the rhombencephalon is Postembryonic Period (10–11 Weeks)
larger than the developing hemispheres. The small cavities During the postembryonic period, CRL is 32–54 mm.
of the hemispheres originating from the dividing Y-shaped The fetus acquires human shape and fetal body becomes
telencephalon, diencephalon (that will form the thalami, longer although the head is still disproportionally large
hypothalamus and the third ventricle) and mesencephalon with a prominent forehead and a flat occiput. The cerebral
(that will later form the nuclei and the aqueduct of Sylvius) hemispheres start being detectable during the 9th week.
may be identifiable. Ossification starts from the occipital bone at 10 weeks.
The umbilical cord is short and appears wider and The cortex is about 1 mm thick at the end of the first
hyperechogenic at the point of insertion in the abdomen; trimester. The lateral ventricles occupy completely the
this is the first sign of bowel herniation into the cord. The anterior part of the head and cover the diencephalon. The
lower limb buds can vaguely be depicted. mesencephalon gradually moves toward the middle of the
brain, third ventricle; after a transient increase, becomes
narrow and the cerebellar hemispheres fuse in the midline
8th Week 11–12 weeks. Fetal heart rate drops to about 165 beats
At 8 weeks, CRL is 15–22 mm, brain vesicles are more per minute at the end of the 11th week. The motion of
prominent and choroid plexuses can be visualized as small the atrioventricular valves and the atrial and ventricular
hyperechogenic areas. The rhombencephalon is still the septa may be visible at 10 weeks. All cardiac structures
largest cavity lying on top of the brain. There is a broad can be visualized at the end of the 11th week. Starting
connection between lateral ventricles, diencephalon and from the end of the 8th week, small bowel herniates into
mesencephalon. Fetal heart rate is about 160 beats per the umbilical cord and gives sonographic appearance of a
minute and the heart occupies more than 50% of the hyperechogenic mass at insertion of the cord. Maximum
thoracic cavity. Atria and ventricles are sometimes visible herniation of the bowel is detectable at the beginning of
at the end of the 8th week. The abdominal cavity is fully 10th week, whereas return of the bowel in the abdominal
occupied by the liver anteriorly and stomach dorsally while cavity begins at 10 weeks and 4 days and is usually
the intestine is herniated into the umbilical cord. Fluid in completed at 11 weeks and 5 days. In 75% of embryos the
the stomach can occasionally be seen toward the end of stomach is visible before the 10th week. The ossification
the 8th week probably as a product of gastric epithelium, centers of the spine and the long bones start being visible
since swallowing movements only start at 11 weeks. The at 10 weeks. The ossification of the spine begins at the
outlines of the skull, spine, and ribs can vaguely be seen. level of cervical vertebrae and spreads caudally to the
Chapter 6  Fetal Anatomy on the First Trimester of Pregnancy 33
thoracic and lumbosacral areas during weeks 12 and 13. anatomy at this gestational period has been reported from
Ossification of the metacarpals and metatarsals can be specialists in fetal echocardiography and has been mainly
identified at 12 weeks. The digits and sometimes the toes limited to high-risk pregnancies.35-45
become visible from 11 weeks. Two studies20,46 examining fetal anatomy at 11–14 weeks
have used the following protocol:
ÀÀ Skull and brain: Examination of the completeness of
Fetal Anatomy at 11–14 Weeks skull, presence of midline in the brain and butterfly shape
Although in general population, structural defects are of the choroid plexuses (Fig. 6.2)
relatively common (3–5%) and cardiac defects are the most ÀÀ Face: Examination of orbits and lenses and view of the
common amongst them, a few studies have addressed the fetal profile (Figs 6.3 and 6.4)
issue of fetal anatomy in low-risk populations as part of ÀÀ Spine: Examination of the alignment of vertebrae and
the 11–14 weeks scan.20,29-34 Visualization of the cardiac skin covering the spine (Fig. 6.5)
Figure 6. 2 Skull and brain Figure 6.3 Face
Figure 6.4 Fetal profile Figure 6.5 Spine

Figure 6.6 Heart—the four-chamber view Figure 6.7 Heart—the three-vessel view
Figure 6.8 Transverse section of the abdomen—the stomach Figure 6.9 Umbilical cord insertion
ÀÀ Heart: Examination of the four-chamber view and great ÀÀ Extremities: Examination of the long bones, fingers,
vessels (three-vessel view) (Figs 6.6 and 6.7) toes, and movement and posture of the joints (Figs 6.12
ÀÀ Stomach: Visualization of the stomach as a hypoechoic and 6.13).
structure at the left upper abdomen (Fig. 6.8) In a study of 1,144 fetuses examined by at 11–14 weeks
ÀÀ Abdomen: Examination of the umbilical cord insertion with a combination of the transabdominal and transvaginal
into the abdominal wall (Fig. 6.9) routes, full check of the fetal anatomy was achieved in 48%
ÀÀ Kidneys: Visualization of the kidneys as hyperechoic of the fetuses, whereas noncardiac anatomy was visualized
structures with a hypoechoic center laterally to the spine in 86% of the fetuses.46 Successful visualization of the fetal
(Fig. 6.10) organs depended on CRL (Table 6.1). The use of transvaginal
ÀÀ Bladder: Visualization of the bladder as a hypoechoic approach increased successful examination of fetal anatomy
structure in the fetal pelvis (Fig. 6.11) from 72–86% of the fetuses (Table 6.2). Transvaginal
Figure 6.10 Fetal kidneys Figure 6.11 Fetal bladder
Figure 6.12 Lower extremity Figure 6.13 Fetal hand
scanning was particularly helpful in examining the face, use of the transvaginal approach increased successful
kidneys and bladder. examination of fetal anatomy from 72–95%.20 In both the
In a screening study for structural abnormalities at 11–14 studies, factors influencing visualization of the fetal organs
weeks using transvaginal ultrasound, fetal anatomy (not were gestation, maternal habitus and uterine position, and
including face and heart) was seen in 94% of the cases.30 the authors stress the contribution of transvaginal ultrasound
Similarly in an anatomical survey of 298 fetuses at 12+0 in completing the examination of the fetus.
to 13+6 weeks of gestation, Braithwaite et al. were able A few studies have addressed the issue of visualizing
to complete the examination of fetal anatomy, including the four-chamber view and outflow tracts at 11–14 weeks
the four-chamber view in 95% of the fetuses.20 With the (Tables 6.3 and 6.4).36-39,44,46,47 Examination of the fetal heart
combination of transabdominal and transvaginal routes, at this early gestation is still mainly restricted to high-risk
the four-chamber view of the heart was seen in 97% of the patients and performed in specialized centers by experts
fetuses, bladder in 98% , head, brain and kidneys in 99% in fetal echocardiography. Visualization rates of the four-
and remaining organs (diaphragm, stomach, abdominal chamber view improved with gestation, remaining poor
wall, spine and extremities) in 100% of the fetuses. The before 11 weeks and increasing to more than 90% during
Table 6.1 Visualization of fetal anatomic structures according to crown-rump-length. Anatomy check I includes all other organs except of
the heart and anatomy check II includes all organs including heart anatomy46
CRL N Anatomy Anatomy Head/ Face Spine Heart Abdomen Stomach Kidneys Bladder Extremities
(mm) check I check II brain
45–54 174 113 38 174 171 172 44 172 166 123 170 174
(64.94%) (21.83%) (100%) (98.27%) (98.85%) (25.28%) (98.85%) (95.40%) (70.68%) (97.70%) (100%)
55–64 400 337 173 400 398 399 183 400 398 341 397 400
(84.25%) (43.25%) (100%) (99.5%) (99.75%) (45.75%) (100%) (99.50%) (85.25%) (99.25%) (100%)
65–74 413 386 233 413 409 413 238 413 412 388 412 413
(93.46%) (56.41%) (100%) (99.03%) (100%) (57.62%) (100%) (99.75%) (93.94%) (99.75%) (100%)
75–82 157 150 105 157 157 157 105 157 157 150 157 157
(95.54%) (66.87%) (100%) (100%) (100%) (66.87%) (100%) (100%) (95.54%) (100%) (100%)
Total 1,144 986 549 1,144 1,135 1,141 570 1,142 1,133 1,002 1,136 1,144
(86.18%) (47.98%) (100%) (99.21%) (99.73%) (49.82%) (99.82%) (99.03%) (87.58%) (99.30%) (100%)

Table 6.2 The contribution of transvaginal scanning in visualizing the lowest detection rate reports on all (major and minor)
fetal anatomy according to crown-rump-length46 anomalies; if only major anomalies are included, the first
CRL (mm) N TAS TAS + TVS trimester scan sensitivity would be 50.8% and the overall
45–54 174 99 (56.89%) 113 (64.94%) ultrasound scan sensitivity 78.8%.34 Detection rates in the
55–64 400 301 (75.25%) 337 (84.25%) two other studies have been calculated excluding nuchal
65–74 413 307 (74.33%) 386 (93.46%) anomalies. The majority of abnormalities diagnosed in
74–82 157 119 (75.79%) 150 (95.54%) the second and third trimesters would not be detectable
Total 1,144 826 (72.20%) 986 (86.18%) in the first trimester including central nervous system
defects (microcephaly, ventriculomegaly, brain atrophy,
Dandy-Walker malformation, cerebellar asymmetry),
the 12th and 13th week (Table 6.3). Similarly, visualization cardiac defects (tetralogy of Fallot, hypoplastic left heart,
of the outflow tracts was achieved in the majority of the ventricular septal defects), renal defects (hydronephrosis,
fetuses examined between 12+0 and 13+6 weeks of gestation. multicystic dysplastic kidneys) and gastrointestinal defects
Only two studies have examined cardiac anatomy as part of (bowel obstruction). However, it is likely that at least some
the routine 11–14 weeks scan.20,46 In the first study of 298 of the cases of neural tube defects and cardiac defects and
women, examination was performed at 12+0 to 13+6 weeks probably all cases of abdominal wall defects and limb
and the four-chamber view was seen in 76% of fetuses reduction defects will in the future be diagnosed in the first
transabdominally, 95% transvaginally and 97% using a trimester. These studies have shown that the first trimester
combined approach. Outflow tracts were not examined.20 scan can detect more than one-third of the major structural
In the second study, 1,144 women were examined at 11+0 to anomalies, including lethal anomalies or those leading to
13+6 weeks of gestation (CRL 45–82 mm). Complete cardiac severe handicap (anencephaly, holoprosencephaly, body
anatomy was seen in 50% of fetuses with visualization of stalk anomaly).
the four-chamber view in 87% of cases and of the three- In conclusion, examination of the fetal anatomy is feasible
vessel view in 50% of cases. during the routine 11–14 weeks scan and the completeness
of the examination mainly depends on maternal habitus
Studies Screening for Structural and gestational age. It is clear that the optimal gestation
for examining both cardiac and noncardiac anatomy starts
Defects by First Trimester Ultrasound from the beginning of the 12th week to the end of the 13th
Three studies on a total of 12,327 pregnancies have week of gestation. Access to the transvaginal approach is
examined the impact of assessing fetal anatomy in the important in completing the examination.
first trimester on the detection rate of structural defects With the modern trend of shifting prenatal diagnosis at
(Table 6.5). The differences in the detection rates can the earliest possible gestation and the advancing technology,
mainly be attributed to differences in protocols, definition it is not difficult to see the 11–14 weeks scan becoming a
and postnatal ascertainment of anomalies. The study with first mini-anomaly scan with the aim to diagnose the
Table 6.3 Visualization rates of the 4-chamber view according to gestational age
Visualization rate % (Number of fetuses examined)
Author 10–10+6 wk 11–11+6 wk 12–12+6 wk 13–13+6 wk
Dolkart and Reimers 0 (8) 30 (10) 90 (10) 100 (13)
199136
Johnson et al 199237 27 (26) 58 (33) 71 (51) 74 (61)
Bronshtein et al 199238 NE 17 (18) 36 (25) 100 (NS)
Gembruch et al 199339 NE 80 (15) 93 (30) 100 (51)
Gembruch et al 2000 47 56 (9) 88 (16) 93 (15) 100 (16)
Haak et al 200244 NE 85 (85) 97 (85) 98 (85)
Souka et al 2004 46 NE 67 (1,144) 87 (1,144) 96 (1,144)
Abbreviations: NE, not examined; NS, not specified
Table 6.4 Visualization rates of the outflow tracts according to gestational age
Visualization rate % (Number of fetuses examined)
Author Vessel 10–10+6 wk 11–11+6 wk 12–12+6 wk 13–13+6 wk
Dolkart and Reimers Aorta 0 (10) 20 (10) 40 (10) 46 (13)
199136
Pulmonary 0 (10 0 (10) 40 (10 38 (13)
Johnson et al 199237 Aorta 4 (26) 24 (33) 59 (51) 62 (61)
Pulmonary 12 (26) 21 (33) 41 (51) 51 (61)
Gembruch et al 199339 Combined NE 67 (15) 80 (30) 100 (51)
Gembruch et al 2000 47 Combined 44 (9) 75 (16) 93 (15) 100 (16)
Haak et al 200244 Aorta NE 33 (85) 77 (85) 95 (85)
Pulmonary NE 75 (85) 89 (85) 98 (85)
Souka et al 2004 46 Combined NE 25 (1,144) 48 (1,144) 61 (1,144)
Abbreviation: NE, not examined
Table 6.5 Screening studies of major structural abnormalities by first trimester ultrasound
Author N Anomalies Prenatal diagnosis
Total 11-13+6 wk
Hernandi and Torocsik, 199730 3,991 40 30 (75.0%) 11 (27.5%)
Economides et al, 1998 33 1,632 13 10 (76.9%) 7 (53.8%)
Carvalho et al, 200234 2,853 66 52 (78.8%) 25 (37.8%)
Drysdale et al, 2002 48 960 18 15 (83.3%) 2 (11.1%)
Total 9,436 137 94 (68.6%) 58 (42.3%)
severest structural anomalies, thus giving the parents earlier cranium and cerebral hemispheres. Animal studies have
reassurance about the wellbeing of their fetus. shown that the absence of skull leads to progressive
degeneration and destruction of the brain tissue. Similarly,
Structural Defects at 11–14 Weeks ultrasound studies have shown that in human embryo acrania
progresses to exencephaly and anencephaly.48-57 Acrania,
Central Nervous System Defects meaning the absence of skull (cranium) is the hallmark of
Acrania/Anencephaly (Birth Prevalence 1 in 1,000) anencephaly in the first trimester. The brain may show signs
The diagnosis of anencephaly in the second and third of degeneration or even appear normal. Several authors have
trimesters of the pregnancy is based on the absence of described cases of anencephaly from as early as 9 weeks;
the appearance of the brain varies from echogenic and are

disorganized with abnormal shape of the skull and head
circumference smaller than the abdominal circumference
to completely normal.49,50,54-56 In the four screening studies
for structural defects by first trimester ultrasound, all cases
of anencephaly were diagnosed in the first trimester.30,32,34,48.
In two screening studies for chromosomal abnormalities by
NT measurement on a total of 6,861 pregnancies, all seven
anencephalic fetuses were correctly identified in the first
trimester.51,57 In another screening study of about 54,000
pregnancies, there were 47 cases of anencephaly.52 In the Figure 6.14 Spina bifida in a 13-week fetus
first phase of the study, sensitivity of the first trimester scan
for diagnosing anencephaly was 74% (23 of 31 cases), but
this increased to 100% (16 of 16 cases) in the second phase
when sonographers were instructed to look for the specific
signs of anencephaly at this early gestation.
Holoprosencephaly (Birth Prevalence 1 in 5,000)

This rare but severe defect covers a spectrum of conditions
where there is a defect in division of the prosencephalon,
frontal part of the brain. There are three types (lobar,
semilobar and alobar holoprosencephaly) depending on the
degree of fusion of the prosencephalon. In the lobar type,
ventricles and thalami are divided, but the cavum septum
pellucidum is absent. In the semilobar type, the lateral
ventricles and thalami are only partially separated, and in
the alobar type there is complete fusion of the ventricles
with a large monoventricle and fused thalami. The defect is
strongly related to chromosomal abnormalities (particularly
trisomies 13 and 18) and other structural defects (mainly
facial clefts). Holoprosencephaly was present in 24% of the Figure 6.15 Lemon sign in a 13-week fetus
46 fetuses with trisomy 13 at 10–14 weeks described by
Snidjers et al.58 The diagnosis of the alobar type has been
reported in the first trimester based on the visualization of of the diagnosis of spina bifida in the second trimester
a single ventricle and fusion of thalami.59-67 In the earliest are scalloping of the frontal bones of the skull (lemon
report of alobar holoprosencephaly, Blaas et al. diagnosed sign) and displacement of the cerebellum (Arnold–Chiari
the defect at 9 weeks and 2 days (CRL 22 mm).66 There was malformation, banana sign).
a small monoventricular endbrain behind the forehead and The diagnosis of spina bifida has been reported in the first
a proboscis. The diagnosis was confirmed a week later. In trimester from as early as 9 weeks.68-72 Blaas et al. identified
four screening studies for structural defects by first trimester the defects in three embryos from high-risk pregnancies at
ultrasound on a total of about 9,500 fetuses, there were four 9 weeks of gestation (CRL 22–28 mm).71 The authors used
cases of holoprosencephaly and three were diagnosed in the a combination of two- and three-dimensional transvaginal
first trimester.30,33,34,46 ultrasound to examine the spine. They noted that scalloping
of the frontal bones and Arnold–Chiari malformation did not
Spina Bifida (Birth Prevalence 1 in 1,000) occur before 12 weeks (Figs 6.14 to 6.16).
Spina bifida is the result of failed closure of the neural In four screening studies for structural defects by first
tube normally occurring during the 6th week, whereas the trimester ultrasound, there were 12 cases of spina bifida on
ossification of spine begins at 10th week. The hallmarks a total of about 9,500 fetuses and 6 were diagnosed in the
fetuses with increased NT and reported sensitivity and
specificity 88% and 97% respectively.43 Another study on
241 fetuses with increased NT at 11–14 weeks (CRL 40–85
mm) identified 28 of the 37 cardiac anomalies in the first
trimester (sensitivity 76%).80
Screening studies for heart defects have so far been
limited to high-risk pregnancies defined by family
history, maternal disease (diabetes, epilepsy) or increased
nuchal thickness and performed in the setting of fetal
echocardiography units by experts in cardiac scanning, thus
explaining the high sensitivities reported. There is a strong
association of increased NT with cardiac defects. A meta-
analysis of screening studies reported that the detection
rates for heart abnormalities were about 37% and 31% for
NT cutoffs of 95th and 99th centiles respectively.81 Fetal
echocardiography during first trimester if possible, should
be included in the routine follow-up of the fetuses with
increased nuchal fluid.
Figure 6.16 Banana sign in a 13-week fetus
Abdominal Wall Defects
first trimester.30,33,34,46 It is of interest that at least in some Exomphalos (Omphalocele, Birth Prevalence 1 in 4,000)
cases the lemon sign and banana sign were present in the In exomphalos there is midline defect of the abdominal wall
first trimester. through which intra-abdominal viscera herniated into a sac.
The umbilical cord inserts at the apex of the sac. Herniation
Heart Defects of the small bowel is only a normal step of the embryonic
Congenital heart defects are amongst the most common development and occurs between 8 weeks and 10 weeks.
structural defects with a birth prevalence of 5–10 per 1,000 The diagnosis of exomphalos is made if the bowel fails to
births. Approximately one half of those will need medical return into the abdominal cavity by 11 weeks or if other
or surgical treatment (major defects) and the other half will viscera are herniated at any gestation.
be asymptomatic (minor defects). First trimester diagnosis Exomphalos is commonly associated with chromosomal
of several cardiac abnormalities has been reported in the abnormalities and syndromes. Chromosomal abnormalities,
first trimester, such as ectopia cordis, common truncus usually trisomy 18, are present in about half of the fetuses
arteriosus, dextrocardia, monoventricular heart, Uhl with exomphalos in first trimester, one-third of cases in
disease, atrioventricular septal defect and ventricular septal second trimester and about 15% at birth. Exomphalos
defect.73-77 may be part of an extended defect in the abdominal wall
In a screening study of 114 pregnancies at risk for cardiac development. If the abnormality involves the cephalic fold,
defects by transvaginal ultrasound at 11–16 weeks of it results in pentalogy of Cantrell (exomphalos, ectopia
gestation, there were six abnormal fetuses scanned at 11–14 cordis, cardiac defects, diaphragmatic hernia, sternal cleft).
weeks and the defect was diagnosed in five (sensitivity If it involves the caudal fold, it results in bladder or cloacal
83%).78 Nuchal fluid was increased in four fetuses. In exstrophy, bowel atresia and vertebral defects.
another small study of 15 high-risk fetuses scanned at 12+0 Many cases with exomphalos have been diagnosed in
to 13+6 weeks.79 The first trimester scans were normal in 10 the first trimester, the earliest case being at 11 weeks for
cases and inconclusive in four cases; one of the two cardiac exomphalos containing liver.82-87 van Zalen-Sprock et al.
anomalies (left isomerism) was identified at 12 weeks reported on 14 cases with exomphalos at 11–14 weeks.86
and a muscular ventricular septal defect was diagnosed Nuchal fluid was increased in eight fetuses and seven of
postnatally (sensitivity 83%). Haak et al. performed those were chromosomally abnormal. Exomphalos contained
first trimester transvaginal fetal echocardiography in 54 bowel only in fetuses with chromosomal abnormality. Liver
was often present in the contents of sac as well as bowel in observed in all of the remaining chromosomally normal
chromosomally normal ones. cases.
In a study of 622 high-risk patients, there were two cases In a study of 622 high-risk patients, there were two
of exomphalos diagnosed in the first trimester.31 In four cases of megacystis diagnosed in first trimester.31 In four
screening studies on a total of about 9,500 patients there screening studies on a total of about 9,500 patients, there
were two cases with exomphalos correctly identified in the were two cases with megacystis correctly identified in the
first trimester.30,33,34,46 first trimester.30,33,34,46
In a study screening for chromosomal defects at 10–14
weeks by NT measurement in about 1,500 patients, the Meckel–Gruber Syndrome (Birth Prevalence 1 in
diagnosis of exomphalos was made at this early gestation.57 10,000)
Finally, in another screening study for chromosomal defects Meckel–Gruber syndrome is a lethal, autosomal recessive
at 11–14 weeks by NT measurement, 15,726 fetuses were condition with variable phenotypic expression. The typical
examined and there were 18 cases of exomphalos.87 The features include encephalocele, bilateral polycystic kidneys
karyotype was normal in seven fetuses; the remaining and polydactyly. Other features may be present such as
eleven fetuses had trisomy 18, 13 or triploidy. This study growth deficiency of prenatal origin, microcephaly, cerebral
showed that the prevalence of exomphalos and risk of and cerebellar hypoplasia, anencephaly, Dandy-Walker
chromosomal defects in affected fetuses is increased in the malformation, absence of the corpus callosum, cleft lip
first trimester because of the strong association with lethal and palate, renal agenesis, hypoplastic bladder, obstructive
chromosomal anomalies.87 uropathy, syndactyly of the fingers and toes. Phenotype
may vary from isolated polydactyly, which may represent
Gastroschisis (Birth Prevalence 1 in 4,000) the mild expression of heterozygote state, to full clinical
In gastroschisis, there is a small defect of the abdominal manifestation of the disease. The diagnosis is based on
wall laterally and usually on the right of the umbilical cord ultrasound examination demonstrating encephalocele,
insertion through which herniation of the viscera (usually usually occipital, enlarged, dysplastic, echogenic kidneys,
small bowel) occurs. Although gastroschisis is as common and polydactyly.
as exomphalos at birth, there are a few cases reported In three studies on a total of 15 pregnancies from high-
in first trimester.88,89 Prenatal diagnosis is based on the risk families, all 8 affected fetuses were correctly diagnosed
visualization of loops of bowel floating in the amniotic in the first trimester.99-101 Another case of the syndrome
fluid. Gastroschisis is rarely associated with chromosomal from a low-risk couple was identified at 13 weeks in a
abnormalities. study screening for chromosomal abnormalities by NT
measurement.100 In four screening studies on a total of about
Defects of the Urinary Tract 9,500 patients, there were two cases with Meckel–Gruber
Megacystis syndrome diagnosed in the first trimester.30,33,34,46 These
Dilatation of urinary bladder in first trimester fetuses has studies have shown that the phenotype of Meckel–Gruber
been reported in association with obstructive uropathy syndrome is present from the first trimester and it is likely
(usually with posterior urethral valves or urethral atresia), that the diagnosis is actually easier at this early gestation
severe renal abnormalities and prune belly syndrome.90-97 when amniotic fluid volume is still within normal range
rather than in second trimester when oligohydramnios
Liao et al. studied 145 fetuses with bladder diameter
hinders detailed ultrasound examination.
more than or equal to 7 mm at 10–14 weeks of gestation.98
Fetuses with mild and moderate megacystis (bladder
diameter 7–15 mm) were chromosomally abnormal in 24% Skeletal Defects
of the cases; in the ones with normal karyotype, spontaneous Caudal Regression Syndrome (Sirenomelia, Birth
resolution occurred in 90% of the cases; but in 10%, there Prevalence 1 in 500,000)
was progressive evolution to obstructive uropathy and/or Caudal regression syndrome is a rare sporadic defect
echogenic kidneys. Fetuses with severe bladder dilatation involving vertebral abnormalities varying from partial
(more than 15 mm) were chromosomally abnormal in 11% sacral agenesis to complete absence of the lumbosacral part
of the cases, but progression to obstructive uropathy was of the spine. Sirenomelia, the extreme form of syndrome,
presents with variable degrees of hypoplasia and fusion
of lower limbs and is associated with genitourinary,
gastrointestinal and central nervous system defects. The
prevalence of sirenomelia is about 250 higher in mothers
with poorly controlled diabetes.
There are five cases of first trimester diagnosis of
sirenomelia, the earliest being at 9 weeks of gestation.102-105
In one case the mother was a diabetic presenting with
ketoacidotic coma.102 Features of the syndrome identifiable
in first trimester are CRL shorter than expected for
gestation, inability to visualize independently the lower
limbs and abnormal movement of the lower limbs, intra-
Figure 6.17 Body stalk anomaly in a 12-week fetus. The arrow points
abdominal cyst and increased NT. to the large abdominal wall defect. Part of the fetal body lies outside
the amniotic cavity and is stuck to the uterine wall
Body Stalk Anomaly (Birth Prevalence 1 in 15,000)
Body stalk anomaly is a rare sporadic anomaly characterized
by anterior wall defect, kyphoscoliosis, limb reduction,
and a rudimentary umbilical cord. Possible pathogenetic
mechanisms include abnormal folding of trilaminar embryo
in the first 4 weeks of gestation, early rupture of amniotic
membrane, and abnormal embryonic blood supply. In
a study of about 106,000 pregnancies for chromosomal
abnormalities by NT measurement, there were 14 cases
of body stalk anomaly and all were diagnosed in the first
trimester.106 In all fetuses, the lower part of the body was
outside the amniotic sac in celomic cavity, possible because
of the early rupture of amniotic membrane (Fig. 6.17). Figure 6.18 Kyphoscoliosis in a 14-week fetus
Nuchal translucency was increased in about 70% of the
cases and the karyotype was normal in all cases. Contrary have been diagnosed in the first trimester and the most
to this theory, Paul et al. presented a fetus with body common ultrasound features include limb shortening and
stalk anomaly at 10 weeks of gestation (CRL 35 mm).107 bowing, limb fractures and hypomineralization of skull and
There were multiple anomalies including clefting defect the spine and increased NT.
of the cranium and brain, anterior wall defect, severe
kyphoscoliosis and deformity of lower limbs. The fetus Achondrogenesis (Birth Prevalence 1 in 40,000)
was inside the amniotic sac, which appeared intact with Achondrogenesis type II is a lethal, autosomal recessive
no sonographic features of rupture. The earliest diagnosis skeletal dysplasia usually presenting with hydrops,
of the defect is at 9 weeks of gestation; fetus was partly severe shortening of the limbs, narrow thorax, and
outside the amniotic cavity, there was an abdominal wall hypomineralization of the vertebral bodies but normal
defect and the lower limbs could not be seen.108 In four mineralization of skull. In the rarer type I of the disease,
screening studies on a total of about 9,500 patients, there there is hypomineralization of skull and rib fractures.
was one fetus with body stalk anomaly diagnosed in first There are two case reports on the first-trimester
trimester.30,33,34,46 sonographic diagnosis of achondrogenesis type II in
high-risk pregnancies; both fetuses had increased NT
Skeletal Dysplasias and short limbs that were abnormally positioned with
Skeletal dysplasias present with a prevalence of about 1 in lack of movement.109,110 There is also a report of fetus
4,000 (Fig. 6.18). Although in some skeletal syndromes the with achondrogenesis type I presenting at 13 weeks with
clinical picture does not become obvious until the second increased NT, short limbs, small thorax and deficient
or even the third trimester, there are skeletal defects that ossification of the skull, vertebral bodies and pelvic bones.111
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94. Yoshida M, Matsumura M, Shintaku Y, et al. Prenatally 111. Meizner I, Barnhard Y. Achondrogenesis type I diagnosed
diagnosed female prune-belly syndrome associated with by transvaginal ultrasonography at 13 weeks’ gestation. Am
tetralogy of Fallot. Gynecol Obstet Invest. 1995;39:141-4. J Obstet Gynecol. 1995;173:1620-2.
95. Fried S, Appelman Z, Caspi B. The origin of ascites in prune 112. Souka AP, Raymond FL, Mornet E, et al. Hypophosphatasia
belly syndrome—early sonographic evidence. Prenat Diagn. associated with increased nuchal translucency: a report of
1995;15:876-7. three consecutive pregnancies. Ultrasound Obstet Gynecol.
96. Hoshino T, Ihara Y, Shirane H, et al. Prenatal diagnosis of 2002;20:294-5.
prune belly syndrome at 12 weeks of pregnancy: case report 113. Makrydimas G, Souka AP, Skentou H, et al. Osteogenesis
and review of the literature. Ultrasound Obstet Gynecol. imperfecta and other skeletal dysplasias presenting with
1998;12:362-6. increased nuchal translucency in the first trimester. Am J
97. Cazorla E, Ruiz F, Abad A, et al. Prune belly syndrome: early Med Genetics. 2001;98:117-20.
antenatal diagnosis. Eur J Obstet Gynecol. 1997;72:31-3. 114. Petrikovsky BM, Gross B, Bialer M, et al. Prenatal diagnosis
98. Liao AW, Sebire NJ, Geerts L, et al. Megacystis at 10-14 weeks of pseudothalidomide syndrome in consecutive pregnancies
of gestation: chromosomal defects and outcome according to of a consanguineous couple. Ultrasound Obstet Gynecol.
bladder length. Ultrasound Obstet Gynecol. 2003;21:338-41. 1997;10:425-8.
99. Pachi A, Giancotti A, Torcia F, et al. Meckel-Gruber syndrome: 115. Hill LM, Leary J. Transvaginal sonographic diagnosis of
ultrasonographic diagnosis at 13 weeks’ gestational age in an short-rib polydactyly dysplasia at 13 weeks’ gestation.
at-risk case. Prenat Diagn. 1989;9:187-90. Prenat Diagn. 1998;18:1198-201.
CHAPTER
7 Ultrasound Imaging of Early

Extraembryonic Structures
Tibor Fekete, Zoltan Papp
Introduction
An estimated 60% of the conception loss occurs during the
first trimester of pregnancy. Fifteen to twenty percent of all
clinically recognized pregnancies end in miscarriage. The
first visible structures in pregnancy are extraembryonic
structures. In order to predict the outcome of pregnancy, we
need to fully appreciate the development and pathological
conditions of early extraembryonic structures.
Gestational Sac
After 7 days of conception, the blastocyst reaches the uterine
cavity. It embeds into the secretory phase endometrium, and
begins to implant. The trophoblast cells penetrate into the
A
endometrium, erode the maternal capillaries, and make
contact with the maternal circulation. The trophoblast and
the decidual cells form the gestational sac. It is the first
visible structure in early pregnancy. It can be detected by
transvaginal ultrasonography after the 4th menstrual week.
The gestational sac is a ring-shaped structure with a
double-layered wall, embedded eccentrically into the
endometrium. It is important to differentiate it from
the pseudogestational sac of ectopic pregnancy (Table
7.1). The pseudogestational sac is in fact a fluid-filled
cavity between the layers of enlarged endometrium. It
has a thin simple wall, and is usually in central position.
Peritrophoblastic activity is never visible in the underlying
1
layers (Figs 7.1A and B).
B
Table 7.1 The difference between the gestational and the
pseudogestational sac Figures 7.1A and B Pseudogestational sac and dilated tube in ectopic
pregnancy
Gestational sac Pseudogestational sac
Localization Lateral Central
Blighted Ovum
Shape Spheroid Ovoid
Contour Thick, double- Thin, mono-layered wall In an embryonic pregnancy, a fertilized ovum develops
layered wall into blastocyst, but the inner cell mass never develops.
Peritrophoblastic Exists Nonexistent The trophoblast cells invade the endometrium and form
circulation the gestational sac. They produce human chorionic
Chapter 7  Ultrasound Imaging of Early Extraembryonic Structures 47
gonadotropins (hCG); therefore, the pregnancy test is trophoblastic system, thus establishing the uteroplacental
positive and clinical signs of pregnancy occur. circulation.
The diagnosis is based on the absence of embryonic Regular placentation supposes a progressive trophoblast
echoes within the gestational sac, large enough for such invasion of spiral arteries. Normally, this process is finished
structures to be visualized (Fig. 7.2). by the 20th week. In the majority of abortions and in
With ultrasound examination, the mean sac diameter preeclampsia, this process is disturbed. The evolving
is the most useful criterion for determining nonviability. chorionic plate becomes thin and fragile, and the trophoblast
If the mean sac diameter is higher than 17 mm that lacks cork, which hinders the maternal flow in first trimester, is
an embryo or more than 13 mm without visible yolk sac, missing.
the probability for nonviable gestation is about 100%. Usually, there is no significant maternal flow in the
Deformed shape, low position and thin decidual reaction 3
intervillous space until the 12th week. If the maternal blood
are strong indicators of nonviable gestations but are not floods into the intervillous space in advance, it increases
2
100% accurate. the pressure and mechanically injures and lifts the thin
When no accurate distinction between viable and chorionic plate which leads to abortion (Fig. 7.3). In fact,
nonviable gestations can be made at a single examination, regardless of its etiology, this process is in the background
serial examination should be carried out before any active of the majority of first trimester abortions.
management is advocated.
Subchorionic Hemorrhage
Chorionic Plate In contrast to subchorionic hemorrhage of chorion laeve,
By the 8th day of development, the blastocyst is partially the hemorrhage of chorion frondosum indicates a bad
embedded in the endometrial stroma. In the area over the prognosis. Subchorionic hemorrhage is a fluid-filled cavity
embryoblast, the trophoblast differentiates into two layers: of variable size and echogenicity under the chorionic
(i) an inner layer, the cytotrophoblast, and (ii) an outer plate. Its incidence in a normal early pregnancy is 2–4%.
zone, the syncytiotrophoblast. The syncytiotrophoblasts It increases the probability of abortion to twice the original
penetrate into the stroma and erode the endothelial lining of incidence. In cases of imminent abortion, it is detected in
maternal capillaries. These congested and dilated capillaries every second pregnancy.
are known as sinusoids. The sincytial lacunae then become To the best of the authors’ knowledge, it is not the
continuous with the sinusoids, and maternal blood enters volume but the position of hematoma that determines the
the lacunar system. As the trophoblast continues to erode prognosis. A subchorionic hemorrhage under the chorion
more sinusoids, maternal blood begins to flow through laeve can reach large dimensions without any serious
Figure 7.2 Blighted ovum in 7-week pregnancy Figure 7.3 Subchorionic hemorrhage in 6-week pregnancy
consequence; while if it is the insertion site of umbilical the primary yolk sac (endoderm). The secondary yolk sac
cord, a small volume can lead to abortion. Subchorionic evolves from the primary yolk sac by the 5th postmenstrual
hemorrhage near the cervix can clear spontaneously from week (29–36 days). By this time, the primary yolk sac
the uterus; thus, prognosis is good. Fresh blood means is absorbed and the secondary yolk sac has completely
immediate clearing, brown bleeding indicates previous developed. The extraembryonic mesoderm which fills
hemorrhage. A hematoma near the fundus can increase the the cavity of the blastocyst is converted into a thin layer,
intrauterine volume significantly, causing the termination covering both the amnion and the yolk sac, forming somato-
4-6
of pregnancy. and splanchnopleura. These two shields communicate only
Mäkikallio et al. measured the pulsatility index (PI) of by the body-stalk.
uterine, arcuate, spiral, umbilical and chorionic arteries The growth rate of the yolk sac is quicker than that of the
in first trimester pregnancies with vaginal bleeding or amnion cavity. At the beginning of the 5th week, it is the
subchorionic hematomas. They found that vaginal bleeding first visible structure in the chorionic cavity. It is a round
with or without a subchorionic hematoma is associated structure with an echogenic rim and a hypoechoic center.
with increased radial artery impedance at the 7th week of At this time, it is 3–4 mm. The secondary yolk sac is the
pregnancy. Persistence of the subchorionic hematoma does unambiguous evidence of intrauterine gravidity. Until there
7
not affect uteroplacental and umbilicoplacental circulation. is a detectable yolk sac inside the uterine cavity, we should
The subchorionic hemorrhage is isoechogenic with the always take ectopic pregnancy into account.8
endometrium, and slow blood flow can be detected inside Around 36–38 postmenstrual days, the embryo becomes
it. With abortion, the hematoma becomes hypoechoic then visible between the amnion cavity and the yolk sac. It is
anechoic. If the hemorrhage does not cause an abortion, an only a 2–3 mm long, linear, hyperechoic structure. Even
increased risk for placental complications can be expected. at this stage, we can detect the embryo’s heart activity,
The risk for preeclampsia, intrauterine growth retardation although there is no detectable circulation in the yolk sac
and cesarean section due to intrauterine asphyxia increases until the 6th week.
significantly. All these complications could probably be By the 9th week, the yolk sac grows to a diameter of 5–6
traced back to the same problem with placentation. The mm, but it begins to degenerate soon after and disappears
9
etiology can be mainly undetermined.
8 by the 12th week.
In cases of retroplacental hematomas relative risk for: Structure of the Yolk Sac
ÀÀ Cesarean delivery : 2.1 The yolk sac is made up of three layers: (i) the inner
ÀÀ Hypertension : 2.1 endoderm, (ii) the middle mesenchymal, and (iii) the
ÀÀ Pre-eclampsia : 4.0 external mesothelial layer.
ÀÀ Placental abruption : 5.6 The inner endodermal layer contains 10–20 µm wide
ÀÀ Placental separation abnormalities : 3.2 columnar cells, with 0.5–1.0 µm long cilia on the surface.
ÀÀ Preterm delivery : 2.3 Inside the cells there are mitochondria, a highly developed
ÀÀ Fetal growth restriction : 2.4 Golgi apparatus, lysosomes, glycogen, and intracellular
ÀÀ Fetal distress : 2.6 vacuoles. These cells are very similar to the liver cells due
In practice, it is advisable to classify every pregnancy to their similar functions. The canalicular network of these
with subchorional hemorrhage among the high-risk group. cells also resembles that of the liver.
Repeated ultrasound imaging due to lack of therapeutic The middle layer is the mesenchymal layer. It contains
results is not advisable. blood vessels, red blood cells, and macrophages. The
vessels spring from the vitellointestinal duct. There is no
Yolk Sac basal membrane between the inner and the middle layer.
The external layer is the mesothelial layer containing
Development of the Yolk Sac 5–10 µm high cells with 2–5 µm microvillous on the
Between the 22nd and 28th postmenstrual days, the embryo surface. The cells are full of intracellular vacuoles.
contains only two layers—the embryonal ectoderm and After the 9th week, its structure changes. The microvillous
the primary endoderm. The two layers form two cavities and the inner cells structures dissolve, and the yolk sac
around the embryo—the amniotic cavity (ectoderm) and begins to degenerate.
Function of the Yolk Sac 12 weeks, there is a noncontinous, low velocity waveform with
13,14
Due to its structure and position, the yolk sac plays an absence of diastolic flow (Figs 7.4A and B).
important role in nutrition transport. The following facts Overall visualization rate for yolk sac vessels was 80%.
support this role: The highest visualization rates were obtained in the 7th
and 8th weeks of gestation reaching values of 90%. In the
ÀÀ The wall and the cavity of yolk sac are in direct contact
same period, the visualization rates of the vitelline duct
with the primitive midgut
arteries were 87% and 91%. A characteristic waveform
ÀÀ Its histological structure is very similar to the liver
profile included low velocity (5.8 ± 1.7 cm/s) and absence
ÀÀ The composition of the celomic fluid is significantly of diastolic flow which was obtained from all examined
different from the amniotic fluid. It contains proteins, yolk sac. The PI showed the mean value of 3.24 ± 0.94.
10
creatinine and hCG in a higher concentration Vitelline vessels showed similar peak systolic velocity (5.4
15
ÀÀ The yolk sac synthesizes numerous proteins, which are ± 1.8 cm/s) and PI values (3.14 ± 0.91).
later produced by the liver including alpha-fetoprotein,
alfa-1-antitrypsine, albumin, prealbumin and transferrin. Abnormalities of Yolk Sac Development
Till the 10th postmenstrual week, these factors are It is evident from the formation and function of yolk sac that
11,12
produced by the yolk sac and after that by the liver. any deviation in these complicated processes could disturb
Circulation of the Yolk Sac

About the end of the 5th week, mesoderm cells located in
visceral mesoderm of the wall of the yolk sac differentiate
into blood cells and blood vessels. Centrally located cells
then give rise to primitive blood cells, while those on the
periphery flatten and form endothelial cells lining blood
islands. Blood islands approach each other rapidly by
sprouting of endothelial cells and after fusion, give rise to
small vessels. At the same time, blood cells and capillaries
develop in the extraembryonic mesoderm of the villous
stems and connecting stalk. By continuous budding,
extraembryonic vessels establish contact with each other
inside the embryo. Intraembryonic blood vessels, including
the heart tube, are established in exactly the same manner
A
as extraembryonic vessels.
The rhythmic contractions of the heart pump the
primitive blood from connecting stalk toward cranial
portion of the embryo. Meanwhile, the intraembryonic
blood vessels protrude into the chorion through body stalk,
and form capillary loops at the axis of villi giving rise to
the placental circulation.
The intraembryonic circulation precedes blood flow in
the intervillous space. Normal placental circulation starts
only after the end of the organogenesis around the 13th
week, which confirms significant role of the yolk sac in
nutritive and transport functions.
Kupesic and Kurjak examined the circulation of yolk sac
and vitelline duct in early pregnancy. Before the 6th week,
there is no detectable circulation in the body-stalk or the yolk B
sac by ultrasound Doppler examination. Between 6 weeks and Figures 7.4A and B Circulation of the yolk sac
the development of embryo. It plays an important role in the

nutritive, metabolic and hematopoietic processes of the first
16
trimester. Any abnormality in the shape, size, structure or
circulation of the yolk sac indicates a major abnormality in
17,18
development.
The absence of yolk sac is the first sonographic indicator
of an early maldevelopment. It is very important ultrasound
finding of a blighted ovum. In this case, we should
distinguish between intrauterine and ectopic pregnancy.
Abnormal yolk sac size is also an indicator of
19
maldevelopment. Lyons established that for a gestational
sac diameter of less than 10 mm, the yolk sac diameter
should be less than 4 mm. A large yolk sac can indicate
poor pregnancy outcome. In the surviving embryos the
probabilities for chromosomal aberrations increase (Fig. 7.5).
Small yolk sac can also predict poor pregnancy
20 21
outcome. Green and Hobbins reported a similar outcome Figure 7.5 Large yolk sac
with diameter less than 2 mm. Küçük and coworkers found
that the yolk sac diameter out of two standard deviations
of the mean for gestational age allowed prediction of an
abnormal pregnancy outcome with sensitivity of 65%,
a specificity of 97%, a positive predictive value of 71%
and a negative predictive value of 95%. An abnormal yolk
sac shape allowed prediction of an abnormal pregnancy
outcome with a sensitivity of 29%, a specificity of 95%, a
positive predictive value of 47% and a negative predictive
22
value of 90.5%.
Changes in echogenicity can also be the same predicting
factors. Presence of hyperechogenic yolk sac is highly
associated with chromosomal aneuploidy between 9th and
23
11th gestational weeks (Fig. 7.6).
Kurjak and co-workers demonstrated the characteristics
of yolk sac circulation. They found a noncontinuous low
velocity waveform with absent diastolic flow. They also
detected three different types of abnormal circulation signals
in patients with missed abortions: (i) irregular blood flow,
15
(ii) permanent diastolic flow, and (iii) venous blood flow. Figure 7.6 Small hyperechoic yolk sac
Table 7.2 Normal and abnormal yolk sac characteristics

Normal findings Abnormal findings
Characteristics Echogenic rim, hypoechoic center Hyperechoic
Shape Round Distorted
Size 3–4 mm in the 5th week Less than 2 mm
5–6 mm in the 10th week or more than 6 mm
Doppler Noncontinuous, absence of diastolic flow Irregular blood flow, permanent diastolic
flow, venous blood flow
Mäkikallio and coworkers examined the Doppler 11. Gitlin D, Perricelli A, Gitlin GM. Synthesis of alfa-
parameters of uterine, spiral, intraplacental, chorionic, fetoprotein by the liver, yolk sac and gastrointestinal tract
umbilical and yolk sac hemodynamics in early pregnancies. of the human conceptus. Cancer Res. 1972;32:979-82.
They found that in patient, who later had preeclampsia at 12. Gitlin D, Perricelli A. Synthesis of serum albumin,
week 8, the maternal intraplacental resistance index (RI) prealbumin, alfa-fetoprotein, alfa-1-antitripsin and
was higher. A week later, the yolk sac RI and umbilical artery transferrin by the human yolk sac. Nature. 1970;228:995-7.
mean velocity were lower. In late first trimester, increased 13. Kurjak A, Kupesic S, Kostovic L. Vascularization of yolk
velocities and RI were observed in chorionic arteries. No sac and vitelline duct in normal pregnancies studied by
transvaginal color and pulsed Doppler. J Perinat Med.
difference in uterine, spiral artery hemodynamics and in
24 1994;22:433-40.
umbilical artery PI was observed.
14. Kurjak A, Kupesic S. Color Doppler in obstetrics,
In diamniotic twin pregnancies, the number of the
gynecology and infertility. Parthenon Publishing Group;
embryos equals the number of yolk sacs. In monochorionic-
1999.
monoamniotic twin pregnancies, a single yolk sac may be
15. Kupesic S, Kurjak A. Volume and vascularity of the yolk
a normal finding. But, in cases of single yolk sac, they are
25 sac assessed by three-dimensional and power Doppler
highly associated with conjoined twins (Table 7.2). ultrasound. Early Pregnancy. 2001;5(1):40-1.
16. Brent RL, Beckmann DA, Koszalka TR. Experimental
References yolk sac dysfunction as a model for studying nutritional
1. Nyberg DA, Laing FC, Filly RA. Ultrasonographic disturbances in the embryo during early organogenesis.
differentiation of gestational sac of early intrauterine Teratology. 1990;41:405-13.
pregnancy from the pseudogestational sac of ectopic 17. Lindsay DJ, Lovett IS, Lyons EA, et al. Endovaginal
pregnancy. Radiology. 1983;146:755-9. appearance of the yolk sac in pregnancy: normal growth and
2. Tongsong T, Wanapirak C, Srisomboon J, et al. Transvaginal usefulness as a predictor of abnormal pregnancy outcome.
ultrasound in threatened abortions with empty gestational Radiology. 1992;183:115-8.
sacs. Int J Gynaecol Obstet. 1994;46(3):297-301. 18. Ferrazzi E, Brambati B, Lanzani A, et al. The yolk
3. Kurjak A, Laurini R, Kupesic S, et al. A combined Doppler sac in early pregnancy failure. Am J Obstet Gynecol.
and morphopathological study of intervillous circulation. 1988;158:137-42.
Ultrasound Obstet Gynecol. 1995;6:116. 19. Lyons EA. Endovaginal sonography of the first trimester of
4. Kurjak A, Schulman H, Zudenigo D, et al. Subchorionic pregnancy. Proceedings of the 3rd International Perinatal
hematomas in early pregnancy: clinical outcome and blood and Gynecologycal Ultrasound Symposium Ottawa,
flow patterns. J Matern Fetal Med. 1996;5:41-4. Ontario. 1994;1-25.
5. Ball RH, Ade CM, Schoenborn JA, et al. The clinical 20. Bromley B, Harlow BL, Laboda LA, et al. Small sac size
significance of ultrasonographically detected subchorionic in the first trimester: a predictor for poor fetal outcome.
hemorrhages. Am J Obstet Gynecol. 1996;174:996-1002. Radiology. 1991;178:375-7.
6. Pearlstone M, Baxi L. Subchorionic hematoma: a review. 21. Green JJ, Hobbins JC. Abdominal ultrasound examination of
Obstet Gynecol Surv. 1993;48:65-8. the first trimester fetus. Am J Obstet Gynecol. 1988;159:165-75.
7. Mäkikallio K, Tekay A, Jouppila P. Effects of bleeding
22. Küçük T, Duru NK, Yenen MC, et al. Yolk sac size and
on uteroplacental, umbilicoplacental and yolk-sac
shape as predictors of poor pregnancy outcome. J Perinat
hemodynamics in early pregnancy. Ultrasound Obstet
Med. 1992;27(4):316-20.
Gynecol. 2001;18(4):352-6.
8. Nagy S, Bush M, Stone J, et al. Clinical significance 23. Szabó J, Gellén J, Szemere G, et al. Significance of hyper-
of subchorionic and retroplacental hematomas detected echogenic yolk sac in the first-trimester screening for
in the first trimester of pregnancy. Obstet Gynecol. chromosome aneuploidy. Orv Hetil. 1996;137(42):2313-5.
2003;102(1):94-100. 24. Mäkikallio K, Jouppila P, Tekay A. First trimester uterine,
9. Jauniaux E, Jurkovic D, Henriet Y. Development of the placental and yolk sac haemodynamics in pre-eclampsia and
secondary yolk sac: correlation of sonographic and anatomic preterm labour. Hum Reprod. 2004;19(3):729-33.
features. Hum Reprod. 1991;6:1160-6. 25. Levi CS, Lyons EA, Dashefsky SM, et al. Yolk sac
10. Jauniaux E, Jurkovic D, Gulbis B. Biochemical composition number, size and morphologic features in monochorionic-
of exocoelomic fluid in early human pregnancy. Obstet monoamniotic twin pregnancy. Can Assoc Radiol J.
Gynecol. 1991;78:1124-8. 1996;47(2):98-100.
CHAPTER
8 Ultrasound Markers of
Aneuploidy in the First Trimester
Zoran Belics, Zoltan Papp
Introduction
With the evolution of ultrasound technology, a large efficiency
gain in detecting aneuploid pregnancies has occurred. The
recent trend is to recognize and to establish useful sonographic
markers as soon as possible, especially at the first trimester
of the pregnancy. Over the last decades, the advancement
of medicine and technique has improved the methods of
detection of chromosomal aberrations. A significant number
of fetal structural anomalies have developed by the end of
the first trimester;1 hence, besides the well-known second
trimester markers, there are real opportunities to recognize
chromosomal abnormality at the early gestational age.
During the first trimester, the ultrasound examination
can be performed with the transvaginal or transabdominal
technique (the recommended procedure is transvaginal
sonogram). The most common chromosomal aneuploidy,
Figure 8.1 Nuchal translucency thickness in a 12-week fetus
such as trisomies 21, 18 and 13, might have a characteristic
appearance at the first trimester; however, the establishing
Because the measurement mistake of a few millimeters
of the early screening methods can give a real opportunity to
can have a major consequence, it is very important to
decrease the prevalence of neonates born with chromosomal
establish the criteria of NT measurement. In the United
aberrations as soon as possible. The early recognition of
States, the recently completed First and Second Trimester
sonographic markers of chromosomal aberrations can be
Evaluation of Risk (FASTER) trial proposed sonographic
helpful in forward prenatal diagnosis. On the other hand,
criteria (Box 8.1) to maximize the quality of NT sonography,
the early diagnosis makes the termination of the pregnancy
which were used successfully.4
possible with less complication and there is time for planning
For the sonographic examination of NT, the section
of further follow-up and interventions. Prenatal cytogenetic
obtained is a midsagittal section of the embryo/fetus [this
analysis should be offered to women with fetal ultrasound
is the section where the measure of the crown-rump length
markers of aneuploidy diagnosed in the first trimester.
(CRL) is obtained]. The procedure of the measurement
should be performed exclusively at the level of maximum
Nuchal Translucency
thickness of the subcutaneous translucency between the
In 1985, Benacerraf et al. presented the ultrasound sign of skin and soft tissues overlying the cervical spine (Fig. 8.2).
enlarged nuchal fold thickness in second trimester fetuses.2 The calipers will be placed “on to on”, perpendicular to
In 1992, Nicolaides et al. described enlarged nuchal the long axis of the fetal body (Fig. 8.2). For the adequate
translucency (NT) in first trimester fetuses with trisomy 21.3 measurement, it is practical to zoom into the selected area.
Nuchal translucency refers to the normal subcutaneous Sometimes, a false-positive result in the measurement can
fluid-filled area between the back of the embryonal/fetal happen if the amnion is not truly separated from the fetal skin
neck and the overlying skin (Fig. 8.1). (the movement of the fetus can account for these situations).
Chapter 8  Ultrasound Markers of Aneuploidy in the First Trimester 53
Box 8.1: Sonographic criteria to maximize quality of nuchal
translucency sonography
• Nuchal translucency ultrasound should only be performed by

sonographers or sonologists trained and experienced in the
technique
• Transabdominal or transvaginal approach should be left to the
sonographer’s discretion, based on maternal body habitus,
gestational age and fetal position
• Gestation should be limited to between 10 weeks 3 days and 13
weeks 6 days (approximate fetal CRL, 36–80 mm)
• Fetus should be examined in a midsagittal plane
• Fetal neck should be in a neutral position
• Fetal image should occupy at least 75% of the viewable screen
• Fetal movement should be awaited to distinguish between
amnion and overlying fetal skin
• Calipers should be placed on the inner borders of the nuchal fold
• Calipers should be placed perpendicular to the long axis of the
fetal body.
• At least three nuchal translucency measurements should be
obtained, with the mean value of those used in risk assessment
and patient counseling
• At least 20 minutes should be dedicated to the nuchal Figure 8.2 (a) The procedure of the nuchal translucency measurement;
translucency measurement before abandoning the effort as failed (b) with the selected area zoomed into the calipers will be placed “on
to on”
Furthermore, the umbilical cord or sometimes the presence

of amnion band can also distract the measurement. For
these reasons, application of the technique and training of
the sonographers is very important.
The NT is usually considered abnormal if it is greater
than 3 mm, but it is known that NT thicknesses extend
with the gestational age. According to the recent most
proposed protocol, if the NT is 3 mm or larger, then genetic
counseling is advisable.
The mechanism of fluid accumulation in the fetal
neck, which produces the enlarged NT, is still unknown.5-8
However, it is possible that the physiopathological process
leading to NT may be related to cardiac malformations,
early hemodynamic disorders of the affected fetuses, or
abnormalities of the extracellular matrix of the skin in Figure 8.3 Enlarged nuchal translucency in a 12-week fetus
fetuses with trisomy 21.9-11
In first trimester scans (11–14 weeks), approximately In conjunction with maternal age, measurement of NT
75–80% of fetuses with trisomy 21 present an enlarged NT thickness between 11 weeks and 14 weeks demonstrated
(Fig. 8.3); however, 5–10% of healthy fetuses also show the a detection rate of 77%.12 A combination of NT thickness
same sign.12-14 Malone and D’Alton evaluated 30 studies on measurement, maternal age indicator and first-trimester
the subject.4 These studies describe 316,311 patients who serum markers should increase detection rates while
were screened with NT sonography during the first trimester avoiding false-positive findings. In this combination, the
of pregnancy.4 The overall sensitivity for trisomy 21 was rate detection is increased from 90 to 92% with a 3% false-
77%, with a false-positive rate of 6% (sensitivities varying positive rate.14-16 Furthermore, the combination of NT test
from 29 to 100%, false-positive rates varying from 0.3 to with the maternal age more than 35 years and ultrasound
11.6%). The study established that abnormal NT is 13 times screening markers in the second trimester (which is
more likely when trisomy 21 is present compared with the practiced in most centers) have shown increase in accuracy
healthy fetuses. of the screening test. However, waiting until the second
trimester to disclose the results and perform the diagnosis cavities completely separated by a nuchal ligament, with or
is suggested.17 without internal trabeculae (septated and nonseptated NCH).
The NT can be also enlarged in other chromosomal The etiopathogenesis of the cystic hygroma is different
aberrations such as trisomies 18 and 13, Turner’s syndrome from NT. The NCH is congenital malformation of the
(monosomy X), Klinefelter’s syndrome and triploidy.12,18 lymphatic system (lymphatic stasis).
Currently, the relatively small experience with 3D The association with chromosomal abnormalities, such
technique of this subject does not show any advance with as Turner’s syndrome (the most common), trisomies 21, 18
the NT measurement. and 13, Klinefelter’s syndrome, has been reported.19-24 The
volume of hygroma and the presence of septa are associated
Cystic Hygromas with higher incidence of chromosomal aberrations.25
Fetal nuchal cystic hygroma (NCH) can be determined as an
area of sonolucency in the soft tissue of the occipital region Fetal Growth Disorders
(Figs 8.4 and 8.5). The NCH consists of two symmetrical The biometry of embryo/fetus in the first trimester consists
of the measurement of CRL (Fig. 8.6). During this time,
biological variation in the fetal size is minimal. Fetal
growth disorders in the first trimester could be associated
with chromosomal aberrations, CRL, compared with what
is expected, is substantially less. The CRL smaller or more
than 7 mm expected indicates a three times higher risk for
chromosomal aberration.26 Trisomy 18 is associated with
severe early onset growth restriction, which is more severe
than in trisomies 21 and 13.27,28
Nasal Bone
The absence of the nasal bone can be a useful ultrasound
marker for identifying fetuses with trisomy 21 in the
first trimester of pregnancy. Among other chromosomal
Figure 8.4 Nonsepta cystic hygroma (sagittal plane) abnormalities, such as trisomies 9 and 18, Turner’s
Figure 8.5 Nonsepta cystic hygroma (transverse section) Figure 8.6 Measurement of crown-rump length at the first trimester
syndrome, different defects of the bone and connective The process of ossification is extremely complex
tissue have been described, and the absence of nasal bone and numerous genetic syndromes and chromosomal
has been recognized. 29 Between 11th and 14th weeks anomalies can be implicated in the origin of alterations
of gestation, the fetal nasal bone can be visualized by and defects in the development of the cranial skeleton.35-38
ultrasonography in 99.5% of chromosomally normal Among other things, the curiosity of the growing of
fetuses.30 This finding is compatible with the results of fetal bone is dependent on the surrounding functional
histological and radiological studies of aborted fetuses, matrix.30 Immunohistochemical studies of fetuses with
which showed that the intramembranous ossification trisomy 21 have shown alterations in the composition
process of the nasal bone first appears at a CRL of 42 mm of extracellular matrix, which might be attributed to
and increases linearly with gestation.31 There is a significant gene dosage effects.10,11,39 This can be supported by the
difference in the rate of visualization of the fetal nasal bones biochemical and molecular-genetic changes in trisomy 21,
in the first trimester in mothers of different ethnic origin.32 namely trisomy 21 is associated with a substantial increase
For visualization of the fetal nose, the obtained section of hyaluronic acid.39 This increase could be a consequence
is a midsagittal view of fetal profile (Fig. 8.7), with an of increased superoxide dismutase, which is encoded in
angle of incidence between the beam of the ultrasound chromosome 21 and protects against free-radical-mediated
transducer and the line traced from front to the chin of the degradation of hyaluronic acid. Likewise, the genes for
fetus at about 45° or 135°. The importance of the angle two of the three polypeptide chains (a1, a2 and a3) of
of insonation cannot be underestimated, nasal bone may collagen type IV are found on chromosome 21 (COL6A1
artificially appear to be absent if the angle is inadequate.33 and COL6A2), and it is known that the dermis of fetuses
In the midsagittal position two echogenic lines can be with trisomy 21 is rich in this collagen.10
seen, superficial line representing the skin of the nose, As a probable consequence of hypoplasia or delayed
and the inner one representing the ossificated nasal bone ossification of the nasal bone (Fig. 8.9) in fetuses with
(Fig. 8.8).34 The echoes from the skin of the nose can be trisomy 21, the nasal bone is not visible in 60–73% of first-
misinterpreted as the nasal bone.30 To avoid this mistake, trimester trisomy 21 fetuses.30,34 However, the prevalence of
the ultrasound transducer must be gently tilted from side to the absent nasal bone among healthy first-trimester fetuses
side to ensure that the nasal bone was seen separately from is low (0.3–0.6%).30,34,40
the nasal skin.30
A full view of the fetal profile had a success rate of 94%,
meaning it was not always possible for sonographers to
confirm the absence or presence of the nasal bone.
Figure 8.7 Visualization of fetal nose in the midsagittal view of the Figure 8.8 3D fetal profile (the end of 12 weeks)
fetal profile
Figure 8.10 Measurement of the fetal bladder in a 12-week fetus
Figure 8.9 Delayed nasal bone at trisomy 21 fetus
Megacystis
During the first trimester of pregnancy, measuring of fetal
bladder is the simplest method for screening the fetal urinary
Figure 8.11 Severe megacystis at the end of first trimester
system (Fig. 8.10). The fetal bladder can be visualized at a
CRL of 67 mm,41 as a spherical hypoechogenic mass within
the fetal pelvis.42 Ductus Venosus Velocimetry
Megacystis at the first trimester fetuses is defined as The ductus venosus is a primary important vascular
enlargement of the fetal bladder (longitudinal diameter of structure during the intrauterine life. The importance of
the fetal bladder is >6 mm) (Fig. 8.11). The megacystis can this structure is carrying well-oxygenated blood from the
be arranged as being either mild-to-moderate (8–12 mm) or placenta and umbilical vein directly to the cerebral and
severe (>17 mm).40,41 The fetal bladder diameter/CRL ratio coronary circulation (through the foramen ovale to the
can be an important sample at the assessment, normal range left atrium). It behaves as an “arterialized” vessel with a
of bladder diameter/CRL is less than 10%.43 high pulsatile flow and forward velocities throughout the
The association with chromosomal abnormalities cardiac cycle.
has been reported.44 There is a correlation between the The ductus venosus blood flow can be detected as
extent of megacystis and risk of chromosomal defects: in early as 8 weeks of gestation.44 For the ductus venosus
the moderate fetal megacystis, the risk of chromosomal velocimetry, the obtained plane is a midsagittal section
aberration is about 25%, in the severe fetal megacystis, this of the fetal trunk (a narrow, trumpet-like structure). The
risk is about 10% at 10–14 weeks of gestation.45 Doppler sample gate must be placed at the initial portion of
the ductus venosus where it originates from the umbilical Fetal Heart Rate
vein (interrogation angle is < 60°). Blood flow in the ductus
is characterized by high velocity during ventricular systole Fetal heart rate (FHR) is detectable at the 6th week of
(s-wave) and diastole (d-wave) and a presence of forward gestation by transvaginal sonography. In this gestational
flow during atrial contraction (a-wave).46 The measurement time the mean heart rate is about 100 beats per minute
of ductus venosus pulsatility index of the veins (DVPIV) (bpm). In normal pregnancy, the FHR increases from about
happened on 3–5 consecutive high-quality ductus venosus 110 bpm at 5 gestational weeks to about 160–170 bpm at 9
waveforms. weeks and then slightly decreases.53 The early increase in
FHR coincides with the morphological development of the
Overlap signals originating from different adjacent
fetal heart, and the subsequent FHR decrease might be the
vessels can cause difficulties in distinction between normal
result of functional maturation of the fetal parasympathetic
and abnormal waveforms. Ductus venosus flow velocity is
system.54 Fetal heart rate abnormalities can be found among
approximately three times higher than flow velocity in the
aneuploid fetuses. In trisomies 21 and 13, monosomy X, the
umbilical vein or inferior vena cava.47
significant mean increase in the fetal heart frequency has
The absent or reversed flow during the a-wave or been described.55 Then again, in fetuses with trisomy 18 or
DVPIV more than 95 percentile (Fig. 8.12) can be sign of triploidy, the mean FHR is significantly reduced.
chromosomal aberration, it has been seen in about 70–90%
of fetuses with a chromosomal abnormality. Among fetuses
with trisomy 13, ductus venosus studies were found to be
Umbilical Cord
more frequently normal.48 Diameter of umbilical cord can be measured during the first
trimester (10–14 weeks scan). There is the observation that
Pulsatility Index of the Umbilical Artery fetuses with chromosomal defects, compared with healthy
fetuses, have an increased diameter of the umbilical cord
Some studies with umbilical artery pulsatility index (UAPI) (above the 95th centile of reference value).56 The presence
have shown that first trimester fetuses with trisomy 21, a of two-vessel cord (one vena and one artery) can also be
significantly higher UAPI value than healthy fetuses.49,50 a marker for fetal aneuploidy (singular umbilical artery).
Intriguing that other studies of the subject did not find About 1% of pregnancies present with a two-vessel cord,
significant difference at the UAPI between fetuses with among these, about 1–10% have an aneuploidy.
trisomy 21 and normal fetuses.51,52 The question is still open
and further large prospective studies are needed to explain Omphalocele
these differences.
The return of intestine into the peritoneal cavity normally
takes place around the 12th week of gestation. Omphalocele
(exomphalos) (Fig. 8.13) is a ventral wall defect characterized
by the herniation of intra-abdominal organs (bowel loops,
stomach, and liver) into the base of umbilical cord, with
a covering amnioperitoneal membrane. The omphalocele
can be diagnosed during the first-trimester scan (above
12th week of gestation). Association with chromosomal
aberrations is 35–58%. 3D first-trimester ultrasonography
can be helpful in identification of the omphalocele.
Other Abnormalities
Fetal kidney and bladder can be clearly seen in the 12th
week of gestation. The size of normal fetal kidney pelvis at
the end of the first trimester has not yet been established.57
Figure 8.12 The reversed flow during the a-wave (fetus with cystic
The fetal pyelectasis is unilateral or bilateral dilatation of
hygroma) the renal pelvis. The proposed 3 mm, as a higher level for
trisomy 18 at midgestation.63 The association of CPCs with

other chromosomal abnormalities is controversial.61,64,65
Fetal structural malformations are evident in the
second and third trimesters. First trimester studies of fetal
anatomy are limited (for the technical reasons and due to
the natural development of the organs). Certain structural
malformations in the first trimester have recently been
described in association with chromosomal abnormalities
(holoprosencephaly, ventriculomegaly, facial cleft,
micrognathia), etc.
Future Possibilities
With the evolution of ultrasound technique, the advancement
of sonographic markers for fetal aneuploidy is expected.
Figure 8.13 12 × 10 mm size omphalocele in a 13-week fetus Experiences with the fetal iliac angle measurement at
the second trimester66-69 can be useful at the first trimester
scan, but this statement is unproven yet. The fetal iliac
bones can be visualized during the first-trimester scan, the
angle between them can be measured (Fig. 8.14). In the
future, large prospective studies are needed to investigate
the usefulness of this marker.
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CHAPTER
9 Early Detection of
Fetal Abnormality
Ritsuko K Pooh
Introduction pregnancy, when huge yolk sac is observed, embryonal

demise may occur within several days. Figure 9.1 shows
After introduction of high-frequency vaginal transducer, a huge yolk sac beside an embryo with normal heartbeat.
transvaginal two-dimensional (2D) ultrasound had Embryonal death was confirmed 1 week later and villous
established a field of sonoembryology, 1 and most of chromosome was trisomy 15. Embryo occasionally grows
the major fetal abnormalities have been detectable in with huge yolk sac. Figure 9.2 shows normal appearance
the first trimester.2 Three-dimensional (3D) ultrasound of early embryo with regular heartbeat of 174 beats per
adds an objective and comprehensive information to 2D minute beside a large yolk sac at 8 weeks and 3 days of
sonographic findings. Recent technology of 3D ultrasound menstrual age. Fetal demise was confirmed on the next day
has provided not only fetal surface imaging but also and villous chromosome was 48, XY, +15,+21 and double
multiplanar image analyses of the embryonal and fetal trisomy. Hyperechogenic yolk sac is also highly associated
structures. Rotation of embryo and close scrutiny of the with chromosomal aneuploidy. Figures 9.3 and 9.4 show an
volume allow the systematic review of anatomic structures, embryo/fetus with normal heartbeat beside a hyperechoic
such as cord insertion, limb buds, cerebral cavities, yolk sac. Abnormal karyotypes of trisomy were confirmed
stomach and bladder.3 Appropriate fetal midsagittal section in both the cases. Thus, careful observation of yolk sac size
after rotating fetal image improved accuracy of nuchal and appearance is necessary in early pregnancy.
translucency measurement.4 Thus, 3D sonoembryology3,5
has been established. Early diagnosis by 3D ultrasound
of amnionicity in twin pregnancy at 6 weeks,6 and alobar
Fetal Structural Anomaly
holoprosencephaly at 9 weeks7 were recently reported. Recently, most of the fetal structural anomalies are
Organ volume analysis is one of the most interesting detectable in the first and early second trimesters by
topics in 3D technology. There are several articles on transvaginal sonography. Transvaginal ultrasound scan
volume analysis in early pregnancy by using 3D ultrasound between 12 and 15 weeks of gestation provides us many
technology. Blaas and his colleagues reported the successful of the fetal information in utero. Facial abnormalities
volume imaging and volumetry of embryonal brain cavity.8,9 including lowset ears, micrognathia and exophthalmos can
Kupesic and her colleagues published their article of be detected (Figs 9.5 and 9.6). Fetal limb abnormalities,
volume assessment of gestational sac and yolk sac.10 In this difficult to be demonstrated by transabdominal sonography
chapter, the authors have introduced sonograms of abnormal in the first half of pregnancy, can be clearly detected by
embryos/fetuses detected by transvaginal sonography. transvaginal approach. Figure 9.7 shows severe clubfeet
in a case of spina bifida, myelomeningocele and severe
kyphosis. Figure 9.8 shows fetal clubfoot at 15 weeks
Abnormal Yolk Sac
in a case with chromosomal aberration. Fetal abdominal
In normal pregnancy, yolk sac diameter showed an increase abnormalities, such as prune-belly syndrome (Fig. 9.9),
from 5 to 11 weeks of menstrual age, followed by a decrease exstrophy of the bladder (Fig. 9.10) and omphalocele
and its disappearance after 12 weeks. Several reports (Fig. 9.11), are easily detectable in the first trimester.
described that abnormal size of yolk sac was significant Spina bifida includes several types of myelomeningocele,
in the subsequent spontaneous abortion. 11-14 In early myelocystocele, meningocele, and myeloschisis.
Figure 9.1 Huge yolk sac. Upper: 2D image with normal regular heartbeat and 3D image. Lower: Three orthogonal
views with volume calculation 7 weeks and 3 days of menstrual age. Regular heartbeats of 120 beats per minute
beside large yolk sac. Embryonal death was confirmed 1 week later. Villous chromosome was trisomy 15
Figure 9.2 Huge yolk sac. Left: 2D image with normal appearance of early embryo and large yolk sac (arrowheads).
Middle: Regular heartbeat of 174 beats per minute. Right: 3D image of fetus and yolk sac (arrowheads). 8 weeks
and 3 days of menstrual age. Fetal demise was confirmed on the next day. Villous chromosome was 48, XY, +15,
+ 21, double trisomy
Chapter 9  Early Detection of Fetal Abnormality 63
Figure 9.3 Hyperechoic yolk sac. Left: 2D image. Right: 3D image. 9 weeks and 1 day of menstrual age. Normal
heartbeat was seen. Embryonal death was confirmed 3 days later. Villous chromosome was trisomy 15
Figure 9.4 Hyperechoic yolk sac. Left: 2D image. Right: 3D image. 11 weeks and 3 days of gestation. Referral
due to nuchal translucency. Normal heartbeat was seen. Amniocentesis resulted in trisomy 18
Figure 9.5 Lowset ear and micrognathia at 15 weeks of gestation. Left: 3D image. Right: Face of aborted fetus.
Growth retardation, single umbilical artery and additional anomalies were observed. Fetal karyotype was trisomy 18
Figure 9.6 Facial anomaly observed in a case of holoprosencephaly at 15 weeks of gestation. Left: 3D image.
Right: Face of aborted fetus. Lowset ear and exophthalmos are demonstrated. Fetal karyotype was partial deletion
of chromosome 9
Figure 9.8 Fetal clubfoot at 15 weeks of gestation. Left: 3D image of fetal

leg. Right: Legs of aborted fetus. This fetus has chromosomal aberration
Although Blaas et al. reported cases of spina bifida

before 10 weeks of gestation, spinal level and degree of
spina bifida are variable and its early detection is quite
difficult.15 Figure 9.12 shows early detection of spina bifida
at 9 gestational weeks. At 9 weeks, vertebral bony structure
is not detectable but neural tube dilatation is clearly
Figure 9.7 Fetus with myelomeningocele, severe kyphosis and demonstrated in the case. Vertebral scoliosis is detectable
clubfoot at 20 weeks of gestation. Upper left: 3D image of fetus from early pregnancy (Fig. 9.13). Pleural effusion is
(transabdominal sonography). Upper right: Aborted fetus. Lower left:
3D image of fetal legs (transvaginal sonography), severe clubfeet are often found in early pregnancy because of congenital
seen. Lower right: Legs of aborted fetus. Fetal karyotype was normal heart diseases and/or chromosomal aberration. In most of
Figure 9.9 Prune-belly syndrome at 11 weeks of gestation. Three orthogonal views and 3D surface
image. Enlarged prune-belly-like bladder is detected. Right photo shows aborted fetus at 12 weeks
of gestation. Fetal karyotype was normal
Figure 9.10 Exstrophy of the bladder in the first trimester. Upper: 2D sagittal (left), coronal (middle) and coronal
color Doppler image (right). Extracorporeal cyst (arrowheads) is seen. Note the umbilical arteries running along
the cyst. Lower: 3D images at 10 weeks (left), 11 weeks (middle) and 12 weeks (right) of gestation. Longitudinal
images show gradual but rapid increase of the outside cyst. No bladder was seen inside of the fetus
Figure 9.11 Omphalocele at 12 weeks of gestation. Left: 3D surface image of the fetus. Omphalocele was seen at the
left side of the fetus. Right: Aborted fetus. Sac of omphalocele was ruptured on delivery. Fetal chromosome was normal
Figure 9.12 Spina bifida at 9 weeks of gestation. Left: 2D sagittal image. Cystic formation was seen (white circle)
at lumbar part. Right: 3D image of neural tube. Clear dilatation of the neural tube is demonstrated (arrows)
Figure 9.13 Severe scoliosis at 12 weeks of gestation. Left: 3D image of fetal back. Severe scoliosis is
demonstrated. Right: Back view of aborted fetus. Fetal karyotype was normal
Figure 9.15 Hydropic fetus at 14 weeks of gestation: three orthogonal

views and 3D surface image. Severe general edema and unilateral
pleural effusion (arrows) are demonstrated. Fetal karyotype was 45, X
Figure 9.14 Pleural effusion at 9 weeks of gestation. Three orthogonal
views and 3D surface image. Bilateral pleural effusion is clearly
demonstrated. Fetal heartbeat was normal and regular. Fetal demise
was confirmed 3 days later and villous karyotype was 45, X, Turner’s
syndrome
cases with early detection of pleural effusion, subsequent

fetal demise may be confirmed. In our series, over 90%
of cases with early pleural effusion were associated with
45, X Turner’s syndrome (Fig. 9.14). Fetal hydrops in the
first trimester is also strongly associated with abnormal
karyotype. Figures 9.15 and 9.16 show hydropic fetus
with pleural effusion or cystic hygroma. In many of the
cases with cystic hygroma, congenital heart disease,
tachycardia and general edema, and fetal chromosome
test may result in abnormal karyotype, especially 45, X.
Figure 9.17 shows hydropic fetus with cystic hygroma,
axillary lymphadenopathy at 15 weeks of gestation.
Congenital heart disease of double outlet right ventricle
was simultaneously detected. Although Turner’s syndrome
was suspected, this case had abnormal wrist flexion and
contracture shown on the right figure. Most cases of 45, X
have no upper limb abnormalities. Fetal demise occurred
3 days later and chromosome was trisomy 18. Congenital
diaphragmatic diseases including diaphragmatic hernia
and eventration of diaphragm highly cause subsequent
hypoplastic lung. Early detection was quite difficult. The
authors had a case with agenesis of diaphragm, which was
strongly suspected from early pregnancy. Figure 9.18 shows
dextrocardia and abnormal lung-liver border at 13 weeks
Figure 9.16 Cystic hygroma at 14 weeks of gestation. Three
of gestation. Left lung was visible at this stage, but became orthogonal views (upper), 3D surface image (lower left) and aborted
completely hypoplastic lung in late pregnancy. fetus (lower right). Fetal karyotype was 45, X
Figure 9.17 Hydrops, cystic hygroma, axillary lymphadenopathy and abnormal wrist flexion and contracture
at 15 weeks of gestation. 2D coronal image (left) and 3D surface image (right). Bilateral pleural effusion is also
demonstrated on the 2D image. In this case, congenital heart disease of double outlet right ventricle was detected.
Fetal karyotype was trisomy 18
Figure 9.18 Congenital diaphragm defect at 13 weeks of gestation. Left: A cutting image of 4D cardiac mode
showing fetal thoracoabdominal part. Dextrocardia (H) and abnormal lung-liver border is demonstrated (arrows).
Left lung was visible at this stage, but became completely hypoplastic lung in late pregnancy. Right is schematic
figure of the left sonographic image. Fetal karyotype was normal
Future Aspects 7. Blaas HG, Eik-Nes SH, Vainio T, et al. Alobar holopro-
sencephaly at 9 weeks gestational age visualized by two- and
Transvaginal sonography and 3D ultrasound had contributed to
reveal pathophysiological natural history of congenital structural
three-dimensional ultrasound. Ultrasound Obstet Gynecol.
abnormalities. Recent advanced technology of 4D ultrasound 2000;15:62-5.
has been adding in utero information of real-time fetal motion 8. Blaas HG, Eik-Nes SH, Kiserud T, et al. Three-dimensional
and positioning and 4D echocardiography. With technological
development of ultrasound, further detailed detection in early
imaging of the brain cavities in human embryos. Ultrasound
pregnancy is expected. Obstet Gynecol. 1995;5:228-32.
9. Blaas HG, Eik-Nes SH, Berg S, et al. In-vivo three-
dimensional ultrasound reconstructions of embryos and
References early fetuses. Lancet. 1998;352:1182-6.
1. Timor-Tritsch IE, Peisner DB, Raju S. Sonoembryology: 10. Kupesic S, Kurjak A, Ivancić-Kosuta M. Volume and
an organ-oriented approach using a high-frequency vaginal vascularity of the yolk sac studied by three-dimensional
probe. J Clin Ultrasound. 1990;18:286-98. ultrasound and color Doppler. J Perinat Med. 1999;27:91-6.
2. Pooh RK. B-mode and Doppler studies of the abnormal fetus 11. Babinszki A, Nyari T, Jordan S, et al. Three-dimensional
in the first trimester. In: Chervenak FA, Kurjak A (Eds). Fetal measurement of gestational and yolk sac volumes as
Medicine. Carnforth: Parthenon Publishing; 1999.pp.46-51. predictors of pregnancy outcome in the first trimester. Am
3. Kurjak A, Kupesic S, Banovic I, et al. The study of J Perinatol. 2001;18:203-11.
morphology and circulation of early embryo by three-
12. Küçük T, Duru NK, Yenen MC, et al. Yolk sac size and
dimensional ultrasound and power Doppler. J Perinat Med.
shape as predictors of poor pregnancy outcome. J Perinat
1999;27:145-57.
Med. 1999;27:316-20.
4. Kurjak A, Kupesic S, Ivancić-Kosuta M. Three-dimensional
transvaginal ultrasound improves measurement of nuchal 13. Stampone C, Nicotra M, Muttinelli C, et al. Transvaginal
translucency. J Perinat Med. 1999;27:97-102. sonography of the yolk sac in normal and abnormal
5. Takeuchi H. Advanced sonoembryology by transvaginal pregnancy. J Clin Ultrasound. 1996;24:3-9.
three-dimensional ultrasound. In: Chervenak FA, Kurjak 14. Lindsay DJ, Lovett IS, Lyons EA, et al. Yolk sac diameter
A (Eds). Fetal Medicine. Carnforth: Parthenon Publishing; and shape at endovaginal US: predictors of pregnancy
1999.pp.16-23. outcome in the first trimester. Radiology. 1992;183:115-8.
6. Babinszki A, Mukherjee T, Kerenyi T, et al. Diagnosing 15. Blaas HG, Eik-Nes SH, Isaksen CV. The detection of
amnionicity at 6 weeks of pregnancy with transvaginal spina bifida before 10 gestational weeks using two- and
three-dimensional ultrasonography: case report. Fertil Steril. three-dimensional ultrasound. Ultrasound Obstet Gynecol.
1999;71:1161-4. 2000;16:25-9.
CHAPTER
10 Echocardiography in
Early Pregnancy
Carmina Comas, Pilar Prats
Abstract (TOP) is essential to assess the actual role of early fetal

echocardiography. At present, early fetal echocardiography
Within the last decade, two significant events have is a promising technique, which can be of considerable
contributed to the increasing interest in early fetal value for patients at high risk. This technique is, however,
echocardiography. First, the introduction of high-frequency currently limited to a few specialized centers.
vaginal ultrasound probes allows detailed visualization of The aim of this review is to explore the possibilities of
cardiac structures at early stage of gestation, making early examining the fetal heart at the early stage of pregnancy.
detection of fetal malformations possible. Second, the This chapter also presents our experience in the first
close relationship observed between some first-trimester multicenter trial in early fetal echocardiography performed
sonographic and Doppler markers and congenital heart in Spain. In accordance with other studies, this experience
defects (CHD) allows an early identification of a high- stresses the usefulness of early echocardiography when
risk group at 11−14 weeks of gestation. In this context, performed by expert operators on fetus specifically at
from the early 1990s, many authors have examined the risk for cardiac defects. Our review of these additional 48
potential role of the transvaginal (TV) approach to obtain cases contributes to the expanding literature on the ability
earlier diagnosis of fetal cardiac malformations. Further of TV ultrasonography to detect fetal heart defects in early
studies have appeared in the literature showing that early pregnancy.
TV echocardiography in experienced hands are a fairly
sensitive investigative tool. Although some malformations
are detected as early as 11 weeks of gestation, the optimal
Introduction
gestational age to perform the early scan is at least 13 Prenatal detection of fetal CHD remains the most
weeks of gestation. Transvaginal ultrasound is the preferred problematic issue of prenatal diagnosis.1 Major CHD are
approach, although most of the authors agree that results the most common severe congenital malformations, with an
can be improved if transabdominal ultrasound is also incidence of about 5 in 1,000 live births, whenever complete
incorporated. The further application of color Doppler ascertainment is done and minor lesions are excluded.1,2
enhances visualization. The sensitivity and specificity of Congenital heart anomalies have a significant effect on
early fetal echocardiography for the detection of heart affected children’s life with up to 25−35% mortality rate
anomalies is acceptable compared to the ones obtained during pregnancy and the postnatal period, and it is during
by mid-gestational echocardiography, showing a slight the first year of life, when the 60% of this mortality occurs.
reduction in detection rates and an increase in false-positive Moreover, major CHD are responsible for nearly 50% of all
and-negative rates. The cardiac anomalies detected at this neonatal and infant deaths due to congenital anomalies, and
early stage of pregnancy are mainly defects involving it is likely to be significantly higher if spontaneous abortions
the four-chamber view, indicating that defects solely are considered. Although CHD used to appear isolated, they
affecting the outflow tracts are difficult to diagnose in are frequently associated with other defects, chromosomal
the first trimester of pregnancy. Heart defects diagnosed anomalies and genetic syndromes. Their incidence is six
early in pregnancy tend to be more complex than those times greater than chromosomal abnormalities and four
detected later, with a higher incidence of associated times greater than neural tube defects.1-3
structural malformations, chromosomal abnormalities and Most major CHD can be diagnosed prenatally by
spontaneous abortions. The neonate follow-up or post- detailed transabdominal second trimester echocardiography
mortem examination in case of termination of pregnancy at 20−22 weeks of gestation. 1,3-6 The identification of
pregnancies at high risk for CHD needing referral to both transabdominal and TV routes seem to offer similar
specialist centers is of paramount importance in order to advantages and disadvantages, and beyond the 18th week
reduce the rate of overlooked defects.6,7 However, the main the transabdominal echocardiography seems to achieve
problem in prenatal diagnosis of CHD is that the majority better results.1,5,16,27,28
of cases take place in pregnancies with no identifiable risk The combination of two-dimensional echocardiography
factors. Therefore, there is wide agreement that cardiac with color Doppler flow imaging proved generally
ultrasound screening should be introduced as an integral helpful, in particular by visualization of blood flow on
part of the routine scan at 20−22 weeks. When applied to both great arteries and of two divided ventricular inflows.
low-risk population, scrutiny of the four-chamber view The addition of color Doppler flow studies provides
allows only the detection of 40% of the anomalies while substantial improvement in the diagnostic accuracy of
additional visualization of the outflow tracts and the great early echocardiography, as was also shown by DeVore
arteries increase the rate up to 60−70%.3-5 for transabdominal sonography in the second half of
Recently, the finding of an increased nuchal pregnancy.29
translucency8,9 or an altered ductus venosus blood flow10,11 at When performing early fetal echocardiography, we
10−14 weeks of gestation have been associated with a high firstly recommend scanning by the TV route, following
risk for CHD and their prevalence increase exponentially the examination by the transabdominal probe when a
with the thickness of nuchal translucency 8 regardless complete study is not possible. The highest frequency must
the fetal karyotype. Since earlier diagnosis of congenital always be used, whatever the route is chosen. Obviously,
malformations is increasingly demanded, the option of an a high-resolution real-time ultrasound has to be used. For
early fetal echocardiography must be taken into account.12-14 color Doppler evaluation, the energy output levels have to
The use of high-frequency vaginal ultrasound probes be lower than 50 mW/cm2 spatial peak-temporal average.
along with substantial improvements in magnification and Since color Doppler is dissipated over a wide area of
processing of the imaging, together with the introduction interest, thermal effects resulting from Doppler insonation
of color Doppler, have extensively contributed to the should not be a matter of concern, unlike pulsed Doppler in
development of the technique, allowing better visualization which the whole energy of the beam is focused at a specific
of cardiac structures earlier in pregnancy.12,15,16 Although location. Besides, the embryonic developmental of the heart
most of the groups perform early fetal echocardiography has been completed by the time the scan is performed.
between 13 and 16 weeks of gestation, we can name it as so
when performed before the 18th week of gestation. Despite Ultrasound Anatomy of
several studies stated that fetal heart examination could be the Normal Heart
incorporated in first or early second trimester examinations,
its use is currently still limited to a few specialized centers. Embryonic heart beat can be detected as early as the 5th
week of gestation, and normal development of its function
shows an increasing heart rate from 80 to 90 beats per
Technical Issues minute at 5 weeks of gestation to 170−180 beats per minute
Regarding early fetal echocardiography, some institutions at the end of the 9−10th week of gestation. As pregnancy
use predominantly the TV approach14,17-22 while others progresses, the control of the heart rate matures with
prefer the transabdominal one.23-26 Most of the authors increasing vagal dominance, and the baseline rate declines
reporting early fetal echocardiography prefer the TV to 145−155 beats per minute with the appearance of beat-
approach due to its increased resolution associated with to-beat variation, most likely resulting from the functional
higher frequency transducers and also because given that adaptation to the development of the heart and autonomic
equivalent transducers frequencies, the TV probes provide nervous system maturation, and remains more or less
better quality images.27 However, most importantly, authors constant during the rest of intrauterine life.30,31
with background training as pediatric cardiologists are more The structural development of the heart begins on
likely to use the transabdominal approach in contrast with day 16 and it is finished by the 10th week. Early fetal
most of obstetricians, who are well used to the TV route. echocardiography has the same goals that the standard one
The superiority of TV sonography is usually well accepted and we advocate to perform it in a segmental approach. The
before the 14th week. Between the 15th and 18th weeks first objective of the examination is to assess the normality
Chapter 10  Echocardiography in Early Pregnancy 73
of the four-chamber view through a transverse section of
the fetal chest: normal situs solitus; normal size and axis
of the heart in relation to the chest; both atria equal in size,
with the foramen ovale flapping within the left atrium;
both ventricles equal in size and contractility; atrial and
ventricular septa are of normal appearance; tricuspid and
mitral valves are normally inserted, opening and closing
together. Color and pulsed Doppler are particularly useful
to confirm normal inflow to the ventricles and to detect
turbulent flow or jets suggesting valve regurgitation. It
is useful to assess the four chambers in different views:
apical, basal and long axis with the interventricular
septum perpendicular to the ultrasound beam in order
to visualize better the integrity of the septum. Then, the
Figure 10.1 Early fetal echocardiography by 2D in a structurally normal
origin and double crossing of the great arteries must be heart. Situs visceral. Left: fetal stomach, cross section of the abdominal
correctly identified: the left ventricle outflow tract, with aorta, spine and liver. Right: four-chambers view. Heart axis pointing
the continuity between the interventricular septum and left, heart occupies one-third of the thorax, majority of heart in left chest
Abbreviations: St, Stomach; AAo, Abdominal aorta; Sp, Spine; RV,
the anterior wall of the ascending aorta; the right ventricle Right Ventricle; LV, Left Ventricle; RA, Right Ventricle; LA, Left Ventricle
outflow tract, more superior, anterior, almost perpendicular
to the axis of the ascending aorta and connecting to the
descending aorta in the three vessels view. Color Doppler
also helps to better visualize the outflow tracts confirm
anterograde flow through the semilunar valves and great
arteries, and makes easier the examination of both aortic and
ductal archs and their confluence. Pulsed Doppler may be
used to assess blood flow through the aortic and pulmonic
valves in order to confirm normal anterograde flow and
to detect very high velocities suggesting valve stenosis.
Finally, color and pulsed Doppler are also very useful to
identify normal systemic and pulmonary venous return.
Figures 10.1 to 10.10 illustrate images obtained at early
fetal scan by 2D echocardiography and color Doppler in
a structurally normal heart. In our experience, the average
duration of the complete fetal cardiac scan is over 15 Figure 10.2 Early fetal echocardiography by 2D in a structurally
normal heart. The four-chamber view: normal situs solitus; normal size
minutes. It essentially depends on the gestational age at the and axis of the heart in relation to the chest; both atria equal in size,
examination, and can be even shorter if there is a favorable with the foramen ovale flapping within the left atrium; both ventricles
fetal lie. In our setting, a subsequent transabdominal equal in size and contractility; atrial and ventricular septa are of
normal appearance; tricuspid and mitral valves are normally inserted
echocardiography is scheduled for all our patients at 20−22 (Abbreviations: RV, right ventricle; LV, left ventricle; RA, right atrium;
weeks of gestation. LA, left atrium; FO, foramen ovale; DAo, descending aorta)
Most of the authors agree that the best window of time to
perform the early echocardiography is between 13 and 16 echocardiography should be preferably performed at 13
weeks of gestation, since a complete cardiac examination is completed weeks of gestation. Using current technology,
rarely achieved before the 13th week of gestation.14,17,18,20-22,26 the four-chamber view and the outflow tracts are often
Articles on early fetal echocardiography demonstrate an demonstrated by two-dimensional echocardiography
increase in visualization rates of the four-chamber view and only, but color Doppler imaging enhances and makes
the outflow tracts in the last decade, with visualization rates the identification of the structures faster, increasing the
greater than 90% at 13 weeks of gestation.28 To maximize success rate of the examination, and allows even earlier
the reduction of non-interpretable examinations, early fetal identification of the structures.
A B A
Figures 10.3A and B Early fetal echocardiography by 2D and
color Doppler in a structurally normal heart. (A) Four-chamber
view-2D. (B) Four-chamber view-2D and color Doppler
(Abbreviations: RV, right ventricle; LV, left ventricle; RA, right atrium;
LA, left atrium; FO, foramen ovale; DAo, descending aorta)
Figure 10.4 The five-chamber view: left ventricle outflow

tract in the long axis view showing the continuity between the
interventricular septum and the anterior wall of the ascending aorta
(Abbreviations: RV, right ventricle; LV, left ventricle; RA, right atrium;
LA, left atrium; AAo, ascending aorta; DAo, descending aorta; IVS,
interventricular septum)
Diagnosis of Congenital Heart Defects

The first diagnosis of a CHD by early echocardiography C
was reported by Gembruch et al.32 in 1990. A complete Figures 10.5A to C Early fetal echocardiography by 2D, color Doppler
and BiFlow in a structurally normal heart. The three-vessel view. Color
atrioventricular canal defect, with complete heart block Doppler is particularly useful to demonstrate the normal V confluence
and atrioventricular valve regurgitation was diagnosed at 11 of the ductal and aortic arch (V sign). Note that normally the trachea
weeks + 4 days of gestation using a 5-MHz TV probe. The is located behind the aortic arch. (A) three-vessels view 2D. (B) three-
vessels view 2D and color Doppler. (C) three-vessels view 2D and BiFlow
same year, Bronshtein et al.33 reported the diagnosis of a (Abbreviations: Ao, aorta; PA, pulmonary artery; SVC, superior vena
ventricular septal defect with overriding aorta and a further cava)
Figure 10.6 Early fetal echocardiography by 2D and BiFlow in a Figure 10.7 Early fetal echocardiography by 2D in a structurally
structurally normal heart. BiFlow is particularly useful to demonstrate normal heart. The short axis view, showing an anterior right ventricle
the crossing of the great arteries (Abbreviations: Ao, aorta; PA, and a posterior left ventricle (Abbreviations: RV, right ventricle; LV,
pulmonary artery) left ventricle)
A B
Figures 10.8A and B Early fetal echocardiography by 2D in a structurally normal heart. The left sagittal view of (A) ductal arch and (B) aortic arch
(Abbreviations: RV, right ventricle; LV, left ventricle; PA, pulmonary artery; DA, ductus arteriosus; DAo, descending aorta; AAo, ascending aorta)
case of an isolated ventricular septal defect with pericardial gestation over a 14-year period of time, with 99% of scans
effusion, both cases at 14 weeks of gestation. Since then, performed at 14−16 weeks of gestation and 86% of them
an increasing number of case reports and series on the early in low-risk population.
diagnosis of CHD have been reported, both in high-risk and Two institutions went further and reported their
low-risk population. Tables 10.1 and 10.2 summarize some experience performing the echocardiography as early as
of the largest and most significant studies on the detection between 10 and 13 weeks of gestation.22,26
of CHD using early fetal echocardiography in high-risk The most frequent fetal heart anomalies diagnosed at
and low-risk pregnancies.14,17-22,24-26,34-46 Obviously, studies early echocardiography are summarized in Table 10.3
in unselected population report less encouraging results, (true positive cases). 14,18-21,24-26,34,35,37,39-42,45-46 Note that
with lower visualization rates and detection rates. The only the main anomaly for each fetus is presented in
largest series was published by Bronshtein et al.20 They the table, even though some fetuses had several cardiac
reported the diagnosis of 173 cases of CHD over 36,323 anomalies. It should be noted that defects, such as small
fetuses evaluated by TV ultrasound at 11−17 weeks of isolated ventricular septal defect or valvular stenosis, are
Figure 10.9 Early fetal echocardiography by 2D in a structurally normal Figure 10.10 Early fetal echocardiography by 2D and power Doppler.
heart. Systemic venous return to the right atrium throws the superior Normal mitral wave flow by power Doppler
and inferior vena cava (Abbreviations: SVC, superior vena cava; IVC,
inferior vena cava)
Table 10.1 Results of early fetal echocardiography to diagnose cardiac defects in high-risk population (only series with at least 10 cardiac
defects diagnosed)
Author, year Route GA Success (%) Risk N Cases 11−16 ws 20−22

(%) weeks (%)
Gembruch, 199314 TV 11−16 90.3 High 114 13 92 100
Zosmer, 1999 24
TA 13−17 High 323 27 89 96.3
Simpson, 2000 25
TA 12−15 98.7 High 229 17 76 94
Huggon, 2002 26
TA 10−14 86.8 High 478 68 94
Haak, 2002 22
TV 10−13 95.5 High 45 13 54
Bronshtein, 2002 20
TV 11−17 > 99 High 6,175 46 > 90
Comas, 2002 21
TV 12−17 94.6 High 337 48 79 96
Lopes, 2003 39
TV 12–16 94,9 High 275 37 89
Weiner, 2002 40
TV 11–14 97 High 392 19 58.3
Carvalho, 2004 41
TA 10–16 96 High 230 14 91.3
McAuliffe, 2005 42
TV 11–16 95 High 160 20 70
Smrcek, 2006 43
TV 11–14 NR High 2160 35 63
Weiner, 2008 45
TV 11-14 94 High 200 19 68
Route : Main approach

TV : Transvaginal
TA : Transabdominal
GA : Range of gestational age at scan, in weeks
Success : Visualization success rate for the complete early fetal echocardiography
N : Total number of pregnancies scanned
Cases : Total number of cardiac defects (prenatal and postnatal)
11−16 weeks : Percentage of the cardiac defects identified at early echocardiography (weeks)
20−22 weeks : Percentage of the cardiac defects identified at mid-trimester echocardiography (weeks)
NR : Not reported
Table 10.2 Detection rate of cardiac defects at early ultrasound to screen for congenital malformations in low-risk population
Author, year GA Success (%) Risk Normal Cases 11−16 weeks (%) 20−22 weeks (%)
Achiron, 199418 13−15 98 Low 660 6 50 50
Hernadi, 1997 34
12 Low 3,991 3 33 100
D'Ottavio, 1997 35
13−15 Low 3,490 8 25 80
Yagel, 1997 17
13−16 99 Low 6,924 66 64 81
Economides, 1998 36
12−13 Low 1,632 3 0 33
Whitlow, 1999 37
11−14 Low 6,443 10 40 60
Guariglia, 2000 38
10−16 Low 3,592 11 18 56
Rustico, 2000 19
13−15 <50 Low 4,785 41 10 32
Bronshtein, 2002 20
11−17 99 Low 30,148 127 97 99
Becker, 2006 44
11−14 Low 3,094 86 84.2 94
Volpe, 2011 46
11−14 Low 4,445 42 62 93
GA : Range of gestational age at scan (weeks)

Success : Visualization success rate for the extended cardiac examination (four chambers + outflow tracts)
Normal : Total number of pregnancies screened
Cases : Total number of cardiac defects (prenatal and postnatal)
11−16 weeks : Percentage of the cardiac defects identified at early scan (weeks)
20−22 weeks : Percentage of the cardiac defects identified at mid-trimester scan (weeks)
Table 10.3 Fetal heart anomalies diagnosed at early echocardiography (true-positive cases at early fetal echocardiography)
True-positive A B C D E F G H I J K L M N O P Q R S Overall
Gembruch, 1993 14
6 1 1 2 2 12
Zosmer, 199924 3 3 2 1 4 2 3 1 4 1 24
Rustico, 200019 2 1 1 1 5
25
Simpson, 2000 3 2 3 2 2 1 13
Huggon, 200226 5 29 12 9 1 1 1 1 1 60
Bronshtein, 2002 20
4 1 4 13 2 9 25 31* 22 5 18 17 3 2 13 169
Comas, 200221 4 8 10 4 1 3 2 2 1 3 38
18
Achiron, 1994 2 2 1 1 1 1 8
Hernadi, 199734 1 1
D’Ottavio, 199735 2 2 4
Whitlow, 199937 1 1 1 3
19
Rustico, 2000 1 2 1 4
Lopes, 200339 2 6 11 5 1 1 1 1 3 2 33
Weiner, 200240 4 1 1 2 2 2 1 13
41
Carvalho 2004 1 3 1 1 1 2 1 3 1 14
McAuliffe, 200442 2 2 2 1 2 2 1 2 14
45
Weiner, 2008 4 1 2 2 1 2 1 13
Volpe, 201146 1 7 4 7 1 2 1 2 1 26
Overall 4 2 23 89 8 59 67 12 49 29 16 6 31 7 19 12 7 13 5 374
A, abnormal venoatrial connections; B, atrial septal defects; C, tricuspid atresia or dysplasia; D, atrioventricular septal defect; E, single
ventricle; F, ventricular septal defects; G, aortic atresia, aortic stenosis, mitral stenosis, hypoplastic left heart; H, pulmonary atresia or stenosis;
I, tetralogy of Fallot; J, transposition of great arteries; K, truncus; L, double outlet right ventricle; M, aortic arch anomalies; N, isomerism;
O, miocardiopathy; P, ectopia cordis; Q, complex cardiac defect, others; R, vascular ring; S, hypoplastic right heart
*This series include cases with tetralogy of Fallot and double outlet right ventricle
not reported in these studies. Table 10.4 summarizes the Furthermore, when the cardiac defects are detected during
published cases of cardiac anomaly not detected in early the early pregnancy, they use to be even more complex,
pregnancy (false-negative cases).14,19-21,24-26,34-37,39-42,45,46 probably corresponding to the most severe spectrum of the
The results of these studies support the use of early disease21,25,26 and use to cause more severe hemodynamic
fetal echocardiography to detect the majority of major compromise in the developing fetus. A common finding
CHD in both low-risk and high-risk populations, during is the presence of a hygroma or hydrops associated with
the first and early second trimester of pregnancy. The CHD, whereas this is not so when the diagnosis is done
cardiac anomalies detected at this early stage of pregnancy later in pregnancy.1,5,21 As a result, many of these fetuses
are mainly defects involving the four-chamber view, such are not going to survive long into the second trimester,
as large ventricular septal defects, atrioventricular septal but this does not argue against early diagnosis. Indeed,
defects and malformations resulting in asymmetry of when the intrauterine demise of the fetus occurs days or
the ventricles, indicating that defects solely affecting the weeks before the delivery, the pathological examination is
outflow tracts are difficult to diagnose in the first trimester certainly more difficult to perform. All these considerations
of pregnancy. Heart defects diagnosed early in pregnancy should be taken into account when counseling the parents
tend to be more complex than those detected later, with a about complex CHD.
higher incidence of associated structural malformations, We have previously published our experience in the first
chromosomal abnormalities and spontaneous abortions. It is multicenter trial in early fetal echocardiography performed
widely accepted that the spectrum of CHD diagnosed during in Spain21 (Figs 10.11 to 10.15). In accordance with other
prenatal life is different from that observed in postnatal studies, this experience stresses the usefulness of early
series, with a higher incidence of associated extracardiac echocardiography when performed by expert operators on
lesions and a significant relationship with chromosomal fetus specifically at risk for cardiac defects. Our review
abnormalities in comparison with postnatal life. 3-5,17 of these additional 48 cases contributes to the expanding
Table 10.4 Fetal heart anomalies not detected at early echocardiography (false-negative cases at early fetal echocardiography)
False-negative A B C D E F G H I J K L M N Overall
Gembruch, 199314 1 1
Hernadi, 199734 1 1 2
D’Ottavio 1997 35
1 3 2 1 7
Economides, 199836 1 1 1 3
Whitlow, 199937 2 1 2 1 1 7
Zosmer, 1999 24
1 1 1 3
Rustico, 200019 1 4 1 2 1 9
25
Simpson, 2000 3 1 4
Comas, 200221 4 1 3 1 1 10
Huggon, 200226 2 2 1 2 7
Bronshtein, 2002 20
1 1 1 1 4
Lopes, 200339 3 1 4
Weiner, 200240 3 1 1 1 6
41
Carvalho 2004 1 1 2
McAuliffe, 200442 3 2 1 6
Becker, 2006 44
1 1 2 1 1 1 7
Weiner, 200845 2 1 1 1 1 6
Volpe, 201146 7 1 2 1 1 1 1 1 15
Overall 34 3 2 1 18 11 8 8 8 1 2 2 2 1 61
A, ventricular septal defects; B, atrial septal defects; C, abnormal venoatrial connections; D, tricuspid atresia or dysplasia; E, atrioventricular
septal defect; F, aortic atresia, aortic stenosis, hypoplastic left heart; G, tetralogy of Fallot; H, transposition of great arteries; I, aortic arch
anomalies; J, myocardiopathy; K, absent pulmonary valve, pulmonary stenosis; L, mitral dysplasia; M, pulmonary stenosis; N, total anomalous
pulmonary venous drainage
literature on the ability of TV ultrasonography to detect relieve anxiety and reduce emotional trauma to the parents
fetal heart defects in early pregnancy. at high risk for CHD. Early prenatal diagnosis of CHD will
allow us to optimize the genetic counseling to the parents
Advantages and Limitations by permitting further testing such as fetal karyotyping and
in those cases with severe defects it may provide the parents
The first benefit of performing early fetal echocardiography with the option of an earlier and safer TOP.13,14,17 In selected
would be an early reassurance of normality in order to cases, there is the possibility of pharmacologic therapy.
Furthermore, the correct timing and place for delivery may
be planned and arranged well in advance.
However, there are certain disadvantages of the
early scanning which reduce its diagnostic accuracy
compared with the conventional examination at 20−22
weeks of gestation.1,5,13,14,17 The TV technique requires a
substantial amount of operator experience, yet it cannot
be learned from the second trimester examination as the
early transabdominal scan. Unfavorable fetal position
or limited angles of insonation due to the less mobile
capacity of the TV probe may not be overcome. Also,
spatial orientation can be challenging by the TV scan. In
such cases, we recommend a transabdominal scan that
will help us to quickly assess the situs and obtain a good
Figure 10.11 Early fetal echocardiography by 2D and power Doppler. spatial orientation. The small size of the fetal heart is an
Normal tricuspid wave flow by power Doppler important limiting factor to obtain an optimal sonographic
A B C
D E
Figures 10.12A to E Atrioventricular septal defect detected at 13 weeks of gestation in a fetus affected by cystic hygroma and trisomy 21. (A)
Note the abnormal reversed A wave in the ductus venosus. (B and C) Note the ventricular septal defect. (D and E) These figures illustrate the
mitral and tricuspid diastolic flow, respectively
http://radiologyme.com/
A B
C D E
Figures 10.13A to E Tetralogy of Fallot detected at 16 weeks of gestation. (A) Note the reverse a wave in ductus venosus flow. (B) Note the
left ventricular septal defect, (C) the dominance of the aorta compared with the small pulmonary artery at the three-vessel view in the upper
mediastinum, (D) cardiac deviation, and (E) aortic misalignment
visualization, and also to obtain a successful pathological although in some rare cases a regression to a less severe
examination, particularly before the 13th week of gestation. form may be observed. In this sense, the false negative
At 13−14 weeks of gestation the transverse diameter of the cases published in literature are particularly instructive
heart at the four-chamber view ranges between 5 and 8 mm, demonstrating these limitations. Another disadvantage of
and the great artery diameter at the level of the semilunar early fetal echocardiography is the possible detection of
valves ranges between 0.8 and 1.8 mm.5 Moreover, this defects that could resolve spontaneously in later pregnancy,
exploration is more time-consuming and requires a high such as muscular ventricular septal defects, resulting in
level of training of the examiner. Finally, the biggest unnecessary anxiety in the parents.
disadvantage of first-trimester echocardiography is the later Therefore, a normal early examination does not preclude
manifestation of structural and functional changes in some a subsequent abnormal heart development at the second
CHD. Some cardiac lesions are progressive in nature, such trimester ultrasound, or even in the third trimester or the
as mild pulmonary and aortic stenosis or coarctation and postnatal period. After a normal early fetal echocardiography,
even hypoplastic left heart syndrome. Some obstructive a conventional transabdominal echocardiography at 20−22
lesions, as a result of a reduced blood flow, may increase weeks of gestation is strongly recommended.
the severity of the lesions, resulting in a restricted growth in
chambers or arteries. This may be the biggest disadvantage Pathological Confirmation
of performing the early scan. Progression usually is toward
a more severe form of lesion that may be sometimes only Pathological confirmation in the case of an early TOP or
discernible in the second or even in the third trimester, perinatal death is particularly important in those areas
A B
C D E
Figures 10.14A to E Hypoplastic left heart at 14 weeks of gestation. (A) Note the identification of CHD markers: increased nuchal translucency,
(B) abnormal ductus venosus flow. (C) Reverse flow at the three-vessels view, (D) hypoplastic left ventricle with reverse flow with color Doppler,
(E) reverse flow in aortic arch
where ultrasound diagnosis is most challenging. Only This method allows a more gentle extraction of the embryo
a complete diagnosis will make an individual genetic or fetus so that a pathological examination for verification of
counseling possible and will validate the accuracy of early the prenatally diagnosed malformation can be performed. A
fetal echocardiography as a diagnostic technique. Therefore, pathological investigation after TOP following the diagnosis
we advocate that a precise pathological report have to be of a CHD should be always recommended, preferably in
compulsory for an adequate assessment of the reliability of referral laboratories, being of paramount importance to
early fetal echocardiography. This is still a major drawback validate early echocardiography. In particular semilunar
in most of the studies.1,5,21,26 valve and aortic arch defects are usually underdiagnosed. We
Termination of pregnancy is an option only before 22 are aware of some cases in which Doppler findings, such as
weeks of gestation in our country. Whenever a termination turbulent flow and very high velocities, are more reliable to
takes place, it is of vital importance to obtain permission for diagnose valve stenosis than pathological examination, even
autopsy in order to confirm the diagnosis and to search for during the second trimester. Indeed, this is a problem and a
any other associated malformations. Ideally this should be major challenge not only for ultrasonographers but also for
performed by a pathologist who is familiar with the small pathologists.
size of the specimen and with special examination techniques
such as dissection microscopy.5,21,22 Current methods of Indications of Early Fetal
terminating early pregnancies other than using prosta-
glandins are less recommended because they do not usually
Echocardiography
allow the retrieval of suitable specimens for appropriate Since most CHD are detected in low-risk pregnancies,
examination to correlate ultrasound and pathological findings. and knowing the high prevalence of heart defects in a
pregnant women.17,20 Indeed, very few cardiac defects

have been identified in the pregnancies in which a
family history was the main indication for the early fetal
echocardiography, which is consistent with the recurrence
rate of 2−3% for siblings. The main value of the early scan
in such family-risk cases lies in the reassurance that it gives
to the parents. As we have previously stated, in most of the
studies the early echocardiography is somewhat less reliable
and may result in a higher false-negative and false-positive
results in comparison with the 20−22 weeks transabdominal
echocardiography. Besides, early echocardiography is most
time-consuming and requires a high level of expertise of
A the examiner. Therefore, it is difficult to offer this scan as
a screening test to the general population. In this context,
the identification of a high-risk collective is of paramount
importance.
Currently, the importance of the aforementioned
limitations of early fetal cardiac examination justifies
restriction of its use to fetuses at high risk of having cardiac
anomalies.5,10,14,18,21,22,26,47 The indications proposed for early
fetal echocardiography are:
À increased nuchal translucency (>95th or 99th centile) is
the main indication of referral in all recently reported
studies,
À abnormal ductus venosus blood flow, regardless the
B
measurement of the nuchal translucency,
À fetuses affected by other structural malformations:
hygroma, hydrops, omphalocele, situs inversus,
arrhythmia,
À monochorionic placentation in multiple gestation,
À suspected cardiac anomalies at screening ultrasound,
À pregestational diabetes of the mother,
À high-risk family, with a previously affected child, a first-
degree relative affected by a congenital heart disease or
a genetic disease in which CHD are common,
À women at high risk of chromosomal abnormality
declining invasive test for karyotyping,
À pregnancies affected by a chromosomal abnormality.
C Currently, as long as the sensitivity, specificity and
Figures 10.15A to C Aortic atresia at 12 weeks of gestation. (A) Note predictive value of early echocardiography are still
aortic reverse flow in three-vessels view, (B) mitral regurgitation and
(C) endocardial fibroelastosis unclear, this examination should be generally reserved
for patients at high risk for CHD. However, only the
non-selected population (incidence of CHD in low risk accumulation of results from carefully collaborative studies
population 1/23820), some authors suggest that an early as the present series will clear define the role of early TV
detailed cardiac examination should be performed in all echocardiography.
Conclusion 4. Allan LD. Fetal cardiology. Curr Op Obstet Gynecol. 1996;
8:142-7.
Fetal echocardiography performed by expert operators is reliable
for an early reassurement of normal cardiac anatomy. 5. Gembruch U. Prenatal diagnosis of congenital heart disease.
• Transvaginal sonography enables good visualization of fetal Prenat Diagn. 1997;17:1283-98.
heart earlier in gestation. The four-chamber view and the 6. Todros T. Prenatal diagnosis and management of fetal
extended examination to the great vessels can be imaged
cardiovascular malformations. Curr Opin Obstet Gynecol.
in almost 100% at 13−14 weeks of gestation. Less than 5%
of patients will need a repeated scan because of inadequate 2000;12:105-9.
visualization 7. Levi S, Schaaps JP, De Havay P, et al. End result of routine
• The combination of transvaginal and transabdominal routes and the ultrasound screening for congenital anomalies. The Belgian
application of color Doppler enhance visualization
• Most CHD are detected in low-risk population. As we cannot
Multicentric study 1984-92. Ultrasound Obstet Gynecol.
perform a targeted fetal echocardiography as a screening 1995;5:366-71.
test, we need to improve the identification of high-risk group 8. Hyett J, Perdu M, Sharland G, et al. Using nuchal translucency
pregnancies. Increased nuchal translucency at 10−14 weeks’ to screen for major cardiac defects at 10-14 weeks of gestation:
scan and, may be, ductus venosus blood flow assessment seem
to be the newest and most promising risk factors for fetal CHD, population based cohort study. Br Med J. 1999;318:81-5.
and may be particularly useful during the first trimester 9. Devine PC, Simpson LL. Nuchal translucency and its
• Currently, early fetal echocardiography should be offered to high- relationship to congenital heart disease. Semin Perinatol.
risk pregnancies. Some authors advocate routine early extended
2000;24:343-51.
cardiac examination in low-risk pregnancies. At present, as
long as the sensitivity, specificity and predictive value of early 10. Matias A, Huggon I, Areias JC, et al. Cardiac defects in
echocardiography are still unclear, this examination should be chromosomally normal fetuses with abnormal ductus
generally reserved for patients at high risk for CHD venosus blood flow at 10-14 weeks. Ultrasound Obstet
• Whenever a normal heart is diagnosed in the early scan, it has to be
supplemented with the conventional transabdominal examination
Gynecol. 1999;14:307-10.
at 20−22 weeks of gestation. 11. Bilardo CM, Müller MA, Zikulnig L, et al. Ductus venosus studies
in fetuses at high risk for chromosomal or heart abnormalities:
Fetal echocardiography performed by expert operators is reliable to
diagnose most major structural heart defects in the first and early relationship with nuchal translucency measurement and fetal
second trimester of pregnancy. outcome. Ultrasound Obstet Gynecol. 2001;17:288-94.
• Cardiac defects diagnosed early in pregnancy tend to be more 12. Johnson P, Sharland G, Maxwell D, et al. The role of
complex than those detected later on and use to cause more
severe hemodynamic compromise in the developing fetus
transvaginal sonography in the early detection of congenital
• Many CHD can be detected at the beginning of the second heart disease. Ultrasound Obstet Gynecol. 1992;2:248-51.
trimester 13. Bronshtein M, Zimmer EZ, Gerlis LM, et al. Early
• The incidence of associated structural malformations, ultrasound diagnosis of congenital heart defects in high-risk
chromosomal abnormalities and spontaneous abortions is
significantly high and low-risk pregnancies. Obstet Gynecol. 1993;82:225-9.
• A complete work-up including pathological and karyotype 14. Gembruch U, Knopfle G, Bald R, et al. Early diagnosis of fetal
evaluation should be warranted in order to provide parents with congenital heart disease by transvaginal echocardiography.
a proper genetic counseling, which is extremely difficult to obtain
Ultrasound Obstet Gynecol. 1993;3:310-7.
if spontaneous loss of the pregnancy occurs
• The small size of specimens at this time of gestation renders 15. Achiron R, Tadmor O. Screening for fetal anomalies during the
pathological examination difficult and requires high expertise first trimester of pregnancy: transvaginal versus transabdominal
and careful inspection, irrespective of the technique used for sonography. Ultrasound Obstet Gynecol. 1991;1:186-91.
termination
• Clinical follow-up in the neonate and postmortem examination 16. D’Amelio R, Giorlandino C, Masala L, et al. Fetal
if TOP is undertaken are essential to assess the actual role of echocardiography using transvaginal and transabdominal
early fetal echocardiography. probes during the first period of pregnancy: a comparative
study. Prenat Diagn. 1991;11:69-75.
17. Yagel S, Weissman A, Rotstein Z, et al. Congenital
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20. Bronshtein M, Zimmer Z. The sonographic approach to 34. Hernadi L, Torocsik M. Screening for fetal anomalies in the
the detection of fetal cardiac anomalies in early pregnancy. 12th week of pregnancy by transvaginal sonography in an
Ultrasound Obstet Gynecol. 2002;19:360-5. unselected population. Prenat Diagn. 1997;17:753-9.
21. Comas C, Galindo A, Martínez JM, et al. Early prenatal 35. D’Ottavio G, Meir YJ, Rustico MA, et al. Screening for fetal
diagnosis of major cardiac anomalies in a high-risk anomalies by ultrasound at 14 and 21 weeks. Ultrasound
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22. Haak MC, Twisk JWR, Van Vigt JMG. How successful is 36. Economides DL, Braithwaite JM. First trimester
fetal echocardiographic examination in the first trimester of ultrasonographic diagnosis of fetal structural abnormalities in
pregnancy? Ultrasound Obstet Gynecol. 2002;20:9-13. a low risk population. Br J Obstet Gynaecol. 1998;105:53-7.
23. Carvalho JS, Moscoso G, Ville Y. First trimester transabdominal 37. Whitlow BJ, Chatzipapas IK, Lazanakis ML, et al. The
fetal echocardiography. Lancet. 1998;351:1023-7. value of sonography in early pregnancy for the detection of
24. Zosmer N, Souter VL, Chan CS, et al. Early diagnosis of fetal abnormalities in an unselected population. Br J Obstet
major cardiac defects in chromosomally normal fetuses Gynaecol. 1999;106:929-36.
with increased nuchal translucency. Br J Obstet Gynecol. 38. Guariglia L, Rosati P.Transvaginal sonographic detection
1999;106:829-33. of embryonic-fetal abnormalities in early pregnancy. Obstet
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25. Simpson JM, Jones A, Callaghan N, et al. Accuracy and
39. Lopes LM, Brizot ML, Lopes MAB, et al. Structural
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26. Huggon IC, Ghi T, Cook AC, et al. Fetal cardiac abnormalities
40. Weiner Z, Lorber A, Shalev E. Diagnosis of congenital
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1990;10:697-705. 2007;24:449-56.
CHAPTER
11 Assessment of Fetal
Central Nervous System
Ritsuko K Pooh, KyongHon Pooh
Introduction Transvaginal Approach

Antenatal evaluation of the fetal central nervous system to the Fetal Brain
(CNS) plays an important role in the field of perinatology. In the middle and late pregnancy, fetal CNS is
The brain rapidly develops in utero and remarkably changes generally evaluated through maternal abdominal wall.
its appearance from the primitive brain structure in early stage By transabdominal sonography, fetal brain is mostly
1
to the well-developed brain in late pregnancy. Introduction demonstrated in transcranial axial sections. Sonographic
of high-frequency transvaginal transducer has contributed to
2
establishing “sonoembryology” and recent general use of
transvaginal sonography in early pregnancy enabled early
3
diagnoses of major fetal anomalies. Furthermore, three-
dimensional (3D) ultrasound (US) has added accurate and
objective information from early gestation till delivery, with
surface anatomy, internal multidimensional analysis, volume
calculation and circulatory visualization. Basic anatomical
knowledge is essential, and transvaginal technique and
3D US are helpful for obtaining orientation of the brain
in neuroimaging. The brain should be evaluated as a 3D
structure. One of the reasons to make fetal neuroimaging
difficult is the lack of neuroanatomical knowledge. Figures
11.1 and 11.2 show basic knowledge of brain anatomy in
the sagittal and coronal sections for neuroimaging diagnosis. Figure 11.2 Basic anatomical knowledge of coronal cutting section
Figure 11.3 shows the ventricular system. of the brain
Figure 11.1 Basic anatomical knowledge of sagittal cutting section of Figure 11.3 Basic anatomical knowledge of ventricular system of
the brain (Abbreviation: CC, corpus callosum) the brain
assessment of the fetal brain in the sagittal and coronal Three-dimensional Transvaginal
sections requires an approach from fetal parietal direction.
Transvaginal sonography of the fetal brain opened a new
Sonography
4 11-13
field in medicine, “neurosonography”. Transvaginal Introduction of 3D US in obstetrics has produced not
approach to the normal fetal brain during the second and only objective imaging of fetal superficial structure but
third trimesters was introduced in the beginning of 1990s. It also a combination of both transvaginal sonography and
was the first practical application of 3D CNS assessment by 3D US may be a great diagnostic tool for evaluation of 3D
5 14-20
two-dimensional (2D) US. Transvaginal observation of the structure of fetal CNS. Three-dimensional transvaginal
fetal brain (Fig. 11.4) offers sagittal and coronal views of the sonography demonstrates bony structure such as cranial os
6-10
brain from fetal parietal direction through the fontanelles (Fig. 11.5) and vertebrae (Fig. 11.6), multiplanar analysis
and/or the sagittal suture as US windows. Serial oblique of inside morphology from early till late pregnancy (Figs
4
sections via the same US window reveal the intracranial 11.7 to 11.9), sonoangiography (Fig. 11.10), and volume
morphology in detail. This method has contributed to extraction and calculation of target organ, i.e. lateral
the prenatal sonographic assessment of congenital CNS ventricle and/or choroids plexus (Fig. 11.11). Some recent
anomalies and acquired brain damage in utero, especially papers described high reliability of 3D fetal brain volume
21,22
when compared with conventional transabdominal method. measurements.
Figure 11.4 Scheme of transvaginal sonography: (Upper left) Lateral view of vertex presenting fetus and
transvaginal transducer. (Upper right) Frontal view of transvaginal approach. Clear imaging is possible
by rotating and angle-changing of the transducer. (Lower left) Scheme of transfontanelle/trans-sutural
approach of the fetal brain. (Lower right) Cranial bony structure from parietal direction. Those spaces
are used as ultrasound windows (Abbreviations: AF, anterior fontanelle; S, sagittal suture; PF, posterior
fontanelle)
Chapter 11  Assessment of Fetal Central Nervous System 87
Figure 11.6 Fetal back and vertebral structure of 16-week normal fetus
(3D US images). (Left) Fetal back surface. (Middle) Inside of the fetus.
Lamina of vertebra and ribs are clearly observed. (Right) Vertebral
bodies and intervertebral disk spaces are seen
Hydrocephalus and Ventriculomegaly

Hydrocephalus and ventriculomegaly are often used
interchangeably to describe dilatation of the fetal lateral
Figure 11.5 Fetal cranial structure in early gestation (3D US images). ventricles. However, they should be distinguished from each
(Upper left) 12 weeks, from the oblique front. (Upper middle) 13 weeks, other to assess the enlargement of ventricles. Hydrocephalus
from the back. (Upper right) 15 weeks, from the top of head. (Lower
left) 12 weeks, from the front. (Lower right) 17 weeks, oblique position.
is a dilatation of the lateral ventricles resulted from
Premature shape of cranial bones, sutures, and fontanelles at 12–13 increased amount of cerebrospinal fluid and increased
weeks change its appearance to the neonatal shape (Abbreviations: intracranial pressure, while ventriculomegaly is a dilatation
AF, anterior fontanelle; PF, posterior fontanelle; ALF, anterolateral
fontanelle; F, frontal bone; P, parietal bone; O, occipital bone; C, coronal of lateral ventricles with non-increased intracranial
suture; M, metopic suture; S, sagittal suture; L, lambdoid suture) pressure, due to hypoplastic cerebrum or other intracerebral
Figure 11.7 Normal intracranial structure at 8 weeks of gestation in parallel cutting slices of three orthogonal views.
Sagittal, coronal, axial sections from above. Premature sonolucent ventricular system is visible
Figure 11.8 Three-dimensional multiplanar image analysis. Three orthogonal views are useful to obtain orientation of the brain structure. The
raw 3D volume dataset can be saved quickly. Saved data can be reviewed on ultrasound devise, and extracted on CD-R(W) or MO disks and
sent for consultation. Off-line image analysis can be done easily and repeatedly
Figure 11.9 Normal intracranial structure at 19 weeks of gestation in parallel cutting slices of three orthogonal views. Sagittal,
coronal, axial sections from above
abnormalities such as agenesis of the corpus callosum. In is difficult to evaluate obliterated subarachnoid space in the
sonographic imaging, these two intracranial conditions axial section. Therefore, it is suggested that the evaluation
can be differentiated by visualization of subarachnoid of fetuses with enlarged ventricles may be evaluated by
space and appearance of choroid plexus. The transvaginal parasagittal and coronal views taken by transvaginal way.
oblique and coronal images demonstrate the obliterated Furthermore, intracranial venous blood flow may be related
subarachnoid space and the dangling choroid plexus in the to increased intracranial pressure. In normal fetuses, blood
case of hydrocephalus (Figs 11.12 and 11.13). In contrast, flow waveforms of dural sinuses, such as superior sagittal
the subarachnoid space and choroid plexus are well sinus (SSS), vein of Galen and straight sinus have pulsatile
23
preserved in the case of ventriculomegaly (Fig. 11.14). It pattern (Fig. 11.15). However, in cases with progressive
Figure 11.10 Three-dimensional power Doppler image of fetal brain circulation. (Left) View from the front. Bilateral
internal carotid arteries (ICA) and middle cerebral arteries (MCA) and branches of MCA are demonstrated. (Right)
Oblique view. Anterior cerebral artery (ACA) and pericallosal artery (PcA) are demonstrated
Figure 11.11 Three-dimensional volume extraction and volumetric analysis of lateral ventricle and choroid plexus.
On three orthogonal sections, the target organ can be traced automatically or manually with rotation of volume
imaging data. After tracing, volume extracted image (right) is demonstrated and volume calculation data are shown.
Middle graphs show nomograms of ventricular size (upper) and choroid plexus size (lower) during pregnancy
hydrocephalus, normal pulsation disappears and blood flow lateral ventricles, (b) increased intracranial pressure, (c)
23
waveforms become flat pattern (Fig. 11.16). In cases with dangling choroid plexus, (d) disappearance of subarachnoid
progressive hydrocephalus, there may be seven stages of space, (e) excessive extension of the dura and SSS, (f)
progression (Fig. 11.17): (a) increased fluid collection of disappearance of venous pulsation and (g) enlarged skull.
Figure 11.12 Ultrasound

images of hydrocephalus at
34 weeks of gestation. Upper:
Coronal images. Septum
pellucidum was destroyed
may be due to enlargement
of bilateral ventricles and
both ventricles were fused.
Dangling choroid plexus is
seen. Lower: Parasagittal
and sagittal images. Dangling
choroid plexus and obliterated
subarachnoid space are seen
Figure 11.13 Hydrocephalus due to aqueductal obstruction at 19 weeks of gestation. (Left figure) Three orthogonal views with anterior coronal
(upper left) and median sagittal (upper right) and axial (lower left) slices. Bilateral ventriculomegaly and third ventriculomegaly (IIIrd v.) are seen. No
enlargement of fourth ventricle indicates obstruction of the aqueduct. (Right figure) Three orthogonal views with parasagittal (upper left) and posterior
coronal (upper right) and axial (lower left) slices. Subarachnoid space is already obliterated and dangling choroid plexus (arrowheads) is seen.
Lower right pink figure shows extracted 3D ventricular image by VOCAL mode. Ventricle in this case was tenfold size of normal 19-week ventricle
Figure 11.15 Normal cerebral venous circulation. (Left) Sagittal image

of color Doppler. (Right) Normal blood flow waveforms of dural sinuses.
In normal fetuses, venous flow always has pulsations (Abbreviations:
SSS, superior sagittal sinus; ICV, internal cerebral vein; G, vein of
Galen; SS, straight sinus)
Figure 11.14 Ultrasound image of ventriculomegaly at 29 weeks of Spina Bifida

gestation. Enlarged ventricle exists but subarachnoid space is well
preserved and no dangling choroid plexus is seen. From those findings,
Spinal dysraphism is the most common abnormality of
nonincreased intracranial pressure (ICP) is estimated. This condition the CNS. Prevalence rate has been declined due to folic
should be differentiated from hydrocephalus with increased ICP acid supplementation and fortification. Spina bifida
aperta, manifest form of spina bifida, is classified into four
types: meningocele, myelomeningocele, myelocystocele,
Transvaginal Assessment of Congenital myeloschisis. Approximately 10–15% of spinal dysraphic
Central Nervous System Anomalies defects are closed and normal skin covers the bony defects
(spina bifida occulta). The open spina bifida with protrusion
Neurulation Disorders (Cranium Bifidum of the spinal cord mainly occurs in the lumbar, thoracolumbar
and Spina Bifida) or lumbosacral regions. Sonographic appearance of
Cranium Bifidum myelomeningocele is shown in Figures 11.20 and 11.21.
Chiari type II malformation is present in almost every case
The calvarial ossification started at 10 weeks of gestation
of myelomeningocele. This malformation is characterized
and the hyperechogenic skull appears in sonographic
by inferior displacement of the lower cerebellum through
image by 11 weeks in normal pregnancy. Cranium
the foramen magnum with obliteration of the cisterna magna
bifidum is classified into four types of encephaloschisis
(banana sign), inferior displacement of the medulla into the
(including anencephaly and exencephaly), meningocele,
spinal canal and deformity of the frontal bone with indentation
encephalomeningocele, encephalocystocele and cranium
(lemon sign). Both banana sign and lemon sign are detectable
bifidum occultum. Encephalocele occurs in the occipital
by sonography until 24 weeks’ gestation (Fig. 11.22); and
region in 70–80%. Many reported remarkable reduction
occasionally the median section of craniovertebral junction
in prevalence of neural tube defects after using folic
24-27 demonstrates the medullary kink. Although the banana sign
acid supplementation and fortification, although
28 persists during pregnancy, the lemon sign may disappear in
some reported no decline of anencephaly rate. Acrania, 30
many cases with advancing gestational age.
exencephaly (Fig. 11.18) and anencephaly (Fig. 11.19),
caused by disorder of neurulation, are not independent
anomalies. It is considered that dysraphia (absent cranial
Disorders of Prosencephalic Development
vault, acrania) occurs in very early stage and disintegration Holoprosencephaly
of the exposed brain (exencephaly) during the fetal period Holoprosencephaly (Fig. 11.23) is caused by the disorder
29
results in anencephaly. of prosencephalic development and is divided into the three
Figure 11.16 Disappearance of venous pulsation in cases with hydrocephalus. Normal dural sinuses have
pulsatile patterns of flow waveform (Fig. 4.26). In cases with progressive hydrocephalus, venous pulsation
disappeared (right figures) may be because of excessive extension of the dura and dural sinuses
Figure 11.18 Acrania at 10 weeks of gestation. (Left) US coronal image

at 10 weeks. Note the normal appearance of amniotic membrane, which
Figure 11.17 Progressive stages of hydrocephalus (Abbreviations: ICP,
indicates this condition is not amniotic band syndrome. (Right) 3D US
intracranial pressure; CP, choroid plexus; SAS, subarachnoid space;
image of the same fetus as left image
SSS, superior sagittal sinus)
subtypes: alobar, semilobar and lobar. Holoprosencephaly Agenesis of the Corpus Callosum
is frequently associated with other malformation, Agenesis of the corpus callosum [(complete agenesis,
chromosomal aberration or Dandy-Walker malformation. partial agenesis and dysgenesis (Fig. 11.24)] leads to
A 75% of holoprosencephaly has normal karyotype, but abnormal induction of medial cerebral convolution.
chromosomes 2, 3, 7, 13, 18 and 21 have been implicated Agenesis of the corpus callosum is associated with
in holoprosencephaly. Particularly, trisomy 13 has most additional cerebral anomalies, noncerebral anomalies
commonly been observed. The facial anomalies, such as and chromosomal aberration. It has been described that
cyclopia, cebocephaly, flat nose and cleft lip, are often isolated agenesis of the corpus callosum per se has little
associated with holoprosencephaly. The characteristic consequence on neurological development. Gupta and
34
appearance of fused ventricles is detectable from the early colleagues reviewed 70 reported cases of agenesis of the
31-33
pregnancy. corpus callosum detected prenatally and described that
Figure 11.19 Anencephaly in middle gestation (same case as Fig. 4.24). (Upper left) US sagittal image at
23 weeks of gestation. (Upper right) US coronal image. (Lower left) 3D US image. (Lower right) External
appearances of stillborn fetus at 25 weeks of gestation. It is clear that exencephalic brain tissue scattered in
the amniotic space compared with this case at 10 weeks
Figure 11.20 Prenatal US image of myelomeningocele, spina bifida at 20 weeks of gestation. (Left) 3D bony
demonstration of lumber spina bifida. Three-dimensional US show the exact level of spina bifida. (Middle) 3D
surface reconstruction of large myelomeningocele (white arrows). (Right) External appearance of aborted fetus
at 21 weeks of gestation. Note the central canal of the spinal cord (black arrow) in large myelomeningocele
Figure 11.21 Three-dimensional US image of myelomeningocele with kyphosis at 16 weeks of gestation. Three orthogonal views and surface
reconstruction image. (Left) Sagittal US image. Spinal cord completely protrudes into the sac surface from spinal canal and severe kyphosis is
seen. (Middle) Axial US view. (Right) Coronal US view of myelomeningocele
Figure 11.22 Chiari type II malformation at 16 weeks of gestation. Chiari type II malformation is observed in most cases with myelomeningocele
and myeloschisis. (Left) Typical lemon sign (arrows). (Middle) Typical banana sign (arrows). (Right) 3D reconstruction internal image of Chiari
type II malformation (arrows)
85% of fetuses without other detectable anomalies carried microcephaly and facial dysmorphism and often associated
a normal development and 15% had a risk of handicap. with Miller-Dieker syndrome and type II has hydrocephalus,
Therefore, prenatal findings suggestive of agenesis of the retinal dysplasia and muscular dysplasia, associated with
corpus callosum should be followed by a careful search Walker-Warburg syndrome and Fukuyama congenital
for associated anomalies and counseling parents should be muscular dystrophy. Antenatal diagnosis of syndromes
prudent if agenesis of the corpus callosum is an isolated associated with lissencephaly before gyral development in
finding. The typical findings of agenesis of the corpus families with prior affected infants has been reported by
callosum are the medial cerebral sulci demonstrated as a demonstration of additional abnormalities, such as bilateral
radial arrangement, enlargement of the posterior horns of cataract35 and hydrocephalus.36 Sonographic detection of
lateral ventricles, steer horn appearance of the anterior horns smooth gyral pattern at 31–32 weeks’ gestation has been
and upward displacement of the third ventricle. In most reported.37 Prenatal sonographic diagnosis of lissencephaly,
cases detected prenatally by sonography, diagnosis was however, without a previous history cannot be reliably made
made by detection of indirect findings. The transvaginal until 26–28 weeks’ gestation, when the normal gyri and
median section of the brain, however, may be most sulci become well defined.
reasonable to directly document the callosal lesion.
Posterior Fossa Anomalies
Migration Disorder Dandy-Walker Complex
Lissencephaly Dandy-Walker complex is used to indicate a spectrum of
Lissencephaly is characterized by a lack of gyral anomalies of the posterior fossa. Classification of Dandy-
development and divided into two types: type I has Walker complex is as follows:
Figure 11.23 Alobar

holoprosencephaly at 20
weeks of gestation. Three
orthogonal images of
intracranial structure show
complete single ventricle
within a single-sphered
cerebral structure. (Lower
right) 3D US image of
fetal face and the face of
aborted fetus at 21 weeks
of gestation. A flat nose with
median cleft lip/palate are
seen
Figure 11.24 Complete

agenesis (upper) and
hypogenesis (lower) of the
corpus callosum. All images
are transvaginal median
(midsagittal) images. Right
images are normal images
of the corpus callosum at
the same gestational age as
each left image
ÀÀ Dandy-Walker malformation (Classic): Enlarged vermis in normal fetuses is demonstrated by sonography from
37
posterior fossa, complete or partial agenesis of the 14 to 18 weeks’ gestation. Bromley and colleagues described
cerebellar vermis, elevated tentorium that 56% of normal fetuses had an open vermis at 14 weeks
ÀÀ Dandy-Walker variant: Variable hypoplasia of the of gestation, 23% at 15 weeks and 6% at 17 weeks. Thus, the
cerebellar vermis with or without enlargement of the cerebellar vermis develops during early second trimester. The
posterior fossa normal sonographic appearance of the open vermis should not
ÀÀ Mega cisterna magna: Enlarged cisterna magna with be interpreted by developmental change of Dandy-Walker
integrity of both cerebellar vermis and fourth ventricle. malformation and its variant, which is described as a small
Dandy-Walker malformation occurs as a part of recognizable defect in the cerebellar vermis without dilatation of the
syndromes, such as Michel’s syndrome and Walker-Warburg cisterna magna. Prenatal diagnosis of Dandy-Walker variant
40
syndrome, and is frequently associated with chromosomal should not be made before 18 weeks. It was described that
aberrations. There often exist additional intracerebral or prenatal diagnosis of Dandy-Walker malformation is possible
41
extracerebral anomalies. Congenital hydrocephalus exists from 14 weeks’ gestation. Although early detection of
38
in 5–10% of cases, but hydrocephalus develops usually Dandy-Walker complex should be done prudently; we had a
39
within 3 months after birth. Antenatal diagnosis should be case with Dandy-Walker malformation which was strongly
performed by a careful observation of the posterior fossa in the suspected from 11 weeks of gestation (Fig. 11.25) because of
axial, coronal and sagittal planes. The closure of the cerebellar abnormal dilatation of the posterior fossa.
Figure 11.25 Early stage of Dandy-Walker malformation at 11 weeks of gestation. Abnormal dilatation of the posterior
fossa (arrowheads). Upper right figure is a sagittal image at the same gestational age in a normal case. Amniocentesis
revealed trisomy 9 mosaicism and the fetus died in utero at 19 weeks
Cerebellar Hypoplasia unilaterally or bilaterally, associated with chromosomal
Cerebellar dysplasia (Fig. 11.26) is often associated with aberration such as trisomy 18. They are depicted in the
chromosomal abnormalities, such as trisomy 18 and others. second trimester and usually spontaneous resolution is
In late pregnancy, prenatal diagnosis of cerebellar dysplasia observed by the 24th week. Choroid plexus cysts per se are
is not difficult because of conspicuous enlargement of usually asymptomatic and benign, but rarely, symptomatic
cisterna magna. However, in the first half of pregnancy, all and disturb cerebrospinal fluid flow.45,46 It is impossible to
normal cases have large cisterna magna. In order to detect differentiate normal from abnormal karyotypes only by
cerebellar dysplasia, therefore, it is recommended to assess location and appearance of choroid plexus cyst (Fig. 11.28).
the development of the cerebellum measuring the cerebellar Isolated choroid plexus cysts may be normal variation. Fetal
transverse diameter in axial image or posterior coronal section. chromosomal examination should be offered if additional
abnormalities are found.
Other Disorders
Arachnoid Cyst
Acquired Brain Abnormalities In Utero
Intracranial Hemorrhage
Arachnoid cyst (Fig. 11.27) is a congenital or acquired
cyst, lined by arachnoid membranes, and filled with fluid Intracranial hemorrhage in utero may be caused by trauma,
collection which is the same character as the cerebrospinal infections, asphyxia, alloimmune thrombocytopenia,
fluid. The number of cysts is mostly single, but two or more intracranial tumor, cord complication, preeclampsia, abruptio
cysts can be occasionally observed. Location of arachnoid placenta and other factors. Hemorrhage is commonly located
cyst is various; approximately 50% of cysts occur from the in the subdural, periventricular and cerebellar regions. Many
Sylvian fissure (middle fossa). Interhemispheric cysts are cases of intracranial hemorrhage detected prenatally have
often associated with agenesis or hypogenesis of the corpus been reported.47-52 The outcome of fetuses with intracranial
callosum. Postnatal prognosis is usually good. hemorrhage has ranged from fetal demise and postnatal death
to a good outcome with normal development.48
Choroid Plexus Cyst
Choroid plexus cysts are defined as cysts with fluid Porencephaly
collection within the choroid plexus with incidence of Porencephaly [(porencephalic cyst, (Fig. 11.29)] is fluid-
0.95–2.8% of all fetuses scanned,42-44 which may exist filled space replacing normal brain parenchyma and may
Figure 11.26 Cerebellar dysplasia (28 weeks of gestation). (Upper left) Transvaginal median image. Small
cerebellum in a normal size of posterior fossa. (Upper right) Transabdominal axial image. (Lower left) Fetal MR
sagittal image. (Lower right) MR axial image. This case has chromosomal aberration of trisomy 18 with other
congenital anomalies such as large VSD, overlapping finger, lowset ears, etc.
Figure 11.27 Fetal

arachnoid cyst at 31 weeks
of gestation. (Upper)
Transvaginal US image.
Sagittal (left) and coronal
(middle, right) sections.
(Lower left) Fetal MR sagittal
image. The cyst occupies
supratentorial to infratentorial
space. Not only cerebrum
but also cerebellums are
compressed by the cyst.
(Lower right) Fetal MR
coronal image. Midline is
conspicuously arcuated.
Scalp and skull bone
are extended due to the
existence of the huge cyst.
Note the difference between
right and left head size
Figure 11.28 Choroid plexus

cysts (CPC) in cases of
trisomy 18 (left) and normal
karyotype (right). (Left
figures) Three orthogonal
views and inside 3D view
of CPC in a case of trisomy
18 at 17 weeks of gestation.
Various additional anomalies
were detected. (Right
figures) Three orthogonal
views and inside 3D view of
CPC in a case with normal
karyotype at 16 weeks. No
additional abnormalities.
Normal postnatal course.
Impossible to differentiate
normal from abnormal
karyotypes only by location
and appearance of choroid
plexus cyst. Detection of
additional anomalies is
important for differentiated
diagnosis
Figure 11.29 Porencephaly at 25 weeks of gestation. (Left) Transvaginal US coronal image. Defect of parietolateral part of the unilateral cerebrum.
This case has also absent septum pellucidum. (Middle) Parasagittal US image. Porencephalic part connects to unilateral ventricle. Echogenicity
of inside ventricular wall indicates intraventricular hemorrhage. (Right) Transabdominal US axial image
or may not communicate with the lateral ventricles or 4. Timor-Tritsch IE, Monteagudo A. Transvaginal fetal
subarachnoid space. Ischemic episode, trauma, demise of neurosonography: standardization of the planes and sections
one twin, intercerebral hemorrhage, infection can cause by anatomic landmarks. Ultrasound Obstet Gynecol.
porencephaly. It is easy to occur when immature cerebrum 1996;8(1):42-7.
has some factors with propensity of dissolution and 5. Monteagudo A, Reuss ML, Timor-Tritsch IE. Imaging
cavitation. Timing of ischemic injury (may be as early as the fetal brain in the second and third trimesters using
transvaginal sonography. Obstet Gynecol. 1991;77(1):27-32.
second trimester) is strongly related to porencephaly.
6. Monteagudo A, Timor-Tritsch IE, Moomjy M. In utero
Future Aspects detection of ventriculomegaly during the second and third
trimesters by transvaginal sonography. Ultrasound Obstet
The assessment of the fetal CNS plays an important role for
the rest of infant’s life. Advanced sonography combined with Gynecol. 1994;4(3):193-8.
methodology of approaching the fetal brain has improved the 7. Monteagudo A, Timor-Tritsch IE. Development of fetal
assessment of fetal intracranial structure and diagnosis of the gyri, sulci and fissures: a transvaginal sonographic study.
prenatal brain abnormalities. Recent remarkable development of
Ultrasound Obstet Gynecol. 1997;9(4):222-8.
three-dimensional/four-dimensional US and advanced magnetic
resonance imaging technology53-55 will produce more accurate 8. Pooh RK, Nakagawa Y, Nagamachi N, et al. Transvaginal
evaluation of the brain morphology. A functional evaluation of the sonography of the fetal brain: detection of abnormal
intracranial condition and a prenatal prediction of neurological morphology and circulation. Croat Med J. 1998;39(2):147-57.
development after birth are also important points in a proper
management for fetuses with intracranial abnormalities, but many 9. Pooh RK, Maeda K, Pooh KH, et al. Sonographic assessment of
uncertain and unknown facts still exist. Further studies on the the fetal brain morphology. Prenat Neonat Med. 1999;4:18-38.
assessment of cerebral function may be expected.
10. Pilu G, Falco P, Milano V, et al. Prenatal diagnosis of
microcephaly assisted by vaginal sonography and power
Doppler. Ultrasound Obstet Gynecol. 1998;11(5):357-60.
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CHAPTER
12 Ultrasonographic Signs of
Poor Pregnancy Outcome
Introduction Spontaneous Interruptions of the

The availability of high resolution sonographic Development of the Conceptus,
instrumentation allows, every time more precisely, to emit Frequency of the Spontaneous
precise diagnosis. As much for the expert sonographist as
Abortion, Causes of the Abortion
for the less experienced ones, the decision of informing
the sonographic exploration performed to a patient as The frequency of spontaneous interruptions of the
corresponding to an interrupted pregnancy or embryonic development of the reproductive process is very high,
demise represents a challenge. As more is the experience mainly when it is considered from the most initial stages.
with the scanner, more and more precociously can be It is calculated that considering the shortcoming of the
confirmed that a pregnancy is not viable. It is not reasonable fecundation, of each 100 potential pregnancies, only
to emit a diagnosis of abortion if doubts exist in this 31 will arrive to term with a live fetus.1,2 The frequency
respect, when most of the patients allow to wait without of the abortion, considering this as the spontaneous
risk for their health. Nonetheless, it is a good practice to interruption of the pregnancy before the fetus has reached
write the diagnosis of suspicion in the clinical history to the viability depends, therefore, on the approach that we
avoid unpleasant situations in the following sonographic use to define that pregnancy exists. When only considering
exploration. It is preferable to repeat the scan a few days the pregnancies reaching implantation (biochemical
later to inform the pregnancy like “not viable” if the pregnancy), the abortion frequency is from 30% to 40%.3,4
diagnosis is not absolutely clear. Whenever doubts exist; Reaching the clinical diagnosis of pregnancy, the frequency
and when the clinical situation allows, it is preferable to descends to 10–15%. If the pregnancy progresses until
perform a second sonographic exploration a few days later, reaching the 12th week, the probability of abortion descends
to confirm or not the diagnosis. to 3–4%. When the embryo is alive in the 12th week, the
The problems for the sonographists, especially for the abortion rate until the 20th week is only 2%.5 Rempen,6
less experienced ones, begin when they are wanting to when finds heartbeat between the 5th week and the 13th
reach definitive conclusions before a first sonographic week, communicates a 8.6% rate of abortions. When the
exploration in which the discoveries do not correspond heartbeat has been detected before the 9th week, the group
exactly to the expected in function of the date of last presents a superior rate of abortions, of 12.5%. If the patient
menstrual period (LMP). It should be interpreted if it is 35 years or older, the frequency ascends to 15.5%, and if
is a pregnancy of less time or an abortion. Some of the vaginal bleeding exists, to 16.3% (Table 12.1).
data that can be obtained will help to emit a diagnosis; Siddiqi7 reports that in pregnancies under 12 weeks,
and in other situations, already in this first sonographic the controls have 5.2% of abortions, while the cases that
exploration should exist enough information to reach a presented bleeding had 16.4%. Also, when the patient is
definitive diagnosis, that is to say that does not require older than 34 years, the frequency ascended to 11.1% in
confirmation with a posterior sonographic exploration. comparison with those patients under 35 years, with only
Repetition of the sonographic exploration, 7–10 days 4.4%. Levi8 finds a 24% rate of abortion when positive
later, should be allowed, in most of the cases, to reach a heartbeat exists, but the embryo has a crown-rump length
definitive diagnosis. (CRL) smaller than 5 mm.
Chapter 12  Ultrasonographic Signs of Poor Pregnancy Outcome 103
Table 12.1 Probability of spontaneous abortion in function of the date the pregnancy. In function of the discoveries of the
sonographic findings. Based on Goldstein (Goldstein SR, 1994) CRL, the LMP is calculated for sonography, the date of
Structure visualized Probability of abortion (%) the conception and the probable date of the childbirth.
Gestational sac 11.5 This is especially true when the pregnancy is of more time
Yolk sac 8.5 than corresponding for the LMP referred by the patient.
Embryo CRL < 5 mm 7.2 When the data of the sonographic exploration correspond
Embryo CRL 6–10 mm 3.3
to pregnancy of less time, that is to say, retarded ovulation,
Embryo CRL > 10 mm 0.5
the approach is different, since the fact of finding a smaller
embryo that one expected already supposes a risk factor for
(Abbreviation: CRL, crown-rump length) poor pregnancy outcome.
A useful tool to adjunct to the ultrasonography is the
Goldstein and colleague9 present their data with great plasmatic determination of the β-hCG hormone (mIU/
clinical applicability allowing to know the probability of ml) between the 4th and 8th week of pregnancy. This
abortion in function of the sonographic findings, as is shown determination is, of among all those that can be performed
in Table 12.1. in this period, the one that better clinical diffusion has
The embryonic and fetal causes, basically chromosomal obtained. Its behavior, although with wide variations from
anomalies, are the most frequent causes of abortion. 10 a pregnancy to other, presents some peculiarities that
The different rates reported depend on the approaches make it very useful in concrete cases. The normal course
used (if only clinical pregnancies are considered or pregnancies duplicate the figures in a period from 2 days to
not). In the 1st week they can overcome 80–90% of the 3 days, while abnormal pregnancies (ectopic or interrupted)
cases. Above the 12th week, the chromosomal anomalies usually show figures of irregular ascent or, even, descend.
and the malformations are less relevant, although they The simultaneity of the biochemical and sonographic data
continue being an important cause. From this moment permits to outline a useful perspective to know the expected
on, the maternal and environmental causes acquire more outcome in normal pregnancies. Essentially, it is necessary
importance. to know the β-hCG system of measure performed in each
The frequency of the spontaneous abortion when is own laboratory.
considered from their very beginning, along with the Based on the sonographic capacity of prediction of
theoretical knowledge of the causes of the abortion, should the actual gestational age of different structures as the
provide a perspective to the obstetrician that, performing diameter of the gestational sac, the yolk sac and the CRL
a sonographic exploration, finds discoveries that cannot with a margin of 1 week, the diameter and growth of each
correspond to those characterizing a normal pregnancy. The structure with the interval of confidence from the moment
precocity of the realization of sonographic explorations in of the appearance are reflected in many tables by different
the pregnancy will allow diagnosing many more cases of authors. Generally, gestational sacs of 3–4 mm of average
spontaneous interruptions of the development of pregnancy. diameter can usually be seen (Fig. 12.1) yolk sacs of
2–3 mm (Fig. 12.2) and embryos with CRL of 2–4 mm
Normal Development in the First (Fig. 12.3). The amniotic vesicle is usually identified at the
same time that the yolk sac (Fig. 12.4). The heart motion
Trimester of Pregnancy can be detected in most of the cases starting from a CRL of
Knowing the chronology of appearance of the visible 3–4 mm (Fig. 12.5), being frequently detected before the
embryonic structures with the sonography and its variations embryonic echoes. Goldstein11 indicates that the heartbeat
is relevant to know when the pregnancy is correctly is even present in the embryo, a few days before we are
evolving or not. able to detect it with the sonographic exploration.
When findings that do not correspond to the gestational All the exposed data correspond to what is possible
age are detected, the first thing to do should be to value to visualize in each moment in normal pregnancies in
the probability that an error exists in the LMP or that patients in which conception took place 14 days after the
ovulation has not been in the 14th day of the cycle. In this LMP. The normal pregnancies that have begun before or
situation, when the embryo is alive (positive heartbeat), after this moment will have a difference with regard to
in most of the cases, the only responsibility is to correctly the prospective findings, but the rhythm of change among
Figure 12.1 Gestational sacs from 3 to 4 mm of diameter can usually Figure 12.2 The yolk sac can be seen when measures 2–3 mm
be seen
Figure 12.3 A 2–4 mm crown-rump length embryo must be seen Figure 12.4 The amniotic vesicle is usually observed at the same
time of the yolk sac
successive sonographic explorations will be the same

described, so, after two sonographic explorations with at
least 1 week of difference, starting from the moment in
which it has been visualized as minimum a gestational sac
of 5–10 mm of diameter, the definitive diagnosis for the
viability of the pregnancy will be obtained.
More than 80% of the sonographic explorations
performed in the first trimester of the pregnancy, in
asymptomatic women without risk factors, will be strictly
normal. Anyway, as more precociously the first sonographic
exploration is performed, higher will be the probability that
we find abnormal data or not rigorously diagnoses, and
with more probability; the repetition of the sonographic
exploration should confirm the normality. A pregnancy of
2 weeks less, in the 10th week will allow seeing a normal Figure 12.5 The heart motion can be detected in most of the cases
sac and an alive embryo of 16 mm of CRL; but if the starting from a crown-rump length of 3–4 mm
sonographic exploration is performed in the 7th week, week, for instance, in an embryo of 4–5 mm in the one that
a small gestational sac of 8 or 10 mm of diameter will, had not seen heartbeat, saw it and it measured 9–10 mm.
probably, be the only finding. The confirmation that a In the second case, in a 21 mm diameter vesicle, in which
pregnancy evolves correctly and with a prediction of good the embryo was not seen, after 1 week a 5–6 mm CRL and
outcome (low abortion probability) is only obtained when positive heartbeat embryo will be observed (Table 12.2).
a live embryo is visualized and history of associated risk According to Daya12 an embryo is not seen until the
does not exist. On the other hand, the confirmation that a gestational sac measures 8.3 mm diameter, coincident with the
pregnancy has been interrupted can only be made when an
embryo is visualized with a certain size without heartbeat.
When there is no embryo, except in cases when the
gestational sac has reached a big size, another sonographic
exploration 7–10 days later is to be performed.
Sonographic Findings to Diagnose

an Interrupted Pregnancy
The two types of spontaneous interruptions of pregnancy
found in patients without bleeding are from a practical point
of view, the differed or missed abortions, and the blighted
ovum or anembryonic pregnancies. Academically, the
differed abortions were considered as those in which the
measured CRL corresponded to 6 weeks less than expected
in an embryo lacking heartbeat (Fig. 12.6). Nowadays,
due to the better accessibility of women to the initial
sonographic exploration, is infrequent to reach so much Figure 12.6 Differed abortions were considered as those in which
the measured crown-rump length corresponded to 6 weeks less than
time without diagnosis, so these types of abortions, when expected in an embryo lacking heartbeat
the interruption is recent and bleeding has not begun, are
called missed abortions. With regard to the anembryonic
pregnancies, their frequency is much lower of what is
thought from a clinical point of view. It would be pregnancy
initially with embryo, that was dead precociously and
was reabsorbed, so is not sonographically visualized. All
the gestational sacs in which an amniotic or a yolk sac is
observed, although embryo is not seen, do not correspond
to anembryonic pregnancies, since these structures require
the development of an embryo to appear (Fig. 12.7).
The false-positive diagnoses, the really important
mistakes, are of two types. The first is when the sonographist
is not able to detect the heartbeat in an embryo that actually
has heart motion, and would be motivated by a small size
of the embryo, inadequate or obsolete team, or suboptimal
visualization due to patient’s characteristics. The other
type of error would be to consider that before a certain
size of gestational sac an embryo must be seen. The error
is motivated by the selection of a low level from which
we already diagnose anembryonic pregnancy, and that
this level could correspond to the highest range in the Figure 12.7 A gestational sac in which a yolk sac is seen although
normality. In the first case it would suppose that after 1 embryo is not observed corresponding to a missed abortion
Table 12.2 Summary of signs corresponding to interrupted pregnancy is 30 mm, in 100% of the normal cases, even embryonic
Embryonic death Absence of heartbeat in embryo of
movements are already present (8 weeks).
(differed or 5 mm crown-rump length as minimum (even Hernadi 14 detects heartbeat in all the live embryos
missed abortion) in first sonographic exploration) reaching 7 mm CRL. This author diagnoses blighted ovum
Blighted ovum or Gestational sac of 25 mm or more or anembryonic pregnancy when the gestational sac is 20
pregnancy without embryo (even in first sonographic
anembryonic exploration)
mm diameter and lacks internal echoes. To confirm the
diagnosis of “embryonic death” at the first sonographic
For some authors, gestational sac of 20 mm
or more without yolk sac exploration, the CRL should be higher than 10 mm. Levi8
Gestational sac of 16 mm or more with yolk considers “not viable” to all gestational sacs of more than
sac and amniotic vesicle without embryo 8 mm of diameter without yolk sac and of 16 mm or more
(“empty amnion”) without embryo. He diagnoses embryonic death when the
Interrupted Successive sonographic explorations: embryo is between 4 and 5 mm CRL. Several cases with
pregnancy Absence of significant changes in two
sonographic explorations separate CRL smaller than 4 mm in those, in which heartbeat was
7–10 days when in the first sonographic not detected, evolved correctly in his series.
exploration a gestational sac of 15–20 mm Brown 15 recommends to wait until 5 mm CRL to
as minimum has been visualized
confirm embryonic demise if heartbeat is not detected.
Bernard,16 in the differentiation among blighted ovum and
41st week of amenorrhea. However, always is to be observed “viable precocious pregnancy”, considers that although the
when the gestational sac reaches 14 mm diameter, in the 46th visualization of sacs with 20 mm or more without embryo
day of amenorrhea (6 weeks and 4 days). Goldstein13 informs is a sign of poor prognosis, definitive signs do not exist, so
that when the pregnancy is correctly developing, the gestational recommends to repeat the sonographic exploration after 1–2
sac is reliably observed in the 5th week. When the sac measures weeks (Table 12.3). Nyberg17 waits to observe a gestational
20 mm diameter, the embryo is observed in 100% of the sac of more than 20 mm of diameter without yolk sac or a
cases. In 6 weeks and 4 days (46th day amenorrhea) heartbeat sac of 25 mm diameter with distorted aspect without embryo
is observed in 100% of the cases, and when the diameter to consider pregnancy as not viable.
Table 12.3 Summary of signs of poor prognosis for fetal viability
Anomalies of the gestational sac Precocious oligoamnion: When the difference between the diameter average of the gestational sac
and the crown-rump length (CRL) is smaller to 5 mm, poor prognosis
Very thin decidual reaction (mm) for the corresponding gestational age (weeks) (>3 difference),
Low implantation
Distorted aspect
Alterations of the heart frequency Bradycardia is always sign of poor prognosis. It should be interpreted in function of the gestational age.
Frequencies under 85 bpm until the 7th week and under 100 bpm from this moment on, poor diagnosis
Small live embryo for the last Especially in women with regular cycles, the visualization of a crown-rump length smaller in at least
menstrual period (LMP) 1 week to the corresponding for the LMP, increases the risk for abortion.
Anomalies of the yolk sac Alterations in the size (big vesicles, more than 6 mm of diameter) increases the risk.
Alterations in the structure (hyperechogenic vesicle) poor prognosis
Reverse implantation Risk for abortion increased
Intrauterine bleeding (hematomas) Big hematomas, mainly retrochorionic, maximum risk.
Subchorionic hematomas located in corpus or fundus more risk that next to the uterine cervix.
If no vaginal bleeding or small size of hematoma, low risk
Fetal movements Absence of fetal movements, starting from the 8th week
Doppler Poor color map around the gestational sac.
Values of Doppler flow in uterine, radial, arcuate, spiral, retrochorial and intervillous arteries, as well
as the umbilical artery in the first trimester of pregnancy have limited clinical applicability
Other factors Existence of associated pathology: myomas, malformations.
Uterine hemorrhage
Maternal age over 35 years.
Antecedent of one or more abortions (as more abortions, more risk)
Serial hormonal determinations. Two β-hCG determinations separate 2–3 days
McKenna18 reports that between the 6th week and the
10th week the amniotic cavity is similar to the size of the
embryo, and the visualization of an amniotic cavity without
embryo corresponded to an “empty amnion” and diagnoses
interrupted pregnancy. This author communicates that
before gestational sac reaches 16 mm or more, when the
yolk sac is identified and neither embryo nor heartbeat is
detected, and an empty amniotic sac is seen, an interrupted
pregnancy can be diagnosed.
Finally, to diagnose the embryonic death, it is necessary
to wait to see an embryo with a 5 mm CRL minimum
lacking heartbeat. For the diagnosis of blighted ovum or
anembryonic pregnancy in a first sonographic exploration,
it appears reasonable to wait for a 25 mm gestational sac,
equivalent to 7 weeks pregnancy with conception till the
Figure 12.8 Gestational sac showing precocious oligoamnion. This is
14th day of the cycle. This corresponds to a pregnancy a good predictor for abortion
in which, in 100% of the cases, an alive embryo would
be visualized if correctly develops. In all other cases, the mm, the abortion occurred in 80% of the cases; when the
sonographic exploration must be repeated after 7–10 days. difference was between 5 mm and 7.9 mm, the abortion
In the great majority of the cases, the second sonography occurred in 26.5% of the cases, and when overcame 8 mm,
will allow us to confirm the diagnosis of normal or occurred in only 10.6% of the cases.21
interrupted pregnancy.
Anomalies of the Heart Frequency Interpreted
Poor Prognosis of Pregnancy: in Function of the Electrocardiogram or
Sonographic Findings Crown-Rump Length (Bradycardia or Relative
Bradycardia)
There exist some circumstances that, when present in a
sonographic exploration performed in the first trimester It is the characteristic of the ascent of the fetal heart
of the pregnancy, hamper the prognosis, although they do rate (FHR) until the 10th week, from 90 bpm in the 1st
not allow the definitive diagnosis of “interruption of the week of visualization up to 180–190 bpm in the 12th
development”, they determine that the prognosis for normal week. From this moment, FHR diminishes progressively
outcome is reduced. In the previous days to the detention until reaching 140–150 bpm in the 20th week. However,
of the development, some phenomena are usually detected. important variations exist in the frequency in every week
However, none of them is sufficiently reliable as to emit of pregnancy among the different authors. Merchiers 22
definitive diagnoses. To be able to diagnose an abortion, or gives importance to that a decrease of the heart frequency
embryonic death, it is necessary to check the existence of takes place on successive sonographic explorations
an embryo of 5 mm CRL like minimum in which heartbeat between two. For Laboda, 23 the FHR under 85 bpm
is lacking exist (Table 12.3). comports very poor prognosis, since in its series, all the
embryos that presented this finding, finished miscarrying.
Anomalies of the Gestational Sac May24 also finds poor prognosis in this finding: 6 out of
The gestational sac and the CRL develop simultaneously. 11 cases with FHR under 85 bpm between the 4.5th and
It is possible to check how between the 6th week and the the 7.3rd weeks miscarried.
10th week the difference usually overcomes 15–20 mm. Benson25 sets the limit in 90 bpm for the whole first
Bromley19 communicates that when the difference between trimester to affirm that a poor prognosis exists. In his
the diameter of the gestational sac and CRL is less than 5 series, all the cases that the FHR is under 70 bpm ended in
mm (precocious oligoamnion), the abortion occurred in abortion: between 70 bpm and 79 bpm, 91% of abortions,
95% of the cases (Fig. 12.8). Dickey20 reports that when and between 80 bpm and 89 bpm, 70% of abortions.
the difference among these two measures was less than 5 Doubilet26 suggests that the FHR more than 100 bpm until
the 6.2nd week and superior to 120 bpm between the 6.3rd measure, of the valuation of their characteristics, and of the
and the 7th weeks are signs of good prognosis. When he epidemic analysis of their association with a poor outcome
observes among the 7th–8th week, an inferior FHR to 110 of the pregnancy.
bpm, considers it a sign of poor prognosis. Stefos27 presents Lindsay31 refers that the existence of a yolk sac of more
in his series that, when exist the FHR under 85 bpm between than two standard deviations above those expected for the
the 6th and 8th weeks, any fetus survives. For this author, gestational age suppose a poor prognosis. In his series,
when between the 6th and the 7th weeks the FHR is between he discussed that any case evolved favorably with a yolk
116 and 125 bpm, the prognosis is good, as is when the FHR sac bigger than 5.6 mm under the 10th week (Figs 12.9
is more than 146 bpm between the 8th and the 9th weeks. to 12.11). This agrees with the data from Kupesic,32 who
Anyway, any finding except the absence of heartbeat is able informs of a poor prognosis in yolk sacs with abnormal
to diagnose the embryonic death definitively. However, the size and abnormal Doppler vascularization. Iniesta and
scientific evidence allows being possible to emit more and Col33 inform that the alterations in the yolk sac as for their
more precise diagnosis. In general, heart frequencies under
80–90 bpm until the 7th week and under 100 bpm from this
moment on is associated with an adverse result, and high
abortion probability.
Anomalies of the Yolk Sac (Size, Shape,

Echogenicity)
The yolk sac is the first extraembryonic structure that
appears and is visible practically in all the pregnancies
between the 5th and the 12th weeks.28 The yolk sac can
be observed initially when the diameter of the gestational
sac reaches 3.7 mm, in the 36th day from the LMP and is
reliably observed when the diameter is 6.7 mm, in the 40th
day of amenorrhea. Even more, for Levi8 the yolk sac should
always be observed when the diameter of the gestational
sac is more than 8 mm (corresponding to 33 days), so that Figure 12.9 Yolk sac of 8 mm (more than two standard deviations)
its absence would suppose for him an approach bigger than
loss gestational sac.
The interest that the knowledge of the visibility of the
yolk sac has for the echographists resided in that is the first
identifiable structure in the gestational sac, preceding 4–7
days to the visualization of the embryo. Their aspect is an
echogenic circle that defines a sonolucent area inside the
chorionic cavity, extra-amniotically located.
Some anomalies are described in their initial development
as the shape and volume alterations.29,30
As a general idea, it is difficult to make important clinical
decisions (as diagnosing a pregnancy interruption) based
on findings related to the yolk sac. This is a structure with
important variations as for their size and dimensions. Also
the visualization is not absolutely safe, even in pregnancies
of normal course. The alterations at their level are usually
late, and it is believed that they are consequence of the
process that determines the abortion, not the cause. Figure 12.10 Giant yolk sac. This sign is rapidly and easily appreciated
However, multiple publications have been in charge of their in the sonographic exploration
Figure 12.11 Yolk sac of 9 mm. This is very sensitive marker for Figure 12.12 The regressive yolk sac is observed by a progressive
abortion increase of the internal refrigency as seen in both yolk sacs of this
multiple pregnancy
size, the shape or the echogenicity are parameters that difference between the gestational age in weeks and the
guide on the normal or pathological development of the trophoblastic thickness in millimeters. A difference of more
pregnancy. Of the 100 patients in their series, 87 (87%) than 3 was highly predictive for poor pregnancy outcome
had a normal development and evolved correctly until the (Fig. 12.13). The sensitivity of this sign in the prediction
end of the first trimester (control group), 13 (13%) had an of spontaneous abortion was 82%, the specificity was 93%,
abnormal course of the pregnancy (study group). Of the the positive predictive value was 63% and the negative
87 patients with correct development, 3 had a diameter of predictive value was 97%.
yolk sac of more than 1 standard deviation (SD). Of the 13
patients with abnormal course, 6 had a diameter of yolk Intrauterine Bleeding (Hematomas)
sac bigger than 1 SD. They conclude that the sensitivity of
The existence of liquid collections, mainly in subchorionic
the size of the yolk sac to predict an abnormal course of
situation, is a relatively frequent finding in the sonographic
the pregnancy is 92.3%, the specificity 66.6%, the vascular
explorations performed during the first trimester of the
placental pathology 96.5% and the vasculitic peripheral
pregnancy (Fig. 12.14). Some of these images are evident,
neuropathy 46% and when some of these anomalies appear,
they have a great size and they coincide with clinical
it is necessary to closely follow the pregnancy.
symptomatology (vaginal bleeding), while others are casual
The regressive yolk sac is sonographically observed
findings in asymptomatic women and have a minimum
by a progressive increase of the refrigency until the more
volume. Discrepancies exist as for the risk that suppose and
extreme form that would be the calcification of the sac
their association with abortion in function of the approaches
(Fig. 12.12).
used for the diagnosis of intrauterine hemorrhage. Dickey35
demonstrated with Doppler color that in 37% of the
Trophoblastic Thickness at the Embryonic sonographic explorations in the first trimester subchorionic
Implantation Site bleeding exists, and that in 47% of the cases, subchorionic
Bajo and Cols34 describe the trophoblastic thickness at the liquid is detected so it concludes that the liquid and the
embryonic implantation site in a prospective, observational subchorionic bleeding are frequent discoveries in the early
study in 592 normal pregnancies in which serial ultrasound pregnancy and they are not associated with embryonic
scans were performed from 5th to 12th weeks of pregnancy. deaths unless accompanied by vaginal bleeding. Stabile36
Trophoblastic thickness was measured at the embryonic states that the existence of small subchorionic hematomas
implantation site to determine the significance of the (<16 ml) in women with genital bleeding does not increase
Figure 12.13 A thin trophoblast is seen in this gestation. A difference Figure 12.14 The existence of liquid collections in subchorionic
of more than three between gestational age in weeks and the situation is a frequent finding in the explorations performed in the first
trophoblastic thickness in millimeters is highly predictive for poor trimester
pregnancy outcome
the risk for abortion in comparison to women with bleeding

without hematoma.
With regard to the meaning diagnosis that has the size
and the localization of the hematoma, Glavind37 does not
find relationship between the size of the hematoma and
the week of pregnancy in which he diagnosed with the
outcome of the pregnancy. For the author, the retrochorionic
or subplacental localization has worse prognosis than the
subchorionic localization (Fig. 12.15). For Kurjak38 the
subchorionic hematomas influence the abortion frequency
(17% in study group versus 6.5% in the control group).
Neither influences the size of the hematoma a lot, being
transcendent the localization. The hematomas in uterine
corpus or fundus have worse prognosis than those located
near the uterine cervix (Fig. 12.16). Kurjak39 finds a higher Figure 12.15 The retrochorionic or subplacental localization has worse
resistance index (RI) of the spiral arteries in the cases with prognosis than the subchorionic localization
retrochorionic hematoma than in the controls, due to the placentae and 2.6 for preterm birth. When comparing
mechanism of compression of the hematoma. For Ball,40 it with controls with bleeding, all the OR increases except
is not clear that the subchorionic bleeding is the cause or the corresponding for abortion. The weight at birth is
simply an underlying process that is the one that produces diminished when comparing it with the two control groups.
the negative effects. He presents an interesting study in The genital bleeding by itself is able to increase the abortion
which he divides the patients in three groups. The first is risk. Bennet41 compares the abortion frequency in women
formed by women that present with subchorionic bleeding; with genital bleeding and subchorionic hemorrhage. When
the second is a control group of women without hematoma; the hematoma is big, the frequency of abortions is 13.8%, if
the third is another control group without hematoma but medium, 9.2%, and 7.7% if small. When the woman is older
with vaginal bleeding. When he performs comparisons than 35 years, the abortion rate is 13.8%, in comparison with
with controls without bleeding, the odds ratio (OR) 2.8 is 7.3% in women younger than 35 years. When the bleeding
obtained for abortion, 4.5 for stillbirth, 11.2 for abruptio appeared before the 8th week, the frequency was 13.7%;
trimester identifies a population of patients at increased risk
for adverse pregnancy outcome.43 In other occasions, they
reach such a volume that cause an effect of occupation of
the chorionic cavity, with effect of fetal death because of
the compression (Fig. 12.17).
Small Crown-rump Length

for the Gestational Age
In general, when a small CRL for gestational age with
positive heartbeat embryo is observed, a pregnancy of less
time is the first diagnosis to approach. This is frequent in
women with long or irregular cycles. However, sometimes
may be observed in normal cycling women. First of all,
the date of conception should be corrected, but data that
Figure 12.16 Hematomas located in uterine corpus or fundus have allow associating this alteration with a higher risk of poor
worse prognosis than those located near the uterine cervix pregnancy outcome exist (Fig. 12.18).
Koornstra44 informs that 22.7% of the embryos from
while if appeared later than the 8th week, the rate is reduced regular cycling women have CRL inferior in 1 week or
to 5.9%. more than expected from the LMP. Analyzing the results,
The presence of scarce quantity of retrochorionic he observes that among these embryos a rate of abortions
fluid has less implication, when it is observed as an of 16% existed in comparison with only 5% in the embryos
isolated finding and in the context of a rigorously normal with a LMP correct size.
sonographic exploration in a pregnancy of normal course. Leelapatana 45 communicates that a small CRL for
The existence of a subchorionic hemorrhage, especially gestational age in comparison with the prospective one
when associated with vaginal bleeding, increases the during the first trimester of pregnancy could be associated
abortion risk and demands to perform other sonographic with triploidies, but not to the 18 and 21 trisomies. Later,
explorations a few days later. New sonographic explorations Besso46 communicated that fetuses finishing in miscarriage
are justified when small or moderate hemorrhage exists. The had a quotient measured CRL/expected CRL of 0.74, in
worst prognoses are the big size hematomas (>40–50 ml), comparison with the 0.98 observed in fetuses that did
especially if located next to uterine neck, in uterine corpus not miscarry. This author does not find differences in the
or fundus. The retrochorionic or subplacental hematomas, quotient among chromosomally normal and abnormal
especially if moderate or big always carry a poor diagnosis. fetuses. The information has also been confirmed in the
The frequency of visualization of these images is low; series from Coulam47 who finds no differences in the
probably, because a rapid coral detachment develops leading frequency of blighted ovum and small CRL for gestational
to the abortion, with bleeding and expulsion of remnants. age among chromosomally normal and abnormal fetuses.
Another uncommon type of hematoma or intrauterine
bleeding is the preplacental that appears after the realization Pattern of Fetal Movements
of invasive techniques that need the introduction of a needle Along the sonographic chronology of findings in a
in the uterine cavity. In general, they are moderate and normal pregnancy, the existence and verification of fetal
evolve favorably although threatened miscarriage in the movements should be contemplated.
first trimester is associated with an increased incidence In a classic publication by Anderson 48 the results
of adverse pregnancy outcome, independently of the presented obtained in a series of 149 cases of threatened
presence of an intrauterine hematoma.42 Nagy43 compared abortion and more than 7 weeks of gestational age. Only
perinatal outcome in 187 pregnant women with intrauterine 2 of 65 pregnancies that later aborted presented fetal
hematoma and 6,488 controls in which hematomas were not movements. On the other hand, 64 of 72 normal pregnancies
detected at first trimester. He concludes that the sonographic presented fetal movements. So the absence of fetal
presence of an intrauterine hematoma during the first movements after a relatively long period of sonographic
of the decidua is progressive, mediated by the action of

proteolytic enzymes that facilitate the penetration and
maternal erosion of the capillary arteries and the formation
of lagoons. That is why exist variations of the flows that can
be measured in the uterine, retrochorionic and intervillous
arteries, along the first trimester of pregnancy (Fig. 12.18).
It is for this reason that the pulsatility index (PI) and
high RI in the first trimester should not be interpreted as
of not well result, like it would be made in the second
trimester as Jaffe informs.50 This author explains51 how the
intervillous circulation persists until the late first trimester.
In complicated pregnancies, analyzed precociously, the
uteroplacental circulation is different to that of normal
pregnancies. In these abnormal pregnancies the intervillous
flow is increased. The hypothesis that is based on other
Figure 12.17 Large hematoma causing some distortion effect in the
gestational sac
studies establishes that the embryo of a pregnancy of normal
course favors an atmosphere with a low concentration of
tisular oxygen in placental tissues. Mercé52 measured in
108 pregnancies between the 4th and the 15th weeks the
velocity of systolic peak, PI and RI in retrochorionic arteries
and fetal umbilical artery. The most precocious sign in
retrochorionic circulation was obtained in the 4.5th week,
and the most precocious of umbilical artery at the end of
the 5th week. Their results indicate that, as gestational
age increases, the systolic peak of the retrochorionic,
intervillous and umbilical arteries increase, while PI and
RI diminish. Kurjak53 again assessed yolk sac morphology
and vascularity and intervillous blood flow in normal early
pregnancy and missed abortion in a prospective analysis of
87 normal pregnancies and 48 missed abortions between 6
and 12 weeks of gestation. He concludes that progressive
decrease of yolk sac vascularity coincides with visualization
Figure 12.18 Small crown-rump length for the gestational age, as of more prominent color-coded areas within the intervillous
referred to gestational sac space. In patients with missed abortion, such changes do
not occur.
In general, most of the authors do not find differences in
exploration, especially above the 8th week, should also be the Doppler indexes among normal outcome pregnancies
considered as a sign of poor prognosis. and those ending in abortion. Jauniaux54 compares 30
confirmed abortions with 30 normal pregnancies. The PI
Doppler Flow Alterations of the uterine artery was higher in the abortions than in the
The number of publications performed on the purpose of normal pregnancies. Differences were not observed in RI
analysis of the Doppler velocimetry in the first stadium and systolic peak of the uterine artery neither in PI nor in RI
of the normal and pathological pregnancies during the of spiral arteries among abortions and normal. This author
last years is abundant. The knowledge of the data that concludes that the velocity of abnormal flow found in some
the investigators contribute has an enormous interest to complicated pregnancies with embryonic death would be
improve our knowledge on the phenomena that exist in related to a defective placentation and “dislocation” of the
the placentation process and development of the embryo. trophoblastic wall, to which the embryonic death follows.
Kurjak49 refers that the process of trophoblastic invasion The premature access of maternal blood to the intervillous
Figure 12.19 The premature access of maternal blood to the Figure 12.20 The use of transvaginal color Doppler is not helpful for
intervillous space has broken the embryonic-maternal interface, predicting pregnancy outcome in cases of living embryo
probably the cause that determines the abortion
space would break the embryonic-maternal interface, and

would be the cause that probably determines the abortion
(Fig. 12.19). Alcazar55 communicates that no apparent
alteration occurs in the early uteroplacental circulation in
patients with threatened abortion with a living embryo,
so the use of transvaginal color Doppler ultrasound is
not helpful for predicting pregnancy outcome in cases of
threatened abortion (Fig. 12.20).
Salim56 measures PI and RI at the level of the corpus
luteum. The pregnancies with threatened abortion or ending
in abortion show higher values than normal pregnancies.
However, he does not observe differences when comparing
data of ectopic pregnancies, hydatidiform moles, or
anembryonic pregnancies (Fig. 12.21).
Alcazar57 measures the flow at the level of the corpus Figure 12.21 The use of transvaginal color Doppler is not helpful for
predicting pregnancy outcome in cases of threatened abortion
luteum, not finding differences among controls, threatened
abortion or blighted ovum. In pregnancies with confirmed
abortion, the values of RI are higher.
References
Other Factors to Consider 1. Barri PN. Pérdidas embrionarias preimplantatorias. In: JM
(Clinical Nature) Carrera, A Kurjak (Eds). Medicina Del Embrión. Barcelona:
Masson; 1996.pp.143-8.
ÀÀ Maternal age—superior to 35–40 years
2. Leridon H. Human fertility. Chicago: Chicago Press; 1977.
ÀÀ Presence of uterine bleeding
3. De la Fuente P. Aborto espontáneo. In: E Fabre (Ed). Manual
ÀÀ Moment of beginning of the uterine bleeding
de Asistencia a la Patología Obstétrica. Zaragoza: INO
ÀÀ Hormonal dynamics determination (β-hCG) Reproducciones; 1997. pp. 73-87.
ÀÀ Reproductive antecedents (one or more previous abortions) 4. Knudsen UB, Hansen V, Juul S, et al. Prognosis of a new
ÀÀ Existence of associate pathology (multiple myomas or pregnancy following previous spontaneous abortions. Eur
submucosa, uterine malformations). J Obstet Gynecol Reprod Biol. 1991;39(1):31-6.
5. Cashner KA, Christopher CR, Dysert GA. Spontaneous fetal 22. Merchiers EH, Dhont M, De Sutter PA, et al. Predictive
loss after demonstration of live fetus in the first trimester. values of early embryonic cardiac activity for pregnancy
Obstet Gynecol. 1987;70(6):827-30. outcome. Am J Obstet Gynecol. 1991;165(1):11-4.
6. Rempen A. The incidence of abortions of viable pregnancies 23. Laboda LA, Estroff JA, Benacerraf BR. First trimester
in the first trimester. Zentralbl Gynakol. 1993;115(6):249-57. bradycardia. A sign of impending fetal loss. J Ultrasound
7. Siddiqi TA, Caligaris JT, Miodovnik M, et al. Rate of Med. 1989;8(10):561-3.
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1988;5(1):1-4. Med. 1991;10(10):591-3.
8. Levi CS, Lyons EA, Zheng XH, et al. Endovaginal US: 25. Benson CB, Doubilet PM. Slow embryonic heart rate in
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9. Goldstein SR. Embryonic death in early pregnancy: a new
26. Doubilet PM, Benson CB. Embryonic heart rate in the early
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10. Philipp T, Philipp K, Reiner A, et al. Embryoscopic and
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involved in the pathogenesis of developmental defects of 27. Stefos TI, Lolis DE, Sotiriadis AJ, et al. Embryonic heart
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11. Goldstein SR. Significance of cardiac activity on endovaginal 28. Cepni I, Bese T, Ocal P, et al. Significance of yolk sac
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19. Bromley B, Harlow BL, Laboda LA, et al. Small sac size trimester subchorionic bleeding detected by color Doppler
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Radiology. 1991;178(2):375-7. pregnancy outcome. Obstet Gynecol. 1992;80(3 Pt 1):415-20.
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of ultrasonographic findings in spontaneous abortions 1996;15(9):645-9.
CHAPTER
13 Placenta and
Transvaginal Sonography
Ashok Khurana
In recent years, transvaginal evaluation of the placenta Placenta Previa

has completely changed the way obstetricians need to
perceive and assess a low lying placenta. Additionally, the The confusion that existed in the “classification” and
number of negative ultrasound examinations in morbid nomenclature of placental location has undergone significant
placental adherence has reduced. This chapter presents clarification over the past decade, and a clinically relevant
the evidence on the safety and accuracy of transvaginal understanding of placental location is now apparent. Terms
placental evaluation and goes on to discuss the manner in such as low-lying placenta, marginal placenta previa, partial
which transvaginal findings should alter clinical protocols placenta previa, and total placenta previa all refer to an
to optimize maternal and fetal outcomes. It also answers a abnormally low placenta. A total placenta previa completely
very pertinent clinical question: How low is low? spans across the internal os (Fig. 13.1). A partial placenta
previa partially spans across the internal os (Fig. 13.2). A
marginal placenta extends down to the internal os but does
Safety and Accuracy of not span across it (Fig. 13.3). It is appropriate to specify the
Transvaginal Ultrasound distance between the lower margin of the placenta and the
internal os.1 A placenta that extends down to the internal os
Transabdominal scans are associated with a false-positive is 0 mm away from the internal os. The amount of placenta
rate of diagnosing placenta previa in about 25% of that overlaps the internal os should also be measured and
cases.1,2 This is consequent to multiple factors, including the distance reported in millimeters.1
a posterior location,3 shadowing from the fetal head,4
maternal abdominal obesity5 and underfilling or overfilling
of the maternal urinary bladder.6,7 Transvaginal scanning
is now an unarguably accurate method for localizing a
low placenta.8-11 As many as 60% of patients will have
a reclassification of placental position on a transvaginal
evaluation1 and a representative study reports a sensitivity
of 87.5%, a phenomenal specificity of 98.85%, a positive
predictive value of 93.3% and a negative predictive value of
97.6%.12 A randomized control study13 has also confirmed
the accuracy of transvaginal studies. In fact, transvaginal
scanning has greatly reduced the incidence of placenta
previa9,14 because of its better delineation of the internal os
and inferior placental margin.
The safety of transvaginal scanning is also not in
doubt3,10 and the technique, in spite of initial skepticism,
Figure 13.1 Complete placenta previa. Transvaginal image shows a
now has widespread acceptance.1 posterior wall placenta spanning across the internal os and extending
As a consequence, the clinical presentation of placenta onto the anterior uterine wall. The ++ calipers measure the extent of
previa has changed and most low-lying placentas are the placenta beyond the internal os. This measurement is clinically
relevant because the greater the extent beyond the os the smaller the
diagnosed during the second trimester anomalies scan. chance of “resolution” of a placenta previa
Chapter 13  Placenta and Transvaginal Sonography 117
Figure 13.2 Partial placenta previa. The lower limit of this low-lying Figure 13.3 Marginal placenta previa. This low-lying placenta extends
placenta extends down to the internal os, partially spans across it, but down to the internal os but does not span across it
does not extend beyond the os
It is also now clear that changes in placental location

occur throughout gestation and are consequent to two
phenomena, formation of the lower uterine segment and
placental trophotropism.11,15,16 Trophotropism is the term
used to describe preferential proliferation of trophoblastic
villi in regions of better endometrial supply along with
atrophy of villi in areas with a poorer blood supply.15,16
Placental position and shape can therefore change as
pregnancy progresses. Trophotropism explains resolution
of placenta previa, increase in pathologic extent of placenta
previa, the development of succenturiate lobes or a
bilobed placenta, odd shaped placentas and abnormal cord
insertions. Over 90% of placentas that are low lying at 20
weeks of gestation will achieve a normal position at term.11
A low placenta is evident in about two-fifths of patients at
Figure 13.4 Marginal placenta previa with a thin beak-like lower
11−14 weeks, in about 1 in 25 patients at 20−24 weeks and edge. The morphology of the inferior edge has a bearing on clinical
about 1 in 50 patients at term.17 Predisposing factors for outcome. Placentas with a rounded lower edge (Fig. 13.5) are more
likely to resolve at term unlike this one, which is likely to persist till term.
placenta previa include previous cesarean section, previous The cervix should be measured in all low placentas. The chances of
cavitary surgery, previous vigorous curettage, multiparity bleeding are higher with a short cervix
and advanced maternal age.15,18,19
Serial evaluation demonstrates placental migration20 and it ultrasound feature that also influences placental migration
is possible to predict which cases will persist to term.14,17,21-25 is the morphology of the inferior edge of the placenta.26
A review of these studies indicates that placentas that Placentas with a thin inferior edge (Fig. 13.4) are more likely
overlap the cervix by a distance greater than 10−15 mm in to persist in a low position compared to those with a thick
the second trimester are likely to be persistently low at term. lower edge (Fig. 13.5).
Most placentas that do not overlap the internal os are likely The risk of bleeding from a placenta previa depends on
to “resolve” at term. Vaginal delivery is generally possible several factors. Irrespective of the distance of a low placenta
once the placenta is 20 mm superior to the internal os. A from the internal os, most patients who do have antepartum
significant number of pregnancies with placentas between bleeding, will not have episodes which are life threatening
10 and 20 mm can also be delivered vaginally. Another or require premature delivery.1 It must be emphasized,
A
Figure 13.5 Low placenta with a round lower edge. This type is more
likely to migrate away from the internal os as pregnancy progresses
to term
however, that pregnancies with a placenta that is within 40

mm of the internal os do have a higher risk of postpartum
hemorrhage.1 The distance of a low-lying placenta from the
internal os does not seem to influence the risk of antepartum
bleeding. This is more influenced by cervical length27 and
the presence of an echo-free space (Fig. 13.6A) in the lower
edge of the placenta overlying the internal os28 (Fig. 13.6B).
Both these factors increase the possibility of the need for
an emergency delivery prior to 34 weeks of gestation.
Most patients without these two features can be managed B
expectantly without hospitalization.29-32 Cervical cerclage Figures 13.6A and B Note the echo-free fluid space between the
for a short cervix with a low placenta is not justified.1,32,33 placenta and the internal os. Low placentas with such morphology
are more likely to bleed
Placenta accreta and vasa previa are intimately associated
with placenta previa.34-36 In this situation timed operative
delivery37,38 in an appropriate setting greatly improves
perinatal outcomes. Evidence of placenta previa should,
therefore, prompt a careful ultrasound evaluation for
placenta accreta and vasa previa.1,35
Placenta Accreta
The term placenta accreta is the generic term for abnormal
adherence of the placenta to the uterus. It is consequential to
a defect in the fibrinoid (Nitabuch’s) layer of the decidua39
underlying the placenta. The term placenta accreta vera
is used when the placenta is adherent to the myometrium
but does not invade it (Fig. 13.7). When myometrial
invasion takes place the term placenta increta is used
Figure 13.7 Placenta accreta. Note the extensively obscured interface
(Figs 13.8A and B). Placenta percreta refers to the situation that should have been seen as a hypoechoic zone between the basal
where invasion extends beyond the uterine serosa and into extent of the placenta and the subplacental myometrium
B
Figures 13.8A and B Placenta increta. 2D and power Doppler studies demonstrate an area of extensive myometrial invasion. The serosal
aspect of the uterus is not invaded. The 3D multislice image (tomographic ultrasound imaging) aids in assessing the entire extent of the
placenta. This low-lying placenta has invaded the posterior uterine wall as well (++)
the urinary bladder (Fig. 13.9) or rectum. The placenta

does not separate after delivery and can result in a situation
of retained placenta, life-threatening hemorrhage or
uterine rupture, not infrequently requiring an emergency
hysterectomy. Risk factors include previous cesarean
section, previous curettage, previous morbid adherence,
a low-lying placenta, advanced maternal age, submucous
fibroids and anomalies of uterine structure such as uterine
horns. 39-42 Accurate prenatal identification of affected
pregnancies allows optimal management because timing
and site of delivery, availability of blood products, and
recruitment of a skilled anesthesia and surgical team can
be arranged in advance. Cesarean section is planned at
36 weeks of gestation to minimize the risk of spontaneous
labor. Surgical planning of the site of incision and the need
Figure 13.9 Low-lying placenta with invasion through the entire
for uterine artery balloon occlusion can be individualized. myometrium and into the wall of the urinary bladder
Detailed maternal and family counseling, including
issues of future fertility, can be taken into consideration
during delivery planning and an option of conservative
management may be offered.
With high-risk patients, a targeted transabdominal
evaluation of the anterior myometrium and bladder wall
is performed using the highest-frequency transducer that
can produce an adequate image (with a “full” bladder).
Transvaginal ultrasound is always performed when the
placenta is low lying.
A multi-feature ultrasound evaluation34,39,43 enhances
the accuracy of detecting the diagnosis, although these
are by no means very sensitive. These include loss of the
retroplacental clear space, reduced myometrial thickness,
placenta previa, placental lacunae, abnormal color Doppler
imaging patterns, an irregular urinary bladder wall and
abnormal 3D power Doppler vascular mapping.
Figure 13.10 Multiple anechoic spaces are often evident in an invasive
The normal retroplacental complex is thinned out (2 mm placenta. These can enlarge and be more extensive giving it a Swiss-
cheese appearance. Note the extensively obscured retroplacental
or less) or obliterated in placenta accreta. The retroplacental
decidual stripe and the extension of the placenta up to the wall of the
complex refers to the hypoechoic space behind the urinary bladder.
placenta that is normally 10−20 mm thick. A retroplacental
hypoechoic line is usually seen with normal placentation.
Absence of this hypoechoic line or clear space has been Placenta previa significantly increases the risk for
described with placenta accreta. However, absence of the placenta accreta: 6.8–10% among affected women.
hypoechoic line has also been seen in normal pregnancies However, only 88% of cases of placenta accreta are
and absence of the clear space alone is not predictive for associated with placenta previa.
placenta accreta. Multiple hypoechoic or anechoic lacunae are often
Reduced myometrial thickness is tricky to evaluate, evident in the placenta (Fig. 13.10). These may give it a
overly subjective, difficult to replicate and reports in Swiss-cheese appearance.
literature are scant. This sign has, therefore, never been Invasion of the bladder or rectum may be evident
reliable. (Figs 13.11A and B).
A B
Figures 13.11A and B Complete placenta previa with a Swiss-cheese morphology extending through the myometrium and into the urinary
bladder
A B
Figures 13.12A and B Color Doppler features of placenta accreta include interruption of myometrial vessels, hyperemia of myometrial
vessels and turbulent flow in lacunae
Color Doppler features include interruption of bulging, heterogeneous signal intensity within the placenta,
myometrial vessels, hyperemia of myometrial vessels and and dark intraplacental bands on T2-weighted images.
turbulent flow in lacunae (Figs 13.12A and B). MRI protocols are, however, cumbersome and demand a
3D power Doppler studies have helped to identify a new meticulous technique.
reliable sign.44 Normal placentas show vessels that run parallel
to the long axis of the uterus. Invasive placentas show branches
Conclusion
that run perpendicular to these main vessels and show a course
running through the myometrium (Figs 13.13A to D). Ultrasound is currently the finest tool for assessing the placenta.
Recent advances in imaging have reduced the gap between
Recent magnetic resonance imaging (MRI) reports negative ultrasound examinations and critical placental disease.
are encouraging.45-48 The most useful findings are uterine
A B
C D
Figures 13.13A to D Three-dimensional (3D) power Doppler of the placenta. The multislice format confirms multiple areas of invasive
placenta. 3D acquisitions and subsequent rendering formats ensure that the placenta is evaluated throughout its extent. Note the multiple
vessels arising radially from the placental vessels in the 3D angio mode rendering (<)
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delivery for ﬁrst birth with placenta praevia and placental 34. Oyelese KO, Smulian JC. Placenta previa, placenta accreta,
abruption in second pregnancy. BJOG. 2007;114(5):609-13. and vasa previa. Obstet Gynecol. 2006;107:927-41.
19. Krasznai I, Rigo Jr J, Boze T. Uncommon type of placentation 35. Bhide A, Thilaganathan B. Recent advances in the
after previous cesarean deliveries. Obstet Gynecol. 2003; management of placenta previa. Curr Opin Obstet Gynecol.
102(3):549-51. 2004;16:447-51.
20. Kurjak A, Barsic B. Changes of placental site diagnosed 36. Finberg H, Williams J. Placenta accreta: prospective
by repeated ultrasonic examination. Acta Obstet Gynecol sonographic diagnosis in patients with placenta previa and
Scand. 1977;56(3):161-5. prior cesarean section. J Ultrasound Med. 1992;11(7):333-43.
21. Smith RS, Lauria MR, Comstock CH, et al. Transvaginal 37. O’Brien JM, Barton JR, Donaldson ES. The management
ultrasonography for all placentas that appear to be low-lying of placenta percreta: conservative and operative strategies.
or over the internal cervical os. Ultrasound Obstet Gynecol. Am J Obstet Gynecol. 1996;175(6):1632-8.
1997;9(1):22-4. 38. Ouellet A, Sallout B, Oppenheimer LW. Outcomes of
22. Lauria MR, Smith RS, Treadwell MC, et al. The use of surgical versus conservative management of placenta
second-trimester transvaginal sonography to predict placenta accreta-percreta: systematic review of literature and case
previa. Ultrasound Obstet Gynecol. 1996;8(5):337-40. series. Am J Obstet Gynecol. 2003;189(6):S130.
23. Becker RH, Vonk R, Mende BC, et al. The relevance of 39. Mazouni C, Gorincour G, Juhan V, et al. Placenta accreta: a
placental location at 20–23 gestational weeks for prediction review of current advances in prenatal diagnosis. Placenta.
of placenta previa at delivery: evaluation of 8650 cases. 2006;28(7):599-603.
Ultrasound Obstet Gynecol. 2001;17(6):496-501. 40. Abramowicz JS, Sheiner E. Ultrasound of the placenta:
24. Taipale P, Hiilesmaa V, Ylostalo P. Transvaginal ultra a systematic approach. Part I: Imaging Placenta.
sonography at 18-23 weeks in predicting placenta previa at 2008;29(3):225-40.
delivery. Ultrasound Obstet Gynecol. 1998;12(6):422-5. 41. Wu S, Kocherginsky M, Hibbard JU. Abnormal
25. Oppenheimer L, Holmes P, Simpson N, et al. Diagnosis of placentation: twenty-year analysis. Am J Obstet Gynecol.
low-lying placenta: can migration in the third trimester predict 2005;192(5):1458-61.
outcome? Ultrasound Obstet Gynecol. 2001;18(2):100-2. 42. Gielchinsky Y, Rojansky N, Fasouliotis SJ, et al. Placenta
26. Ghourab S. Third-trimester transvaginal ultrasonography accretae—summary of 10 years: a survey of 310 cases.
in placenta previa: does the shape of the lower placental Placenta. 2002;23(2-3):210-4.
43. Comstock CH. Antenatal diagnosis of placenta accreta: a 46. Mazouni C, Gorincour G, Juhan V, et al. Placenta accreta: a
review. Ultrasound Obstet Gynecol. 2005;26(1):89-96. review of current advances in prenatal diagnosis. Placenta.
44. Shih JC, Palacios Jaraquemada JM, Su YN, et al. Role of 2007;28(7):599-603. Epub 2006 Sep 7.
three-dimensional power Doppler in the antenatal diagnosis of 47. Lim PS, Greenberg M, Edelson MI, et al. Utility of ultrasound
placenta accreta: comparison with gray-scale and color Doppler and MRI in prenatal diagnosis of placenta accreta: a pilot
techniques. Ultrasound Obstet Gynecol. 2009;33(2):193-203. study. AJR Am J Roentgenol. 2011;197(6):1506-13.
45. Lax A, Prince MR, Mennitt KW, et al. The value of speciﬁc 48. Baughman WC, Corteville JE, Shah RR. Placenta accreta:
MRI features in the evaluation of suspected placental spectrum of US and MR imaging findings. Radiographics.
invasion. Magn Reson Imaging. 2007;25(1):87-93. 2008;28(7):1905-16.
CHAPTER Assessment of Placental Vascularization
14 by Three-dimensional Power Doppler

Ultrasound: Placental Biopsy in
Normal Pregnancies
Introduction Three-dimensional Power Doppler

Until the advent of power Doppler, the studies about “Placental Vascular Biopsy”
intraplacental circulation were very scarce. Probably, neither Through the current technology, 3D power Doppler
pulsed Doppler nor conventional color Doppler has enough angiography is not able to assess the placental vascular tree
technical and methodological guarantees to accomplish it. as a whole. Except for the first gestational trimester,3 the
On the contrary, power Doppler is characterized by a high insonation angle of ultrasound (US) transducers is lesser
sensitivity and independence from the angle of insonation than the largest placental diameters allowing only a partial
that render it the ideal method to assess tissue perfusion. visualization. To overcome this problem, the so-called
Some in vitro assays have confirmed that power Doppler “placental vascular biopsy” method has been developed.
intensity is well correlated to blood flow. Furthermore, it The power Doppler window, with previously defined
has been demonstrated recently in vivo a good correlation settings [pulse repetition frequency (PRF) = 600 Hz and
between power Doppler (as “fractional moving blood flow wall motion filter = 50 Hz], is placed over the placenta
volume”) and blood perfusion in sheep’s adrenal glands as so that it includes completely the thickness of the
determined by radioactive microspheres.1 intraplacental vascular tree between chorionic and basal
An intelligent association of power Doppler and three- plates. On the place where the villous vascularity is best
dimensional (3D) image also called 3D power Doppler visualized, surgeons fit the 3D volume box at an angle
angiography allows the morphological study of the vascular of 35°. The patient is asked to remain as still as possible
tree and a quantification of vascular density, blood flow and and avoiding fetal movements the volume acquisition is
perfusion in different regions and organs, among which is done. The acquisition time ranges 10−15 seconds and each
the placenta. The placental villous tree study has a great complete sonographic examination lasts for 10−15 minutes.
“a priori” interest mainly by two reasons: (i) fetal growth To analyze the acquired placental volumes, the computer
alterations are associated to an abnormal and deficient program VOCAL (virtual organ computer-aided analysis)
placental vascularization and (ii) moreover, it has been integrated within the sonography system is applied. Through
suggested that intraplacental blood flow decrease can be the multiplanar method the three spatial planes from the
ahead of umbilical resistance increase in the follow-up of placental volume obtained are explored to find and select
growth restricted fetuses.2 the highest placental vascularity zone as depicted by power
Since several years ago, our group has developed a Doppler. On the A plane, we set the limits of a virtual
technique called “placental vascular biopsy” to study reference axis between basal and chorionic plates (both
the placental vascularization through 3D power Doppler of them excluded); and within those limits, a sphere is
application. In the present chapter authors have described automatically generated by rotating around that mentioned
the acquisition of technical aspects, the reproducibility axis. Once we make sure that the sphere encloses placental
of the method and the evolution of 3D Doppler indices thickness as desired, the sample is accepted and volume and
in normal gestations. These are the essential grounds for Doppler vascular indices are calculated. If placental thickness
further assessment on the diagnostic potential of this new is not properly selected or some chorionic or basal plate
method in abnormal pregnancies, especially in fetal growth vessels are included by mistake, the axis reference limits
restriction. must be redefined and a new calculation is made (Fig. 14.1).
Figure 14.1 “Placental vascular biopsy” technique by 3D power Doppler angiography
Three-dimensional volume is integrated by units named The “placental vascular biopsy” technique using a sphere
“voxels”. Voxels contain all the information about color as a volume of study has an advantage, and that is of the
and gray scale using an intensity scale ranging 0−100. sphere being a regular geometrical structure, the different
According to these values, VOCAL automatically displays rotation steps available (6º, 9º, 15º and 30º) will not influence
three power Doppler indices expressing number of vessels, on parameter variability.4,5 An irregular placental volume
blood flow and tissue perfusion: selection between both placental plates should include a
ÀÀ Vascularization index (VI) measures the number of color greater placental volume, but we must assume a greater
voxels in the sample volume, thus expressing vascular variability related to the rotational technique6 (Fig. 14.2).
density as a percentage One of the technical problems with 3D power Doppler
ÀÀ Flow index (FI) is the mean color of all the color voxels, placental vascularization assessment is that of placental
so it represents the mean intensity of blood flow site insertion. Because of the color of power Doppler
ÀÀ Vascularization flow index (VFI) is the mean color value angiography changes due to the attenuation produced by
in all color and gray voxels within the sphere, represents the transducer/object distance, results could be influenced
this way both vascularization and flow; in other words, according to placental site insertion. 1 To avoid this
tissue perfusion. inconvenience all “biopsies” had been taken from anterior
Chapter 14  Assessment of Placental Vascularization by Three-dimensional Power Doppler Ultrasound 127
Figure 14.2 Irregular placental volume technique. This method includes a greater placental volume but could mean a greater variability
of the measurements
uterine wall insertion, and lateral or fundus when placenta examinations in 30 normal pregnancies.5 Three-dimensional
was located posteriorly. Doppler indices show a good reproducibility with ICC near
to 0.90, and mean differences between two consecutive
Validation of the “Placental Vascular examinations below 1 for all studied parameters. Placental
Biopsy” Method volume, GI and VFI present the best reproducibility and
To validate the technique, its reproducibility was firstly intraobserver agreement (Table 14.2).
studied in one only term placenta. Ten volumes were These results are in the same level of agreement
consecutively acquired and five VOCAL calculations were than those from adnexal tumors evaluated through 3D
obtained from each of them.4 For all 3D Doppler indices, power Doppler taking a cube as volume of interest. Its
a good intraobserver agreement was demonstrated with intraobserver and interobserver agreement for VI, FI
intraclass correlation coefficients (ICC) more than 0.90. and VFI are considered appropriate for the study of such
Variation coefficients are inferior to 10% for gray index lesions.7 A good reproducibility of 3D Doppler indices to
(GI) and FI. On the other hand, VI and VFI show variation evaluate ovarian8,9 and endometrial9 vascularization has
coefficients greater than 20% (Table 14.1). also been reported. Endometrial 3D Doppler indices show
Reproducibility of the method for different gestational intraobserver and interobserver ICC near to 1,9 whereas
ages has also been evaluated by two consecutive same indices show an intraobserver agreement ICC more
Table 14.1 Indices of intraobserver agreement for the study of Table 14.2 Intraclass correlation coefficients and confidence interval
the placental vascular parameters by 3D power Doppler (n = 50) and intraobserver differences (mean and SD) for the parameters of the
study of placental vascularity by 3D power Doppler (n = 60)
Parameters Mean SD VC ICC
PV (ml) 66.49 14.52 21.83 0.54 Parameters ICC 95% confidence Mean SD
interval ICC difference
GI (units) 45.67 2.17 4.75 0.97
PV (ml) 0.98 0.96–0.99 0.04 1.47
VI (%) 20.58 4.45 21.62 0.94
GI (units) 0.94 0.88–0.97 0.44 1.56
FI (units) 44.98 2.80 6.22 0.91
VI (%) 0.88 0.76–0.94 -0.83 4.52
VFI (units) 9.35 2.38 25.45 0.92
FI (units) 0.88 0.76–0.94 -0.52 2.82
(Abbreviations: PV, placental volume; GI, gray index; VI, vascularization VFI (units) 0.89 0.79–0.95 -0.31 1.71
index; FI, flow index; VFI, vascularization flow index; SD, standard
deviation; VC, variation coefficient; ICC, intraclass correlation coefficient) (Abbreviations: PV, placental volume; GI, gray index; VI,
vascularization index; FI, flow index; VFI, vascularization flow index;
SD, standard deviation; ICC, intraclass correlation coefficient)
than 0.80 and interobserver more than 0.70 (except the FI)
in the study of ovarian vascularization.8,9
Three-dimensional Doppler Indices

During Normal Gestation
Three-dimensional power Doppler angiography allows
the complete visualization of the villous vascular tree as a
whole from its start at the chorionic plate to the last branches
approaching basal plate. By this way, it is possible to depict
the vascular villous branches of first, second and third
order, although power Doppler cannot detect vessels from
the terminal villi.2 Fetal-placental vessels at the chorionic
plate and uteroplacental vessels (arcuate, radial and spiral)
at the basal plate can also be identified (Fig. 14.3).
A subjective analysis of the villous vascular tree during
normal gestation shows that, to the 20th week, only the
vessels from chorionic and basal plates are usually registered
or at least a minimal development of first order vessels (Figs Figure 14.3 Placental vascular tree depicts by 3D power Doppler
14.4A and B). During the second trimester, it is possible to angiography (Abbreviations: UV, umbilical vessels; VV-1, vascular
visualize the vessels of the first and second order villous villous branches of 1st order; VV-2, vascular villous branches of
2nd order; VV-3, vascular villous branches of 3rd order; AR, arcuate
branches (Figs 14.4C and D). Finally, at the third trimester, vessels; RA, radial vessels; SP, spiral vessels)
the 3D power Doppler angiography depicts the villous tree
vascularization as a whole (Figs 14.4E and F). the detection rate for third and fourth order villous arteries
The morphological study of the villous tree through 3D increases typically between 28th and 38th gestational
power Doppler angiography has also been tested by some weeks.2
other authors.10,11 Like us, they agree that this method It seems obvious that 3D power Doppler angiography
facilitates visualization of vessels from first, second and is superior to 2D as it makes possible the morphological
third order villi,10,11 with an even greater detection rate study as well as the calculation of vessel number, blood flow
than 2D Doppler.11 The possibility to see the fourth order and tissue perfusion by 3D Doppler indices.12 The study
villous vessels with bidimensional (2D) power Doppler of Yu et al.12 assessed an irregular and undefined surface
in normal pregnancies has been reported, although as we placental volume in a 100 normal pregnancies between
have previously pointed out, the vessels from terminal villi 20th and 40th weeks. This author proved that 3D Doppler
cannot be depicted. In this way, it has been published that indices increase significantly with gestational age.12
Figures 14.4A to F Placental vascular tree throughout the normal pregnancy. (A) Villous vessels at 16th week; (B) Villous vessels at 20th
week; (C) Villous vessels at 25th week; (D) Villous vessels at 30th week; (E) Villous vessels at 34th week and (F) Villous vessels at 38th week
The placental volume obtained using placental vascular to the results we have obtained during the study of 86
biopsy technique increases progressively and significantly normal pregnancies between 15th and 40th gestational
with gestational age (Table 14.3 and Fig. 14.5A) according weeks. This result is consistent with the expected normal
Table 14.3 Regression equations for the placental volume by 3D vessels (VI) would reach its maximum during the second
biopsy (PV) and the indices of vascularization index (VI), flow index trimester, with a tendency to decrease slightly in term
(FI) and vascularization flow index (VFI) from the placental vascular
biopsy according to gestational age (weeks) gestation (Table 14.3 and Figs 14.5B and C). Finally, the
VFI or placental perfusion is determined by the behavior of
Parameters Constant b c SD r p
those two indices, from which it is calculated (Fig. 14.5D).
PV -13.375 0.893 — 117.20 0.46 < 0.01 The difference between our results and the previously
VI -19.668 2.144 -0.033 77.29 0.29 < 0.05 reported 12 result could be explained by the different
FI 17.930 0.565 — 53.98 0.58 < 0.01 techniques of placental volume acquisition, but could
VFI -6.530 0.678 -0.010 32.76 0.32 < 0.01
also be other factors implied. Another issue about power
Doppler quantification, especially those due to attenuation
and different presets of the equipment, could have an effect
increase of the placental thickness along gestation. All 3D on the results.1
Doppler indices are significantly related with gestational All 3D Doppler indices are significantly correlated with
age, but with some variations. fetal biometrical parameters, except for the VI and fetal
The VI shows a smaller regression coefficient (r = 0.29; weight. Nonetheless the correlation is stronger between
p < 0.05), a greater scattering of values, a curve flattening the FI and sonographic variables of the fetal growth
from 30th week and a decrease from 37th week onward. (Table 14.4). This suggests the possibility to apply this
The FI proves the best correlation (r = 0.58; p < 0.01) and technique to the assessment of fetal growth.12
increases linearly along gestation. Provided that, while the Three-dimensional Doppler indices are also related to
villous tree blood flow (FI) rises linearly and progressively conventional Doppler parameters. In a study on 60 normal
during the entire pregnancy, the number of villous tree pregnancies from 13th to 41st weeks, we have confirmed
A B
C D
Figures 14.5A to D Three-dimensional Doppler indices throughout the normal pregnancy
(Abbreviations: PV, placental volume; VI, vascularization index; FI, flow index; VFI, vascularization flow index)
Table 14.4 Correlation of placental volume by 3D biopsy (PV), Table 14.5 Correlation of the vascularization index (VI), flow index
vascularization index (VI), flow index (FI) and vascularization flow (FI) and vascularization flow index (VFI) of the placental vascular
index (VFI) of the placental vascular biopsy with the biometrical biopsy with Doppler velocimetry of umbilical and retroplacental
sonographic parameters of fetal growth (n = 52) vessels (n = 60)
Parameters BPD HC AC FL Weight Parameters USV URI UPI RSV RRI RPI MVV
PV 0.46 **
0.51 **
0.46 **
0.48 **
0.44 ** PV 0.48 **
-0.56 **
-0.56 **
0.11 -0.26 -0.21 0.40**
*
VI 0.28* 0.27* 0.25 0.27* 0.20 VI 0.47 **
-0.50 **
-0.51 **
-0.05 -0.34 *
-0.30 *
0.37**
FI 0.64** 0.62** 0.64** 0.64** 0.60** FI 0.52** -0.49** -0.50** 0.00 -0.17 -0.15 0.32*
VFI 0.33** 0.31** 0.31** 0.32** 0.27* VFI 0.50 **
-0.52 **
0.53 **
-0.04 -0.35 *
-0.30 *
0.36**
(Abbreviations: BPD, biparietal diameter; HC, head circumference; (Abbreviations: USV, umbilical systolic velocity; URI, umbilical resistance
AC, abdominal circumference; FL, femur length. *p < 0.05; **p < 0.01) index; UPI, umbilical pulsatility index; RSV, retroplacental systolic velocity;
RRI, retroplacental resistance index; RPI, retroplacental pulsatility index;
MVV, mean venous velocity. *p < 0.05; **p < 0.01)
a significant correlation between placental volume, VI, An intraplacental vascular resistance greater to
FI and VFI and peak systolic velocity, resistance index the umbilical is associated with increased gestational
(RI) and pulsatility index (PI) of the umbilical artery and complications.20 When it is obtained by multigate spectral
mean velocity in the umbilical vein. We have also found a Doppler, it is more sensitive and goes ahead of umbilical
significant relation, with smaller correlation coefficients, Doppler alterations in the detection of fetal growth
between intraplacental VI and VFI and the retroplacental restriction. 15 Evaluating the color mapping by power
RI and PI (Table 14.5). These results could be described as Doppler, a significantly decreased number of villous
: it is evident that umbilical blood flow, both venous and arteries of the first, second and third order and the absence
arterial, depends directly on placental vascularity and villous of fourth order vascular branches has been demonstrated
blood flow so the correlation seems logical. Moreover, in pregnancies with fetal growth restriction.2
considering power Doppler does not differentiate arteries “Placental vascular biopsy” can be useful to verify this
from veins within the villous tree, as they are quantified as a hypothesis. As a first approach, studying five cases with
whole, which would explain better their relation to umbilical fetal growth restriction (with US detection and postnatal
venous flow. Nevertheless, correlation between VI and VFI confirmation) and normal umbilical artery Doppler results, we
and retroplacental flow is not so evident. In our opinion, it have found that three of them showed a reduced VI/placental
could indicate that “placental vascular biopsy” includes the volume ratio according to the normal parameters. A large
intervillous flow whose increasing magnitude would clarify prospective study is obviously necessary to assess the predictive
the significant relation between the intraplacental and the and diagnostic capability of this technique in a population at
uteroplacental circulations. high risk for fetal growth restriction (Figs 14.6A and B).
Placental Biopsy in Fetal Growth Conclusion

Fetal growth restriction is associated to an abnormal and In conclusion, the “placental vascular biopsy” technique by 3D
deficient development of placental vascular tree13,14 that power Doppler is a suitable method in the routine assessment
of the placental vascular tree during human pregnancy. Three-
can be assessed by umbilical artery Doppler. Nevertheless, dimensional Doppler indices show a satisfactory reproducibility
umbilical Doppler alterations reflect pathological vascular and they change significantly along with the increasing
changes in the villous tree with some delay, which confer gestational age. Also the intraplacental FI increases linearly
and progressively during all the gestation period, the VI shows
this method a low diagnostic sensitivity. 15 Vascular a plateau in the third trimester and decreases by term gestation.
resistance in the umbilical artery is modified when 70% of These indices correlate well with fetal growth sonographic
parameters and the fetoplacental and uteroplacental Doppler. All
placental vessels become affected.16-19 Given that, one can
of that constitute the “placental vascular biopsy” as a new tool to
assume that the blood flow in the intraplacental vascular investigate fetal growth alterations and the associated placental
tree can be altered in some cases in which umbilical Doppler vascular tree lesions.
is normal.2
B
Figures 14.6A and B Decreased placental vascularity in a case of intrauterine fetal growth restriction
References 3. Hafner T, Kurjak A, Funduk-Kurjak B, et al. Assessment

of early chorionic circulation by three-dimensional power
1. Welsh A. Quantification of power Doppler and the index Doppler. J Perinat Med. 2002;30(1):33-9.
‘fractional moving blood volume’ (FMBV). Ultrasound 4. Mercé LT, Bau S. “Biopsia vascular placentaria” mediante
Obstet Gynecol. 2004;23(4):323-6. mapa de amplitud tridimensional: validación de la técnica.
2. Mu J, Kanzaki T, Tomimatsu T, et al. Investigation of Rev Es Ultra Obs Gin. 2003;1:1-5.
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in growth-restricted fetuses. Am J Obstet Gynecol. of placental vascularization by three-dimensional power
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6. Raine-Fenning NJ, Clewes JS, Kendall NR, et al. The 13. Todros T, Sciarrone A, Piccoli E, et al. Umbilical
interobserver reliability and validity of volume calculation Doppler waveforms and placental villous angiogenesis in
from three-dimensional ultrasound datasets in the in vitro pregnancies complicated by fetal growth restriction. Obstet
setting. Ultrasound Obstet Gynecol. 2003;21(3):283-91. Gynecol. 1999;93(4):499-503.
7. Pairleitner H, Steiner H, Hasenoehrl G, et al. Three- 14. Kingdom J, Huppertz B, Seaward G, et al. Development of the
dimensional power Doppler sonography: imaging and placental villous tree and its consequences for fetal growth.
quantifying blood flow and vascularization. Ultrasound Eur J Obstet Gynecol Reprod Biol. 2000;92(1):35-43.
Obstet Gynecol. 1999;14(2):139-43. 15. Yagel S, Anteby EY, Shen O, et al. Placental blood flow
8. Jarvela IY, Sladkevicius, Tekay AH, et al. Intraobserver measured by simultaneous multigate spectral Doppler
and interobserver variability of ovarian volume, gray-scale imaging in pregnancies complicate by placental vascular
and color flow indices obtained using transvaginal three- abnormalities. Ultrasound Obstet Gynecol. 1999;14(4):262-6.
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Obstet Gynecol. 2003;21:277-82. velocity waveforms and placental resistance: pathological
9. Raine-Fenning NJ, Campbell BK, Clewes JS, et al. correlation. Br J Obstet Gynaecol. 1985;92(1):31-8.
The reliability of virtual organ computer-aided analysis 17. Trudinger BJ, Stevens D, Connelly A, et al. Umbilical artery
(VOCAL) for the semiquantification of ovarian, endometrial flow velocity waveforms and placental resistance: the effects
and subendometrial perfusion. Ultrasound Obstet Gynecol. of embolization of the umbilical circulation. Am J Obstet
2003;22(6):633-9. Gynecol. 1987;157(6):1443-8.
10. Pretorius DH, Nelson TR, Baergen RN, et al. Imaging of 18. McCowan LM, Mullen BM, Ritchie K. Umbilical artery
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Obstet Gynecol. 1998;12(1):45-9. 19. Fok RY, Pavlova Z, Benirschke K, et al. The correlation of
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CHAPTER
15 Cervical Measurements
and Preterm Labor
Aris Antsaklis, G Daskalakis
Introduction of preterm labor, (ii) asymptomatic women at high-risk of

preterm delivery, (iii) asymptomatic women at low-risk of
Preterm delivery is one of the main causes of perinatal preterm delivery, (iv) women with multiple gestations, and
mortality and morbidity and it accounts for 60–80% of (v) pregnancies complicated by preterm premature rupture
deaths of infants without congenital anomalies.1 Moreover, of membranes (PPROM).
preterm neonates are at high-risk of developing cerebral
palsy, visual and hearing impairment and chronic lung
disease, while 40–60% of them need special educational
Technique
support. The preterm delivery rate varies between 5 The cervix can be assessed by transabdominal, transvaginal
and 7% in Europe and 11 and 12% in the United States. or transperineal ultrasonography. The main disadvantage
Despite the advances in obstetric care and neonatology, of the transabdominal route is the need for a full bladder.
the rate of preterm delivery was not decreased but in Unfortunately, this artificially lengthens the cervix. Moreover,
fact increased.2 This is mainly attributed to the increased it was found that the success of the cervical visualization
number of preterm births among multiple gestations, the transabdominally depends on the cervical length. In a study
trend toward iatrogenic premature delivery in conditions by To et al.5 it was found that transabdominal US evaluation
such as hypertension or intrauterine growth restriction as of the cervix increased from 13 to 51% as the length of the
well as the more accurate estimation and registration of cervix increased from 20 mm to 40 mm.
gestational age. Neonatal survival improves as gestational When transvaginal sonography (TVS) is used, the
age progresses. It increases from approximately 50% at 25 bladder should be emptied and the woman is placed in the
weeks of gestation to over 97% at 33 weeks of gestation.2 dorsal lithotomy position. Then the probe is inserted in the
It is therefore logical as the major benefits from delaying anterior vaginal fornix and a sagittal view of the cervix
delivery are seen in this period, that greater attention has is obtained (Fig. 15.1). It is important not to exert undue
been focused on early preterm labor (before 32 weeks). pressure on the cervix, thus avoiding false elongation of
Extensive research has been made so far in methods its length. The picture should be magnified to at least 75%
of predicting preterm delivery in both asymptomatic and of the screen. When a clear image of the cervix is obtained
symptomatic patients. The absence of reliable criteria for and the endocervical mucosa is visualized along the cervical
the selection of at-risk patients, as well as the absence canal, the calipers are placed at the internal and external
of effective interventions to prevent prematurity are os. Any funneling as well as its shape is recorded. Given
responsible for the controversial results reported in different the substantial intraobserver and interobserver variations
studies. During the last few years, a clear relationship has that occur with digital examinations, it has been proved
been established between decreased cervical length and that transvaginal ultrasonography is a reproducible method
the risk of spontaneous preterm delivery. Many studies of examination.3,4 A curved cervix can be measured either
dealing with the ultrasonographic evaluation of the cervix following the curvature, or as a straight line between the
during the course of pregnancy have suggested that cervical inner and outer cervical os. In a study by To et al.5 it was
changes may detect or exclude the risk of preterm delivery. shown that at 23 weeks of gestation the prevalence of
Unfortunately, the heterogeneity of most of them resulted curvature was higher when the cervical length was longer,
in mixed performance of this procedure as a screening while it was not found in cases of short cervices (<15 mm).
test. Ultrasound (US) examination of the cervix has been They concluded that cervical curvature has no implications
applied mainly in five categories: (i) women with symptoms in the screening test when such a cutoff is used.
Chapter 15  Cervical Measurements and Preterm Labor 135
incompetence, and therefore identification of high-risk
cases.10,12,13 Maternal postural challenge and straining
have also been performed by a few groups,14,15 in order to
examine the cervix more reliably, but these tests have a poor
reproducibility.
Recently, three-dimensional (3D) TVS has been
proposed for the evaluation of cervical morphology. Bega
et al.16 showed that 3D US gave more accurate estimation
of the cervical length compared to two-dimensional (2D)
US. In a study on multiple gestations, Strauss et al.17 failed
to show any additional benefit from the use of 3D versus
conventional US for the measurement of the cervical length.
Similar findings were observed in a study by Hoesli et al.18
who compared 3D to 2D US for the measurement of the
Figure 15.1 Normal cervical length (transvaginal ultrasound)
cervical volume.
Transvaginal Sonography in Women with

Transperineal approach is an alternative method of
Symptoms of Preterm Labor
cervical sonographic evaluation. In a study by Owen et
al.6 comparing transvaginal and transperineal sonography Several methods for predicting preterm delivery in
a poor correlation between the two methods was seen. In symptomatic patients have emerged during the last decade.
another study Carr et al.7 managed to measure the cervical Among them, the most frequently used are the evaluation
length in all cases and in 95% of cases with transvaginal of uterine contractions by uterine activity monitoring and
and translabial sonographic evaluation respectively. More digital examination of the cervix. However, neither the
recently, Cicero et al.8 showed that in the vast majority frequency nor the intensity of uterine contractions can
of cases cervical assessment can be performed by the distinguish true from false preterm labor.19,20 It is also
transperineal approach. This method could be the method of difficult to examine the part of the cervix, which is above the
choice in patients objecting to TVS, or in those with preterm vaginal fornices, by digital examination. On the other hand,
rupture of membranes, where transvaginal US should be transvaginal ultrasonography has the potential to provide
better avoided for fear of infection. objective and repeatable measurements of cervical length.
Several other cervical characteristics, such as the Murakawa et al.21 examined 32 women by TVS with
presence of funneling and the cervical index (CI) [(funnel threatened preterm labor and found that the risk of preterm
length + 1)/cervical length] can be determined by US. delivery was high when the cervical length was less than 30
The shape (Y- or U-shaped), the width, the length and the mm. Moreover, all women with a cervical length of less than
percentage of funneling have also been evaluated. Berghella 20 mm delivered preterm. Two other studies compared the
et al. 9 suggested that funneling was an independent diagnostic performance of cervicovaginal fetal fibronectin
predictor of preterm delivery. Guzman et al.10 compared (fFN) and transvaginal sonographic evaluation of the
various sonographic cervical parameters and failed to uterine cervix in symptomatic patients. They reported that
show any advantage of funnel width, funnel length, the combined use of the cervical ultrasonography and fFN
percentage of funneling or CI calculation over a cervical testing improves the diagnostic efficiency of any of these
length measurement of less than 25 mm for the prediction methods alone.22,23 More recently, Rozenberg et al.24 in a
of preterm birth. It seems that a short cervix and funneling similar study of 76 symptomatic patients failed to show
usually coexist.11 Therefore, a single measurement of the any significant additional benefit from the performance of
cervix is enough, because funneling is not an independent fFN testing over the single transvaginal ultrasonographic
variable for the prediction of preterm birth in most measurement of cervical length. Crane et al.25 evaluated
of the cases. Several studies proposed transfundal or singleton and twin pregnancies with preterm contractions
suprapubic pressure in order to detect cervical shortening. and found that transvaginal sonographic measurement of
They suggested that this was the earliest sign of cervical the cervix was a good predictor of preterm delivery and it
had a better predictive value in singletons than in twins. Sonography of the Cervix in High-risk
Tsoi et al. 26 examined 216 symptomatic women with Asymptomatic Women
singleton pregnancies and observed that a cervical length
The high-risk population for preterm delivery includes
measured by transvaginal US of less than 15 mm could
women with a previous history of preterm delivery or
distinguish those at risk of delivery within 7 days. Tekesin
rupture of the membranes, repeated mid-trimester pregnancy
et al.27 evaluated 68 patients with threatened preterm labor
losses, cervical surgery, congenital uterine anomalies or
and observed that the risk of preterm delivery increased in
diethylstilbestrol exposure. Many studies have reported
patients with a cervical length of less than 25 mm. They
on cervical sonography for the prediction of preterm
also found that a quantitative US tissue characterization of
delivery in this population. Berghella et al.32 prospectively
the cervix was the best predictor of preterm delivery.
evaluated 96 high-risk women between 14 and 30 weeks
Authors prospectively evaluated 172 women with with both cervical ultrasonography and manual examination
singleton pregnancies and symptoms of preterm labor. of the cervix. The relative risk of preterm delivery using a
Gestational age ranged between 24 and 34 weeks. All cervical length cutoff of 25 mm between 16 and 20 weeks
women underwent cervical assessment with transvaginal was 4.8 (95% CI 2.1–11.1, p = 0.0004). Moreover, cervical
ultrasonography and were given intravenous tocolytics. ultrasonography was a better predictor of preterm delivery,
The only parameter evaluated was cervical length. Using than manual examination of the cervix. Guzman et al.12
a cutoff for the cervical length of 20 mm the method had a examined high-risk women by serial transvaginal cervical
sensitivity of 56%, a positive predictive value of 90% and ultrasonography with transfundal pressure. Examinations
a specificity of 96%. Moreover, it had an excellent negative were performed until the cervical length decreased to less
predictive value of 79%, meaning that it can identify a than 10 mm. They concluded that the shortening of the
group of women who are at low-risk for preterm delivery, cervical length, or the prolapse of the membranes into the
allowing a reduction in the number of tocolytic treatments. cervix following transfundal pressure, has a significant
Other investigators suggested that funneling may be a predictive value for preterm delivery. In another study
predictor of preterm delivery in symptomatic patients.28,29 Guzman et al.33 examined high-risk women between 15
In contrast, Crane et al.25 and Hincz et al.23 reported that and 24 weeks and found that transfundal pressure was the
funneling was not an independent predictor of preterm most predictive method to detect cervical incompetence,
delivery in symptomatic women. Hincz et al. 23 also compared to coughing and standing. Andrews et al.34 studied
observed that there was a higher incidence of funneling 69 high-risk women between 16 and 30 weeks by serial
with the advancement of gestational age, a finding which TVS. They noted that a cervical length below the 10th
was first seen by Iams et al.30 who reported that funneling percentile or funneling of the internal os was associated with
is probably normal after 32 weeks of gestation. Moreover, higher risk of preterm delivery within 2–4 weeks from the
Berghella et al.31 found that, although funneling was a good examination. Cook and Ellwood35 examined prospectively
predictor of preterm delivery in the second trimester, it was 120 high-risk women by transvaginal US and reported that
of limited value in symptomatic patients after 32 weeks. endocervical canal length less than 21 mm before 21 weeks
Transvaginal US can be used as a screening test for was associated with delivery less than 34 weeks in 95%
preterm delivery in symptomatic patients. It can be used of them. Additionally, if the canal length was less than 33
easily by physicians with the equipment and experience, and mm, 95% of the women delivered in less than 37 weeks.
it can reliably diagnose patients who are in true preterm labor Owen et al.6 performed cervical sonography between 16
when they present with preterm contractions, reducing the and 19 weeks on 183 high-risk women and they found that
false positive results. Consequently, different management a cervical length of less than 25 mm was associated with
protocols can be used for symptomatic patients, depending a relative risk of preterm delivery before 32 weeks of 3.3
on cervical length. A more aggressive tocolytic treatment (95% CI 2.1–5.0; sensitivity = 19%, specificity = 98%,
in combination with fetal lung maturation should be positive predictive value = 75%). They also observed that
considered for those with a short cervix. In contrast, patients serial cervical measurements up to 24 weeks significantly
with a long cervix should be managed in an outpatient improved the prediction of spontaneous preterm birth (p
basis, avoiding prolonged hospitalization and potentially = 0.03). Using the shortest ever measured cervical length
dangerous tocolytic treatments. on serial evaluations, after any dynamic shortening, the
relative risk of a cervical length of less than 25 mm for observed that the majority of preterm deliveries occurred in
preterm birth increased to 4.5 (95% CI 2.7–7.6). Guzman women with endovaginal ultrasonographic measurements
et al. 10 compared various sonographic parameters to below the median. In a similar study Tongsong et al.41
predict preterm birth on 469 high-risk gestations which reported that a cervical length of less than 35 mm between
were prospectively evaluated between 15 and 24 weeks. 28 and 30 weeks had a sensitivity for delivery before 37
They examined funnel width and length, percentage of weeks of 65.9% and a specificity of 62.4%. Iams et al.42
funneling, cervical length and CI and they concluded that performed vaginal ultrasonography in 2,915 low-risk
a cervical length of less than or equal to 25 mm was equal women at 24–28 weeks. They reported that the relative
to the other cervical parameters as a predictor of preterm risk of preterm delivery increased as the length of the
delivery. The sensitivities for delivery at less than 28, 30, 32 cervix decreased. For cervical lengths below the 50th
and 34 weeks were 94%, 91%, 83% and 76%, with negative percentile at 24 weeks, the relative risk was 2.35; while at
predictive values of 99%, 99%, 98% and 96% respectively. 28 weeks, it was 3.52 (p < 0.001). Heath et al.43 performed
They also observed that the rate of preterm delivery at less ultrasonographic cervical measurements in more than
than 34 weeks increased dramatically when the cervical 2,500 singleton low-risk pregnancies and examined the
length was 15 mm and that the placement of a cerclage relation between cervical length and the risk of preterm
did not influence the positive and negative predictive delivery at less than or equal to 32 weeks. They found that
values. Vendittelli et al.36 in a prospective study on 200 approximately 2% of their population had a cervical length
high-risk women reported that a cervical length of less of less than 15 mm and that this group contained about 90%
than 30 mm had a relative risk of preterm delivery of 2.79 and 60% of the women delivering at less than or equal to
(95% CI 1.7–4.59). The presence of funneling of greater 28 and 32 weeks respectively. Taipale et al.44 performed
than or equal to 5 mm gave a relative risk of 1.39 (95% CI transabdominal and transvaginal ultrasonographic
0.99–1.95). Obido et al.37 showed that a cervical funneling measurements of the cervix at 18–22 weeks in 3,694
of more than 75% or a cervical shortening of less than 10 singleton pregnancies. When the cervical length was less
mm were predictive of PPROM. In a similar study Guzman than 29 mm, the relative risk for preterm delivery before
et al.38 showed that a progressive cervical shortening of less 35 weeks was 8; while, when the dilatation of the internal
than or equal to 20 mm before 24 weeks suggested cervical os was 5 mm, the relative risk was 28. Hassan et al.45 in a
incompetence. Incompetent cervices had significantly retrospective cohort study, examined cervical length with
greater cervical shortening compared to competent ones transabdominal ultrasonography followed by transvaginal
(p < 0.001). MacDonald et al.13 prospectively evaluated ultrasonography if cervical length was less than 30 mm.
106 high-risk women and found that the opening of the They reported that the odd ratios for delivery before 32
cervical os at rest or in response to transfundal pressure weeks for cervical lengths less than or equal to 10, 15, 20,
was the earliest US feature of cervical incompetence. 25 and 30 mm were respectively 29.3, 24.3, 18.3, 13.4 and
Recently, Berghella et al.39 performed transvaginal cervical 3.2. A cervical length of less than or equal to 15 mm had, for
sonography in 183 high-risk women between 10 and 14 preterm delivery less than or equal to 32 weeks, a positive
weeks and concluded that this period was not appropriate predictive value of 47.65% and a negative predictive value
for screening for preterm delivery, as in most cases cervical of 96.7%, a sensitivity of 8.2%, and a specificity of 99.7%.
changes develop after this gestational age. To et al.46 measured cervical length prospectively in 6,819
singleton pregnancies at 22–24 weeks and looked for the
presence of funneling. Funneling was present in about 4%
Sonography of the Cervix
of pregnancies and its presence was strongly related to a
in Low-risk Population
short cervical length. A cervical length less than or equal
In comparison to women at high-risk of preterm delivery, to 15 mm was found in 1.6% of women. The odd ratios
pregnant women without risk factors have a low prevalence for preterm delivery were for a short cervix 24.9 and for
of preterm birth of about 4–8%. However, more than half funneling 1.8. They concluded that funneling did not
of the preterm births occur in these low-risk women. It is provide a significant additional contribution to cervical
therefore of great importance to examine the potential of length in prediction of delivery before 33 weeks. Hibbard
cervical screening in this population. In 1990, Andersen et et al.47 in a prospective study of 760 women looked at
al.40 evaluated 178 women with singleton gestations and cervical length measurements at 16–23 weeks, and the
mean cervical length was 38.5 mm. The relative risks for gestation. The sensitivity, specificity, positive and negative
delivery before 35 weeks were 4.5, 7.5 and 7.8 for the 10th, predictive values of a cervical length greater than 35 mm
5th and 2.5th percentiles respectively. Recently, Conoscenti for predicting delivery greater than or equal to 34 weeks
et al.48 examined the value of cervical length measurement were 49%, 94%, 97% and 31% respectively. Guzman et al.52
at 13–15 weeks of gestation in an unselected population studied 131 twin pregnancies on 524 occasions between 15
and found that this is not a reliable screening procedure for and 28 weeks with transvaginal cervical ultrasonography
spontaneous preterm delivery before 37 weeks. Carvalho and transfundal pressure. They measured funnel width and
et al.49 compared cervical length measurements obtained length, cervical length, percentage of funneling and the CI.
at 11–14 weeks to those obtained at 22–24 weeks and They concluded that a cervical length of less than or equal
correlated the measurements with time of delivery. They to 20 mm between 15 and 28 weeks was at least as good
found that there was a spontaneous shortening of the as other ultrasonographic cervical parameters at predicting
cervix from the first to the second trimester of pregnancy, spontaneous preterm birth. Yang et al.53 studied 65 twin
which was more rapid in those women who delivered pregnancies prospectively with transvaginal or translabial
prematurely and those who had a history of previous US of the cervix at 18–26 weeks. They suggested that both
preterm delivery. Authors also evaluated 1,197 singleton cervical length less than or equal to 30 mm and cervical
low-risk pregnancies at 23 weeks, with transvaginal funneling were independently and strongly associated
sonographic cervical assessment. The preterm delivery rate with high risk for preterm delivery. Conversely, a cervical
before 37 weeks in our population was 8.7%, confirming length greater than 35 mm was associated with very low
that this was a low-risk population. The distribution of risk (4%) for preterm birth. Skentou et al.54 examined 464
cervical length was normal and the mean cervical length twin pregnancies with TVS of the cervix and in about
was 38 mm (range: 2–70 mm). Less than 20 mm length of 8% of them found a cervical length of less than or equal
the cervix were found in 17 women (1.4%). Women with to 20 mm. This group of women contained about 40%
a cervical length less than 20 mm had 3.31 times increased of those who delivered spontaneously before 33 weeks.
risk for prematurity (95% CI 10.14-1.08) (p = 0.03). The The usefulness of cervical length measurement before 30
presence of funneling gave a relative risk for preterm weeks was confirmed in a retrospective review study by
delivery of 2.07 (95% CI 0.94–4.54) (p = 0.07). Shapiro et al.55 Similar results were reported by Iams et
al.56 who compared maternal serum relaxin, cervical length
and preterm birth in twins. They also found no correlation
Sonography of the Cervix in
between relaxin and cervical length, thus suggesting that
Multiple Pregnancies
relaxin does not contribute to the higher risk for preterm
Multiple pregnancies are generally considered as high risk birth in twin gestations. Different conclusions were reported
for preterm delivery as the mean gestational age at birth is by Ong et al.57 who found that cervical measurements were
35 weeks for twins and 33 weeks for triplets. Although the not predictive of preterm delivery in twins. Only a cervical
number of published trials in multiples is significantly fewer length of less than 20 mm was predictive of delivery within
compared to singletons, sonographic assessment of the 1 week. Soriano et al.58 examined prospectively 54 twin
cervix appears to be of value in this population. Goldenberg pregnancies conceived after infertility treatment, with
et al.50 prospectively screened 147 twin pregnancies at transvaginal ultrasonographic assessment of the cervix.
24–28 weeks for more than 50 potential risk factors for They reported that a cervical length of more than 35 mm
spontaneous preterm birth. They found that at 24 weeks a at 18–24 weeks identified pregnancies at low risk for
cervical length less than or equal to 25 mm was consistently delivery before 34 weeks. In a prospective study on 251
associated with preterm birth. The odd ratios for preterm twin gestations, Vayssiere et al.59 performed transvaginal US
birth at less than 32, 35 and 37 weeks were 6.9, 3.2 and assessment of the cervix. They observed that cervical length
2.8, respectively. At 28 weeks, the same cutoff for the and funneling both predicted the very preterm birth. For
cervical length was not a strong predictor of spontaneous spontaneous delivery before 32–35 weeks, the sensitivity
preterm birth. Imseis et al.51 showed that a transvaginal of cervical length less than or equal to 25 mm was 100
ultrasonographic measurement of the cervix of greater than and 54%, respectively and the specificity was 84 and 87%
35 mm at 24–26 weeks in twin pregnancies can identify respectively. The sensitivity of funneling was 86 and 54%
women who are at low risk for delivery before 34 weeks of and the specificity 78 and 82%, respectively.
Ultrasonographic cervical screening has been shown Interventions for Cervical Incompetence
to be also useful in triplet pregnancies. Ramin et al.60
performed transperineal ultrasonographic measurements
Based on Ultrasonographic Findings
of the cervix in 32 triplet pregnancies between 10 and 32 It is obvious that ultrasonographic cervical assessment is
weeks and found that a short cervix and funneling could extremely useful as a screening method for preterm delivery.
predict preterm delivery. To et al.61 measured cervical length However, the usefulness of a screening test depends on our
by transvaginal US at 23 weeks in 43 triplet pregnancies. ability to intervene, so that to change the final result. So
The rate of preterm delivery increased with decreasing far, there has not been clear evidence that any treatment
cervical length at 23 weeks from 8% at 36–48 mm to 11% is of benefit in case of a short cervix. What seems to be
at 26–35 mm, 33% at 16–25 mm and 67% at 15 mm or less. more promising is the placement of a cervical cerclage,
Guzman et al.62 evaluated 51 triplet pregnancies between which has been shown to lead to an increase in cervical
15 and 28 weeks with transvaginal cervical sonography and length. Guzman et al.67 examined 31 high-risk women with
transfundal pressure. The cervical parameters evaluated transvaginal US and transfundal pressure. In 14 cases there
were funnel width and length, cervical length, percentage was dilatation of the internal os or protruding membranes.
of funneling and CI. They concluded that cervical lengths of Thirteen of them were treated by cerclage. Of the cerclage
less than or equal to 25 mm between 15 and 24 weeks and cases, nine delivered at term, three delivered preterm and
less than or equal to 20 mm between 25 and 28 weeks were two miscarried. The patient who did not undergo cerclage
at least as good as other sonographic cervical parameters also miscarried. Heath et al.68 used transvaginal US to
for the prediction of spontaneous preterm birth. In 45 triplet measure cervical length at 23 weeks in 2,702 women with
pregnancies examined prospectively with transvaginal singleton pregnancies. In 43 cases the cervical length was
cervical assessment, Maymon et al.63 found that a cervical less than or equal to 15 mm. In 21 cases the pregnancy was
length less than or equal to 25 mm was the best predictor managed expectantly and in 22 cases a Shirodkar suture was
for delivery before 33 weeks of gestation. inserted. The two groups did not differ in ethnic or obstetric
characteristics. In the expectant management group, the
prevalence of preterm delivery before 32 weeks was 52%;
Sonography of the Cervix in Preterm
whereas in the cerclage group, it was only 5%. Berghella et
Premature Rupture of Membranes al.69 examined 168 high-risk women with TVS between 14
One of the main causes of preterm delivery is PPROM. and 24 weeks. The subgroup of women with either a cervical
Ultrasonographic cervical assessment has been used in this length of less than 25 mm or funneling of more than 25%
group of patients. Carlan et al.64 studied the use of TVS or both was offered McDonald cerclage. No difference in
in PPROM and found no relationship between a cervical the rate of preterm delivery was shown between the groups
length cutoff of 30 mm and latency period. Moreover, with or without cerclage. McDonald et al.13 followed 106
endovaginal US in these patients did not appear to increase high-risk women with serial transvaginal ultrasonographic
the incidence of maternal infection. In a similar study Rizzo measurements of the cervix. Eleven women who were
et al.65 examined the value of ultrasonographic assessment initially found to have an opening of the internal cervical
of the cervix for the prediction of the interval from os, progressed to a short cervix of less than 10 mm. Nine
admission to delivery in women with PPROM between of them had cervical cerclage. Ten out of eleven had a live
24 and 32 weeks. They found that a cervical length of less birth. Hibbard et al.70 examined 85 patients with a cervical
than 20 mm and/or funneling, or a CI of more than 0.5 were length less than or equal to 30 mm. Of these, 43 had cerclage
associated with a short-time interval from admission to and 42 had bed rest, tocolytics or no treatment. The mean
delivery. Recently, Gire et al.66 evaluated the usefulness of gestational age at delivery and birth weight were the same
transvaginal US in the determination of the risk of preterm in both groups. Hassan et al.71 in a retrospective study
delivery and chorioamnionitis in 101 singleton pregnancies looked at 70 patients with a short cervix detected by US, of
affected by PPROM. They found that a cervical length whom 25 underwent cerclage. No reduction in the rate of
of less than 20 mm at admission was associated with a spontaneous preterm delivery was observed in the cerclage
significant risk of early delivery. Moreover, no relation group. An increase in cervical length following cerclage
was found between cervical length and chorioamnionitis placement was observed by O’Connell and Lindow,72 in
or neonatal sepsis. 14 patients with a history of preterm delivery. The same
finding was also observed by Dijkstra et al.73 who looked at intensive care unit or neonatal death, was significantly
80 women with a prophylactic (n = 50), or urgent cerclage higher in the bed rest group than in the cerclage group (8
(n = 30). All had transvaginal ultrasonographic evaluation of 16 versus 1 of 19 respectively; p = 0.005).
before and after cerclage. However, this increase in cervical
length after cerclage was not predictive of term delivery. Conclusion
Novy et al.74 reported on a historical cohort of patients The use of cervical assessment with US has been well-established.
It is a widely accepted and well-standardized method which can
presenting between 18 and 27 weeks with early cervical
be easily performed in both high-risk and low-risk patients as a
changes or with cervical effacement and dilatation. Patients screening test for preterm delivery. All it requires is a well-trained
were allocated to either cerclage or bed rest, while all operator and a few minutes to spend on the evaluation of the
cervix. Although it has a high negative predictive value in a high-
received tocolytics, antibiotics and indomethacin. Cerclage risk population, it has a low sensitivity and positive predictive value
was associated with improved perinatal outcome, but in a low-risk population because of the low prevalence of preterm
this finding could be attributed to the concurrent use of delivery. Therefore, the cut-off value should be carefully selected
in order to have an acceptable sensitivity and specificity of the
antibiotics and indomethacin. A prospective cohort study test. It was shown that as the cut-off point was increased, the
of 128 twin pregnancies who underwent transvaginal sensitivity increased, but the specificity and the positive predictive
sonographic cervical length measurement, between 18 and value decreased.44 Unfortunately, there is no cervical length below
which all women deliver preterm and no cervical length above
26 weeks was performed by Newman et al.75 Cerclage was which all women deliver at term. The main issue with the cervical
offered to women with cervical lengths less than or equal screening is the type of intervention following a short cervical
to 25 mm. It was found that mid-trimester cerclage did not length measurement. Prospective randomized trials evaluating
cerclage must be performed in high-risk patients detected by
alter the risks of prematurity associated with a shortened transvaginal sonographic cervical screening, in order to confirm a
cervical length. Only two prospective randomized trials potential benefit of cerclage. Such trials should be large enough
have been published so far. In the first of that Rust et al.76,77 and apart from the cerclage efficacy they have to examine the best
surgical technique, the time of intervention, and the use of tocolytic
examined 113 patients between 16 and 24 weeks. All of agents and of antibiotic treatment following cerclage. Moreover,
them had cervical funneling more than 25% of the total the combination of cervical sonographic and biochemical or
endocrinological findings may help us to better identify candidates
cervical length, or a shortened distal cervix less than 25
for intervention.
mm and were randomly assigned to McDonald cerclage
or no cerclage. All women were treated identically before References
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15. Sherif LS, Shalan HM. Detection of pregnant women at risk membranes. Am J Obstet Gynecol. 1994;171(4):956-64.
of cervical incompetence by transvaginal sonography during 29. Timor-Tritsch IE, Boozarjomehri F, Masakowski Y, et al.
straining. J Obstet Gynaecol Res. 1997;23(4):353-7. Can a “snapshot” sagittal view of the cervix by transvaginal
16. Bega G, Lev-Toaff A, Kuhlman K, et al. Three-dimensional ultrasonography predict active preterm labor? Am J Obstet
multiplanar transvaginal ultrasound of the cervix in Gynecol. 1996;174(3):990-5.
pregnancy. Ultrasound Obstet Gynecol. 2000;16(4):351-8. 30. Iams JD. Cervical ultrasonography. Ultrasound Obstet
17. Strauss A, Heer I, Fuchshuber S, et al. Sonographic cervical Gynecol. 1997;10(3):156-60.
volumetry in higher order multiple gestation. Fetal Diagn 31. Berghella V, Kuhlman K, Weiner S, et al. Cervical funneling:
Ther. 2001;16(6):346-53. sonographic criteria predictive of preterm delivery.
18. Hoesli J, Surbek DV, Tercanli S, et al. Three-dimensional Ultrasound Obstet Gynecol. 1997;10(3):161-6.
volume measurement of the cervix during pregnancy 32. Berghella V, Tolosa JE, Kuhlman K, et al. Cervical
compared to conventional 2D-sonography. Int J Gynaecol ultrasonography compared with manual examination as
Obstet. 1999;64(2):115-9. a predictor of preterm delivery. Am J Obstet Gynecol.
1997;177(4):723-30.
19. Eganhouse DJ. A comparative study of variables differentiating
33. Guzman ER, Pisatowski DM, Vintzileos AM, et al. A
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comparison of ultrasonographically detected cervical
20. Iams JD, Casal D, McGregor JA, et al. Fetal fibronectin
changes in response to transfundal pressure, coughing, and
improves the accuracy of diagnosis of preterm labor. Am J
standing in predicting cervical incompetence. Am J Obstet
Obstet Gynecol. 1995;173(1):141-5.
Gynecol. 1997;177(3):660-5.
21. Murakawa H, Utumi T, Hasegawa I, et al. Evaluation of 34. Andrews WW, Copper R, Hauth JC, et al. Second-trimester
threatened preterm delivery by transvaginal ultrasonographic cervical ultrasound: association with increased risk for
measurement of cervical length. Obstet Gynecol. 1993; recurrent early spontaneous delivery. Obstet Gynecol.
82(5):829-32. 2000;95(2):222-6.
22. Rizzo G, Capponi A, Arduini D, et al. The value of fetal 35. Cook CM, Ellwood DA. The cervix as a predictor of preterm
fibronectin in cervical and vaginal secretions and of delivery in “at-risk” women. Ultrasound Obstet Gynecol.
ultrasonographic examination of the uterine cervix in predicting 2000;15(2):109-13.
premature delivery for patients with preterm labor and intact 36. Vendittelli F, Mamelle N, Munoz F, et al. Transvaginal
membranes. Am J Obstet Gynecol. 1996;175(5):1146-51. ultrasonography of the uterine cervix in hospitalized women
23. Hincz P, Wilczynski J, Kozarzewski M, et al. Two-step with preterm labor. Int J Gynaecol Obstet. 2001;72(2):117-
test: the combined use of fetal fibronectin and sonographic 25.
37. Obido AO, Berghella V, Reddy U, et al. Does transvaginal Maternal-Fetal Medicine Units Network. Am J Obstet
ultrasound of the cervix predict preterm premature rupture Gynecol. 1996;175(4 Pt 1):1047-53.
of membranes in a high-risk population? Ultrasound Obstet 51. Imseis HM, Albert TA, Iams JD. Identifying twin
Gynecol. 2001;18(3):223-7. gestations at low risk for preterm birth with a transvaginal
38. Guzman ER, Mellon C, Vintzileos AM, et al. Longitudinal ultrasonographic cervical measurement at 24 to 26 weeks’
assessment of endocervical canal length between 15 and gestation. Am J Obstet Gynecol. 1997;177(5):1149-55.
24 weeks’ gestation in women at risk for pregnancy loss or 52. Guzman ER, Walters C, O’reilly-Green C, et al. Use of
preterm birth. Obstet Gynecol. 1998;92(1):31-7. cervical ultrasonography in prediction of spontaneous
39. Berghella V, Talucci M, Desai A. Does transvaginal preterm birth in twin gestations. Am J Obstet Gynecol.
sonographic measurement of cervical length before 14 2000;183(5):1103-7.
weeks predict preterm delivery in high-risk pregnancies? 53. Yang JH, Kuhlman K, Daly S, et al. Prediction of preterm birth
Ultrasound Obstet Gynecol. 2003;21(2):140-4. by second trimester cervical sonography in twin pregnancies.
40. Andersen HF, Nugent CE, Wanty SD, et al. Prediction of risk Ultrasound Obstet Gynecol. 2000;15(4):288-91.
for preterm delivery by ultrasonographic measurement of 54. Skentou C, Souka AP, To MS, et al. Prediction of preterm
cervical length. Am J Obstet Gynecol. 1990;163(3):859-67. delivery in twins by cervical assessment at 23 weeks.
41. Tongsong T, Kamprapanth P, Srisomboon J, et al. Single Ultrasound Obstet Gynecol. 2001;17(1):7-10.
transvaginal sonographic measurement of cervical length 55. Shapiro JL, Kung R, Barrett JF. Cervical length as a
early in the third trimester as a predictor of preterm delivery. predictor of preterm birth in twin gestations. Twin Res.
Obstet Gynecol. 1995;86(2):184-7. 2000;3(4):213-6.
42. Iams JD, Goldenberg RL, Meis PJ, et al. The length of
56. Iams JD, Goldsmith LT, Weiss G. The preterm prediction
the cervix and the risk of spontaneous premature delivery.
study: maternal serum relaxin, sonographic cervical length,
National Institute of Child Health and Human Development
and spontaneous preterm birth in twins. J Soc Gynecol
Maternal Fetal Medicine Unit Network. N Engl J Med.
Investig. 2001;8(1):39-42.
1996;334(9):567-72.
57. Ong S, Smith A, Smith N, et al. Cervical length assessment
43. Heath VC, Southall TR, Souka AP, et al. Cervical length at
in twin pregnancies using transvaginal ultrasound. Acta
23 weeks of gestation: prediction of spontaneous preterm
Obstet Gynecol Scand. 2000;79(10):851-3.
delivery. Ultrasound Obstet Gynecol. 1998;12(5):312-7.
58. Soriano D, Weisz B, Seidman DS, et al. The role of
44. Taipale P, Hiilesmaa V. Sonographic measurement of uterine
sonographic assessment of cervical length in the prediction
cervix at 18-22 weeks’ gestation and the risk of preterm
of preterm birth in primigravidae with twin gestation
delivery. Obstet Gynecol. 1998;92(6):902-7.
conceived after infertility treatment. Acta Obstet Gynecol
45. Hassan SS, Romero R, Berry SM, et al. Patients with an
Scand. 2002;81(1):39-43.
ultrasonographic cervical length ≤15 mm have nearly a
50% risk of early spontaneous preterm delivery. Am J Obstet 59. Vayssiere C, Favre R, Audibert F, et al. Cervical length and
Gynecol. 2000;182(6):1458-67. funneling at 22 and 27 weeks to predict spontaneous birth before
46. To MS, Skentou C, Liao AW, et al. Cervical length and 32 weeks in twin pregnancies: a French prospective multicenter
funneling at 23 weeks of gestation in the prediction of study. Am J Obstet Gynecol. 2002;187(6):1596-604.
spontaneous early preterm delivery. Ultrasound Obstet 60. Ramin KD, Ogburn PL, Mulholland TA, et al.
Gynecol. 2001;18(3):200-3. Ultrasonographic assessment of cervical length in triplet
47. Hibbard JU, Tart M, Moawad AH. Cervical length at 16- pregnancies. Am J Obstet Gynecol. 1999;180(6 Pt 1):1442-5.
22 weeks’ gestation and risk for preterm delivery. Obstet 61. To MS, Skentou C, Cicero S, et al. Cervical length at
Gynecol. 2000;96(6):972-8. 23 weeks in triplets: prediction of spontaneous preterm
48. Conoscenti G, Meir YJ, D’Ottavio G, et al. Does cervical delivery. Ultrasound Obstet Gynecol. 2000;16(6):515-8.
length at 13-15 weeks’ gestation predict preterm delivery 62. Guzman ER, Walters C, O’reilly-Green C, et al. Use of
in an unselected population? Ultrasound Obstet Gynecol. cervical ultrasonography in prediction of spontaneous
2003;21(2):128-34. preterm birth in triplet gestations. Am J Obstet Gynecol.
49. Carvalho MH, Bittar RE, Brizot ML, et al. Cervical length 2000;183(5):1108-13.
at 11-14 weeks’ and 22-24 weeks’ gestation evaluated by 63. Maymon R, Herman A, Jauniaux E, et al. Transvaginal
transvaginal sonography, and gestational age at delivery. sonographic assessment of cervical length changes during
Ultrasound Obstet Gynecol. 2003;21(2):135-9. triplet gestation. Hum Reprod. 2001;16(5):956-60.
50. Goldenberg RL, Iams JD, Miodovnik M, et al. The preterm 64. Carlan SJ, Richmond LB, O’Brien WF. Randomized trial
prediction study: risk factors in twin gestations. National of endovaginal ultrasound in preterm premature rupture of
Institute of Child Health and Human Development membranes. Obstet Gynecol. 1997;89(3):458-61.
65. Rizzo G, Capponi E, Angelini A, et al. The value of 72. O’ Connell MP, Lindow SW. Reversal of asymptomatic
transvaginal ultrasonographic examination of the uterine cervical length shortening with cervical cerclage: a
cervix in predicting preterm delivery in patients with preliminary study. Hum Reprod. 2001;16(1):172-3.
preterm premature rupture of membranes. Ultrasound Obstet 73. Dijkstra K, Funai EF, O’Neil L, et al. Change in cervical
Gynecol. 1998;11(1):23-9. length after cerclage as a predictor of preterm delivery.
66. Gire C, Faggianelli P, Nicaise C, et al. Ultrasonographic Obstet Gynecol. 2000;96(3):346-50.
evaluation of cervical length in pregnancies complicated 74. Novy MJ, Gupta A, Wothe DD, et al. Cervical cerclage in
by preterm premature rupture of membranes. Ultrasound the second trimester of pregnancy: a historical cohort study.
Obstet Gynecol. 2002;19(6):565-9. Am J Obstet Gynecol. 2001;184(7):1447-54.
67. Guzman ER, Rosenberg JC, Houlihan C, et al. A new 75. Newman RB, Krombach RS, Myers MC, et al. Effect
method using vaginal ultrasound and transfundal pressure of cerclage on obstetrical outcome in twin gestations
to evaluate the asymptomatic incompetent cervix. Obstet with a shortened cervical length. Am J Obstet Gynecol.
Gynecol. 1994;83(2):248-52. 2002;186(4):634-40.
76. Rust OA, Atlas RO, Jones KJ, et al. A randomized trial
68. Heath VC, Souka AP, Erasmus I, et al. Cervical length at
of cerclage versus no cerclage among patients with
23 weeks of gestation: the value of Shirodkar suture for the
ultrasonographically detected second-trimester preterm
short cervix. Ultrasound Obstet Gynecol. 1998;12(5):318-
dilatation of the internal os. Am J Obstet Gynecol.
22.
2000;183(4):830-5.
69. Berghella V, Daly SF, Tolosa JE, et al. Prediction of preterm 77. Rust OA, Atlas RO, Reed J, et al. Revisiting the short cervix
delivery with transvaginal ultrasonography of the cervix in detected by transvaginal ultrasound in the second trimester:
patients with high-risk pregnancies: does cerclage prevent why cerclage therapy may not help? Am J Obstet Gynecol.
prematurity? Am J Obstet Gynecol. 1999;181(4):809-15. 2001;185(5):1098-105.
70. Hibbard JU, Snow J, Moawad AH. Short cervical length by 78. Althuisius SM, Dekker GA, Hummel P, et al. Final results
ultrasound and cerclage. J Perinatol. 2000;20(3):161-5. of the Cervical Incompetence Prevention Randomized
71. Hasssan SS, Romero R, Maymon E, et al. Does cervical Cerclage Trial (CIPRACT): therapeutic cerclage with
cerclage prevent preterm delivery in patient with a short bed rest versus bed rest alone. Am J Obstet Gynecol.
cervix? Am J Obstet Gynecol. 2001;184(7):1325-9. 2001;185(5):1106-12.
CHAPTER
16 Transvaginal
Assessment of the Cervix
Cihat Sen, Yesin Bulbul Baytur
Introduction the transvaginal technique, the cervical distortion is avoided

because the transvaginal probe is in close proximity to the
Transvaginal ultrasonography has recently been shown as cervix and the fetal presenting part does not interfere with
an objective and reliable method to evaluate the cervix. cervical measurements.12 At the beginning, it was thought
Assessment of the cervix is mainly used for predicting that transvaginal ultrasound might create a discomfort for the
preterm deliveries in high- and low-risk populations, women and an extra-cost for the hospitals and practitioner.
deciding therapeutic cerclage, observation of the patients However, today transvaginal approach is widely used in
after placing cerclage, differentiating true and false labor obstetric and gynecologic practice and these concerns are not
and predicting successful labor induction. Cervical length the case anymore. Although it was also suggested that repeated
measured by transvaginal ultrasound to predict preterm transvaginal scans might cause infections, it was shown that
birth was first published by Andersen et al.1 who found that there is no association between the risk of infection and the
a cervix of less than 39 mm before 30 weeks of gestation measurement of the cervix by transvaginal sonography.
was a significant risk factor for early delivery, related to
This chapter focuses on the appropriate measurement
cervical length. Since this time, this observation was studied
technique of the cervix and the pitfalls of the measurement,
by many other investigators for the risk of preterm labor
the place of the cervical assessment in the prediction of
in high-risk population.2-6 Until today, several studies have
preterm delivery and therapeutic cerclage, progesterone
attempted to predict the onset of preterm labor using risk-
treatment for prevention of preterm delivery, and finally,
scoring systems based on epidemiological data or digital
the place of the cervical measurement in the prediction of
examination of the cervix.7,8 However, digital examination
the successful labor induction.
of the cervix during pregnancy is not objective and has
limitations.9 Ultrasonographic examination of the cervix
provides an objective and noninvasive method (despite Measurement, Assessment,
uncomfortable for the patient) for the assessment of the
and the Pitfalls
cervix. It gives valuable information about cervical length
and also dynamic changes like endocervical dilatation, The appropriate measurement of the cervix is the first and
bulging of the membranes. the most important step for establishing a correct diagnosis
Transabdominal, transperineal, translabial or transvaginal and avoiding unnecessary interventions. The patient is
techniques have been used for evaluation of the cervix examined in the supine position on an examination bed with
in different studies.10-12 The transvaginal approach offers the hips and the knees flexed and empty bladder. Firstly,
significant advantages over the other techniques. Translabial the transvaginal probe is placed in the anterior fornix of
or transperineal imaging is not always able to provide adequate the vagina. Sagittal view of the cervix with the echogenic
visualization of the cervix because of maternal obesity or endocervical mucosa along the length of the canal is obtained
acoustic shadowing from rectal gas or the symphysis pubis. (Fig. 16.1). Special care must be taken to avoid exerting
Acoustic shadowing from the rectum or the symphysis undue pressure on the cervix. For the correct evaluation
pubis during examination may also limit the accuracy of the and measurement of the cervix, hallmarks for the external
measurement by falsely shortening the cervical length.13 The and internal os are more important. Therefore, callipers
cervix can be visualized by transabdominal sonography in only are used to measure the distance between the triangular
42% of women, unless the urinary bladder is full. However, area of echodensity at the external os and the V-shaped
bladder filling causes apparent lengthening of the cervix.14 In notch at the internal os (Fig. 16.2).15 Each examination is
Chapter 16  Transvaginal Assessment of the Cervix 145
Figure 16.1 Sagittal view of the cervix with the echogenic endocervical Figure 16.3 In case of curved cervix, dividing the cervix into two
mucosa different parts, and to measure these parts separately
presence of funneling, V-shape and U-shape appearance

of the cervix, funnel length, funnel width, percentage of
funneling [considered to be funnel length/(funnel length +
cervical length) × 100%] and cervical index [considered
to be (1 + funnel length)/cervical length] may be assessed
(Figs 16.4A and B).21 However, the phenomenon called
funneling and is difficult to quantify, not consistent and it
might change within hours, sometimes minutes.22 It is more
accurate to concentrate on measurement of the cervical
length only.
For the assessment of the cervical length, the following
criteria are mandatory:
Figure 16.2 Measurement of cervical length between the triangular
ÀÀ The internal os should be clearly visible as a flat dimple
area of echodensity at the external os and the V-shaped notch at the
internal os or an isosceles triangle
ÀÀ The whole length of the cervical canal should be clearly
performed for 3–5 minutes to observe whether any dynamic visible
cervical changes that may occur. The cervix is measured ÀÀ The external os appears symmetrical
three times and the shortest measurement is used.16 Some ÀÀ The external surface of the cervix on the screen should
sonographers measured cervix dividing two different parts be clearly identified.
and used the sum of two measurements, if the cervix is too The distance from the surface of the posterior lip to the
curved (Fig. 16.3).17 But it does not matter because what we cervical canal should be identical to the distance from the
are looking for is the shortening of the cervix. In shortened anterior lip. Before introducing the standards mentioned
cervix, the cervix would not be curved. Therefore, the only above, the mean cervical length has been found as 33.7 mm
important point is to take a measurement between external with an interobserver average discrepancy of 3.04 mm
and internal os correctly. (range 0–6 mm). After the implementation of these quality
If the uterus is in extremely flexed anteverted position control standards, the mean cervical length has been found
and it is not possible to depress the handle of the probe as 35.3 mm and the average interobserver discrepancy
any further toward the bed, the patient is asked to place improved and has been found as 1.24 mm (range 0–4 mm).18
her clenched fists under her buttocks.18 Transfundal or Transvaginal measurement of the cervix is a method
suprapubic pressure may further increase the positive that can be learnt easily. In a study, the learning curve and
predictive value (PPV) of transvaginal sonography and the principal learning steps of the cervical measurement
some authors use it, (10, 19’da 114), but many authors do were investigated and found that 23 supervised ultrasound
not always use it.15,19,20 Besides the cervical measurement, scans are necessary for an operator with no experience in
Figures 16.4A and B Presence of the funnel, the V-shape appearance of the cervix, measurement of the cervical length, the funnel length,
and the funnel width; (B) Presence of the funnel, the Y-shape appearance of the cervix, measurement of the cervical length, the funnel
length and the funnel width
transvaginal ultrasound, substantially fewer are required for cervical volume calculation does not seem to be justified
an operator already familiar with this approach for other for this purpose because of difficulty in volume acquisition.
indications.23 However, some anatomical and technical
pitfalls may hamper the correct measurement and the Prediction of the Preterm Delivery
sonographer should take into consideration these problems
during the examination. The anatomical difficulties include
by Transvaginal Measurement of the
difficult identification of the internal os due to undeveloped Cervix
lower uterine segment, focal myometrial contraction, rapid Preterm birth is the most important cause of infant morbidity
and spontaneous cervical change and endocervical polyps. and mortality in developed countries, and complicates
The technical problems are incorrect interpretation for 6–8% of all pregnancies in Europe.27 Several studies
dilatation of internal os because of vaginal probe orientation have attempted to predict preterm deliveries, including
and the artificial lengthening of the endocervical canal risk-scoring systems based on epidemiologic data, digital
because of distortion of the cervix by the transducer.24 examination of the cervix, biochemical markers like fetal
The three-dimensional (3D) multiplanar volume fibronectin and IL-6 in the cervicovaginal secretions and
assessment of the cervix, probably, increases the PPV of home uterine activity monitoring other than measurement
cervical ultrasonography in predicting preterm delivery.25 of the cervix.28-30 There is evidence that short cervical length
Screening high-risk women could be achieved by conventional in the midtrimester is associated with increased risk of
two-dimensional transvaginal ultrasound and the diagnosis preterm delivery.2,15,31 Serial measurements may improve the
of true preterm labor may be improved by 3D multiplanar prediction of preterm birth compared with a single cervical
transvaginal ultrasound assessment of the cervix. However, measurement.2 It may be appropriate to define a nomogram
in the low-risk population, cervical length measurement was of mean cervical lengths and their standard deviations for
found superior to cervical volume measurement assessed by every week of gestation in order to detect deviations from
3D ultrasound for identifying women with increased risk of the normal range clinically as early as possible.
spontaneous preterm delivery.26 Cervical ultrasonography appears to be more efficient
Recently, Barber et al. conducted a prospective as a short-term than as a long-term predictor, so serial
observational study to compare standard transvaginal examinations in a time interval of 10–14 days for women
ultrasound measurement of cervical length and VOCAL with short cervical length should be recommended.32 The
cervical volume in 306 asymptomatic women at 20–22 normal ranges according to gestational weeks have been
weeks of pregnancy.27 They concluded that cervical volume defined in singleton (Table 16.1) and twin pregnancies (Table
as measured by VOCAL technique was useful but not 16.2).32-34 Furthermore, no differences were found between
superior to 2D transvaginal cervical measurement and the multiparas and the nulliparas in terms of cervical length.33
Table 16.1 Normal ranges and standard deviations according to The limitations of the studies for assessing cervical
gestational weeks in singleton pregnancies32 length measurement include the absence of standardization
Weeks of N Mean cervical Standard of gestational age at the time of evaluation, different cut-off
gestation length (mm) deviation levels and different definitions of preterm birth (<32, <35,
20 29 40.3 5.7 <37 weeks). The characterization and the results of these
21 25 38.7 5.6 studies are summarized in Table 16.3. The sensitivities of
22 23 39.6 5.3 cervical length for detecting preterm delivery are higher in
23 22 41.4 6.0 at-risk patients, especially with a history of midtrimester
24 27 39.1 5.6 pregnancy loss than in general populations.30 A review of
25 36 38.3 4.8 35 studies using cervical length to predict preterm delivery
26 36 36.0 4.8
found sensitivities from 68 to 100% and specificities from
27 31 36.2 6.4
44 to 79%.30 In a prospective observational study of 760
women between 16 and 22 weeks of gestation, the mean
28 41 37.7 4.9
cervical length was found 38.5 ± 8 mm at 19.9 ± 1.5 weeks
29 71 37.4 4.7
with the tenth, fifth, two and a half percentiles were 30, 27
30 88 38.3 5.1
and 22 mm respectively. Relative risk (RR) for spontaneous
31 86 36.9 5.4
preterm delivery before 37 weeks were 3.8, 5.4 and
32 68 33.7 6.5 6.3 for the tenth, fifth, two and a half percentiles
33 57 34.5 7.7 respectively. Relative risk before 35 weeks were 4.5,
34 29 34.5 7.3 7.5 and 7.8; and before 32 weeks were 5.2, 9.7 and 8.4
for tenth, fifth, two and a half percentiles respectively.
Multiple logistic regression analysis confirmed that cervical
Table 16.2 Normal ranges and standard deviations according to
gestational age in twin pregnancies34
length was a significant predictor of preterm birth before 35
weeks, and that multiparas had a 43% greater risk compared
Gestational age Mean cervical 95% confidence
with nulliparas.35 In this study, it was shown that for each
(weeks) length (mm) (95% interval (mm)
prediction interval) 1 mm decrease in cervical length below the mean, the risk
13 47 (44–50) 29–65 of preterm delivery increased by 10.3%.
14 46 (43–49) 28–64 In another study comparing home monitoring of uterine
15 45 (43–48) 28–63
activity, fetal fibronectin in cervicovaginal secretion,
Bishop score and transvaginal measurement of the cervical
16 45 (42–47) 27–62
length at 22–24 weeks, cervical length was a significantly
17 44 (42–46) 26–61
better predictor than the others. At 27–28 weeks, no test
18 43 (41–45) 25–61
was superior to any other. At 31–32 weeks, cervical length
19 42 (41–44) 25–60
and Bishop score were both significantly better than the
20 42 (40–43) 24–59
frequency of contractions in predicting preterm delivery.28
21 41 (39–42) 23–58 On the other hand, in a recent review, it was stated that
22 40 (39–41) 22–58 transvaginal ultrasound measurement is a complementary
23 39 (38–41) 22–57 method to digital examination and the evidence that
24 39 (37–40) 21–56 transvaginal scanning of the cervix improves outcome in
25 38 (36–39) 20–55 symptomatic women is insufficent.37 Owen et al.2 have
26 37 (35–39) 19–55 compared the efficacy of sonographic cervical findings in
27 36 (34–38) 19–54 high-risk women between single measurement at 16–19
28 35 (33–37) 18–53 weeks of gestation and serial measurements up to 24 weeks
29 35 (33–37) 17–52 of gestation with 2 weeks interval for predicting preterm
30 34 (32–36) 16–52 delivery before 35 weeks of gestation. A cervical length
31 33 (31–36) 15–51
of less than 25 mm at the initial sonographic examination
was associated with the RR for spontaneous preterm birth
32 32 (30–35) 15–50
of 3.3 [95% confidence interval (CI), 2.1–5.0; sensitivity
19%; specificity 98%; PPV 75%). Neither funneling cervical lengths of 25 mm or less (12.9% in twins compared
nor dynamic shortening were significant independent with 8.4% in singletons).38 This is not surprising because
predictors of spontaneous preterm birth. Compared with a the rate of early preterm delivery in twins is much higher
single cervical measurement at 16–19 weeks of gestation, than in singletons. In singleton pregnancies the exponential
serial measurements at up to 24 weeks significantly increase in risk for early preterm delivery is observed in
improved the prediction of spontaneous preterm birth (RR patients with cervical length below 15 mm, whereas in
increased to 4.5 with 95% CI, 2.7–7.6; sensitivity 69%; twins and in triplets this threshold is 25 mm.38,39 Imseis
specificity 80%; PPV 55%).2 Heath et al.31 have measured et al.6 measured cervical length at 24–26 weeks of gestation
the cervix in 2,567 low-risk patients at 23 weeks. They in women with twin gestations for assessing the ability of
found cervical length less than or equal to 15 mm was in transvaginal cervical length to predict women who would
1.7% of the cases and this group contained 86%, 58% and deliver after 34 weeks without intervention. They found the
20% of pregnancies that delivered spontaneously at less best cut-off value as 35 mm to identify the patients who are
than or equal to 28, 32 and 36 weeks, respectively. The at low risk for delivery before 34 weeks of gestation.
risk for delivery at less than or equal to 32 weeks decreased Transvaginal measurement of the cervical length in
from 78% at a cervical length of 5 mm to 4% at 15 mm women presenting with threatened preterm labor helps to
and 0.5% at 50 mm. distinguish between true and false labor in singleton and
Measurement of the cervix before 16 weeks of gestation twin pregnancies.19,22,40 Rageth et al.22 in a retrospective
for predicting subsequent preterm delivery or cervical study reported that the hospitalization rate and use
incompetence is not a reliable screening procedure. Before of unnecessary tocolytics decrease significantly after
16 weeks of gestation, identification of the internal os is introducing the cervical length measurement in patients
difficult due to undeveloped lower uterine segment. The admitted with preterm labor. At the same time, this approach
studies in low-risk women showed that a shortened cervix in may offer cost savings compared with treatment of all
early gestation was a weaker predictor of preterm delivery women with threatened preterm labor and may indicate
than if seen later in the midtrimester.17,36 But in high-risk lung maturation treatment more precisely.41
women, the early detection of a short cervix is strongly Transvaginal cervical measurement is also used in
associated with subsequent preterm birth.37 In a recent pregnancies complicated by preterm premature rupture
trial, it was found that, transvaginal cervical measurement of membranes (PPROM). In the absence of clinical or
between 11–13 weeks of gestation for prediction of preterm biological signs of chorioamnionitis, management of
delivery is a useful screening test when combined with affected pregnancies is usually expectant in PPROM
maternal characteristics such as maternal height, age, racial cases. Predicting the interval between membrane rupture
origin and parity.40 and birth may be useful. Digital examination appears to
In multiple pregnancies, the measurement of the cervix be ineffective and even harmful because of the risk of
is more important than singleton pregnancies. Multiple infection. Ultrasonographic cervical length measurements
pregnancies are differed from the singleton pregnancies may predict the latency period between admission and
in terms of the rate of early preterm delivery. In singleton delivery without increasing the risk of infection like
pregnancies, the rate of spontaneous delivery at or before 32 neonatal sepsis and chorioamnionitis.42,43
weeks is 1–2%, whereas in twin pregnancies it is reported There is an association between cervical length and
as 5–10%.15 Furthermore, it has been reported that prelabor demographic characteristics and previous obstetric history.
uterine activity in multiple pregnancies, starting from as Cervical length was significantly shorter in women of Afro-
early as 20 weeks of gestation, is significantly greater than Caribbean origin compared to Caucasians, those aged less
that in singleton pregnancies.4 Thus, the onset of labor any than 20 years, those with a low ponderal index, those with
time during pregnancy may not necessarily be a sudden a history of previous miscarriage or preterm delivery and
event, but rather a culmination of many silent uterine in drug abusers.44,45 In a large multicentric observational
and cervical changes. There are different results in the study, transvaginal measurement of cervix at midgestation
literature with regard to measurement time, cut-off levels was carried out in 58807 singleton pregnancies.49 They
and the definition of preterm birth4,14,15,38,39 (Table 16.3). conducted a logistic regression model for the prediction
The median cervical length in twins is similar to that in of preterm birth with maternal characteristic, obstetric
singleton pregnancies, but a higher proportion of twins have history and midtrimester cervical length. For a 10% screen
Table 16.3 Studies for prediction of preterm delivery by ultrasonographic measurement of the cervical length
Study Population Time of the Cutoff Delivery time Results
measurement (weeks)
Tongsong et al. Singletons 28–30 weeks < 35 mm <37 Sensi 65%, Speci
20
62%, 1995 Low-risk PPV 37%
Rozenberg et al. Singletons 24–34 weeks 26 mm <37 PPV 50%,
5
1997 with signs of NPV 89%
premature labor
Imseis et al. Twins 24–26 weeks < 35 mm <34 Sensi 49%, Speci 94%,
6
1997 NPV 31%
PPV 97%,
Souka et al. Twins 22–24 weeks < 25 mm <28 Sensi 100%
15
1999 <30 80%
<32 47%
<34 35%
Hibbard et al. Singletons 16–22 weeks 10, 5 and 2.5 <37 Sensi 13–44%
35
2000 unselected percentiles <35 Speci 90–99%
<32 PPV 15–47%
NPV 80–98%
Guzman et al. Twins 15–20 weeks 20 mm <28 Speci 97%, NPV 99%
21
2000 <30 Speci 98%, NPV 98%
<32 Speci 99%, NPV 95%
<34 Speci 100%, NPV 89%
PPV 80–100%
39
To et al. 2000 Triplets 22–24 weeks 30 mm <33 Sensi 67%
25 mm Sensi 50%
15 mm Sensi 33%
Skentou et al. Twins 22–24 weeks 20 mm <33 The ratio of preterm
38
2001 delivery is 17%
Maymon et al. Triplets From 26 weeks < 25 mm 33 Sensi 94%
4
2001 up to delivery Speci 45%
Owen et al. Singletons 16–19 weeks, < 25 mm <35 Sensi 19%, Speci 98%,
2
2001 High risk Single from 16 PPV 75%
up to 23 weeks PPV 55%
serially
(Abbreviations: Sensi, sensitivity; Speci, specificity; PPV, positive predictive value; NPV, negative predictive value)
positive rate, models using cervical length and obstetric Cervical length measurement for prediction of preterm
history had a sensitivity of 80.6%, 58.5%, 53% and 28.6% birth was also assessed in women underwent large loop
for extreme, early, moderate and mild spontaneous preterm excision of transformation zone for cervical lesions.51
birth, respectively. The authors found that the rate of spontaneous preterm
Transvaginal cervical length measurement was assessed birth before 34 weeks of gestation was higher in women
in women with uterine anomalies such as bicornuate or with loop excision when compared to women not have
didelphus for prediction of preterm birth.50 It was found this intervention (3.4 vs 1.3%, p = 0,0002). They also
a positive predictive value 37.5% and negative predictive have shorter cervix (32 mm vs 34 mm, p<0,0001). The
value 100% for prediction of preterm birth before 35 weeks transvaginal cervical length measurement successfully
of gestation using cut-off value of 30 mm cervical length predicted spontaneous preterm birth with a 52.6% detection
in these group of women. rate at a 10% false-positive rate in these women.
Therapeutic Cervical Cerclage for cervical length was significantly associated with a shorter
length of gestation, lower birth weight and delivery before
Prevention of Preterm Delivery 34 weeks of gestation. None of these outcomes was altered
Cervical insufficiency is a rare cause of preterm delivery. by cerclage placement.16
The diagnosis is usually made after exclusion of other It was suggested that the absence of benefit might
potential causes of recurrent pregnancy loss. A transvaginal have been a result of inconsistent cerclage placement in
cervical cerclage may be inserted prophylactically before proximity to the internal os. Rust et al.51 have investigated
pregnancy or during the first trimester or it may be placed whether cerclage location closer to the internal os is related
therapeutically during later pregnancy after detection to perinatal outcome. They found that the length of the
of cervical changes. The Oxford trial concluded that 25 cervix below the level of cerclage is not related to duration
prophylactic cerclage should be performed to prevent only of pregnancy in women treated with cerclage.51 Rozenberg
one cervical insufficiency.46 The results of randomized et al.52 have compared the effects of cerclage performed
trials have not generally supported the use of prophylactic with a modified Shirodkar procedure or with McDonald’s
cerclage, probably due to patient selection, which was technique using transvaginal ultrasound measurement of the
essentially based on obstetric history. In a systematic distance between the external os and the suture. They found
review, it was shown that elective cerclage has a significant that the anterior colpotomy of the Shirodkar procedure
effect in preventing spontaneous preterm birth before 34 increased the distance between the external os and the
weeks of gestation.47 However, the authors stated that the cerclage by a mean of 2.7 mm, but there were no significant
clinical decision on whether a woman at risk should have differences between the Shirodkar and the McDonald group
cerclage would depend not only on the effectiveness of the with regard to the functional cervical length before and
intervention but also on the adverse effects and costs of the after procedure or the number of deliveries before 32 and
procedure. A more effective approach for identifying the 34 weeks. Alfirevic et al.59 reviewed literature to assess
high-risk group for preterm delivery may be transvaginal whether the use of cervical cerclage in singleton pregnancy
sonographic measurement of cervical length. In CIPRACT at high-risk of pregnancy loss based on a woman’s history
study, it was found that transvaginal ultrasonographic and/or ultrasound finding of short cervix and/or physical
follow-up examination of the cervix could save the majority examination improves subsequent obstetric care and fetal
of women from unnecessary intervention. Placement of a outcome. They included 12 trials ( involving 3328 women).
therapeutic cerclage before 27 weeks of gestation in women They found that cerclage was not effective in term of
that have a cervix shorter than 25 mm may reduce the perinatal deaths and neonatal morbidity, despite significant
incidence of preterm delivery before 34 weeks of gestation reduction in preterm births (average RR 0.80; 95%0.69
among high-risk patients.48 In a report of a nonrandomized to 0.95). Cervical cerclage was associated with higher
trial, cerclage was performed in 24 women having a short rate of maternal side effects including vaginal discharge,
cervix (15 mm) at 23 weeks of gestation.49 Placement of a bleeding and fever (average RR 2.25; 95% CI 0.89 to 5.69).
Shirodkar suture in women with a very short cervix may There was not any difference between history- indicated
be associated with a tenfold reduction in risk for preterm and ultrasound-indicated subgroups. There were more
delivery. It has been suggested that there is a benefit in cesarean section in the cerclage group. Cerclage, vaginal
performing cerclage rather than continuing expectant progesterone treatment and cervical pessary compared
management in cases with sonographic appearance of for prevention of preterm birth and it was not found any
cervical incompetence. 30 However, in a recent large statiscally significant difference between these three
randomized controlled trial, it was shown that the insertion strategy regarding perinatal losses, neonatal morbidity and
of a Shirodkar suture in women with a short cervix (15 mm) preterm births, apart from a higher incidence of preterm
at 22–24 weeks of gestation does not substantially reduce births before 34 weeks of gestation with progesterone group
the risk of preterm delivery before 33 weeks of gestation.50 versus cervical pessary (32% vs 12%; relative risk 2.70,95%
These data have also been confirmed in twin gestations. CI 1.10 to 6.67).60
In a prospective cohort study of 147 consecutive twin In the last decade, a series of randomized trials performed
pregnancies, cervical length was measured between 18 and using progesterone in women with short cervix.61,62 Although
26 weeks of gestation and a McDonald suture was placed in these trials now have demonstrated that using progesterone
women with cervical length shorter than 25 mm. Decreasing either vaginally or intramuscular injection was beneficial
reducing preterm births in about half of the patients, there is 2. Owen J, Yost N, Berghella V, et al. Mid-trimester endovaginal
a continuing debate about beneficial effect in the subgroups sonography in women at high risk for spontaneous preterm
such as multiple pregnancies, more useful administration birth. JAMA. 2001;286(11):1340-8.
route and formula. The beneficial effect of progesterone in 3. Soriano D, Weisz B, Seidman DS, et al. The role of
singleton pregnancies was not demonstrated in multiples. sonographic assessment of cervical length in the prediction
of preterm birth in primigravidae with twin gestation
conceived after infertility treatment. Acta Obstet Gynecol
Transvaginal Cervical Length Scand. 2002;81(1):39-43.
Measurement in Predicting 4. Maymon R, Herman A, Jauniaux E, et al. Transvaginal
sonographic assessment of cervical length changes during
Successful Labor Induction triplet gestation. Hum Reprod. 2001;16(5):956-60.
Preinduction cervical assessment has traditionally been 5. Rozenberg P, Goffinet F, Malagrida L, et al. Evaluating the
accomplished through the Bishop score. Recently, risk of preterm delivery: a comparison of fetal fibronectin
transvaginal ultrasonographic measurement of cervical and transvaginal ultrasonographic measurement of cervical
length has been introduced for this purpose.53-56 The digital length. Am J Obstet Gynecol. 1997;176(1 Pt 1):196-9.
6. Imseis HM, Albert TA, Iams JD. Identifying twin
examination of the cervix is a subjective method and it is
gestations at low risk for preterm birth with a transvaginal
not possible to have information for the length of the cervix
ultrasonographic cervical measurement at 24 to 26 weeks’
in case with the dilatation more than finger. gestation. Am J Obstet Gynecol. 1997;177(5):1149-55.
Induction of labor is carried about 20% of pregnancies. 7. Creasy RK, Gummer BA, Liggins GC. System for predicting
However, approximately 20% or more of women having spontaneous preterm birth. Obstet Gynecol. 1980;55(6):692-5.
induction of labor end up having a cesarean delivery. Some 8. Bouyer J, Papiernik E, Dreyfus J, et al. Maturation signs of
recent studies have reported that transvaginal sonographic the cervix and prediction of preterm birth. Obstet Gynecol.
assessment of the cervix may provide a more sensitive 1986;68(2):209-14.
prediction of successful induction, compared to the Bishop 9. Romero R, Gomez R, Sepulveda W. The uterine cervix,
score.53,54 Rane et al. suggested that preinduction cervical ultrasound and prematurity. Ultrasound Obstet Gynecol.
length provides useful information of the likelihood of 1992;2(6):385-8.
vaginal delivery within 24 hours of induction and of the 10. Jackson GM, Ludmir J, Bader TJ. The accuracy of digital
induction-to-delivery interval. Nulliparous women with examination and ultrasound in the evaluation of cervical
a cervical length less than 20 mm can be counseled that length. Obstet Gynecol. 1992;79(2):214-8.
11. Bowie JD, Andreotti RF, Rosenberg ER. Sonographic
they have an 80% chance of delivering within 24 hours of
appearance of the uterine cervix in pregnancy: the vertical
induction and those with a cervix measuring more than 30
cervix. AJR Am J Roentgenol. 1983;140(4):737-40.
mm have about a 90% chance of remaining undelivered.
12. Onderoğlu LS. Digital examination and transperineal
Multiparous women with cervical length less than 20 mm ultrasonographic measurement of cervical length to
can be counseled that they have a 90% chance of delivering assess risk of preterm delivery. Int J Gynaecol Obstet.
within 24 hours of induction and those with a cervix 1997;59(3):223-8.
measuring more than 30 mm can be advised that they have 13. Carr DB, Smith K, Parsons L, et al. Ultrasonography
approximately a 60% chance of remaining undelivered at for cervical length measurement: agreement between
this interval. However, it was also reported that transvaginal transvaginal and translabial techniques. Obstet Gynecol.
ultrasound did not predict successful labor induction as 2000;96(4):554-8.
well as digital examination in a study including post-term 14. To MS, Skentou C, Cicero S, et al. Cervical assessment at
pregnancies.57 Because of the different results of the studies the routine 23-weeks’ scan: problems with transabdominal
in the literature, this issue should be investigated more in sonography. Ultrasound Obstet Gynecol. 2000;15(4):292-6.
larger studies before a definite conclusion. 15. Souka AP, Heath V, Flint S, et al. Cervical length at 23 weeks
in twins in predicting spontaneous preterm delivery. Obstet
Gynecol. 1999;94(3):450-4.
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early in the third trimester as a predictor of preterm delivery. 35. Fujita MM, Brizot Mde L, Liao AW, et al. Reference range
Obstet Gynecol. 1995;86(2):184-7. for cervical length in twin pregnancies. Acta Obstet Gynecol
21. Guzman ER, Walters C, O’Reilly-Green C, et al. Use of Scand. 2002;81(9):856-9.
cervical ultrasonography in prediction of spontaneous 36. Hibbard JU, Tart M, Moawad AH. Cervical length at 16-22
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23. Vayssière C, Morinière C, Camus E, et al. Measuring 38. Berghella V, Talucci M, Desai A. Does transvaginal
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and duration of a learning method. Ultrasound Obstet weeks predict preterm delivery in high-risk pregnancies?
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24. Yost NP, Bloom SL, Twickler DM, et al. Pitfalls in 39. Berghella V, Tolosa JE, Kuhlman K, et al. Cervical
ultrasonographic cervical length measurement for predicting ultrasonography compared with manual examination as
preterm birth. Obstet Gynecol. 1999;93:510-6. a predictor of preterm delivery. Am J Obstet Gynecol.
25. Rozenberg P, Rafii A, Sénat MV, et al. Predictive value 1997;177(4):723-30.
of two-dimensional and three-dimensional multiplanar 40. Greco E, Gupta R, Syngelaki A, et al. First-trimester
ultrasound evaluation of the cervix in preterm labor. J screening for spontaneous preterm delivery with maternal
Matern Fetal Neonatal Med. 2003;13(4):237-41. characteristics and cervical length. Fetal Diagn Ther. 2012;
26. Hoesli IM, Surbek DV, Tercanli S, et al. Three dimensional 31(3):154-61.
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27. Barber MA, Medina M, Cabrena F, et al. Cervical length vs 42. To MS, Skentou C, Cicero S, et al. Cervical length at
VOCAL cervical volume for predicting preterm delivery in 23 weeks in triplets: prediction of spontaneous preterm
asymptomatic women at 20–22 weeks pregnancy. J Obstet delivery. Ultrasound Obstet Gynecol. 2000;16(6):515-8.
Gynecol. 2012,32(7):648-51. 43. Fuchs I, Tsoi E, Henrich W, et al. Sonographic measurement
28. Hoesli I, Tercanli S, Holzgreve W. Cervical length of cervical length in twin pregnancies in threatened preterm
assessment by ultrasound as a predictor of preterm labour— labor. Ultrasound Obstet Gynecol. 2004;23(1):42-5.
is there a role for routine screening? BJOG. 2003;110(Supp 44. Mozurkewich EL, Naglie G, Krahn MD, et al. Predicting
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29. Iams JD, Newman RB, Thom EA, et al. Frequency of uterine Gynecol. 2000;182(6):1589-98.
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N Engl J Med. 2002;346(4):250-5. evaluation of cervical length in pregnancies complicated
30. Coleman MA, Keelan JA, McCowan LM, et al. Predicting by preterm premature rupture of membranes. Ultrasound
preterm delivery: comparison of cervicovaginal interleukin Obstet Gynecol. 2002;19(6):565-9.
46. Krebs-Jimenez J, Neubert AG. The microbiological effects 58. Rozenberg P, Sénat MV, Gillet A, et al. Comparison of
on endovaginal sonographic assessment of cervical length. two methods of cervical cerclage by ultrasound cervical
J Ultrasound Med. 2002;21(7):727-9. measurement. J Matern Fetal Neonatal Med. 2003;13(5):
47. Palma-Dias RS, Fonseca MM, Stein NR, et al. Relation of 314-7.
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2004;37(5):737-44. Cochrane Database Syst Rev. 2012;18;4:CD008991.
48. Heath VC, Southall TR, Souka AP, et al. Cervical length at 23
60. Alfirevic Z, Owen J, Carreras Moratonas E, et al. Vaginal
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progesterone, cerclage or cervical pessary for preventing
and previous obstetric history. Ultasound Obstet Gynecol.
preterm birth in asymptomatic singleton pregnant women
1998;12(5):304-11.
with history of preterm birth and a sonographic short cervix.
49. Celik E, To M, Gajewska K, et al. Cervical length and
Ultrasound Obstet Gynecol. 2012, Sep 18. (e pub ahead of
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print).
development and validation of a model to provide
individualized risk assessment. Ultrasound Obstet Gynecol. 61. Fonseca EB, Celik E, Parra M, et al. Progesterone and the
2008;31:549-54. risk of preterm birth among women with a short cervix. N
50. Crane J, Scott H, Stewart A, et al. Transvaginal Engl J Med. 2007;357(5):462-9.
ultrasonography to predict preterm birth in women with 62. Romero R, Nicolaides K, Conde-Agudelo A, et al. Vaginal
bicornuate or didelphus uterus. J Matern Fetal Neonatal progesterone in women with an asymptomatic sonographic
Med. 2012;25(10):1960-4. short cervix in the midtrimester decreases preterm delivery
51. Poon LC, Savvas M, Zamblera D, et al. Large loop excision and neonatal morbidity: a systematic review and meta-
of transformation zone and cervical length in the prediction analysis of individual patient data. Am J Obstet Gynecol.
of spontaneous preterm delivery. BJOG. 2012; 119(6): 692-8. 2012,206:124,1-19.
52. MRC/RCOG Working Party on Cervical Cerclage. 63. Ware V, Raynor BD. Transvaginal ultrasonographic cervical
Final report on the Medical Research Council/Royal measurement as a predictor of successful labor induction.
College of Obstetricians and Gynaecologists multicentre Am J Obstet Gynecol. 2000;182(5):1030-2.
randomised trial of cervical cerclage. Br J Obstet Gynaecol. 64. Rane SM, Pandis GK, Guirgis RR, et al. Preinduction
1993;100(6):516-23. sonographic measurement of cervical length in prolonged
53. Bachmann LM, Coomarasamy A, Honest H, et al. Elective pregnancy: the effect of parity in the prediction of induction-
cervical cerclage for prevention of preterm birth: a systematic to-delivery interval. Ultrasound Obstet Gynecol. 2003;
review. Acta Obstet Gynecol Scand. 2003;82(5):398-404. 22(1):40-4.
54. Althuisius SM, Dekker GA, van Geijn HP, et al. Cervical
65. Rane SM, Guirgis RR, Higgins B, et al. Preinduction
incompetence prevention randomized cerclage trial
sonographic measurement of cervical length in prolonged
(CIPRACT): study design and preliminary results. Am J
pregnancy: the effect of parity in the prediction of the need
Obstet Gynecol. 2000;183(4):823-9.
for cesarean section. Ultrasound Obstet Gynecol. 2003;
55. Heath VC, Souka AP, Erasmus I, et al. Cervical length at 23
22(1):45-8.
weeks of gestation: the value of Shirodkar suture for the short
cervix. Ultrasound Obstet Gynecol. 1998;12(5):318-22. 66. Pandis GK, Papageorghiou AT, Ramanathan VG, et al.
56. To MS, Alfirevic Z, Heath VC, et al. Cervical cerclage for Preinduction sonographic measurement of cervical length
prevention of preterm delivery in women with short cervix: in the prediction of successful induction of labor. Ultrasound
randomised controlled trial. Lancet. 2004;363(9424):1849-53. Obstet Gynecol. 2001;18(6):623-8.
57. Rust OA, Atlas RO, Meyn J, et al. Does cerclage location 67. Chandra S, Crane JM, Hutchens D, et al. Transvaginal
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2003;189(6):1688-91. labor induction. Obstet Gynecol. 2001;98(1):2-6.
CHAPTER
17 Cervix in the First

Trimester of Pregnancy
Panos Antsaklis, Aris Antsaklis
Introduction of earlier detection of women at risk for PTD even before

14 weeks of gestation and evaluates whether application of
Preterm delivery (PTD), defined by World Health these methods to these at risk patients earlier in pregnancy
Organization as birth before the completion of 37 weeks can have even better results and decreases further the rate
of gestation, is the leading cause of perinatal mortality and of PTD.
long-term morbidity.1-3 However, the relationship between
neonatal mortality and morbidity with gestational age Cervical Length Measurement During
(GA) is not linear and decreases significantly after 32−34
weeks, reaching results similar to term newborns.4-5 The
the First Trimester of Pregnancy
incidence of PTD in developed countries is reported around Most studies suggest that CL measurement at 11−14
5−10%.6-10 Reports from USA suggest that the incidence of weeks of gestation does not appear to be predictive of
PTD increased by at least 33% during the last 20 years.11-12 PTD (Table 17.1).33-37 These results were verified by a
This is primarily due to an increase of late PTD (34−36+6 recent study from our center, with a low-risk population
weeks), while the incidence of PTD before 34 weeks of which consisted of 1,511 women, with a viable singleton
gestation remains stable since 1990, at around 2.9−3.6%.3,13 pregnancy. Measurement of CL at 11−14 weeks of
For the year 2005 the incidence of PTD was calculated as pregnancy did not show any predictive value for PTD
9.6%, which corresponds to 12.9 million births worldwide.14 before 35 weeks, or even before 32 weeks of gestation and,
Preterm delivery accounts for 75% of perinatal although statistically it appeared to have a predictive value
mortality—60% is due to infants born before 32 weeks— for PTD before 37 weeks of gestation, the sensitivity and
and more than half of the long-term morbidity and specificity were very low (AUC = 0.6, 95% CI: 0.54−0.66,
neurological disabilities in newborns.11,15,16 In 2001, PTD p = 0.001). It was also noticed that CL less than 25 mm is
surpassed birth defects as the leading cause of neonatal a rare finding before 14 weeks of gestation.35
mortality.17 In 2005, the cost of PTD in USA was more than Before 14 weeks of gestation, almost all women
$26.2 billion.15 It is of great interest in obstetrics to find including those at high-risk for PTD or those who will
methods in order to primarily predict PTD and eventually eventually have an early PTD usually have CL more than
prevent it. Transvaginal ultrasound (TVU) measurement 25 mm.22,34 In a big study from Greece with more than 1,000
of the uterine cervical length (CL) at 20−24 weeks of women, only one woman was identified with CL less than
gestation has been reported so far as the best method for the 25 mm, who had one previous term delivery, no history of
prediction of PTD.18-21 The shorter the CL in mid-trimester, cervical treatment and in the current pregnancy the patient
the higher the risk of PTD.18,20,22-26 What is more, the use of delivered at term. Even for women who underwent cervical
vaginal progesterone in women that were found to have a cerclage because of previous obstetric history, none of
short cervix at 20−24 weeks of gestation, appears to be an them had CL less than 25 mm. Guzman et al. studied 469
effective method of treatment for these women, as some high-risk women for PTD, and found only two with short
recent studies show that it can reduce the rate of preterm CL at 15 weeks of gestation. Both women had a history of
births even by 45%.27-29 Additionally, recent studies have previous second trimester loss.47 In a recent study from our
evaluated the use of cervical pessaries in selected cases, e.g. center there were included 19 women with previous history
in women with cervical incompetence, and showed that it of late miscarriage (at 16−23 weeks) and 14 with previous
may prevent PTD.30-32 The development of such methods history of very PTD (24−32 weeks). None of these women
that appear to decrease the risk of PTD promotes the need had short CL and their average CL was 39.9 mm (range
Chapter 17  Cervix in the First Trimester of Pregnancy 155
Table 17.1 Studies for prediction of preterm delivery by early ultrasonographic measurement of cervical length
Reference Year Study No. (N) GA at CL CL Cutoff Mean CL Predictive of
population (weeks) (mm) (mm) PTD
Zorzoli et 1994 Unselected 154 12

al.38 No
Hasegawa et 1996 Low risk 298 8−12 <30 No
al.39
Rosenberg et 1995 Unselected 280 1st 37 ± 5.9 Term No
al.40 Trimester 36 ± 5.2 <25 weeks
Zalar41 1998 Unselected 373 11 <40 48.2 ± 8.8 All Yes
(11.3±1.9) <30 46.7 ± 6.4 Primip
49.5 ± 9.8 Multip
Naim et al.42 2002 Low risk 154 < 16 <30 31 (20%) Yes
30 − 35 59 (38%)
35 − 40 44 (29%)
>40 20 (13%)
Berghella et 2003 High risk 183 10 − 13+6 <25 33.7 ± 6.9 Preterm No
al.34 35.0 ± 6.8 Term
Carvalho et 2003 Unselected 529 11 − 14 <20 42.4 All No
al.37 42.7 Term
40.6 Preterm
Conoscenti 2003 Unselected 2,469 13 − 15+6 44.2 ± 5.4 All No
et al.33 44 ± 5 Term
44 ± 6 Preterm
Tsikouras et 2007 High risk 500 9 − 12 <30 216 (43%) Yes
al.43 ≥30 284 (57%)
Ozdemir et 2007 Unselected 152 10 − 14 <27 40.9 ± 4.8 Term No
al.36 <39 38.6 ± 6.3 Preterm
Antsaklis et 2009 Unselected 1,113 11 − 14 <27 40.6 ± 5.5 All No
al.35 <30 40.8 ± 5.5 Term
38.9 ± 5.5 Preterm
Greco et al.44 2011 Unselected 1,508 11 − 14 endocx 32.4 All Yes
cx-isth 45.3 All
endocx 32.5 >34 weeks
cx-isth 45.4 >34 weeks
endocx 27.5 <34 weeks
cx-isth 41.4 <34 weeks
Souka et al.45 2011 Unselected 528 11 − 14 endocx 33 All Yes
Shorter <37 weeks
Shorter <34 weeks
Shorter <32 weeks
Greco et al.46 2012 Unselected 9,974 11 − 14 endocx 32 Term Yes
31 34−36 weeks
29 <34 weeks
(Abbreviations: GA, gestational age; CL, cervical length; No, number of patients; PTD, preterm delivery; Endocx, endocervical length; Cx-isth,
cervicoisthmic length)
31−50 mm, median = 40 mm).35 According to Berghella at 11−14 weeks was 0.09%, possibly due to the fact that
et al., CL less than 25 mm before 15 weeks of gestation is the population was low risk, with a low incidence of PTD.
seen only in a small percentage (~5%) of women, mainly The findings that CL is rarely less than 25 mm before 14
with history of previous second trimester loss or in women weeks have been verified in different studies.34,35
with a history of a large cervical cone biopsy.34 In a recent The mean CL at first trimester has been calculated in
study the percentage of women with CL less than 25 mm many studies. Antsaklis et al. calculated the mean CL at
40.8 ± 5.5 mm for deliveries greater than or equal to 37 Cervicometry in the First Trimester:
weeks (1,018 women, range: 20−62 mm, 5th percentile =
33 mm) and 38.9 ± 5.5 mm for deliveries less than 37 weeks
Newer Data
(94 women, range: 26−54 mm, 5th percentile = 30 mm). Studies have showed that CL at 11−14 weeks does not
These findings were in consistence with Ozdemir et al. appear to be predictive of PTD. 33-35 These however
who studied 152 asymptomatic women and calculated the are relatively limited studies and have been suggested
mean CL at 10−14 weeks as 40.9 ± 4.8 mm and 38.6 ± 6.3 that further research should be undertaken to assess if
mm, for term and PTD respectively.36 Conoscenti et al. in ultrasound examination before 14 weeks can indeed
an unselected population of 2,469 women, who underwent provide information about the individual risk of PTD, and
CL measurement at 13−15+6 weeks, found the mean CL to if at that GA the cervix of women who will eventually
be 44 ± 5 mm for term and 44 ± 6 mm for PTD.33 There deliver prematurely will have any differences compared
were two differences in the two studies, first the mean to women who will deliver at term. However, Greco
GA at examination (14+2 weeks ± 4 days in Conoscenti et al. proposed a new method for the measurement of CL
et al. vs 12+1 weeks ± 2 days in study by Antsaklis et al.) in the first trimester of pregnancy, making a distinction
and second the rate of PTD (<37 weeks), which was 1.7% between the endocervix and the isthmus, which appears
(42/2,469) for the Italian group versus 8.5% (94/1,113) in as a myometrial thickening between the endocervix and
the Greek group,35 which could explain the discrepancy the gestational sac. They suggested that what should be
in the results. Carvalho et al. had similar results and these measured is first the linear distance between the two
results were also consistent with two previous studies.37,41,48 ends of the glandular area around the endocervical canal
Berghella et al. in 183 high-risk pregnancies calculated the (endocervical length) and second the shortest distance
mean CL as 35.0 ± 6.8 mm and 33.7 ± 6.9 mm for term and between the glandular area and the gestational sac (isthmic
PTD respectively.34 This was a very high-risk population length), distinguishing between the endocervix and the
compared to the populations of previous studies and that isthmus (Figs 17.1A and B). They studied 1,492 women
could explain the differences in the measurements. and they found that the endocervical length at 11−14
Most studies had very low-risk populations, with a PTD weeks is shorter in pregnancies resulting in spontaneous
rate less than 34 weeks of less than 1.3%. Also, from the delivery before 34 weeks than in those delivering after 34
Greek study 11 women who underwent cervical cerclage, weeks. They also suggested that they found no significant
due to previous obstetric history and seven women who had differences in the length of the whole length of the cervico-
a late miscarriage between 16−23 weeks, were excluded isthmic complex, between the women who delivered before
from the study. Especially for the later population CL and after 34 weeks, and that could explain the failure
measurement before 14 weeks could be more informative, of previous studies to show any predictive value of CL
as changes in the cervix could have started becoming visible. measurement in the first trimester.44 Following this study
Measurement of the CL before 14 weeks has not been Souka et al. measured with the same method the CL in
found to be predictive of PTD.22,33-35 Only a limited number 800 women with singleton pregnancies and showed that
of studies have shown association between short CL early CL at 11−14 weeks of gestation predicted PTD before
in pregnancy and PTD.41,42,48,49 In these studies the CL was 34 weeks (odds ratio, 0.746; 95% confidence interval,
measured after 15 weeks,49 or the studied population was not 0.649−0.869) and PTD before 32 weeks (odds ratio, 0.734;
homogenous in terms of GA at which the examination was 95% confidence interval, 0.637−0.912).45 A more recent
performed,42 or the study population was very high-risk.43 Two study by Greco et al. showed that CL at 11−14 weeks of
studies which compared the CL in first and second trimester gestation is shorter in women who have spontaneous PTD
did not show any predictive association of the CL at 10−14 than in those women who deliver at term, and by using an
weeks for PTD or any statistical difference of the CL between algorithm combining maternal characteristics and CL about
women who delivered at term and preterm.36,37 An explanation 55% of women who will deliver before 34 weeks can be
could be that it is difficult to measure the cervix before 14 identified, at a false positive rate of 10%.46 These studies
weeks, as it cannot be easily distinguished from the lower show some predictive value of the measurement of the
uterine segment, since the gestational sac has not reached a endocervical length in the first trimester of pregnancy for
sufficient size to expand the lower part of the uterus.50-52 PTD, and the results of bigger studies are awaited.
Figures 17.1A and B Transvaginal ultrasound pictures illustrating (A) the cervicoisthmic complex and (B) the measurement of the length
of the endocervix (A to B) and the isthmus (C to D)
Table 17.2 Studies comparing cervical length at first and second trimester
Reference Year Study No. GA at CL GA at CL 2nd Mean CL Predictive
population (N) 1st trimester trimester change of PTD
(weeks) (weeks) (mm)
Carvalho et al.37 2003 Unselected 529 11−14 22−24 3.4 Term Yes
13.9 Preterm
Ozdemir et al.36 2007 Unselected 152 10−14 20−24 3.1 Term Yes
10.2 Preterm
Antsaklis et al.* 2009 Unselected 833 11−14 20−24 3.2 Term Yes
7.3 Preterm
Souka et al.45 2011 Unselected 528 11−14 20−24 2.36 All Yes
3.53 Hx CxS
6.29 Hx PTD
(Abbreviations: Hx CxS, history of cervical surgery; Hx PTD: history of preterm delivery; *unpublished data from Antsaklis et al.)
Cervicometry in the First and Second In authors’ center they performed a study with similar
design that compared the cervical shortening from 11−14
Trimesters weeks to 20−24 weeks in 833 low-risk women. The
There are only a few studies that have focused on the cervical shortening was 7.3 mm for the preterm group
changes that occur to the CL from the first to the second and significantly higher than that in the term group (3.2
trimester of pregnancy and their predictive value for PTD mm) (Antsaklis et al. unpublished data). More recently
(Table 17.2). Carvalho et al. studied the CL of 529 women Souka et al. in a study with 800 women performed serial
both at 11−14 weeks and at 22−24 weeks of gestation ultrasound measurements of the cervix at 11−14 weeks,
and reported that the shortening of the CL was more 16−19 weeks and 20−24 weeks of pregnancy, including
significant in women who eventually delivered preterm maternal characteristics and history of cervical surgery,
(13.9 mm) than those who delivered at term (3.4 mm) and showed that women with history of cervical surgery and
it was an independent predictor of PTD.37 A few years later with a history of PTD had a more significant decrease in
Ozdemir et al. examined 152 low-risk patients at similar the CL from first to second trimester and that by combining
GAs, 10−14 and 20−24 weeks. The cervical shortening all these parameters a short cervix at 20−24 weeks could
was more prominent in the group that delivered preterm be predicted at the 11−14 weeks scan, helping to identify
(10.2 mm) compared to that delivered at term (3.21 mm).36 earlier women at risk for PTD.45,53
Conclusion 13. Barfield WD, Weisman LE, Kim MS. (2009). Late preterm
infants, UpToDate. Available from http://www.uptodate.
The role of CL measurement at 11−14 weeks of gestation for the
prediction of PTD is not well defined yet. Most studies show that com/home/content/topic.do?topicKey=neonatol/35419
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and newer studies that proposed measuring the endocervical worldwide incidence of preterm birth: a WHO systematic
length avoiding the lower uterine segment (isthmic part) show more
promising results for the prediction of PTD. Further research should review of maternal mortality and morbidity. Bull World
be undertaken to assess if ultrasound examination before 14 weeks Health Organ. Available from http://www.who.int/bulletin/
can indeed provide information about the individual risk of PTD volumes/88/1/08-062554.pdf.
and if at that GA the cervix of women who will eventually deliver 15. Williamson DM, Abe K, Bean C, et al. Current
prematurely will have any differences compared to women who will
deliver at term. Shifting the prediction of PTD and the identification research in preterm birth. J Womens Health (Larchmt).
of high-risk women for PTD before 14 weeks of pregnancy is of 2008;17(10):1545-9.
great interest in obstetrics as it could give the opportunity for early 16. Green NS, Damus K, Simpson JL, et al. March of Dimes
intervention and that hopefully could be a significant step for the Scientific Advisory Committee on Prematurity. Research
development of an effective strategy for the prevention of the
greatest obstetric complications and PTD. agenda for preterm birth: recommendations from the March
of Dimes. Am J Obstet Gynecol. 2005;193(3 Pt 1):626-35.
17. Spong CY. Prediction and prevention of recurrent
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Obstet Gynecol. 1995;172:S348 (Abstract 316). 1002.
CHAPTER
18 Transvaginal Sonography in
Multiple Pregnancy
Ulrich Honemeyer, Asim Kurjak, Jose Bajo Arenas
Introduction Other important improvement is an option to observe

fetal movements in three dimensions. Much more
The usage of assisted reproduction techniques (ART)
information regarding the quality of movements can be
has resulted in an enormous increase in the incidence of
recognized. Therefore, complete re-evaluation of our
multiple pregnancies throughout the world. The triplet birth
comprehension of fetal behavior in multiple pregnancy
rate in the Netherlands increased from 10/100,000 in 1970
should be accomplished.
to 60/100,000 in 1994.1 Seoud et al. reported an incidence
of 2.6% triplet gestations from ART.2 Multiple pregnancies Two-dimensional Sonography in
are associated with a higher risk of perinatal and neonatal
morbidity and mortality. Borlum reported a fetal mortality Diagnosing Multiple Pregnancy
rate of 64/1,000 in triplet pregnancies in Denmark.3 The diagnosis of multiple pregnancy (triplets, quadruplets,
Introduction of ultrasound has revolutionized the quintuplets, etc.) with 2D US usually requires a long
antenatal diagnosis of multiple pregnancy. Thirty years examination period and an experienced ultrasonographer.
ago, twins were most often overlooked, whereas triplets If one uses transvaginal sonography (TVS), multifetal
were diagnosed only after the delivery of second infant. pregnancies can be diagnosed as early as 5–6 weeks of
After the introduction of the ultrasound into routine prenatal gestation (Fig. 18.1). An early diagnosis can be associated
care, however, the confidential diagnosis or exclusion of with numerous pitfalls. One embryo arises usually from a
multiple pregnancies became practical reality. single gestational sac. However, two embryos arise from a
Two-dimensional sonography (2D US) is still the single gestational sac in monozygotic twins. The number
primary modality for diagnosing and evaluating multiple of gestational sacs always correlates to the number of
pregnancy. Despite that, some of the limitations of 2D US placentas and very often to the number of embryos, but
can be overcome by three-dimensional sonography (3D not always. Therefore, reliable prediction of the number
US), this technique was complementary method to 2D US of embryos on the basis of the number of gestational sacs
by which additional information that assists in the clinical is not accurate. Even a finding of a gestational sac with a
management sometimes could be provided. The main single yolk sac does not exclude monoamniotic (MA) twins.
drawbacks of 3D US include, time-consuming and the need Only one (large or irregular) yolk sac can be seen in MA
for absence of fetal activity which is the precondition for twin pregnancies.4 Therefore, until 7th week of pregnancy
qualitative 3D imaging. when the embryo is recognizable sonographically, reliable
Acceleration in scanning and rendering capabilities of counting of the embryos is not possible. Only number of
the last generation of 3D machines provided 3D imaging the embryos is important for final diagnosis of the number
almost in real time. Stated another way, surface rendered of multiples.
and multiplanar images can be observed in near real time. Three gestational sacs have to be recognized in the case
This imaging technique is characterized as four-dimensional of trichorionic-triamniotic triplets (Fig. 18.2). However,
sonography (4D US). If one performs 4D US, accomplishing even when two gestational sacs are seen, the diagnosis of
of 3D image reconstruction is less time consuming because triplets is not yet excluded and the possibility of dichorionic-
simultaneous with probe movement adequate image is triamniotic triplets (complex chorionicity) should be taken
displayed. Therefore, 4D US is more suitable and acceptable in consideration. Only counting the number of embryos is
for routine prenatal care than 3D US. essential for diagnosis of triplets.
Chapter 18  Transvaginal Sonography in Multiple Pregnancy 161
Figure 18.1 Transvaginal ultrasound of triplets at 6 weeks of gestation. Figure 18.3 Diagnosis of the viability of each triplet. Color Doppler
There is a high probability for triplets as each gestational sac contains reveals three viable embryos
a single yolk sac. However, quadruplets cannot be excluded from this
static sonogram
Most Common Pitfalls in

Two-dimensional Diagnosis
À Undercounting
À Pitfalls in chorionicity and amnionicity determination.
Late Appearing Twin or “Undercounting”

Pregnancy number before the 6th week is determined by
counting the number of gestational sacs. Using this method,
the examiner must be aware of what has been characterized
as the late-appearing twin phenomenon—“undercounting”.
The late appearance of twins is recognized on the basis
of the discrepancy between two sonograms, in which
comparison of an initial sonogram, usually obtained at
Figure 18.2 Transvaginal ultrasound of triplets at 8 weeks of gestation.
5.0–5.9 weeks and a subsequent sonogram, 6 or more
Three embryos in three gestational sacs (Abbreviation: TCTA, weeks demonstrates more embryos or fetuses than the
trichorionic-triamniotic triplets) previously counted gestational sacs. There are two types
of undercounting: (i) polyzygotic and (ii) monozygotic.
Polyzygotic undercounting overlooking and under-
Determination of cardiac activities is another important counting the number of gestational sacs: Polyzygotic
prognostic factor. The chance of delivering twins when two undercounting is a result of the limitations of 2D TVS.
chorionic sacs are seen is 57%, but when two cardiac activities The anatomy of the female reproductive tract as well
(two viable embryos) are present, the chance increases to 87%. as contemporary probe design limits the number of
Similarly, the chance of delivering triplets after visualization examination planes to the sagittal and transverse. Since
of three gestational sacs is 20%, but with three viable the uterus can only be examined in these two planes, it is
embryos, the chance increases to 68%.5 The viability of each possible that an examiner fails to visualize the total number
embryo can be confirmed using color Doppler imaging of the of gestational sacs on a single screen. Stated in other way,
corresponding fetal circulation (Fig. 18.3). one or more gestational sacs may be overlooked. This
problem is enhanced in high-order multiple pregnancy in diagnostic accuracy, 3D US is very time consuming method,
which it is impossible to visualize all gestational sacs on what sometimes makes it unacceptable in everyday work.
a single screen (Figs 18.4 and 18.5). Therefore, the risk If one performs 4D US, less time is needed for surface
of undercounting is correlated to the number of embryos. rendering and multiplanar reconstruction of region of
Undercounting of the number of gestational sacs is the most interest. Therefore, 4D US in recent future should be the
common pitfall during the first trimester. This pitfall can method of choice for accurate counting of gestational sac
be avoided either by conventional or by 3D US. in high-order pregnancy.
How the undercounting phenomenon can be avoided by
2D US is illustrated in Figures 18.4 and 18.5. Sometimes, Chorionicity and Amnionicity Determination During
detailed 2D examination characterized by slight probe the Second Trimester
movement can reveal an additional gestational sac. During the second trimester, chorionicity can be determined
Three-dimensional sonography offers two options’ which directly and indirectly. Direct determination of chorionicity
are advantageous for avoiding undercounting. These are the is based on the counting of placentas. This method is easy
analysis of a coronal plane in a multiplanar view and surface to perform when the placentas are separated. Unfortunately,
rendering (Fig. 18.6). Coronal plane is the most informative in multichorionic pregnancies, fusion of different placentas
plane and is obtained exclusively by 3D US. Detailed occurs during the second trimester. Distinguishing
analysis of the plane often reveals the additional gestational between single and fused placenta is accomplished by
sac. Surface rendering provides spatial imaging. Careful considering the so-called “twin peak” sign. “Twin peak”
analysis of such images eliminates the risk of overlooking a sign (lambda sign) is a triangular projection of a placental
gestational sac in high-order multiple pregnancy. At present, tissue beyond the chorionic surface, extending between
it is the safest means to accomplish gestational sac counting. the two chorionic layers of the intertwin membrane. It
In situations where more than three gestational sacs provides reliable evidence that there are two fused placentas
are suspected on conventional sonographic examination, (dichorionic-diamniotic) rather than a single shared
the additional use of 3D US is recommended. Despite placenta (monochorionic-diamniotic).5
A B C D
Step 1 Step 2 Step 3 Step 4
Figures 18.4A to D Undercounting the number of gestational sacs

False diagnosis of twins: On the left side two gestational sacs are depicted (A). Slight probe movement gradually reveals the
third gestational sac in the middle (B to D). This problem can be avoided with the use of 3D scanning and surface rendering.
Progressive appearance of the third gestational sac following the probe movement:
Step 1: Only two gestational sacs are seen (A).
Step 2: The third sac appears between the first two gestational sacs (distinguishing between intermembranous fluid accumulation) (B).
Step 3: An ovoid shape clearly confirms the third gestational sac (C).
Step 4: The dimension of the third gestational sac is similar to the other two (D).
A B
Figures 18.5A and B Gestational sac undercounting in quadruplet Figure 18.6 Three-dimensional (3D) diagnosis of an accurate
pregnancy: False diagnosis of triplets. (A) Three gestational sacs are number of gestational sac. Final diagnosis of quadruplets with 3D
depicted; (B) Slight probe movement reveals the fourth gestational surface rendering mode. In contrast to two dimensional (2D) manual
sac (B) slicing, an analysis of 3D volugrams reveals the accurate number of
gestational sacs
The junction of two placentas can be visualized in the Three-dimensional Multiplanar Imaging
early second trimester using high-resolution 2D US. When Multiplanar imaging offers an option of synchronous
lambda sign is seen, bichorionic pregnancy is diagnosed scanning in three orthogonal sections, including even
(Figs 18.7A and B). coronal section. Computer data processing provides
Assessment of the junction of interfetal membranes: The numerous sections unobtainable by 2D US. Multiplanar
junction of three interfetal membranes represents ipsilon view will result in simultaneous depiction of three sections
“Y” zone (Figs 18.8A to C). Sepulveda et al. reported orthogonal one to the others. Two of them (transverse and
about a complete correlation between the findings at the longitudinal) are dependent on angle of insonation, whereas
ipsilon zone and TVS at 6–7 weeks.6 However, in advanced the third one (coronal) is not. This section is orthogonal to
pregnancy, when placentas cannot be seen, then examiner the insonation beam.
should examine junction between the membranes. Advantages of multiplanar imaging over sectional
The absence of the “Y” zone does not exclude imaging are presented in Table 18.1. If one performs
trichorionic triplets. In second trimester, the ipsilon zone multiplanar imaging, numerous pitfalls can be avoided.
can be absent in cases in which the interfetal membranes They are systematically presented as follows.
do not intersect. Therefore, ipsilon zone assessment should
be combined with other parameters for determination of Table 18.1 Advantages of multiplanar imaging in management of
chorionicity.3 multiple pregnancy
First trimester
Three-dimensional Sonography in • Elimination of undercounting phenomenon
Diagnosing Multiple Pregnancy • Improved prediction of spontaneous abortion
• Improved prenatal classification of uterine anomaly
Three-dimensional sonography provides completely new Second trimester
modality of sonographic scanning including coronal section
• Improved diagnosis of vanishing phenomenon
imaging, 3D reconstruction and volumetric calculations.
• Early detection of fetal anomalies
Improved visualization rate, depiction of the spatial
• Improved evaluation of fetal malformation
relationship, “sculpture-like” plastic imaging and volume
• Improved determination of placentation
measurement are the main benefits of this new technology.
A B
Figures 18.7A and B Two lambda signs on single placental disk confirm trichorionic-triamniotic triplets. (A) The determination of chorionicity is
based on the counting of placental disks; (B) Chorionicity corresponds to the number of fused placentas instead of the number of the visualized
placental disks
A B C
Figures 18.8A to C Variants of “Y” junction. (A) “Y” zone in early second trimester three gestational sacs are seen; (B).“Y” zone in late second
trimester represents the junction site of fetal membranes; (C) Three dimensional determination chorionicity in the late second trimester. The
“Mercedes” sign represents the junction of fetal membranes
Elimination of Undercounting Phenomenon high-order multiple pregnancies (Figs 18.9A to D). Before
Three-dimensional volume acquisition provides the introduction of 3D US, 11% of dichorionic twins were
possibility of simultaneous depiction of three orthogonal initially undercounted as singletons, and 16% of high-order
planes of examinations. Moreover, it is possible to perform multiple gestation were also undercounted.7
systematic examinations of acquired volumes with three
different directions of scanning. For example, frontal (coronal) Improved Prediction of Spontaneous Abortion
plane enables examination of the uterine cavity in sections First-trimester spontaneous abortions can be predicted from
which are unobtainable with conventional 2D US. Further, alterations in the gestational sac size. For this purpose,
3D US enables the appropriate counting of gestational sacs nomograms relating the ratio of mean sac diameter to
without any risk of undercounting even for less experienced crown-rump length (S/CR) to the gestational age [last
ultrasonographers. Therefore, interobserver variability in menstrual period (LMP)] were constructed.8 Using this
detecting the number of gestational sacs is significantly lower. method, a sensitivity of 78.3%, a specificity of 97.8% and
Even quadruplets and quintuplets are recognizable without a false-positive rate of 2.2% can be achieved. Therefore, S/
any difficulties. This advantage strongly suggests that 3D US CR measurement in early pregnancy is a simple and reliable
should become the new standard in the early management of method of predicting first trimester abortions.
Figures 18.9A to D Three-dimensional

multiplanar view in determination of accurate
number of gestational sac. Transvaginal
multiplanar view of triplet pregnancy at 12
weeks. An example to illustrate possible pitfall
regarding undercounting of the gestational sacs.
The advantages of coronal section are presented
(C). In transverse section only two gestational
A B sacs are present (A), whereas on a sagittal
section (B) only single gestational sac is seen.
On a coronal section, three gestational sacs
with Y-sign are seen (C). The most informative
mode of three-dimensional sonography is its
surface rendering mode (D). Using this mode,
in addition to the correct number of embryos,
separation phenomenon can be seen which was
unobtainable with conventional sonography.
Using conventional 2D sonography, sagittal (A)
and transverse sections (B) of the uterus are seen.
First two images (A, B) represent the limits of 2D
in which twin pregnancy is diagnosed. However,
on the third section-coronal plane (C) three
gestational sacs are clearly seen. This is finally
C D confirmed by 3D reconstruction (D)
However, because of limitations regarding probe malformations, direct examination of the uterine fundus
manipulations due to the anatomy of female reproductive was required, either by way of laparotomy, laparoscopy or
tract and contemporary probe design, some sections introduction of dye via cervix. Stated another way, accurate
are unobtainable by 2D US. Using this method, the prenatal classification was unachievable without invasive
examiner should be aware that sometimes all gestational procedures.
sacs are impossibly visualized in sections referenced for If on the other hand, one perfoms 3D US on a multiplanar
measurement of the gestational sac diameter. This method view analyzing the coronal section, pregnancy number and
was often useless before the introduction of multiplanar type of malfomation can be seen. Since coronal section
imaging. is unobtainable by transvaginal two-dimensional US,
whenever multiple pregnancy is recognized in a malformed
Prenatal Classification of Uterine Anomalies uterus, an additional 3D examination is recommended. A
In 1988, the American Fertility Society (AFS), now known singleton pregnancy in didelphic uterus is presented in
as the American Society for Reproductive Medicine Figure 18.10.
(ASRM), formalized the system currently in use for
classification of uterine anomalies. In this system, Müllerian Improved Detection Rate of Anomalies
anomalies are divided into seven groups.9 Classification In a singleton pregnancy, the empiric risk for major fetal
of uterine malformations is important because successful malformations is approximately 3%. In trichorionic triplets,
pregnancy outcome of twin gestations was considered the empiric risk for major fetal malformations within each
possible in the following groups: II (unicornuate uterus), fetus is independent of the others, so that the probability of
III (uterus didelphys) and IV (bicornuate uterus).10-12 By having at least one malformed fetus is approximately 9%.14
the way of reference, successful twin pregnancy required According to the data from Eurofetus study, the sensitivity
that each fetus occupies a separate horn of the didelphic of a routine 2D US for detecting malformation is 61.4%,15
uterus. 10 Despite this general proposition, Vecek and and the sensitivity is lower in multiple pregnancy, as a
colleagues recently reported successful twin pregnancy consequence of overcrowding. Because 3D US offers an
with both fetuses occupying the same horn.13 Before the ideal visualization rate of the desired structure, achieved
introduction of 3D US for accurate classification of uterine by manipulation within the volugram data, it is reasonable
Table 18.2 Malformations in multiple pregnancy

Unique to twinning
• Twin-to-twin transfusion syndrome
• Conjoined twins
• Trap (acardia)
• Fetus in fetu
Not unique to twinning
• Neural tube defects
• Hydrocephalus
• Congenital heart disease
• Esophageal atresia
• Anorectal atresias
• Intersex
• Genitourinary anomalies
examiner must be aware that diagnostic criteria proposed

by Maggio et al. is sometimes problematic because two
cases of false-positive diagnosis of conjoined twins have
been reported.22,23 Unfortunately, two-dimensional TVS
Figure 18.10 A singleton pregnancy in didelphic uterus. Three- limits the number of examination planes to sagittal and
dimensional sonographic examination of malformed uterus provides transverse. Since the uterus can only be examined in these
sonographer with an accurate classification of uterine anomaly and
pregnancy number. For this purpose, coronal section is important
two planes, it is possible that the examiner fails to visualize
because it provides visualization of fundal region and length of septum the coronal section through fetus. Stated another way,
conjoined twins can be overlooked. This problem can be
to expect that use of this technology will increase the solved using both modalities of the 3D US, the multiplanar
sensitivity of detection of malformations in multifetal along with the surface rendering view. Using multiplanar
pregnancies. Furthermore, 3D US improves diagnostic imaging, the visualization rate of coronal sections through
capability by offering more information in evaluating fetal the fetus is 100% due to the unlimited number of sections,
malformations, particularly in terms of malformations of which can be generated by data manipulation. Maymon et
the cranium, face, spine, extremities, and body surface.16 al. reported that in a case of conjoined twins at 10 weeks of
Malformations in multifetal pregnancies: A wide variety pregnancy, the exact area could be successfully identified
of malformations may be present in multifetal pregnancy. by transvaginal 3D US.24 We diagnosed this anomaly at
Malformations unique for twins (MUT) is the term applied 12 weeks of amenorrhea in a fetus of 27 mm in length,
to the malformations that occur exclusively in multiple showing two separated heads with the joining at level of
pregnancy, whereas malfomations not unique for twins the thorax (Figs 18.12A to J). The fetal orientation remained
(MNUT) is the term applied to the malformations that also unchanged despite manipulation with the transvaginal probe
occur in singletons, but they are more common in twins and prolonged scanning by multiple sonographers.
(Table 18.2). A development of a fetiform mass inside a more mature
Knowledge of sonoembryology enables the diagnosis of fetus is characterized as fetus in fetu (FIF).25,26 The true
fetal malformations in the first trimester. Three-dimensional incidence of FIF is unknown, although it has been estimated
sonography is useful to visualize embryos and early fetuses and to be 2 per million births.27 Jones et al. in 2001 reported
to recognize their surface morphology17 (Figs 18.11A to C). about the 3D US imaging of a highly developed FIF with
Of the MUT, 3D US is useful for confirmation of spontaneous movement of extremities. 28 In contrast to
suspicion of conjoined twins and fetus in fetu (FIF). ease of the diagnosis with 3D imaging, a FIF with even
Maggio and colleagues reported in 1985 about the first- an extraordinarily high degree of differentiation is very
trimester ultrasonic diagnosis of conjoined twins.18 Since difficult to distinguish by 2D US. Nonetheless, an increasing
then, several groups confirm their proposed diagnostic number of reports use 2D US examination which follow the
criteria.19-21 Despite great progress concerning early (first minimal criteria for diagnosis proposed by Willis.29 This
trimester) diagnosis, delineating organ sharing cannot includes the presence of an axial skeleton or fetus with
be accomplished before the second trimester. Moreover, metameric organization, skin coverage, encapsulation and
A B C
Figures 18.11A to C Comparison between two- and three-dimensional sonoembryology. Both modalities provide an examiner with essential
information concerning the management of twin pregnancy including number of fetuses and chorionic status. The advantages of spatial visualization
in early pregnancy include improved visualization of both fetuses and their gestational sacs. The relationship between the size of fetus and
gestational sacs can be assessed on single image, whereas for the same effect several 2D images are required
a two-vessel cord.29 Since, 3D US is capable of generating study, the sensitivity of routine 2D US for detection of
a 3D surface view of the structure encapsulated within a malformation in singleton pregnancy is 61.4%.10 On the
fluid-filled sac, it should be used for this purpose. With other hand, the sensitivity in multiple pregnancy has been
this technique, a highly fetiform shape and axialization reported between 39% and 87%.31,32 Neural tube defects
could be recognized easily even by less experienced include anencephaly, acrania, encephalocele and the various
sonographers who could not envision FIF as the basis of 2D forms of spina bifida. Screening for these anomalies is
US. Distinguishing between FIF and teratoma sometimes recommended during the first trimester because reports
can be problematic. Therefore, whenever a cystic mass is document the successful diagnosis in the embryonic
recognized at specific locations within a fetus, an additional period. 28-30 The detection rates of these anomalies in
3D examination is recommended. The prenatal sonographic singleton pregnancy are high except for spina bifida.
differentiation between FIF and teratoma is related to the The morphological anomalies of acrania and anencephaly
degree of differentiation of the anomaly. In high degree can be confirmed even before 10 weeks of pregnancy. Bonilla-
differentiated FIF, the visualization of the presence of Musoles and colleagues reported two-dimensional diagnosis of
fetiform mass is essential. However, in a FIF with a low two cases of anencephaly at 10 weeks of gestation.33 Takeuchi
degree of differentiation, the diagnostic criterion is based diagnosed acrania by conventional 2D US at 8 weeks and 5
on the presence of a rudimentary spinal architecture, which days of amenorrhea in a fetus of 18 mm in maximum length,
confirms the embryonic development beyond the primitive showing an irregular shape of the head with neither cranium
streak stage. This is in contrast to the classic embryonic nor brain vesicle development.34 A 3D surface rendered
concept, which postulated that teratomas do not develop image facilitated confirmation of this diagnosis because it
beyond the primitive streak stage of 12–15 days.29 showed characteristics of the anomaly more clearly. It is
Among MNUT, 3D US can be advantageous for generally believed that the absence of the cranial vault leads
confirmation of suspicion of neural tube defects. Twins to the disintegration of the exposed brain during fetal period,
may be concordant or discordant for congenital anomalies. resulting in clinical anencephaly. Bronshtein and Ornoy
Concordance for congenital malformations is defined as reported a case which detailed the progression from acrania
the presence of concordant anomaly in both twins, whereas to anencephaly.35 Spina bifida is associated with anencephaly
discordance for congenital malformations is characterized between 9% and 30% cases.36 Using 3D US, Bonilla-Musoles
with the presence of an anomaly in only one of a twin pair. reported diagnosis of spina bifida at 9 weeks.37 Therefore,
Monozygotic twins are at higher risk for such anomalies whenever anencephaly is found in the embryonic period,
than dizygotic twins. 30 Under these circumstances, an additional 3D scan of the fetal spine is recommended.
discordance for major malformation in a twin pair does not The multiplanar view is particularly useful in localizing
imply dizygotic or dichorionic status. spinal defects accurately in fetuses with spina bifida and in
Two-dimensional sonography is the primary modality for determination of the exact location of the extracranial mass and
detection of congenital anomalies. According to Eurofetus amount of extracranial tissue in fetuses with encephalocele.38
A B
G
Contd...
Contd...
H I J
Figures 18.12A to J Conjoined twins at 12 weeks of gestation by two-dimensional transvaginal sonography: (A) Shows sagittal section through
the conjoined twins, which reveal almost normal appearance. If one concludes on the basis of this section the diagnosis of conjoined twins are
overlooked; (B) Shows transverse sections through fetal heads which reveal two normal heads adjacent to each other. At the base of the head,
it is shown that these twins have common thorax and abdomen. Transversal sections provide sonographer with additional information about
the shared structures; (C) Shows three-dimensional scan of same conjoined twins: Surface rendered reconstruction of conjoined twins is useful
for classification of malformation-thoracophagus. Unfortunately, on this no information about the shared inner organs can be obtained due to
limitation of visualization of superficial structures, coronal section through the fetus which reveals a fetus with two heads and single trunk. This
finding is indicative for diagnosis of conjoined twins. An early diagnosis of conjoined twins requires detailed examination of fetus in these sections:
sagittal, coronal and transverse. Avoiding of this recommendation can be an origin of pitfall, because the appearance of conjoined twins in sagittal
section can be almost normal as shown in Figure (A); (D) Shows conjoined twins at 12 weeks of gestation by two-dimensional power Doppler:
Power Doppler analysis is useful in delineating the extent of organ sharing in the first trimester. Early diagnosis and precise delineation of the
shared organs of conjoined twins are essential for appropriate management of twin pregnancy. On the coronal section, shared fetal circulation
with single heart can be seen. On transversal section, separated cerebral circulations are clearly visible. Conjoined twins in a triplet pregnancy at
9 weeks of gestation by two-dimensional transvaginal sonography; (E) Shows section through the gestational sac without clear demonstration of
triplets with two conjoined embryos; however, hyperechogenic yolk sacs are visible; (F) Shows 3D surface rendered view displaying clearly caudal
conjunction of two embryos; (G and H) Targeted interrogation with color Doppler visualizes conjoined embryos with caudal vascular anastomosis
of the two embryonic circulations; (I and J) Color and power Doppler are able to detect ectopia cordis in one of the two conjoined embryos. The
patient had spontaneous miscarriage one week later
Improved Determination of Placentation In the case of dichorionic-triamniotic triplets (complex

Using 2D US, membranes can be evaluated, counted and placentation), the placenta is represented by the T-sign
measured only when they are at 90°. In other words, the and lambda sign with one thin and one thick membrane.
orientation of the membranes studied should be positioned Using conventional sonography, it is difficult to distinguish
parallel with the transducer crystal array. Clearly, 3D US between a single placenta and fused placentas of the twins
enables us to achieve a “perfectly” oriented picture. The rate and this is especially so in triplet pregnancy. Such complex
of appropriate chorionicity determination should be ideal placentation types can be examined more easily using 3D
(100%) in the second and third trimesters (Fig. 18.13A). US regardless of the gestational age.
The most revealing area in which to study the chorionicity
and amnionicity of the multifetal pregnancy is the location Three-dimensional Spatial Reconstruction
within the uterine cavity in which the membranes change the Integration of data obtained by volume scanning can be used
orientation of their surfaces from covering the placenta(s) or to depict 3D plastic (sculpture-like) reconstruction of the
the uterine wall to meet each other and to form the interfetal region of interest (ROI). Three-dimensional reconstruction
or intertwin membrane. Using 2D US, this area should be can be presented in surface mode. In the surface mode,
studied by placing the scanning plane at 90° to the plane of only the signals from the surface of ROI are extracted and
the intertwin membrane. This fact explains the potential role displayed in plastic appearance. Surface rendering provides
of 3D US in the examination of the origin of the intertwin an examiner with additional information confirming
membranes. The most important step in management of the normal anatomy either evaluation of the extent of
the triplet pregnancy is determination of the number of lesion (Fig. 18.12C). Surface rendering provides spatial
placentas. When placentas are separate, this is not a problem. reconstruction of intertwin area, which may be useful in
Unfortunately, the placentas are usually fused (Fig. 18.13B). distinguishing between conjoined twins from MA twins
A B
Figures 18.13A and B (A) Three-dimensional lambda sign and intertwin membrane: Spatial reconstruction
of membrane take-off site provides easier differentiation between dichorionic and monochorionic placentation.
Furthermore, membrane thickness can be simultaneously evaluated. Therefore, 3D US is more comprehensive
tool for understanding of accurate placentation; (B) Three-dimensional image of bichorionic-biamniotic twins in the
second trimester of gestation. With one well-made three-dimensional scan one can get same amount of information
like in detailed and time-consuming two-dimensional examination. Figure 18.12C shows that on single image,
chorionicity and external frontal anatomy can be evaluated. Furthermore, orientation of one twin toward other can
be simultaneously assessed
positioned next to each other. At present, it is the safest pregnancy, an important parameter for confirmation of early
means to accomplish this distinction. concordant growth. The prognostic significance of early
With 3D US, conjoined twins can be demonstrated in discordant growth in multiple pregnancy is still a matter
three perpendicular, two-dimensional planes (i.e. sagittal, of controversy. Some authors report about an association
coronal and transverse) which are simultaneously displayed of early discordant growth with major anomalies and poor
on the monitor, allowing access to an almost infinite pregnancy outcome.40,41 Others note, early discordant growth
array of sections in any desired plane. On the other hand, and normal pregnancy outcomes were reported.42 All cases
surface rendering enables assessment of their topographic of discordant growth were after in vitro fertilization-embryo
orientation to each other. From these acquired 3D volumes, transfer (IVF-ET); however, Gassner et al. proposed the
the exact area of conjunction can be analyzed to assist in use of sonographic placental volumetry as a means of early
planning the postnatal management. detection of chromosomal anomaly in multiple pregnancy.43
These authors described a dichorionic twin pregnancy,
discordant in growth with the distinctly small placental
Volumetric Calculations volume of a growth restricted fetus at 12 weeks of gestation.
Three-dimensional measurement of the organ volume These two markers were present before a severe heart defect
(volumetry) is possible using sequential step slicing and bilateral cleft lip and palate were sonographically
measurements of areas through the volugram of the targeted recognizable. It seems reasonable that placental volume
organ, whereas volume assessment by 2D US only includes should be the recommended criterion for distinguishing
an approximation of volume based on assumption that fetal between pregnancy at risk and without risk for major
organs have an ideal geometric shape. Three-dimensional anomalies and poor outcome in multiples.19 Small placental
volumetry is carried out in all three planes using the contour volume, in addition to growth restriction of one fetus early
mode, in which the volume from the measured circumferences in the course of a twin pregnancy, could be an important
and the distances between them are computed by a software. early marker influencing the decision for chorionic villous
Three-dimensional volumetry of first trimester gestational sampling at 12 weeks instead of amniocentesis at 16 weeks
sac volume is superior to 2D volumetry in its estimation, but and could precede an earlier selective pregnancy termination
is without prognostic significance for outcomes in singleton of a triploid twin, if indicated and desired.
pregnancy.39 Despite this, our group considers comparison Placental volumetry is easy to perform when the
between volume of each gestational sac in multiple placentas are separate. Unfortunately, fusion of separate
A C
B D
Figures 18.14A to D (A) Monochorionic-monoamniotic twins. Single amniotic cavity, a single placenta and two umbilical cords are criteria for
diagnosis of this placentation. Unfortunately, this placentation is associated with several life-threatening complications including: preterm labor,
congenital abnormalities and cord entanglement; (B) Two-dimensional image of cord entaglement: Two-dimensional sonography is uncapable
of distinguishing adjacent and entangled umbilical cord; (C) Two-dimensional color Doppler visualization of umbilical cord entanglement. (D)
Two-dimensional power Doppler reconstruction of umbilical cord entanglement
placentas often occurs during the second trimester accomplished utilizing the Doppler amplitude mode.44,45
multichorionic pregnancies. Therefore, volumetry should be The implementation of 3D power Doppler imaging permits
performed at the end of the first trimester or at the beginning the physician to investigate the anatomy and topography of
of the second trimester. hemodynamics within the particular organ or ROI.
Monoamniotic twinning is the condition characterized by
Three-dimensional Angio Mode a single amniotic cavity, a single placenta and two umbilical
Three-dimensional angio mode operates on the basis cords inserted close to each other. Cord entanglement is
of high-energy powered Doppler. Its greater sensitivity a complication specific for MA twins. The diagnosis of
is related to direction-independent scanning and better cord entanglement with 2D real-time sonography usually
detection of smaller vessels. This mode provides optimal requires a long examination period. Due to limitations of
visualization and selective 3D reconstruction, even of sectional imaging, the examination is informative only
tortuous parts of vessels and blood flow arborization. More in terms of quality and number of loops (Figs 18.14A to
recently, 3D reconstruction of the vascular channels has been D). The main problem is distinguishing between adjacent
and entangled cords. Cords positioned close to each other

without torsion is defined as adjacent umbilical cords,
whereas cords torqued over each other is called cord
entanglement.
Three-dimensional power Doppler examination permits
imaging of specific curvatures of the umbilical cord.
Moreover, the number of loops involved in the entanglement
can be determined easily. Counting the number of the
loops involved in entanglement provides a useful basis for
longitudinal assessment of the effects of entanglement, i.e.
tightening and subsequent fetal compromise.
Two types of the umbilical cord knots are possible:
(i) true and (ii) false. A focal redundancy of the vessels,
which sonographically appears as a vascular protuberance
that does not persist in all scanning planes, is called a
Figure 18.15 Three-dimensional power Doppler reconstruction
false-umbilical cord knot. 46 This condition should be of umbilical cord. Three-dimensional power Doppler provides an
distinguished from the true-umbilical cord knot which is a examiner with possibility to differentiate between false and true knots
potentially life-threatening condition (Fig. 18.15). in multiamniotic or umbilical cord entanglement and adjacent cords in
monoamniotic pregnancies
Four-dimensional Sonography in If, on the other hand, one performs 3D US, the complete
Multiple Pregnancy anatomy of both fetuses can be visualized simultaneously.
In spite of this progress, the technology is not suitable for
Real-time 2D US enabled visualization of spontaneous behavioral research because the images are static. Moreover,
motor activity in the singleton pregnancy. Reinold was fetal movements, the focus of interest for behavioral studies
one of the first to describe fetal activity using ultrasound, cause significant artifacts in visualization.
stressing the spontaneous character of early prenatal All these problems are resolved by four-dimensional
movements.47 Two types of motor activity are possible sonography (4D US) which provides spatial visualization
in multiple gestation: (i) spontaneous and (ii) stimulated. of the fetal anatomy and movements almost simultaneously
Spontaneous motor activity is defined as each embryonic with their appearance. Simultaneous visualization of
or fetal activity which is not evoked by internal or external the entire anatomy (head, body, and extremities) of two
stimuli. On the other hand, activity evoked by intertwin or more fetuses along with their movements allows
contacts is characterized as stimulated activity. Spontaneous the characterization of the type of movements, isolated
motor activity precedes stimulated activity, in terms of movements of each fetus, as well as intertwin contacts
gestational age of onset. and interactions (Fig. 18.16). Movement activity of each
The effect of prenatal reactions evoked by internal stimuli fetus can be easily determined in the first and early second
was the focus of interest of the systematic research initiated trimesters.49 Simultaneous visualization of motor activity of
by the group Arabin et al.48 These investigators used real- each fetus enables study of their isolated motoric activity
time 2D US for detection and evaluation of the intertwin (Figs 18.17 and 18.18).
contacts. However, due to sectional imaging, simultaneous It is possible to determine that one twin is active,
visualization of both fetuses and assessment of their motor whereas the co-twin or co-triplets are active or not. The
activity was impossible. Therefore, the motor activity of Arabin group defined intertwin contacts for the first time.43
a single fetus only provided a limited information. The According to this group, those movement patterns consist of
same limitation applies to the intertwin area when it is initiations and reactions of both twins which are sometimes
tomogramically visualized. Therefore, using this method difficult to distinguish by real-time 2D US, as many last no
to distinguish between spontaneous and stimulated motor longer than a few seconds. Using 4D US, complex parts
activities is not only difficult but sometimes impossible also. of these interactions could be analyzed for the first time.
Figure 18.16 Comparison between two techniques for evaluation of fetal behavior. Using realtime two-dimensional sonography hand-to-head
contact together with head-to-head intertwin contact can be recognized. Due to sectional imaging, it is impossible to categorize hand to head contact.
Image sequence shows advantages of spatial visualization. Hand-to-head movement can be differentiated to the hand-to-ear contact with following
the movement of the right hand forward. Head-to-head intertwin contact can be determined in details. Forehead of one twin contacts with cheek
of cotwin. Furthermore, facial expression of one twin is discernible
Figure 18.17 Figure sequence illustrates reconstruction of fetal motoric activity in twins at 13 weeks of pregnancy. It provides us with an option
of separated evaluation of fetal activity of each twin. Twin A is passive, whereas triplet B is active. One can see change of position of twin B
due to stretching movement pattern. It causes the change of postures. Moreover, this technique provides better assessment of combined hand
and leg movements. At first fetal hand it is positioned in front of the fetal face. During the movement, it is recognizable that fetal hand moved
from central part of face to the mouth region. Furthermore, leg movements could be assessed. At first, it is clearly visible that leg participates in
movement pattern due to visible change of their direction to uterine wall
Furthermore, 4D US is useful in evaluation of the altered XXX and some activities, such as yawning and stretching,
motor development such as in pathologic pregnancy.43 The are even not present.43 This is particularly important in
delay in activity pattern is described in twins with triploidy dizygotic twinning.
Figure 18.18 Figure sequence illustrates reconstruction of fetal motoric activity in twins at 13 weeks of pregnancy. Four-dimensional sonography
provides us with an option of separated evaluation of fetal activity of each twin. Twin A is active, whereas twin B is passive. One can see change
of position of twin’s A hand due to isolated hand movement. It seems that fetus is trying to release itself from the umbilical cord around the
neck. This may indicate that sensory development is going on at this gestational age. Umbilical cord causes tactile stimulus on fetal skin what
provokes hand movements
Conclusion References
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dimensional sonography should be used as complementary
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Four-dimensional sonography has several advantages over 3D 4. Bromley B, Benacerraf B. Using the number of yolk sacs to
US, which include more economic concerning, time consuming,
elimination of movement artifacts and visualization of fetal movement
determine amnionicity in early first trimester monochorionic
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rendered or multiplanar view is compensated with mentioned 5. Finberg HJ. The “twin peak” sign: reliable evidence of
advantages.
dichorionic twinning. J Ultrasound Med. 1992;11(11):571-7.
Despite 4D US is primarily reserved for evaluation of movement
of structures, although faster achievement of 3D images was 6. Sepulveda W, Sebire NJ, Odibo A, et al. Prenatal
noticed. Therefore, using 4D US is beneficial before the onset of determin ation of chorionicity in triplet pregnancy by
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and size of gestational sac leading to elimination of undercounting Gynecol. 1996;88(5):855-8.
phenomenon and improved prognosis, spontaneous pregnancy
reduction. Moreover, volumetric studies in multiple pregnancies 7. Doubilet PM, Benson CB. “Appearing twin”: undercounting
are less time consuming. of multiple gestations on early first trimester sonograms. J
It is expected that using 3D and 4D ultrasound new information Ultrasound Med. 1998;17(4):199-203.
regarding the exact determination of accurate number of gestational 8. Tadmor OP, Achiron R, Rabinowiz R, et al. Predicting first-
sacs, risk of spontaneous abortion and further analysis of inter-
human contacts will appear. Furthermore, 3D power Doppler trimester spontaneous abortion: ratio of mean sac diameter
ultrasound enables confidential differentiation between life- to crown-rump length compared to embryonic heart rate. J
threatening cord abnormalities such as cord entanglement and Reprod Med. 1994;39(6):459-62.
true umbilical cord knots and false-positive results achieved with
2D power Doppler ultrasound.
9. The American Fertility Society. The American Fertility
Society classification of adnexal lesions, distal tubal
Four-dimensional sonography is undoubtedly new powerful
imaging tool whose total scientific and clinical potential we shall occlusion, tubal occlusion secondary to tubal ligation,
be discovering in the coming decade. tubal pregnancies, müllerian anomalies and intrauterine
adhesions. Fertil Steril. 1988;49(6):944-55.
10. Green WM, Berry S, Wilkinson G. Twin pregnancy in a 26. Hoeffel CC, Nguyen KQ, Phan HT, et al. Fetus in fetu: a case
bicornuate uterus. J Clin Ultrasound. 1979;7(4):303-4. report and literature review. Pediatrics. 2000;105(6):1335-44.
11. Nahra-Lynch M. Toffle RC. Multiple gestation in a unicornuate 27. Grant P, Pearn JH. Foetus-in-foetu. Med J Aust. 1969;1(20):
uterus. A case report. J Reprod Med. 1997;42(7):451-4. 1016-9.
12. Gerris J, Eulaers E, Joostens M, et al. Successful triplet 28. Jones DC, Reyes-Múgica M, Gallagher PG, et al. Three-
pregnancy in a patient with a unicornuate uterus with a dimensional sonographic imaging of a highly developed
cavitary communicating rudimentary horn. Hum Reprod. fetus in fetu with spontaneous movement of extremities. J
1993;8(2):338-41. Ultrasound Med. 2001;20(12):1357-63.
13. Vecek N, Solak M, Tripalo A. A successful twin pregnancy in 29. Willis RA. The structure of teratoma. J Pathol Bacteriol.
single horn of didelphic uterus. Gynecologia et Perinatologia. 1935;40:1-36.
2003;12:180. 30. Hall JG, Lopez-Rangel E. Embryonic development and
14. Pryde PG, Isada NB, Johnson MP, et al. Triply discordant monozygotic twinning. Acta Genet Med Gemellol (Roma).
triplets: probability, management options and risks. Am J 1996;45(1-2):53-7.
Med Genet. 1992;44(3):361-4. 31. Edwards MS, Ellings JM, Newman RB, et al. Predictive
15. Grandjean H, Larroque D, Levi S. The performance of value of antepartum ultrasound examination for anomalies in
routine ultrasonographic screening of pregnancies in the twin gestations. Ultrasound Obstet Gynecol. 1995;6(1):43-9.
Eurofetus study. Am J Obstet Gynecol. 1999;181(2):446-54. 32. Allen SR, Gray LJ, Frentzen BH, et al. Ultrasonographic
diagnosis of congenital anomalies in twins. Am J Obstet
16. Xu HX, Zhang QP, Lu MD, et al. Comparison of two-
Gynecol. 1991;165 (4 Pt 1):1056-60.
dimensional and three-dimensional sonography in evaluating
fetal malformations. J Clin Ultrasound. 2002;30(9):515-25. 33. Bonilla-Musoles FM, Raga F, Ballester MJ, et al. Early detection
of embryonic malformations by transvaginal and color Doppler
17. Yonemoto H, Yoshida K, Kinoshita K, et al. Embryological
sonography. J Ultrasound Med. 1994;13(5):347-55.
evaluation of surface features of human embryos and
early fetuses by 3-D ultrasound. J Obstet Gynaecol Res. 34. Takeuchi H. Two- and three-dimensional sonoembryology
2002;28(4):211-6. in the embryonic period. In: Kurjak A, Chervenak FA,
Carrera JM (Eds). The Embryo as a Patient. Carnforth, UK:
18. Maggio M, Callan NA, Hamod KA, et al. The first-trimester
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ultrasonographic diagnosis of conjoined twins. Am J Obstet
35. Bronshtein M, Ornoy A. Acrania: anencephaly resulting from
Gynecol. 1985;152(7 Pt 1):833-5.
secondary degeneration of a closed neural tube: two cases in
19. Lam YH, Sin SY, Lam C, et al. Prenatal sonographic the same family. J Clin Ultrasound. 1991;19(4):230-4.
diagnosis of conjoined twins in the first trimester: two case
36. Fiske CE, Filly RA. Ultrasound evaluation of the normal
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and abnormal fetal neural axis. Radiol Clin North Am.
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of conjoined twins. Harefuah. 1993;124(12):741-4, 796.
37. Bonilla-Musoles F. Three-dimensional visualization of the
21. Tongsong T, Chanprapaph P, Pongsatha S. First-trimester human embryo: a potential revolution in prenatal diagnosis.
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Ultrasound Obstet Gynecol. 1999;14(6):434-7. 38. Dyson RL, Pretorius DH, Budorick NE, et al. Three-
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2000;20(2):169-70. volumetry of first trimester gestational sac: a comparison of
23. Weiss JL, Devine PC. False positive diagnosis of conjoined conventional with three-dimensional ultrasound. J Perinat
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2002;20(5):516-8. 40. Dickey RP, Olar TT, Taylor SN, et al. Incidence and
24. Maymon R, Halperin R, Weinraub Z, et al. Three- significance of unequal gestational sac diameter or embryo
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1998;11(4):292-4. 41. Weissman A, Achiron R, Lipitz S, et al. The first-trimester
25. Jeanty P, Caldwell K, Dix PM. Fetus in fetu. Fetus. growth-discordant twin: an ominous prenatal finding. Obstet
1992;2:6518-9. Gynecol. 1994;84(1):110-4.
42. Kurjak A, Kos M, Vecek N. Pitfalls and caveates in ultrasound 46. Dudiak CM, Salomon CG, Posniak HV, et al. Sonography
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I (Eds). Triplet Pregnancies and Their Consequences. 47. Reinold E. Clinical value of fetal spontaneous movements
Carnforth, UK: Parthenon Publishing; 2002.pp.85-105. in early pregnancy. J Perinat Med. 1973;1(1):65-72.
43. Gassner R, Metzenbauer M, Hafner E, et al. Triploidy
48. Arabin B, Bos R, Rijlaarsdam R, et al. The onset of inter-
in a twin pregnancy: small placenta volume as an early
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sonographical marker. Prenat Diagn. 2003;23(1):16-20.
in early twin pregnancies. Ultrasound Obstet Gynecol.
44. Downey DB, Fenster A, Williams JC. Clinical utility of
1996;8(3):166-73.
three-dimensional US. Radiographics. 2000;20(2):559-71.
45. Downey DB, Fenster A. Vascular imaging with a three- 49. Vecek N, Solak M, Erceg-Ivkosic I. Four-dimensional
dimensional power Doppler system. AJR Am J Roentgenol. sonography in multiple pregnancy. Gynecologia et
1995;165(3):665-8. perinatologia. 2003;12:157.
Section 3
GYNECOLOGY AND INFERTILITY
¯¯ Uterine Lesions
¯¯ 2D and 3D Power Doppler Ultrasound Study of Endometrium as Implantation Marker
¯¯ Follicular Monitoring
¯¯ Asymptomatic Simple Ovarian Cyst in Postmenopausal Women: Syndrome of “Visible Ovary”
¯¯ Transvaginal Sonography in Evaluation of Functional Ovarian Cysts
¯¯ Baseline Scan and Ultrasound Diagnosis of PCOS
¯¯ Hormone Replacement Therapy: Ultrasound Role
¯¯ Ectopic Pregnancy
¯¯ Female Pelvic Floor: Descriptive Anatomy and Clinical Exploration by Transvaginal Ultrasound
Echography
¯¯ Sonography of the Pelvic Infection
¯¯ Sonohysterography
¯¯ Transvaginal Sonography in Postmenopausal Women
¯¯ Use of Different Ultrasound Techniques in the Field of Urogynecology
CHAPTER
19
Uterine Lesions
Sanja Kupesic Plavsic, Asim Kurjak, Jose Bajo Arenas
Introduction vascularity, enabling visualization of the overlapping

vessels and assessment of their relationship to other
The aim of this chapter is to investigate the role of color vessels or surrounding tissue. Power Doppler ultrasound
Doppler and three-dimensional ultrasound (3D US) in compared to standard color Doppler has the advantage
the evaluation of the uterine lesions. Morphological and of more sensitivity to low velocity flow, overcoming the
vascular criteria assessed by different forms of ultrasound angle dependence and aliasing. Using contrast agents, it is
are listed for each type of the uterine lesions. possible to enhance the 3D power Doppler examination rate
The uterus lies in the middle of the pelvis with its of small vessels.
long axis perpendicular to the ultrasound probe. Using In this chapter, the authors have compared the findings
two-dimensional ultrasound (2D US), the examination of uterine lesions assessed with conventional B-mode and
of the uterine lesions is limited to transverse and sagittal transvaginal color Doppler ultrasound on one side and three-
planes, which give an inadequate view of the uterus and dimensional and power Doppler ultrasound on the other.
uterine pathology. Three-dimensional ultrasound provides
simultaneous display of coronal, sagittal and transverse
planes. Volume data can be viewed using a standard
Normal Uterus
anatomic orientation demonstrating entire volume and Two-dimensional ultrasound imaging of the uterus is
continuity of curved structures in a single image. More limited due to the movement of the transducer, allowing
accurate evaluation of numerous sections through the sagittal and transverse planes through the uterus. Three-
studied organ becomes possible due to no limitation of dimensional sonography permits multiplanar display of all
number and the orientation of reformatted planes. When three perpendicular sections: (i) coronal, (ii) sagittal, and
three perpendicular planes are simultaneously displayed (iii) transverse plane. The coronal plane of the uterus enables
on the screen, sagittal plane is chosen for volume to visualize both horns of the endometrium and the cervix at
measurements, while the other two planes are used to ensure the same time. The normal uterus is usually presented by a
that the entire pathology is included in the measurement. convex shape of the endometrium and myometrium in the
Surface rendering mode allows exploration of the outer fundus. Blood vessels of the uterus and endometrium can
or inner contour of the lesion, while “niche aspect” be detected by color and power Doppler ultrasound, where
presents detection and analysis of the selected sections of endometrium and myometrium constitute an anatomical
the uterine lesion. Three-dimensional ultrasound offers and functional unit. Uterine arteries branch off the internal
improved visualization of the lesions, more accurate volume iliac arteries. Ultrasonically, they look like hyperechoic
estimation, retrospective review of stored data, assessment structures running along the cervix and the isthmic part of
of tumor invasion and using rendered images, it can identify the uterus. Arcuate arteries are tortuous anechoic structures
more accurately location of abnormalities needing surgical that spread through myometrium. Radial arteries penetrate
intervention. vertically the myometrial layers of smooth muscle cells.
Three-dimensional sonohysterography is very useful Spiral arteries supply stratum functional of endometrium.
in the evaluation of the uterine cavity and is more useful Their shape and size change during menstrual cycle
than hysterosonography by two-dimensional transvaginal and they shed during menstruation together with the
ultrasound in cases of submucous myomas and polyps. glandular tissue. During pregnancy, these arteries become
The three-dimensional power Doppler system improves uteroplacental decidual arteries. Basal arterioles supply
the information available on normal and abnormal (tumoral) endometrial stratum basale. They do not change during
180 Section 3  Gynecology and Infertility
menstrual cycle. Color Doppler research has determined Endometrial Polyps

that every blood vessel in the body has its own typical
waveform. This waveform changes under the influence of Endometrial polyps develop as solitary or multiple, soft,
hormones, ischemia, internal or external vasoactive factors. sessile or pedunculated tumors, containing hyperplastic
The vessels in genital tract undergo cyclic changes dictated endometrium.1,2 Clinically, asymptomatic or symptoms,
by the hormonal cycle. During the menstrual phase, due to like infertility, bleeding, infection, endometritis or pain,
hormonal deprivation and alterations in the spiral arteriolar are usually present in patients with endometrial polyps.
system, spiral arteries undergo increased coiling and Ultrasonographic appearance of endometrial polyps is
cause a circulatory stasis, which leads to tissue ischemia. best imaged during the early proliferative phase of the
Vasoconstriction of the spiral arterioles and necrosis of their menstrual cycle or during the secretory phase after injection
walls result in bleeding. Anechoic areas, that are sometimes of a negative contrast medium into the uterine cavity. The
visualized, indicate endometrial breakdown. Later on, a vascularization of polyps is supported by already existing
mixed appearance with anechoic area (indicating blood) vessels originating from terminal branches of the uterine
and hyperechoic parts (exfoliated endometrium and clots) arteries assessed by transvaginal color Doppler ultrasound.
can be observed. During the late menstrual phase, the It is possible to identify flow in regularly separated vessels
endometrium appears sonographically as a thin, single-line, and analyze the velocity of blood flow through them. The RI
with slightly irregular echogenic interface. In this phase, is moderate, usually higher than 0.451,3 (Fig. 19.1). Infection
the uterine artery shows high resistance index (RI). In the or necrosis of polyps may lower the impedance to blood flow
early follicular phase, the endometrium is imaged as a (RIMIN = 0.37). The importance of endometrial polyps lies
hyperechoic line with endometrial thickness of less than in the fact that marked reduction in blood flow impedance
5 mm, but is not always possible to visualize the endometrial- noted on the periphery and/or within the endometrial polyps
myometrial junction. As the ovulation approaches, the glands may lead an inexperienced ultrasonographer to a false-
become numerous and the expected endometrial thickness positive diagnosis of endometrial malignancy.
is about 10 mm. A triple-line endometrium is typical of the Tamoxifen is a nonsteroidal antiestrogen that is widely
periovulatory phase. The hyperechoic echo that represents used in the hormonal therapy of breast cancer. However,
the endometrial-myometrial junction becomes more the weak estrogen-like effect that tamoxifen has on the
prominent and does not produce posterior enhancement. endometrium is a cause of great concern. Patients using
The central echogenic interface probably represents the tamoxifen should, therefore, be monitored at regular
mucus. Doppler velocimetry of the spiral arteries shows intervals, since several studies have described cases
progressive diminution of resistance indices. Secretory
phase is characterized by hyperechoic and homogenous
endometrium with a loss of the triple-line morphology and
surrounding anechoic halo. During this phase of the cycle,
the ultrasonographic image of the endometrium shows
increased echogenicity with respect to the myometrium.
The interface of the myometrium with the endometrium is
still visible as a hypoechoic zone. Maximum echogenicity is
seen in the mid-luteal phase, when the endometrium appears
homogeneously hyperechoic. Posterior enhancement
is a sonographic characteristic of this phase. Doppler
velocimetry demonstrates further decrease of the vascular
resistance in uterine and spiral arteries being the lowest in
the mid-luteal phase.
Since changes in the texture and volume of the
endometrium can be precisely observed using 3D US and
retrospectively reviewed or consulted with colleagues,
Figure 19.1 Transvaginal color Doppler scan of a small endometrial
this method may become a method of choice for scanning polyp. Note the moderate resistance (RI = 0.56) signals obtained from
endometrial pathology in multitude of clinical conditions. the periphery of this lesion (right)
Chapter 19  Uterine Lesions 181
of endometrial cancer associated with this therapy. A than with TVS, transvaginal sonohysterography, transvaginal
wide spectrum of pathological uterine findings has been color Doppler or hysteroscopy according to Bonilla-Musoles
described in association with long-term tamoxifen therapy et al.11 Using the multiplanar views, polypoid structures
at a dose of 20 mg/day.4 These findings include epithelial can be nicely visualized, allowing for the optimal plane to
metaplasia, simple and atypical hyperplasia, endometrial present their pedicle. Surface rendering mode can suppress
polyps and endometrial carcinoma.5 Endometrial changes undesirable echoes allowing seeing the polypoid structure
are characterized sonographically by abnormal endometrial in continuity with the endometrial lining.12
thickening and non-homogeneous hyperechogenicity, with Gruboeck et al. 13 performed the measurements of
multiple, small cystic structures. At least three studies have endometrial thickness assessed by conventional 2D US and
indicated that tamoxifen treatment in postmenopausal endometrial volume assessed with 3D US in symptomatic
breast cancer patients is associated with a high incidence of postmenopausal patients and they compared the results.
endometrial polyps.6-8 Achiron and colleagues7 found that The endometrial thickness was similar in patients with
a peculiar endometrial honeycomb appearance, manifested endometrial hyperplasia and polyps, but the endometrial
on gray-scale transvaginal sonography (TVS), occurred in volume in hyperplasia was significantly higher than the
44% of this population and was associated with the same volume in patients with polyps. In conclusion, the difference
high incidence (40%) of endometrial polyps. The effect between endometrial hyperplasia and polyps cannot be
of tamoxifen on endometrial blood flow is less evaluated. detected by the measurement of endometrial thickness,
Achiron and his group described blood flow changes in the but with 3D volume measurement. Polyps are localized
endometrial and subendometrial regions. In asymptomatic thickenings of the endometrium not affecting the whole
postmenopausal patients receiving tamoxifen, whose of the uterine cavity and, therefore, their volume is much
endometrial thickness was less than 5 mm, increased smaller, while the maximum thickness is similar to that of
endometrial blood flow with significant reduction of the hyperplasia. The volume measurement is performed using
RI compared to untreated, control menopausal women longitudinal plane delineating the whole of the uterine
was reported. Another study by the same authors5 found cavity in a number of parallel longitudinal sections, 1–2
that women with thick endometrium and particularly those mm apart. Then, the endometrial volume is calculated
with endometrial polyps presented a significantly lower RI, automatically by the inbuilt computer software program.
compared to those with thin endometrium (mean RI of 0.39
versus 0.79). The RI values returned to normal, following
Intrauterine Synechiae (Adhesions)
resection of the endometrial polyps, thus supporting a
benign transitory effect of long-term tamoxifen therapy on Destruction of the basal layer of the endometrium may
the endometrium. result in scarring and development of bands of scar
The data from Goldstein et al.9 suggests that the objective tissue (synechiae) in the uterine cavity. This damage of
assessment of blood flow impedance [RI, pulsatility index endometrium may occur as a result of a too vigorous
(PI)] in endometrial polyps and the size of these polyps curettage of an advanced pregnancy. Tuberculosis may also
cannot replace surgical removal and pathologic evaluation cause uterine adhesions. Menstrual pattern is characterized
to predict histologic type. Patients with nonfunctional by amenorrhea or hypomenorrhea. Ultrasound scan of
polyps were older and less likely to have vaginal bleeding. a patient with Asherman’s syndrome shows a mixed
Perez-Medina et al.10 evaluated the efficacy of color picture—in some parts of uterine cavity, no endometrium
Doppler exploration for assessing atypia inside endometrial can be visualized and, in others, the endometrium appears
polyps (polyp stalk). Thirty-five polyps (out of 106) with normal. If there are adhesions in the uterine cavity, they are
sonographic indications of atypia were pathologically visualized as hyperechoic bridges. Intrauterine adhesions
confirmed. Sonographic indications of atypia inside do not display increased vascularity on color Doppler
16 polyps were not confirmed. Three nonquestionable examination (Fig. 19.2). They are better visualized during
endometrial polyps had atypia inside them. They concluded menstruation, when intracavitary fluid outlines them. The
that low Doppler resistance (RI < 0.50) is highly predictive second option is sonohysterography.
of atypia inside endometrial polyps. Sonohysterography performed with 3D US has several
Three-dimensional hysterosonography can better advantages over that with conventional 2D US. It gives more
visualize the uterine cavity and the endometrial thickness accurate information about the location of abnormalities,
Figure 19.2 Transvaginal sonogram of an infertile patient with Figure 19.3 “Swiss cheese” appearance of the myometrium showing
intrauterine synechiae. Note the hyperechoic bridges within the increased vascularity typical of adenomyosis
endometrial cavity
which is very important for preoperative assessment and Two-dimensional ultrasound findings include “Swiss
distinguishing pathologies. Furthermore, the uterus is for cheese” appearance of the myometrium due to areas
shorter time distended compared to the time necessary of hemorrhage and clots within the muscle (Fig. 19.3).
for 2D examinations, which results in better patients’ Disordered echogenicity of the middle layer of the
acceptance. However, according to Momtaz et al.14 in cases myometrium is usually present in severe cases. Sometimes
of intrauterine adhesions, the use of echogenic contrast the uterus is generally hypoechoic, with the large cysts rarely
media (e.g. Echovist, Schering) is more accurate than saline- seen. Using hysterosonography, contrast medium penetrates
contrast 3D sonohysterography. Intrauterine synechiae can the myometrium. Color Doppler characteristics present
be accurately visualized on both multiplanar and rendered increased vascularity by moderate vascular resistance
imaging traversing the uterine cavity.12 Weinraub et al.12 within the myometrium (RI = 0.56 ± 0.12), while the RI
concluded that surface rendering in cases of equivocal of the uterine arteries show a decreased value compared
signals confirmed their presence, appearance, actual size, to controls.15 Statistically significant differences exist
volume and relationship to the surrounding structures. between adenomyosis and uterine malignancies in both RI
Three-dimensional ultrasound is helpful in delineation and maximum velocity. However, no significant difference
of intracavitary adhesions and determination of their was noted between adenomyosis and myoma in the RI, but
location, which assists in surgical planning. In the cases a slight difference was observed in the maximum velocity.16
of bridging adhesions, the degree of cavity obliteration is In some cases, transonic areas may not represent
accurately assessed. Similarly, this technique is beneficial adenomyosis, but prominent vessels or other conditions
for differentiation between small polyps and adhesions. which give rise to hyperemia. Lee et al.17 performed the
study which confirmed the superiority of three-dimensional
power Doppler sonography (3D PDS) compared to
Adenomyosis
transvaginal color Doppler ultrasound in the detection of
Adenomyosis of the uterus is a condition in which clusters flow in the areas of adenomyosis. Women with a provisional
of endometrial tissue grow into the myometrium. It may be diagnosis of adenomyosis, listed for hysterectomy were
localized close to endometrium or it may extend through studied. Gray scale ultrasound was first used to screen
the myometrium and serosa. Adenomyosis affects 20% of for the presence of adenomyosis using predetermined
women, mainly multiparous. The uterus can be normal- ultrasound criteria. Then 3D PDS of adenomyotic areas
sized or enlarged with symptoms, such as dysmenorrhea, was performed. Ultrasound findings, such as distribution
pelvic pain and menometrorrhagia. of vessels and pattern of flow in adenomyotic foci, were
compared with histological results. The same method was impedance and number of years from menopause,19 one can
used for tracing regular vessels’ course in this abnormality. estimate the risk of uterine malignancy in postmenopausal
Using 3D PDS the authors were able to demonstrate the patients with decreased vascular resistance.
perfusion in adenomyotic foci as well as the vessels’ Emoto et al.20 examined the usefulness of transvaginal
distribution and their branching pattern. color Doppler ultrasound in differentiating between
endometrial hyperplasia and endometrial carcinoma and
Endometrial Hyperplasia in predicting tumor spread in patients with carcinoma.
No significant difference was found in the mean value of
The endometrial thickness in postmenopausal women is no endometrial thickness between patients with hyperplasia
more than a thin line of 1–3 mm. Abnormal endometrial (n = 18 patients; 16.2 ± 15.9 mm) and patients with
thickness may be detected in some benign uterine conditions, carcinoma (n = 53 patients; 18.7 ± 17.1 mm). Intratumoral
as well as in the endometrial malignancy. Endometrial blood flow was detected in significant numbers of patients
thickness greater than 14 mm in premenopausal and greater who had endometrial carcinoma (71.7%; 38 of 53 patients)
than 5 mm in postmenopausal women should be further compared with patients who had endometrial hyperplasia
investigated.1 Using B-mode TVS alone, it is not possible to (5.6%; 1 of 18 patients; p < 0.0001). Thus, no patients with
distinguish endometrial hyperplasia from carcinoma. More hyperplasia showed any blood flow in the endometrial
accurate diagnosis of endometrial pathology can be obtained lesions, transvaginal color Doppler may be more useful
by color and pulsed Doppler sonography.2,3 Color Doppler in differentiating between endometrial hyperplasia and
findings characteristically for endometrial hyperplasia carcinoma than measuring endometrial thickness by
include peripheral distribution of the regularly separated transvaginal gray-scale sonography. For patients with
vessels with RI significantly higher (mean RI = 0.55 ± 0.05) carcinoma, the detection of intratumoral blood flow may be
(Fig. 19.4) than in carcinoma (mean RI = 0.42 ± 0.02).18 helpful in distinguishing between low-grade and high-grade
However, reliable differentiation between endometrial tumors and predicting myometrial invasion. However,
hyperplasia and carcinoma is not possible due to an overlap intratumoral blood flow analysis using RI, PI, or peak
in the endometrial thickness measurements, as well as systolic velocity (PSV) may not be useful for predicting
due to controversial results of blood flow measurements tumor spread before surgery.
assessed by transvaginal color Doppler ultrasound. Since Jarvela et al.21 evaluated the possible hemodynamic
there is a positive correlation between arterial blood flow changes in uterine blood flow using transvaginal color
Doppler ultrasonography after thermal balloon endometrial
ablation therapy. Thermal balloon endometrial ablation
therapy induces a rise in uterine blood flow impedance, but
not until 6 months after the treatment. The rise in impedance
may be due to fibrosis in the uterine cavity which thermal
balloon therapy has been shown to produce.
More recently, with the aid of 3D US, endometrial volume
measurements became possible. According to Gruboeck
et al.13 endometrial volume was successfully measured in
94.2% of patients, while in others the presence of anterior
uterine wall myomas caused acoustic shadowing on 3D
records. The volume of the endometrium was measured
by delineating the uterine cavity on parallel longitudinal
sections 1–2 mm apart. The sections were added together
using inbuilt computer software to calculate the volume.
The endometrial volume was significantly lower in patients
Figure 19.4 Transvaginal color Doppler scan of an asymptomatic with benign pathology such as hyperplasia (mean 8.0 ml,
postmenopausal patient with thickened endometrium. Moderate SD 7.81 ml) than in patients with endometrial carcinoma
vascular resistance signals (RI = 0.48) were isolated from the periphery
of the endometrium. Histopathology demonstrated endometrial (mean 39.0 ml, SD 34.16 ml). Normal endometrial volume
hyperplasia in this study was 0.9 ml (SD 1.72 ml).
Our group reported on the use of 3D PDS in patients with

endometrial hyperplasia;21 we were able to demonstrate
regularly separated vessels at the periphery of the examined
endometrium.
Bonilla-Musoles et al. have suggested that in patients
on hormone replacement therapy or tamoxifen, 3D
sonohysterography allowed for differentiation of normal
proliferative from hyperplastic endometrium.11
Endometrial Carcinoma
Endometrial carcinoma is the most common gynecological
malignancy in many countries with the reported incidence
of about 10% in postmenopausal patients presenting uterine
bleeding. Early transabdominal sonographic investigations
have demonstrated that increased endometrial thickness is
associated with endometrial neoplasms in postmenopausal Figure 19.5 Transvaginal color Doppler scan of endometrial carcinoma
vessels. Peritumoral vessels demonstrate low resistance index (RI = 0.38)
women, but the quality of transabdominal sonographic
images is affected by obesity, retroversion of the uterus
and an unfilled bladder, factors that do not influence to be more helpful. Gruboeck et al.13 compared endometrial
transvaginal sonographic visualization of the endometrium. thickness and volume in patients with postmenopausal
Ultrasound findings assessed by conventional B-mode bleeding and examined the value of each parameter in
sonography include increased endometrial thickness greater differentiating between benign and malignant endometrial
than 5 mm in postmenopausal women or greater than 8 mm pathology. Each patient underwent three-dimensional
in perimenopausal women, hyperechoic endometrium, free ultrasonography for the measurement of endometrial
fluid in the cul-de-sac, intrauterine fluid or possible invasion thickness and volume. The results were compared to the
in patients with disrupted endometrial-subendometrial histological diagnosis after endometrial biopsy or dilatation
layer. In addition, color and pulsed Doppler improves and curettage. The mean endometrial thickness in patients
diagnostic accuracy, because the endometrial carcinoma with endometrial cancer was 29.5 mm (SD 12.59) and the
shows abnormal blood flow due to tumor angiogenesis.22 mean volume was 39.0 ml (SD 34.16). The optimal cut-off
Endometrial blood flow is absent in normal, atrophic and value of endometrial thickness for the diagnosis of cancer
most cases of endometrial hyperplasia, while, according was 15 mm, with the test sensitivity of 83.3% and positive
to our investigation,18 in 91% of the cases of endometrial predictive value of 54.4%. With a cutoff level of 13 ml, the
carcinoma areas of neovascularization were demonstrated diagnosis of cancer was made with the sensitivity of 100%.
as intratumoral or peritumoral (Fig. 19.5). Neovascular One false-positive result in a patient with hyperplasia gave a
signals from the central parts of the lesion demonstrate specificity of 98.8% and positive predictive value of 91.7%.
low vascular resistance (RI = 0.42 ± 0.02), while increased According to Gruboeck et al.13 the endometrial volume was
vascularity signals surrounding the lesion are suspected significantly higher in patients with carcinoma than those
for invasion. If the myometrial vessels are invaded, low with benign lesions. The measurements of endometrial
vascular resistance is detected due to incomplete or absent volume were superior to that of endometrial thickness as
membrane and leaky structure. a diagnostic test for the detection of endometrial cancer in
Conventional 2D US measurements of endometrial symptomatic postmenopausal women. Increasing volume
thickness have disadvantages in distinguishing patients size is associated with the severity or higher grade of the
with benign and malignant endometrial pathology due to endometrial carcinoma and also with progressive myometrial
varying thickness and interference of other pathology like invasion. The depth of myometrial invasion showed positive
polyps or hypoplasia. correlation with both endometrial thickness and volume.
In distinguishing cancer from benign pathology, Only patients with tumor volume larger than 25 ml had
endometrial volume measurements assessed by 3D US seems evidence of pelvic node involvement at operation.
Bonilla et al. 11 suggest that 3D hysterosonography patients with benign endometrial lesions and in 5 patients
allowed for better visualization of myometrial invasion, with endometrial malignancy. Dichotomous branching
playing a significant role in staging malignant tumors in the and randomly dispersed vessels were detected in 91.67%
future. Using simultaneous display of the transverse plane of the patients with endometrial carcinoma, while single
with 3D US, it is possible to detect infiltration of cervical vessel arrangement and regular branching were typical for
or endometrial carcinoma into the bladder or rectum. benign lesions. Three-dimensional PDS accurately detected
In our study,23 apart from endometrial volume, other 3D structural abnormalities of the malignant tumor vessels such
sonographic and power Doppler criteria for the diagnosis as microaneurysms, arteriovenous shunts, tumoral lakes,
of endometrial malignancy included subendometrial halo, elongation and coiling. Combining morphological and power
irregularity, presence of the intracavitary fluid, chaotic Doppler criteria, the diagnosis of endometrial carcinoma
vessel’s architecture and branching pattern (Table 19.1). had a sensitivity of 91.67%. One false-positive result was
In patients with endometrial carcinoma, mean endometrial obtained in a patient with endometrial hyperplasia and one
volume was 37.0 ± 31.8 ml (Table 19.2). The endometrial false-negative in a patient with endometrial carcinoma
volume in hyperplasia had the mean value of 7.82 ± 7.60 receiving tamoxifen therapy. In this case, endometrial lesion
ml and was significantly higher than the volume in patients demonstrated regularly separated peripheral vessels was
with polyps (mean 2.63 ± 2.12 ml). In patients with normal falsely interpreted as hyperplasia.
or atrophic endometrium, the mean volume was 0.8 ± 1.51 Kupesić et al. 24 performed staging of endometrial
ml. Subendometrial halo was regular in all patients with carcinoma by 3D power Doppler. The objective of this
benign endometrial pathology, whereas 8 out of 12 patients study was to evaluate the accuracy of three-dimensional
with endometrial carcinoma had irregular endometrial- power Doppler in determining the depth of myometrial
myometrial border. Intracavitary fluid was present in 4 invasion in patients with proved adenocarcinoma of the
Table 19.1 Three-dimensional sonographic and power Doppler criteria for the diagnosis of endometrial malignancy
3D sonographic and power Doppler Scores
criteria
Endometrial volume <13 ml 0
≥13 ml 2
Subendometrial halo Regular 0
Disturbed 2
Intracavitary fluid Absent 0
Present 1
Vessel’s architecture Linear vessel arrangement 0
Chaotic vessel arrangement 2
Branching pattern Simple 0
Complex 2
Total score
Total score = sum of individual scores

Cutoff score = greater or equal to 4 is associated with a high risk of endometrial malignancy
(Source: Reference 23, with permission)
Table 19.2 Volume and vascularity of the endometrial lesions (N = 57) obtained by three-dimensional power Doppler sonography
Histopathology N V (SD) ml Regular endometrial halo (%) Intracavitary fluid (%) Neovascular signals (%)
Normal and/or atrophic endometrium 10 0.8 (1.51) 100 20.00 0
Endometrial hyperplasia 27 7.82 (7.60) 100 37.00 0
Endometrial polyp 28 2.63 (2.12) 100 35.71 3.57
Endometrial carcinoma 12 37.0 (31.8) 66.67 41.67 100
(Abbreviation: SD, Standard deviation Source: Reference 23, with permission)

Table 19.3 Invasion of endometrial carcinoma assessed with the with angiogenesis and vascular endothelial growth factor
aid of three-dimensional power Doppler sonography (3D PDS) levels and might play an important role in predicting tumor
Invasion 3D PDS Pathohistology progression and metastasis in endometrial carcinoma.
Superficial* 17 18 Alcazar et al.26 correlated intratumoral blood flow as
Deep** 5 4 assessed by transvaginal color Doppler ultrasound (RI and
PSV) with tumor histopathologic characteristics, tumoral
*Invasion into less than a half of the total myometrial thickness
**Invasion into more than a half of the myometrial thickness stage and risk for recurrence in endometrial carcinoma.
(Source: Reference 24, with permission) Significantly lower RI was found in tumors with the
following characteristics—infiltrative growth pattern,
grade 3, infiltrating greater than or equal to 50% of the
endometrium, relative to the amount of myometrial invasion myometrium, cervical involvement, lymph-vascular space
measured in histopathological analysis (Table 19.3). Thirty- invasion, lymph node metastasis, stage greater than or equal
four patients with histologically proved adenocarcinoma to Ic and high risk for recurrence. Significantly higher PSV
of the endometrium were analyzed. Deep myometrial was found in tumors that were grade 3, infiltrating greater
invasion (>50%) was present at postoperative histology in than or equal to 50% of the myometrium, stage greater than
5/22 (22.73%) women, while superficial was reported in or equal to Ic and with a high risk for recurrence. Their data
17/22 (77.23%) women. Three-dimensional power Doppler indicate that a correlation between intratumoral blood flow
demonstrated a sensitivity of 100% (5/5) and a specificity of features and histopathological characteristics, tumor stage,
94.44% (17/18) for deep invasion, with a positive predictive and risk for recurrence exists in endometrial cancer.
value (PPV) of 83.33% (5/6) and a negative predictive value Yaman et al. 27 evaluated the reproducibility of
(NPV) of 100% (17/17). In only 1 patient with adenomyosis, transvaginal three-dimensional endometrial volume
invasion was overestimated by 3D power Doppler. Data measurement in patients with postmenopausal bleeding
showed acceptable accuracy in determining the depth of and compared the reproducibility of this technique to that
myometrial invasion in patients with adenocarcinoma. of two-dimensional endometrial thickness measurement.
Three-dimensional power Doppler can potentially detect Endometrial volume and thickness measurements by 3D
lesions that require aggressive intervention and thus direct and 2D US respectively show good reproducibility, but the
to proper treatment. reproducibility of 3D US is better.
Lee et al.25 evaluated the relationship between blood
flow in the tumor assessed by color Doppler ultrasound,
microvessel density immunohistochemically, and vascular
Leiomyoma
endothelial growth factor levels in endometrial carcinoma. Leiomyomas are the most common tumors of the female
Significantly lower RIs were noted in tumors of stage II pelvis and occur in 20–25% of women of reproductive
or greater (0.37 compared with 0.50, p < 0.001), of high age, arising from the smooth muscle and soft tissue of
histologic grade (grade 3) (0.34 compared with 0.49, p = the uterine fundus and corpus, while 3% originate from
0.004), with deep myometrial invasion (one-half depth cervix.28 Myomas are usually multiple and of various
or greater) (0.39 compared with 0.49, p = 0.002), with sizes. Intramural tumors are the most common, while the
lymphovascular emboli (0.38 compared with 0.49, p<0.001) submucosal are the least common. If they extend outward,
or with lymph node metatasis (0.30 compared with 0.49, they become either pedunculated or subserosal.29 Symptoms
p < 0.001) compared with stage I tumors and tumors of of submucous leiomyomas include metrorrhagia, pelvic
histologic grade 1 or 2, with superficial myometrial invasion, pain or infertility, whereas most subserosal leiomyomas
without lymphovascular emboli or with no lymph node are asymptomatic.
metastasis. Increased vascular endothelial growth factor On the gray-scale ultrasound, the uterine leiomyomas
levels and microvessel density also were detected in tumors may be represented with uterine enlargement, distortion of
of stage II or greater, with lymphovascular emboli or with the uterine contour and varying echogenicity depending on
lymph node metastasis. Resistance index, microvessel density the amount of connective or smooth muscle tissue.
and vascular endothelial growth factor levels in the tumor Transvaginal color Doppler sonography demonstrates
showed linear correlations. Blood flow assessed by color vascularization on the periphery of the myoma of uterine
Doppler ultrasound has histologic and biologic correlations origin, with the RI of 0.54 ± 0.08, allowing better delineation
In our recent study,23 we evaluated myometrial lesions,
morphology, volume and vascularization with 3D US and
PDS. The mean volume of the leiomyomas undergoing
surgery was 78.52 ± 51.8 ml. In 84.38%, 3D power Doppler
detected regular vascularity at the periphery, while in
cases of secondary degenerative lesions, the findings were
suggestive of neovascularity, irregular branching and chaotic
vascular arrangement because necrosis, inflammation
and degeneration altered the leiomyoma vasculature. We
concluded that because of the low positive predictive value
of 16.67%, this method should not be used for the evaluation
of myometrial pathology, both benign and malignant.
Leiomyosarcoma
Uterine sarcoma is a rare tumor, accounting for only 1–3%
Figure 19.6 Transvaginal color Doppler scan of the uterus with a of all genital tract tumors and 3–7.4% of malignant tumors
leiomyoma in the posterior wall and superimposed color Doppler (left). of the corpus uteri,33 characterized by early dissemination
Waveform analysis (right) indicates the high velocity (120.8 cm/s) and
moderate resistance of the tumor blood flow (RI = 0.56, PI = 0.88) and poor prognosis for survival. Through the years,
several questions regarding these tumors have remained
unanswered and a method for its early and correct diagnosis
of the tumor (Fig. 19.6). Blood vessels in the central part is still unknown. Furthermore, uterine sarcoma is expected
of the myoma in case of necrosis, inflammation or other to be more common in the near future, as gynecologists
degenerative changes demonstrate lower RI. Uterine are more commonly using the conservative treatment of
arteries present lower impedance to blood flow in patients uterine myomas. Abnormal vaginal bleeding is the most
with myomas (RI = 0.74 ± 0.09) compared to normal (RI common presenting symptom in patients with uterine
= 0.84 ± 0.09).30 sarcoma. Lower abdominal pain or pressure and a palpable
Using simultaneous display of three perpendicular abdominal mass are additional findings. An enlarged bulky
planes, assessed by 3D US, demonstrates the accurate uterus is palpated, and/or the tumor may be seen protruding
location of myomas, size and its relationship to the through the cervix. Dilatation and curettage may be helpful
endometrium that is very important in therapy planning. in distinguishing benign from malignant pathology only
Patients receiving medical therapy, such as gonadotropin- if the tumor is submucous. Clinically, a rapid increase in
releasing hormone, may be followed with serial 3D the size of a uterine tumor after the menopause arouses
US scans to estimate myoma size and effectiveness of suspicion of sarcoma.
the therapy. Hysterosonography by 3D US is valuable Ultrasonically, leiomyosarcoma is presented as
in obtaining submucous myomas.11,12,31,32 Balen et al.31 solid or solid-cystic structure, altering echogenicity
found that 3D US and sonohysterography was useful in of the myometrium. On transvaginal color Doppler,
demonstrating the position of submucosal myomas. They neovascularization of leiomyosarcoma is detected at the
studied both saline and a positive ultrasound contrast agent border or in the center of the tumor (Fig. 19.7) with high
(Echovist) and found the positive contrast superior when blood flow velocity and low impedance to blood flow
looking at the cavity wall. Weinraub et al.12 found that the (RI = 0.37 ± 0.03), with irregular, thin, randomly dispersed
negative contrast was better for evaluating the accurate vessels (Fig. 19.8). When cutoff value for RI of less than
contents of the uterine cavity delineating of the outer surface 0.40 was used, this method reached the sensitivity of
of lesions, whereas positive contrast only created a cast of 90.91%, specificity 99.82%, PPV of 71.43% and NPV of
the cavity. 99.96%.34 Because of their rarity, uterine sarcomas are not
One limitation of scanning the uterus with myomas suitable for screening. Transvaginal ultrasound can detect
by 3D or 2D US is due to a significant shadowing from differences in myometrial tissue density and therefore can
calcification. be used for detection of uterine sarcoma, but because of low
Figure 19.7 Transvaginal color Doppler scan of a uterine tumor. Figure 19.8 Areas of neovascularization with low impedance to flow
Note the prominent areas of tumor angiogenesis demonstrated by the (RI = 0.38) are typical of uterine sarcoma
colored zone. Histopathology revealed uterine sarcoma
specificity, this method is not appropriate as a screening Conclusion

procedure. Transvaginal sonography allows detailed analysis of the endometrial
Szabo et al.35 investigated uterine vascularity by color thickness and texture. Blood flow studies can be efficiently used to
monitor endometrial development and distinguish between benign
and pulsed Doppler in cases of uterine leiomyomas and and malignant uterine cavity lesions. It is hoped that color Doppler
uterine sarcomas and determined the efficiency of uterine findings may help to reduce invasive procedures, such as dilatation
blood flow analysis in differentiating between them. The and curettage or hysteroscopy, for detection of the uterine cavity
lesions. This would decrease both the potential risks and the
mean intratumoral RI and PI were significantly lower and economic costs. Transvaginal color and pulsed Doppler sonography
the intratumoral PSV was significantly higher in patients represents a noninvasive diagnostic tool that can be used repeatedly
with sarcomas than in patients with uterine leiomyomas. for assessing vascularity in endometrial lesions. The application
of transvaginal color Doppler to the postmenopausal population
Marked reduction of RI and PI and increased PSV could be for screening of endometrial carcinoma may be a viable option, if
found in the leiomyoma cases, which showed large size and/ combined with ovarian screening in the same scan. In this way, the
or necrotic, degenerative and inflammatory changes. When capital costs would be shared and oncological preventive medicine
for women could be initiated. The use of this technique could also
a cutoff value of 0.5 for the RI was considered, the detection result in a reduction in dilatation and curettage operations, with
rate for uterine sarcoma was 67% and the false-positive rate considerable reduction of both the potential risks and the economic
was 11.8%. These results suggest that the intratumoral RI costs of the operation.
Assessment of vascularization of uterine tumors, if used together
detected by color and pulsed Doppler ultrasonography in with analysis of morphology and size, can increase our accuracy in
themselves could be poor for the preoperative differential differentiating between uterine sarcoma and leiomyoma. However,
it is unrealistic to expect Doppler studies to clarify confounding
diagnosis of uterine sarcoma.
histological findings. It seems that the multiparameter sonographic
In our study,23 1 patient with uterine leiomyosarcoma was approach, which includes morphology and size depicted by
examined with 3D and power Doppler ultrasound. Enlarged transvaginal ultrasonography and color flow imaging with pulsed
Doppler analysis of neovascular signals, can help in the diagnosis of
volume of the tumor (97.2 ml) and irregular, randomly uterine sarcoma in high-risk groups such as postmenopausal patients
dispersed vessels both in the central and peripheral with a rapidly enlarging uterus. Therefore, serial measurements are
parts of the tumor were obtained using this method. The recommended for evaluation of myometrial density, follow-up of the
tumoral growth and detection of the impedance to blood flow. Only
diameters of these vessels were “uneven”, with numerous such complex observations can lead to proper diagnosis of these
microaneurysms and stenosis. Because of the same rare tumors, which have an unpredictable prognosis.
problems mentioned in the paragraph about leiomyoma, Three-dimensional and power Doppler ultrasound is a new
diagnostic technique and its role in the assessment of uterine
low positive predictive value of 3D PDS and small number lesions has yet to be investigated. Three-dimensional ultrasound
of patients involved in the study, this technique is not
acceptable for the evaluation of myometrial lesions. Contd...
Contd... 11. Bonilla-Musoles F, Raga F, Osborne NG, et al. Three-
offers improved visualization of uterine lesions providing dimensional hysterosonography for the study of endometrial
simultaneous display of coronal, sagittal and transverse planes, tumors: comparison with conventional transvaginal
displays entire volume demonstrating continuity of curved structures sonography, hysterosalpingography, and hysteroscopy.
in a single image, offers more accurate volume estimation using Gynecol Oncol. 1997;65(2):245-52.
a standard anatomic orientation, retrospective review of stored
data, more complete viewing of pathology using rendered images, 12. Weinraub Z, Maymon R, Shulman A, et al. Three-
identifying the location of abnormalities and assessment of tumor dimensional saline contrast hysterosonography and surface
invasion. Three-dimensional sonohysterography demonstrates rendering of uterine cavity pathology. Ultrasound Obstet
the exact location of intrauterine pathology. It seems that 3D PDS
has brought us a little closer to better understanding of malignant
Gynecol. 1996;8(4):277-82.
tumor angiogenesis. Interactive rotation of power Doppler rendered 13. Gruboeck K, Jurkovic D, Lawton F, et al. The diagnostic
images provides improved visualization of the tumor vasculature. value of endometrial thickness and volume measurements
This method permits the ultrasonographer to view structures in
by three-dimensional ultrasound in patients with
three dimensions interactively rather than having to assemble
the sectional images in his/her mind. Contrast agents are another postmenopausal bleeding. Ultrasound Obstet Gynecol.
possibility for enhancing the three-dimensional power Doppler 1996;8(4):272-6.
examination by increasing the detection rate of small vessels. 14. Momtaz M, El Ebrashi A. 3D sonohysterography in the
evaluation of the uterine cavity. Syllabus. Las Vegas,
October 1999.
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New York: Churchill Livingstone; 1995.pp.325-39. 16. Hirai M, Shibata K, Sagai H, et al. Transvaginal pulsed
2. Fleischer AC, Kepple DM, Entman SS. Transvaginal and color Doppler sonography for the evaluation of
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Rottem S (Eds). Transvaginal Sonography, 2nd edition. 17. Lee SL, Busmanis I, Tan A. 3D – Angio of adenomyotic
New York: Elsevier; 1991. pp 109-30. uteri. Syllabus. Las Vegas, October 1999.
3. Kurjak A, Kupesić S. Transvaginal color Doppler and pelvic 18. Kupesić-Urek S, Shalan H, Kurjak A. Early detection of
tumor vascularity: lessons learned and future challenges. endometrial cancer by transvaginal color Doppler. Eur J
Ultrasound Obstet Gynecol. 1995;6(2):145-59. Obstet Gynecol Reprod Biol. 1993;49(1-2):46-9.
4. Ismail SM. Pathology of the endometrium treated with 19. Kurjak A, Kupesić S. Ovarian senescence and its
tamoxifen. J Clin Pathol. 1994;47(9):827-33. significance on uterine and ovarian perfusion. Fertil Steril.
5. Achiron R, Grisaru D, Golan-Porat N, et al. Tamoxifen and 1995;64(3):532-7.
the uterus: an old drug tested by new modalities. Ultrasound 20. Emoto M, Tamura R, Shirota K, et al. Clinical usefulness
Obstet Gynecol. 1996;7(5):374-8. of color Doppler ultrasound in patients with endometrial
6. Lahti E, Blanco G, Kauppila A, et al. Endometrial changes in hyperplasia and carcinoma. Cancer. 2002;94(3):700-6.
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Obstet Gynecol. 1993;81(5 (Pt 1)):660-4. endometrial ablation therapy induces a rise in uterine blood
7. Achiron R, Lipitz S, Sivan E, et al. Changes mimicking flow impedance: a randomized prospective color Doppler
endometrial neoplasia in postmenopausal, tamoxifen-treated study. Ultrasound Obstet Gynecol. 2001;17(1):65-70.
women with breast cancer: a transvaginal Doppler study. 22. Folkman J, Long DM Jr, Becker FF. Growth and metastasis
Ultrasound Obstet Gynecol. 1995;6(2):116-20. of tumor in organ culture. Cancer. 1963;16:453-67.
8. Exacoustos C, Zupi E, Cangi B, et al. Endometrial 23. Kurjak A, Kupesić S. Three dimensional ultrasound
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Gynecol. 1995;6(6):435-42. 24. Kupesić S, Kurjak A, Zodan T. Staging of endometrial
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10. Perez-Medina T, Bajo J, Huertas MA, et al. Predicting 25. Lee CN, Cheng WF, Chen CA, et al. Angiogenesis
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CHAPTER
20 2D and 3D Power Doppler

Ultrasound Study of Endometrium
as Implantation Marker
Introduction Endometrial Thickness

Assessment of the endometrium by ultrasound is of Endometrial thickness is the maximum distance between
great interest for a better management of reproductive the echogenic myoendometrial interfaces measured in
technologies. This is true for two reasons. First, the success the longitudinal axis (Figs 20.1A and B). It is a simple
of the embryo transfer procedure is conditioned by the and reproducible measurement that has proved a good
intrinsic embryo quality and endometrial receptivity. And intraobserver and interobserver agreement.1
second, it has been proposed that ultrasound and Doppler Endometrial thickness is independent of the ovarian
parameters would properly evaluate endometrial receptivity. stimulation protocol 2 with no significant differences
Therefore, ultrasound and Doppler of the endometrium between the human chorionic gonadotropin (hCG)
become clinical markers of implantation. administration day and the embryo transfer day. 3
Up to now, two-dimensional (2D) ultrasound enabled us Nonetheless, it has been advised to perform several
to measure two endometrial markers of implantation: the measurements to avoid the variability from 1.3 to 2.8 mm
thickness and the morphological pattern. Actually, pulsed due to uterine contractions.4
and color Doppler made possible the study of endometrial In assisted reproductive technology (ART) there is no
and uterine perfusion involved in the implantation process. significant difference between the endometrial thickness of
New perspectives for the study of the endometrium as conceptional (n = 514; 8.6–11.8 mm) and non-conceptional
an implantation marker are now open with the advent of cycles (n = 1110; 8.6 – 11.9 mm).5 However, in conceptional
three-dimensional (3D) ultrasound and Doppler. Three- cycles an accelerated endometrial growth during the luteal
dimensional volumetry allows a more accurate endometrial phase is detected, reaching significant differences 14 days
measurement as it has been before. In a similar way, 3D after the day of oocyte retrieval.6,7
power Doppler gives us information about the number In pregnancy prediction, endometrial thickness shows a
of endometrial vessels and the blood flow through them. highly negative predictive value (NPV) = (87–100%) but,
In advance, these variables are much more precise than with a lot of false-positives.5 Anyway, the endometrium is
Doppler velocimetry to assess endometrial perfusion. This non-receptive when its thickness is less than 7 mm at the
is the time to see authors’ expectancies and hopes fulfilled, hCG administration day. An endometrial thickness greater
and if this undeniable technological advance will be a than 14 mm8 is also a poor prognostic factor, but this is not
diagnostic improvement of implantation markers. shared by all authors.9
In an oocyte donation program with hormone replacement
Two-dimensional Ultrasound and treatment, it has been demonstrated that pregnancy rates
decrease as endometrial thickness decreases. When
Doppler of the Endometrium endometrial thickness is greater than or equal to 9 mm, a
The main implantation ultrasound markers are the pregnancy rate of 68% is reached, and reduces to 20% with
endometrial thickness and its morphological pattern. The endometrium lesser than 6 mm.10 Although it is possible
endometrial color mapping and the vascular resistance to achieve conception with an endometrium thinner than
of the spiral and radial arteries are used for the study of 4 mm,11 this is a poor prognostic factor and will warrant a
endometrial perfusion. further endometrial study.10
A B
Figures 20.1A and B Measurement of endometrial thickness and echogenicity patterns: (A) multilayered proliferative endometrium or “triple
line” pattern and (B) endometrium nonmultilayered
In authors’ study group on 40 in vitro fertilization (IVF) significant differences in the morphological endometrial
cycles they found that more than 50% of the endometrium pattern have been found between the hCG day and the
had a thickness of 11–15 mm and showed a pregnancy transfer day either.3
rate higher than 50%. Thicker than this the pregnancy rate The “triple line” endometrium is the parameter that best
decreases, but not significantly. With endometrium thinner reflects the endometrial receptivity, whereas a “non-triple
than 9 mm, there were no pregnancies. And only a 12.5% line” pattern is associated frequently to non-pregnancy
of gestations were achieved with an endometrial thickness cycles.5 Like the endometrial thickness, the “triple line”
between 9 and 11 mm (Table 20.1). pattern has a high false-positive rate. Despite this, it can
be useful as NPV = 75%–100%.
Endometrial Pattern The implantation and pregnancy rates decrease
The endometrial pattern is the relative echogenicity progressively as the myometrial echogenicity increases,
showed by the endometrium with respect to the adjacent measured on the day of hCG administration.7,16 Therefore,
myometrium. Its importance as implantation marker is there is an inverse relationship between the endometrial
based on that it reflects the histological development.12 echogenicity degree and the pregnancy chance. Although it
Up to four patterns of endometrial echogenicity have is possible to achieve a pregnancy with a “non-triple line”
been described.13 However, a “triple line” endometrium pattern, the probability is very low.15
will be adequate as an implantation marker14 (Figs 20.1A According to authors’ results, the “non-triple line”
and B). This endometrial pattern appears unchanged after endometrium (20%, 8/40) showed a lower pregnancy
any ovarian stimulation protocol and by the hormonal rate (37.5%) compared to that of “triple line” (68.5%).
replacement treatment before embryo transfer. 15 No Some authors consider better to combine thickness and
endometrial pattern as endometrial predictors.9 In authors’
Table 20.1 Pregnancy rate according to endometrial thickness
on the day of hCG administration in 40 IVF cycles cases all gestations achieved with a “non-triple line”
Endometrial No. of cases n (%) Pregnancy rate
endometrium had a thickness greater than 11 mm.
thickness n (%)
<9 mm 2 (5) 0 (0) Doppler of the Endometrium
9–11 mm 8 (20) 1 (12.5) Endometrial Doppler should reflect more appropriately
11–15 mm 21 (52.5) 11 (52.4) the endometrial perfusion and uterine receptivity because
>15 mm 9 (22.5) 4 (44.4) the endometrium is the place where implantation occurs.17
The Doppler study of the endometrial spiral arteries
(Abbreviations: hCG, human chorionic gonadotropin; IVF, in vitro
fertilization) and subendometrial radial arteries (Fig. 20.2) proved a
Chapter 20  2D and 3D Power Doppler Ultrasound Study of Endometrium as Implantation Marker 193
Table 20.2 Pregnancy rate according to endometrial blood flow
type on the day of hCG administration in 40 IVF cycles
Endometrial blood No. of cases n (%) Pregnancy rate
flow n (%)
Type 0 5 (12.5) 1 (20)
Type I 17 (42.5) 6 (35)
Type II 12 (30) 5 (42)
Type III 6 (15) 4 (67)
(Abbreviations: hCG, human chorionic gonadotropin; IVF, in vitro

fertilization)
is very difficult to achieve implantation despite a good

endometrial thickness.24
On 40 cycles of IVF, authors have found that more than
Figure 20.2 Flow velocity waveform of subendometrial-endometrial 70% of cases have an endometrial flow Type I or II the day
artery on hCG administration day
of hCG administration and in this group the pregnancy rate
decreased resistance on the oocyte retrieval day18 and on is 38%. However, it is more interesting to confirm that the
the embryo transfer day19 when pregnancy is achieved. pregnancy rate increases progressively as vascularization
Using color 19-21 or power Doppler 17 four types of rises, reaching a 67% when the color signal reaches the
endometrial mapping have been established: (i) Type center of the endometrium (Table 20.2).
0 or negative flow when only surrounding myometrial When a pregnancy is achieved in absence of endometrial
vessels are seen without reaching the endometrium, (ii) and subendometrial flow, on the day of embryo transfer,
type I or peripheral flow if the Doppler signal reaches more than a half of these pregnancies will finish as
the hyperechogenic endometrial outer layer, (iii) Type II spontaneous miscarriage,22 suggesting that the development
or intermediate flow when color mapping occupies the of the endometrial vascular tree is very important in the
outer half of the endometrial hypoechogenic thickness, support of the initial stages of gestation.
and (iv) type III or central flow, if the vessels arrive to the
endometrial cavity invading all the endometrial thickness, Three-dimensional Ultrasound and
(Figs 20.3A to D). Power Doppler is advisable for two Power Doppler of the Endometrium
reasons: to detect the signal from vessels with low velocity
blood flow and to avoid the signal loss due to a 90° angle Three-dimensional ultrasound has a remarkable
incidence of the ultrasound beam associated to conventional methodological advantage that is the simultaneous
color Doppler.17 assessment of the endometrial volume and its perfusion.
The absence of an endometrial and myometrial After displaying the endometrial volume and its vessels
subendometrial color mapping means a complete failure20 through 3D power Doppler angiography, a program named
or significant decrease22,23 of implantation, whereas the virtual organ computer-aided analysis (VOCAL) is applied
pregnancy rate increases when the vessels reach the to calculate the endometrial perfusion by applying three
subendometrial halo and the endometrium.20,22 In a study power Doppler indices.25 The vascularization index (VI)
of more than 600 cycles evaluated by color Doppler on measures the number of color voxels in the endometrial
the embryo transfer day it was found that implantation volume, representing the number of endometrial vessels
and pregnancy rates were 24.2% and 47.8%, respectively expressed as a percentage. The flow index (FI) is the
when endometrial and subendometrial flow was detected; average color value in all color voxels, meaning the average
15.8% and 29.7% if only subendometrial flow was detected intensity of endometrial blood flow. The vascularization
and 3.5% and 7.5% when neither subendometrial nor flow index (VFI) is the average value of the color in all
endometrial flow were registered.22 Women with a great gray and color voxels of the endometrial volume, expressing
endometrial flow area as measured by power Doppler have this way the vascularization as well as the flow of the
a greater pregnancy probability, whereas below 5 mm2 it endometrium (Fig. 20.4).
A B
C D
Figures 20.3A to D Endometrial amplitude mapping: (A) Type 0: only myometrial vessels can be seen without reaching the subendometrial
halo, (B) Type I: color signal reaches the hyperechogenic outer layer of the endometrium, (C) Type II: color mapping occupies the outer half
of the endometrial hypoechogenic thickness, and (D) Type III: color reaches the endometrial cavity invading the entire endometrial thickness
Endometrial Volume in different ways, with their actual volume measured

using a water displacement technique.32 All the methods
Although the endometrial volume can be assessed by 2D
applied (conventional and rotational angles of 30°, 15°,
ultrasound, 3D ultrasound is the only procedure that permits
9° and 6° in B and C planes) resulted highly reliable by
a reliable calculation.26
showing differences inferior to 4% over the real volume
The endometrial volume measurement is very and ICC greater than 0.99. However, the measurements
reproducible by 3D ultrasound 27,28 being even more performed with rotations of 6° and 9° were significantly
reproducible than the measurement of endometrial more reliable than those calculated with an angle of 30°
thickness.29,30 The best reproducibility is achieved by or with the conventional technique. The authors advise
the rotational method with a rotation step of less than the use of a rotation of 9° since it is as reliable as the 6°
30 degree30 and a minimum of 12 planes using the VOCAL but significantly faster in its acquisition. There are no
software.31 A rotation angle inferior to 30° is associated significant differences neither between two observers nor
to coefficients of variation less than 1% and intraclass the different measurement planes.32
correlation coefficients (ICC) greater than 0.94.30 From the above mentioned facts, authors evaluated
This technique has been recently validated by the reproducibility of the endometrial volume calculated
comparing the volume of several objects measured with 3D ultrasound, by comparing the volume acquisition
Figure 20.4 Three-dimensional power Doppler indices of the endometrium obtained by

VOCAL software (Abbreviations: MG, mean gray value; VI, vascularization index; FI, flow
index; VFI, vascularization flow index)
from A and C planes applying rotations of 15° and 9°. Table 20.3 Intraobserver differences (mean and SD), ICC and
This distinction was considered of importance because the r of the endometrial volume according to planes (A and C) and
degrees (15° and 9°) with VOCAL imaging program (n = 50)
volume acquisition is usually made from a longitudinal
uterine section (plane A) although the plane C is advised for EV Mean SD ICC 95% CI r
volume calculation. On the other hand, 15° (12 planes) and difference
9° (20 planes) seem to be the most reproducible rotational A Plane 15° 0.06 0.43 0.98 0.96–0.99 2.64
angles. Twenty-five patients under ovarian stimulation 9° –0.07 0.50 0.97 0.94–0.99 0.98
with gonadotropins for intrauterine insemination (IUI) (11 C Plane 15° –0.08 0.65 0.97 0.93–0.99 1.26
patients) or IVF (14 patients) have been studied in this way. 9° –0.11 0.49 0.98 0.96–0.99 0.96
Endometrial volumes were obtained from a longitudinal
(Abbreviations: EV, endometrial volume; ICC, intraclass correlation
uterine section on the day of hCG administration. Two coefficient; SD, standard deviation; CI, confidence interval; r,
consecutive volumes were acquired with a 5 minute repeatability coefficient (1.96 × 2 within—subject variance); VOCAL,
interval, gathering a total of 50 endometrial volumes. The virtual organ computer aided analysis)
results are discussed in Table 20.3. Intraclass correlation

coefficients are similar for both planes and for the different with the VOCAL program using a 9° rotational step
rotational steps and show a high reliability of the technique regardless of the longitudinal or coronal plane (Fig. 20.5).
(0.93–0.99). The repeatability coefficient (r) or the The relationship between the uterine and endometrial
maximum difference probably to occur among repeated volume shows a good correlation to the day of the menstrual
measurements is inferior using a 9° angle for any of the cycle.33 Nonetheless, the value of this measurement has
planes (plane A: 0.98; plane C: 0.96), although “r” is only proven to be more interesting as a clinical marker of
slightly different from the calculated using a 15° for the C pituitary suppression and uterine receptivity in the ARTs.
plane (1.26). In the A plane, using 15°, the measurement Firstly, the available results suggest that the endometrial
shows a higher repeatability coefficient. After these results, volume calculated by 3D ultrasound is an adequate
authors performed an estimate of the endometrial volume parameter to diagnose the pituitary suppression and
Figure 20.5 Assessment of endometrial volume with VOCAL software. Authors use the coronal
plane and 9 degrees by showing better reproducibility
non-suppression after the administration of GnRH to 3 ml and in these cases no pregnancy was achieved.
(gonadotropin-releasing hormone) agonists in IVF Nearly a half of the cases developed a volume from 3 to 6 ml
cycles.34,35 However, it is preferable to choose a different with a pregnancy rate of 41%. Finally, a third of the patients
threshold for the diagnosis of suppression (as defined by had a volume greater than 7 ml with a pregnancy rate of
a serum estradiol concentration <150 pmol/L or 40 pg/ml) 50%. In the entire study group the pregnancy rate reached
than the non-suppression (serum estradiol concentration = the 40% (16/40). These results confirm the difficulty to
150 pmol/L or 40 pg/ml). An endometrial volume inferior to obtain a pregnancy when the endometrial volume is smaller
1.48 ml identifies the 92% of suppressed patients but only than 3 ml and show some linear relationship between the
the 42% of suppression failures, whereas a volume = 0.50 ml increase of the volume and the easiness to get a pregnancy.
detects the 90% of non-suppressions. The endometrial
volume has turned to be superior to the endometrial Three-dimensional Doppler Indices of
thickness only when non-suppression is evaluated.35 Endometrial Perfusion
The implantation and pregnancy indices were previously Very few studies have evaluated the reproducibility of 3D
demonstrated to be significantly lower when the endometrial Doppler indices in the assessment of the vascularization
volume is less than 2 ml and no pregnancy is achieved when and perfusion of the endometrium.41 The intraobserver
it is inferior to 1 ml.36 The difficulty to obtain a pregnancy and interobserver reliability to assess the endometrial and
with endometrial volumes greater than 8 ml has also been
communicated.37 Other authors find no relationship between Table 20.4 Pregnancy rate according to endometrial volume on
the day of hCG administration in 40 IVF cycles
the endometrial volume and the pregnancy rate in an IVF
program.38,39 When this parameter was applied in an IUI Endometrial No. of cases n (%) Pregnancy rate
volume n (%)
program, an endometrial volume less than 2 ml in the day
< 3 ml 4 (10) 0 (0)
of IUI was demonstrated to have a significantly smaller
3–6 ml 22 (55) 9 (40.9)
pregnancy probability (6%) when compared to patients
> 7 ml 14 (35) 7 (50)
with greater volumes (22%).40
Authors’ experience on 40 IVF cycles appears in Table (Abbreviations: hCG, human chorionic gonadotropin; IVF, in vitro
20.4. A 10% of women had an endometrial volume inferior fertilization)
subendometrial perfusion is very high showing ICC greater The higher repeatability coefficients belong to the VI
to 0.985. Only the subendometrial flow index (SEFI) shows while the lower ICC is showed by the FI. These results are
reliability significantly smaller, although exceptionally in agreement with previous findings about endometrial and
high.41 ovarian vascularization assessment by 3D power Doppler.42
We have also obtained an adequate reproducibility of The endometrial flow index (EFI) shows only an ICC of 0.70
endometrial (Table 20.5) and subendometrial Doppler on the plane C with 15°, being lower for the other options. It
indices (Table 20.6), although with ICC lower than those is worth remembering that as a general rule an ICC above 0.70
previously published. In a more comprehensive way authors is considered acceptable.43 The best SEFI is observed for the
observed that the endometrial as well as the subendometrial C plane with 9° (ICC = 0.88 and r = 4.30).
vascularization (defined as an outer layer of 2 mm around The first reported results, applying 3D power Doppler
the myoendometrial interface) are more reproducible in indices on the first day of ovarian stimulation as predictors
plane C and with a 9° rotational step than it is when 20 of IVF cycle outcome, concluded that the SEFI is an
planes from the coronal plane are evaluated. However, some important prognostic factor of the success of the treatment.25
details must be analyzed. Nonetheless, the results were surprisingly quite the opposite
The endometrial vascularization index (EVI) is more of what authors expected. That is, the conception cycles
reproducible on the A plane with rotation of 9° (ICC = 0.94 showed vascularization, FI and VFIs significantly lower
and r = 8.11) whereas the subendometrial vascularization than those of non-conceptional cycles. According to other
index (SEVI) is more reproducible in the plane C with 9°, authors, a better functional status of the endometrium
showing the highest ICC (0.97) and the lower repeatability after GnRh agonist treatment would be expressed by low
coefficient (9.11). The endometrial vascularization flow 3D power Doppler indices, increasing the possibility of a
index (EVFI) has the greater ICC (0.94) and the smaller successful implantation.25
“r” coefficient (2.54) on the A plane with 9°, while the The VFI on the hCG administration day has proved to be
subendometrial VFI is more reproducible on the C plane a good pregnancy predictor in IVF cycles, being superior
(ICC = 0.97 and r = 3.81). to the endometrial volume, FI and VI. A VFI above 0.24
Table 20.5 Intraobserver differences (mean and SD), ICC and r of the endometrial 3D Doppler indices according to planes (A and C) and
degrees (15° and 9°) with VOCAL imaging program (n = 50)
Doppler indices Mean difference SD ICC 95% CI r
A plane 15° –1.26 5.24 0.91 0.81–0.96 10.35
9° –1.00 4.10 0.94 0.87–0.97 8.11
EVI
C plane 15° –1.92 4.95 0.92 0.83–0.96 10.23
9° –1.63 4.42 0.94 0.86–0.97 9.07
A plane 15° –0.43 2.01 0.68 0.40–0.85 3.96
9° –0.23 2.08 0.63 0.32–0.82 4.03
EFI
C plane 15° –0.21 2.01 0.70 0.43–0.86 3.88
9° –0.35 2.16 0.66 0.37–0.84 4.21
A plane 15° –0.38 1.66 0.90 0.78–0.95 3.28
9° –0.28 1.29 0.93 0.85–0.97 2.54
EVFI
C plane 15° –0.53 1.60 0.90 0.80–0.96 3.25
9° –0.40 1.52 0.91 0.82–0.96 3.02
[Abbreviations: EVI, endometrial vascularization index; EFI, endometrial fIow index; EVFI, endometrial vascularization flow index; ICC,
intraclass correlation coefficient; SD, standard deviation; CI, confidence interval; VOCAL, virtual organ computer aided analysis; r, repeatability
coefficient (1.96 × 2 within—subject variance)]
Table 20.6 Intraobserver differences (mean and SD), ICC and r of the subendometrial 3D Doppler indices according to planes (A and C)
and degrees (15° and 9°) with VOCAL imaging program (n = 50)
Doppler indices Mean difference SD ICC 95% CI r
A plane 15° –2.32 8.79 0.84 0.66–0.92 17.48
9° –0.30 6.45 0.93 0.84–0.97 12.40
SEVI
C plane 15° –3.01 5.39 0.95 0.88–0.98 11.92
9° –1.92 4.32 0.97 0.93–0.99 9.11
A plane 15° –0.34 3.40 0.73 0.48–0.87 6.56
9° –0.09 2.29 0.86 0.72–0.94 4.41
SEVFI
C plane 15° –0.77 2.67 0.80 0.60–0.91 5.35
9° –0.73 2.11 0.88 0.75–0.95 4.30
A plane 15° –0.75 3.56 0.86 0.71–0.94 6.99
9° 0.37 3.03 0.92 0.83–0.97 5.86
SEFI
C plane 15° –1.06 2.43 0.94 0.87–0.97 5.11
9° –0.67 1.86 0.97 0.93–0.99 3.81
[Abbreviations: SEVI, subendometrial vascularization index; SEFI, subendometrial fIow index; SEVFI, subendometrial vascularization flow
index; ICC, intraclass correlation coefficient; SD, standard deviation; CI, confidence interval; VOCAL, virtual organ computer aided analysis; r,
repeatability coefficient (1.96 × 2 within—subject variance)]
showed a sensitivity of 83.3% and a specificity of 88.9%, In a 25% of cycles we found an intermediate endometrial
positive predictive value (PPV) of 93.8% and NPV of development (from 3 to 6 ml) with an intermediate VI as
72.3%. The pregnancy rate was 33% (18/54). 44 When well (10–35). In these cycles, the pregnancy rate is 60%,
the subendometrial flow is studied on the transfer day, a above the average pregnancy rate which was 40% (16/40).
significantly high FI was found in the group of patients that For any endometrial thickness superior to 3 ml showing
got pregnant37 (Fig. 20.6). a subendometrial vascularization greater than 35%, the
Authors’ results evaluating the subendometrial flow on pregnancy rate falls below the mean down to 31%.
the day of hCG administration in 40 IVF cycles appear
on Table 20.7. In general the intermediate values of
vascularization, FI and VFIs show the best outcomes and Table 20.7 Pregnancy rate according to subendometrial 3D power
Doppler indices on the day of hCG administration in 40 IVF cycles
are present in the 40–50% of patients. Another interesting
Doppler indices No. of cases n (%) Pregnancy
finding is that below a VI of 10, there is no pregnancy which rate n (%)
happens in the 12.5% of patients. When blood flow is very
<10 5 (12.5%) 0 (0%)
high, as measured by any of the indices, the pregnancy rate
Vascularization index 10–35 18 (45%) 11 (61.1%)
is lower although differences are not significant.
Finally, authors assessed jointly the endometrial volume >35 17 (42.5%) 5 (29.4%)
and Doppler indices in an attempt to find a better predictive <28 12 (30%) 1 (8.3%)
factor of the success of the technique. The best combination Flow index 28–34 20 (50%) 12 (60%)
is achieved with the VI (Table 20.8). When the endometrial >34 8 (20%) 3 (37.5%)
volume is below 3 ml or the VI is less than 10 which <6 10 (25%) 1 (10%)
occurs in the 30% of patients, no pregnancy is achieved.
Vascularization 6–12 17 (42.5%) 10 (58.8%)
On the contrary, an exceptionally favorable situation flow index
>12 13 (32.5) 5 (38.5%)
appears when the endometrial development is above 7 ml
with a SEVI between 10% and 35%. In these cases (6/40; (Abbreviation: hCG, human chorionic gonadotropin; IVF, in vitro
15%), the pregnancy rate is very high (5/6 cases; 83%). fertilization; VF, vascularization flow)
Figure 20.6 Subendometrial 3D power Doppler indices on the hCG day in IVF cycle
(Abbreviations: MG, mean gray value; VI, vascularization index; FI, flow index; VFI,
vascularization flow index)
Table 20.8 Pregnancy rate according to endometrial volume and Contd...

SEVI on the day hCG of administration in 40 IVF cycles between the “fractional moving blood volume” as a technique to
quantify power Doppler and the real perfusion of sheep adrenal
Parameters No. of cases n (%) Pregnancy rate
glands as evaluated by radioactive microspheres.46 As a conclusion,
n (%)
when 3D ultrasound and 3D power Doppler parameters have been
EV <3 ml or VI <10 8 (20) 0 (0) applied to ARTs as outcome predictors, although studies are still
EV >3 ml + VI >35 16 (40) 5 (31.2) scarce, they show very promising results. Obviously, authors need
larger prospective studies showing the real predictive value and
EV 3-6 ml + VI 10 (25) 6 (60) clinical applicability of this technique for daily practice.
10–35
EV >7 ml + VI 6 (15) 5 (83.3)
10–35 References
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(Abbreviations: SEVI, subendometrial vascularization index; hCG,
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CHAPTER
21
Follicular Monitoring
Introduction Follicular Assessment

The advances in ultrasound technology have changed the Antral follicles in the early follicular stage of the menstrual
management of infertility. With the advent of color Doppler, cycle start growing under the effect of endogenous or
pulse Doppler, 3D ultrasound and 3D power Doppler, the exogenous FSH. The dominant follicle is selected very
previously unexplained causes of failure of fertilization early during the menstrual cycle and becomes apparent as
and implantation can now be explained. 3D and 3D early as 5th day on ultrasound. Many a times the follicle
power Doppler can now be used for the assessment of the that appears to be a leading follicle on day five scan may
maturity of the follicle and receptivity of the endometrium not be the follicle that would ultimately grow and give
and can give better idea about the functional maturity of ovum. The fate of the follicle can be decided by size, rate
the follicle and the endometrium, to decide the timing of of growth (as high as >2.3 mm/day in conception cycles)
human chorionic gonadotropin (hCG) administration for internal echogenicity and wall thickness.
all assisted reproductive techniques for better pregnancy A follicle that is of greater than 10 mm in diameter grows
rates. The accuracy of diagnosis and monitoring of at a rate of 2–3 mm/day has no internal echogenicity and has
infertility treatments, such as ovulation induction, has thin (pencil line like) walls is not only more likely to become
greatly increased because of the availability of sophisticated the leading follicle but will also give mature healthy ovum.
ultrasound technology and equipment.1 The growing follicle can be assessed by transvaginal
Assessment of the follicular maturity and endometrial sonography. The shape changes from round to polygonal
receptivity and the time of hCG is one of the key factors for when there are multiple follicles due to pressure effect from
success of all ART procedures. The follicular maturity can adjacent follicles. In such follicles the follicular volume
be assessed by oestradiol levels, but frequent assessment of would have to be considered instead of a single diameter
blood oestradiol level is a cumbersome procedure. Since the and is calculated as (D1 × D2 × D3) × 0.523, where D1,
advent of the transvaginal ultrasound this has been a preferred D2 and D3 are three diameters of follicles in perpendicular
method for the assessment of follicle and endometrium. planes using B mode ultrasound. The follicle shape may
Earlier the follicular size of 16–18 mm and the become ellipsoid if pressure is applied by the transvaginal
endometrial thickness of 8 mm were considered optimum probe on the follicle and therefore scans should be done
parameters for hCG administration for ovulation trigger. with only optimum pressure applied by the probe.
But this is assessing only the anatomical maturity of
follicle and endometrium. Maturation of the follicle and
B Mode Features of a Mature Follicle
the endometrium, ovulation and leutinization is a process of
multiple biochemical, morphological and vascular changes. The follicular diameter is measured when the follicle is
The vascular changes are reflection of the biochemical seen as a rounded structure, or at least three measurements
changes and can be studied by color Doppler. 3D ultrasound must be taken perpendicular to each other and take a mean
gives a better assessment of the follicular and endometrial measurement as follicular diameter. A mature follicle is
size, i.e. the anatomical maturity, than 2D ultrasound 16–18 mm (Fig. 21.1A), has thin walls, regular round
and 3D power Doppler give not only qualitative but also shape and no echogenicity in the lumen and shows a thin
quantitative idea of global vascularity, i.e. the reflection of hypoechoic rim surrounding the follicle and sometimes
functional or physiological maturity. (about 35–40%) cumulus like shadow may be seen. This
Chapter 21  Follicular Monitoring 203
A B
Figures 21.1A and B Preovulatory follicle on B mode, 6–8 hours before rupture
thin hypoechoic rim and cumulus like shadow develops Implications of Flow Parameters on
approximately 36 hours before rupture. A flimsy irregular
line is seen inside the follicle parallel to the wall about 6–8
Ovum Quality
hours before rupture (Fig. 21.1B). Ovarian flow correlates well with oocyte recovery rates and
hence may be useful in determining the most appropriate
Doppler Features of time to administer hCG to optimize recovery rate. Higher RI
indicates higher resistance flow to the follicle meaning lower
a Good Pre-hCG Follicle flow during diastolic phase and so reduced phasic oxygen
Increase in perifollicular vascularity of dominant follicle supply to the ovum and hence lack of maturity. Lower PSV
in theca layer starts developing as early as 8th day of the again indicates lower blood supply and hence lack of maturity.
cycle. Fall in perifollicular RI starts 2 days before ovulation, It has been quoted in a study by Nargund et al.4-6 that embryos
reaches nadir at ovulation, remains low for 4 days and produced by fertilization of the ova obtained from the follicles
then with gradual rise reaches 0.5 in mid luteal phase.2 which had a perifollicular PSV of less than 10 cm/sec, are less
When functionally mature, on color Doppler, the follicle likely to be grade 1 embryos and also have higher chance of
shows blood vessels covering at least three-fourths of the chromosomal malformations. In the same study it has been
follicular circumference (Fig. 21.2). Chui et al. graded the shown that the probability of developing a grade 1 or 2 embryo
follicular flow on the day of oocyte collection as grade is 75% if PSV was greater than 10 cm/sec, 40% if PSV was
1–4 when in a single cross area slice the flow covered less less than 10 cm/sec, 24% if there was no perifollicular flow.
than 25%, 25–50%, 50–75% greater than 75% of follicular There is yet another study that supports this finding. Oocytes
circumference. The conception was related to grade 3–4 from severely hypoxic follicles are associated with high
vascularity.3 frequency of abnormalities of organization of chromosomes
On pulse Doppler these blood vessels show an RI of on metaphase spindle and may lead to segregation disorders
0.4–0.48 and PSV of greater than 10 cm/sec (Figs 21.3A and catastrophic mosaics in embryo.7
and B). The PRF settings for color Doppler are set at 0.3
and wall filter at the lowest. The perifollicular vessels are
only those that obliterate the follicular wall with color. If
Our Data
the follicular wall is seen and the vessel is seen just besides Authors’ unpublished data of more than 1,000 intrauterine
it, it is not a perifollicular vessel. insemination (IUI) cycles has shown that when the
Volume Ultrasound for Follicular

Assessment
We use 3D USG and 3D power Doppler for the assessment
of these follicles. We studied 500 IUI cycles that were all
monitored for ovulation by 2D and color Doppler. When
the follicles appeared mature as per the above mentioned
features, 3D and 3D power Doppler was done for all and
the values of 3D and 3D power Doppler indices were
studied and plotted on the graphs for conception and non-
conception cycles. We used Voluson 730 Expert (GE) for
our studies. Once the follicles of greater than or equal to 16
mm for gonadotropin stimulation or greater than or equal
to 18 mm for CC stimulated cycle is seen and assessed by
color Doppler, the volume box is switched on. The size
of the volume box should be enough to include the whole
follicle and at least a surrounding 5–7 mm margin. The
Figure 21.2 Preovulatory follicle with vascular ring surrounding the angle of the volume should be large enough to cover the
follicle whole follicle from edge to edge. The acquired volume is
seen as follicle in three perpendicular planes on the screen.
Using the vocal software with 15° angle the follicle is
perifollicular RI greater than 0.53 and PSV less than traced at its circumference at every 15° rotation (Fig. 21.4)
9 cm/sec, 12 hours before hCG injection, the conception and at the end the command ‘done’ is given, the volume
rates were only 8.3% and 10% respectively as compared is ultimately accepted, or any corrections required may be
to 32.8% and 28.2% respectively and individually when made and the machine then calculates the volume of the
perifollicular RI less than 0.50 and PSV greater than follicle.
11 cm/sec.
Follicular RI (1,025 cases)

Volume Ultrasound Parameters of
Foll. RI 0.56–0.53 0.53–0.50 <0.50 Good Pre-hCG Follicle: Follicular
Conc. 05 71 170 Volume
Non Conc. 58 373 348 On 3D the follicular volume of 3–7.5 cc has been found
Total 63 444 518 to be optimum in our study8 (Fig. 21.5). This agrees with
Follicular PSV (1,025 cases) the study by Witmack et al.9 which says that, in IVF-ET
Foll. PSV <9 9–10 10–11 >11 cycles, follicles with mean follicular diameter of 12–24
Conc. 04 14 38 190
mm are associated with optimal rates of oocyte recovery,
fertilization and cleavage. This corresponds to the follicular
Non Conc. 36 92 168 483
volumes of between 3 ml and 7 ml. The accuracy of 3D
Total 40 106 206 673
USG measurement of follicular volume compared to
(Conc, conceived cases; non conc, nonconceived cases)
the standard 2D techniques by comparing the volume of
individual follicles estimated by both methods with the
We have, therefore, always preferred to wait with no corresponding follicular aspirates: using the formula of
extra medication when patient is on clomiphene citrate ellipse the limits of agreement between aspirates, and
stimulation or continue with the same dose of gonadotropin calculated volume was +3.47 to –2.42 as compared to
till we get proper perifollicular RI and PSV, although +0.96 to –0.43 when calculated by 3D ultrasound using
sometimes the follicular size may reach up to 22 mm. VOCAL.10. This is because 3D ultrasound measurement
Almost 90% of the times, the desired RI and PSV are is not affected by the follicular shape as the changing
reached by the time follicular size is 20 mm maximum. contours are outlined serially to obtain the specific volume
A B
Figures 21.3A and B Preovulatory follicle with pulse Doppler showing low resistance flow
Figure 21.4 Calculating follicular volume by vocal
measurement. Though the follicles of less than 10 mm in i.e. walking through the volume and rotating the volume. Or
diameter, cannot be assessed accurately by 3D ultrasound one can also use tomographic ultrasound imaging (TUI) in
because limits of agreement are too wide in this range. all three planes, with a slice thickness of 0.5 mm, zoom the
image so that only the follicle can be seen on each image
Cumulus and slices are examined one by one or in a set of four for the
After the volume calculation the follicle is seen plane by presence of cumulus like echo. If it is seen on one plane it is
plane in the acquired volume by translation and rotation, confirmed on the other two planes and also on the rendered
Figure 21.5 Follicular volume by vocal
image. Using a combination of surface smooth and light

gradient mode for rendering with high threshold can show
beautiful cumulus (Fig. 21.6). Authors in their study of 500
IUI cycles have been able to locate the cumulus in 94.6%
of cases in conception cycles and in 53% of non-conception
cycles by surface rendering usually and TUI (0.5 mm slices)
sometimes. In IVF cycles also, we have been able to predict
the number of ova that we would obtain on retrieval by the
number of cumulus containing follicles. Feichtinger et al.
in their study have shown presence of cumulus in follicles
greater than 15 mm by 3D ultrasound.11 Follicles without
visualization of cumulus in all three planes are not likely
to contain mature oocytes. Poehl et al. also showed in
their study that appearance of the intrafollicular cumulus
structures by 3D ultrasound was correlated with the recovery
rate of the mature oocytes.12 They also found a significant
correlation between the number of detected cumuli and the
number of retrieved oocytes (p < 0.0001), mature oocytes Figure 21.6 Cumulus oophorus in preovulatory follicle
(p < 0.0001) and number of fertilized oocytes (p < 0.0001).
Therefore visualization of the cumulus by 3D ultrasound related to the stromal blood flow index.13 It has also been
is a positive indicator of mature oocytes in both IUI and suggested that the follicles containing oocytes capable to
IVF procedures and has been found to be an indicator of produce a pregnancy have a perifollicular vascular network
successful fertilization in IVF cycles also. more uniform and distinctive.14
After having measured the volume of the follicle and
3D PD for Follicular Assessment looking for the presence of the cumulus, we switch over
It has been shown that follicular fluid concentrations of to power Doppler. The PRF settings are fixed at 0.3, and
leptine, a follicular angiogenesis related factor, are inversely wall filter at the lowest. A 3D volume with power Doppler
Figure 21.7 Calculating the shell volume of the follicle for perifollicular 3D PD assessment
A B
Figures 21.8A and B Angiomode of the perifollicular vascularity
is taken the volume angle same as that for the follicular options are open to accept the region of interest (ROI) or
volume is selected. Again on the screen, the follicle is to select one of the options for the shell volume. We select
seen in three perpendicular planes but this time with blood an option for the outside shell with the wall thickness of 2
vessels as seen on power Doppler. Again switch on the vocal mm, which has been found to be the most appropriate to
and calculate the follicular volume. At the end of the last include the perifollicular vessels (Figs 21.7 and 21.8). Then
scroll around the follicle, click the ‘done’ switch and the accept this and switch on the volume histogram. When this
most optimum. About 68.4% of patients conceived when

the VI was between 6 and 18 and 50% when it was between
18 and 20. However, the pregnancy rates were less than
25% when VI was less than 6 and only 7.4% when VI was
greater than 20. It was only 7.4% of patients with FI less
than 27 who conceived whereas beyond 27, the conception
rates rose consistently. It was 50% with FI between 27 and
35, and 70% when FI was between 35 and 43 and almost
all patients had conceived when FI was greater than 43
(Fig. 21.10).
Meaning that even when the follicle appeared mature
according to the 2D ultrasound and color and pulse Doppler
parameters, the pregnancy rates were significantly better
only when the follicular volume was between 3 cc and 7.5 cc,
Figure 21.9 Histogram for perifollicular flow giving VI, FI and VFI cumulus was present and the perifollicular VI and FI values
values
were as mention above.
volume is accepted it gives you the follicular volume as the Follicular volume (500 cases)
reference volume, the shell volume as the volume of the Foll. Vol. <3 3–5 5.1–7 >7
wall and the whole combined volume. So for all practical Conc. 15 94 85 20
purposes we usually omit taking the volume of the follicle Non Conc. 46 89 66 95
without the power Doppler first as this vocal calculation Total 61 173 151 115
with power Doppler will give us the follicular volume
Follicular VI (500 cases)
also. Moreover the same volume can be assessed for the
Foll. VI <6 6–18 18.1–20 >20
cumulus also as described earlier and that saves time spent
on each patient for acquiring and calculating one extra Conc. 6 115 83 10
volume dataset. So, then when we switch over to volume Non Conc. 20 55 83 128
histogram, we get a graph which shows the calculation of Total 26 170 166 138
the gray voxels and the color voxels in the given volume Follicular FI (500 cases)
and these values are displayed on the screen as VI, FI and Foll. FI <27 27–35 35.1–43 >43
VFI values. VI indicates the abundance of the color voxels Conc. 12 100 76 26
in the given volume, FI indicates the intensity of the color Non Conc. 153 100 32 1
in the given volume and VFI is the ratio of the abundance Total 165 200 108 27
and intensity, meaning it gives idea about the general
(Conc., conceived cases; non conc., nonconceived cases)
perfusion status of the given volume (Fig. 21.9). This
means volume histogram or the 3D power Doppler indices
give the quantitative assessment of global vascularization A study by Kupesic and Kurjak shows that when the ratio
and perfusion of the given volume. So after calculating the of follicular volume to blood flow index (FV/FI) is between
volume of the follicle and the shell volume when we switch 0.4 and 0.6 the pregnancy rates are 39%, if greater than 0.6,
on the volume histogram, the VI, FI and VFI values that it is 52% and when less than 0.4, it is only 21%.15
we get are the perifollicular vascualrization and perfusion This explains us the failure to achieve pregnancy in IUI
indices. This gives idea about global follicular vascularity cycles and failure to retrieve ova or achieve fertilization in
rather than interrogation of only one or two vessels when IVF cycles even when hCG is given after proper assessment
we use 2D with Doppler. of follicle by 2D and color Doppler ultrasound. Although
it is possible to assess the follicular flow as expressed by
the peak systolic velocity and perifollicular color map,16,17
3D PD Indices and Follicular Quality it is the 3D power Doppler which proves the most precise
In authors’ study 8 they have found perifollicular VI information about the vascularization and follicular blood
between 6 and 20 and perifollicular FI greater than 35 as flow.18
Figure 21.10 Calculating endometrial volume by vocal
Doppler Parameters of Follicle and gonadotropin 10,000 was given to all patients for follicular
rupture. Every alternate patient was taken for double IUI,
Time of Intrauterine Insemination irrespective of color Doppler findings. Single IUI was done
Going a little further from this stage, hCG plays a major role between 36 and 38 hours and double IUI were done at 12–14
in inducing influx of blood within follicles. At the LH surge hours and 36–38 hours. Post wash sperm count between 7 and
the perifollicular PSV is 10 cm/sec. The follicular PSV goes 10 million/ml.
as high as 45 cm/sec before an hour of ovulation under the The results clearly showed that no matter what protocol
effect of rising LH. This means that if the follicle is said was used; the conception rates were significantly high in
to be functionally mature when PSV is 10 cm/sec, i.e. the patients in whom double IUI was done when perifollicular
time when the LH surge starts and under the effect of that PSV was greater than or equal to 20 cm/sec on the day of
LH, the perifollicular PSV keeps on rising constantly. This hCG, as compared to when single IUI was done. When
derives that a rising PSV with steady low RI suggests that perifollicular PSV on the day of hCG was between 15
the follicle is close to rupture. and 20 cm/sec the conception rates were only minimally
Based on these facts, authors did a study to find out if double increased with double IUI. Although the conception rates
IUI can increase the pregnancy rate in patients who have a pre- were similar for single or double IUI when perifollicular
hCG perifollicular PSV greater than 15 cm/sec. Around 300 IUI PSV on the day of IUI was less than 15 cm/sec (Fig. 21.11).
cycles were studied, with three different stimulation protocols.
The protocols were only Clomiphene citrate 100 mg from day
5 to day 9, Aromatase inhibitor tablet Letrozole 100 mg from
Endometrial Evaluation
day 3 to day 7, followed by rFSH (recombinant FSH) 75 IU Implantation has been weakest link in the success of
till the follicle size of 16–18 mm was achieved, and only rFSH infertility treatment. Endometrium is a receptor organ for
from 3 of the cycle till the desired follicular size was achieved. majority of the hormones involved in fertility, and therefore
All the patients who had unexplained infertility were between study of its morphology and vascularity is thought to
23 and 29 years of age and had a body mass index (BMI) of explain the mysteries of implantation failure. Therefore,
between 23 and 27. Color and pulse Doppler was done for all like follicle, endometrium is also assessed by transvaginal
patients. Stimulation was continued till optimum flows were 2D ultrasound and color Doppler before planning for hCG
also seen apart from the size of the follicle. Human chorionic during any assisted reproductive technologies.
A B
Figures 21.12A and B Endometrial-myometrial junction
Figure 21.11 Pre-hCG perifollicular 3D PD values Figure 21.13 Most receptive endometrium grade A—multilayered
Popularly multilayered endometrium is considered

as a desired endometrial pattern. Morphologically the
B Mode Features of Endometrium endometrium is graded as the best grade A, when it is a
triple line endometrium with the intervening area is as
with Good Receptivity hypoechoic as the anterior myometrium. The echogenicity
On transvaginal sonography an endometrial thickness of is attributed to the development of multiple vessels
minimum 6 mm is required on the day of hCG, but 8–10 penetrating in the endometrium producing multiple tissue
mm is optimum. Endometrial thickness has more negative interfaces and therefore causing the echogenicity and due
predictive value for implantation. Morphology of the to glycogen storage in the endometrial columnar epithelium
endometrium is as important as thickness of the endometrium. (Fig. 21.13). The endometrium is graded as intermediate
In all the healthy endometria, the endometrial-myometrial or grade B (Fig. 21.14) when it is multilayered or triple
interface is always seen as a clear hypoechoic halo line with hypoechoic intervening area. In Grade C or the
surrounding the whole endometrium (Figs 21.12A and B). most unfavorable endometrium would be a homogenous
Breach or irregularity of endometrial-myometrial junction isoechoic endometrium19 (Fig. 21.15). Although some
is an indication of unhealthy endometrium and therefore studies have shown no significant difference in pregnancy
poor receptivity. rates amongst different morphological patterns.
Figure 21.14 Multilayered endometrium grade B—intermediate Figure 21.15 Isoechoic homogenous grade C endometrium
Doppler Features of Endometrium Although in authors’ unpublished data of more than

1,000 IUI cycles, when color Doppler studies were done
with Good Receptivity 12 hours before hCG injection, they have found only 7.3%
There are several reports by different groups20 that agree on pregnancy rates for zone 1 and 13.4% for zone 2 vascularity.
the fact that implantation rates can be more correlated to The conception rates with zones 3 and 4 the pregnancy rates
the vascularity of the endometrium rather than the thickness were comparable and were 35.8 and 38.3%, respectively.
and morphology of the endometrium. Zone of vascularity (1,025 cases)
Segmental uterine artery perfusion demonstrates Zaidi et al. found that absence of flow in the endometrial
significant correlation with hormonal and histological and subendometrial zones on day of hCG indicate total
markers of uterine receptivity, reaching the highest failure of implantation. 20 The vessels that reach the
sensitivity for subendometrial blood flow. 15 On color endometrium are the spiral arteries. The pulse Doppler of
Doppler the endometrium which is mature shows vascularity these arteries should have an RI of between 0.6 and 0.8,
in zones 3 and 4 or may be called subendometrial and and PI of between 1.1 and 2.3 for the endometrium to be
endometrial layers (Figs 21.16A to D). The zones of called mature for implantation (Fig. 21.17).
vascularity are defined according to Applebaum21 as: zone 1
Vascular zone 1 2 3 4
when the vascularity on power Doppler is seen only at
endometrial-myometrial junction, zone 2 when vessels Conc. 10 52 100 84
penetrate through the hyperechogenic endometrial edge, Non Conc. 125 336 181 137
zone 3 when it reaches intervening hypoechogenic zone Total 135 388 281 221
and zone 4 when they reach the endometrial cavity. The (Conc., conceived cases; non conc., nonconceived cases)
pregnancy rates related to the zones of vascular penetration:
26.7% for zone 1, 36.4% for zone 2 and 37.9% for zone 3. Uterine Artery Doppler
One more comparison of two studies have also shown
similar results22 Moreover the pulse Doppler analysis of the uterine artery
waveform is done and its RI should not be more than 0.9
À Zone 1 3.5–7.5% 5.2%
and PI should be less than 3.2 (Figs 21.18A and B). Several
À Zone 2 15.8–29.7% 28.7% authors have shown that the optimum uterine receptivity
À Zone 3 24.2–47.8% 52% was obtained when average pulsatility index of the uterine
À Zone 4 67.3% 74% artery was between 2 and 3 on the day of transfer or on
A B
C D
Figures 21.16A to D Endometrial vascularity zones
ascending branch of uterine artery was greater than 3.

Fecundity rate was 18% when PI less than 2 and 19.8%
when between 2 and 3. This probably can be explained
on the basis that the uteri having fibroids or adenomyosis
show fairly high uterine artery blood flow velocities but
lower resistance indices. A study by Cacciatore et al.
suggest that implantation is unlikely when PI is greater
than 3.3 and RI greater than 0.95 or when no velocities are
seen at the end of the diastole.27 Although uterine artery
impedance is usually low in superovulated cycles. In
authors’ unpublished data of more than 1,000 IUI cycles,
when color Doppler studies were done 12 hours before
hCG injection, they have found no conceptions when
uterine artery PI greater than 3.5.
Volume Ultrasound Assessment of

Figure 21.17 Pulse Doppler of endometrial vascularity Endometrium
When endometrial and the uterine artery parameters are
23,24
the day of hCG. Coulam et al. have also shown that optimum as described above, the volume of the endometrium
no pregnancy was achieved after embryo transfer when with power Doppler is acquired and then the endometrial
uterine artery PI was above 3.3 in an IVF program.25 Tsai volume is calculated by vocal, tracing the outer edge of the
and colleagues26 evaluated the prognostic value of uterine hyperechoic outer rim of the endometrium and accept the
perfusion on day of hCG for IUI cycles and showed that volume (Fig. 21.10). The endometrium up to the internal os
no pregnancy occurred when the pulsatility index of is taken into calculation. For accurate measurements, a good
A B
Figures 21.18A and B Preovulatory uterine artery waveform
contrast in the image is necessary. Select smaller angles of

rotation for VOCAL. Fluid in the endometrial cavity can
be a source of error. For endometrial volume the inter CC
definition of internal os and (interobserver variation) was
0.82 and intra CC (intraobserver variation) was 0.90, the chief
source of error being definition of endometrial margins.28
3D and 3D PD Features of Good

Endometrial Receptivity
Authors’ study8 showed that at endometrial volume of less
than 2 cc no pregnancies occurred. With endometrial volume
of 2–3 cc only 16.66% of patients conceived, between 3
cc and 5 cc 47% and when the endometrial volume was
between 5 cc and 7 cc 61.5% patients conceived.
Figure 21.19 Histogram of endometrium showing VI, FI, and VFI
values
Endometrial volume (500 cases)
Endo. Vol <2 2–3 3.1–5 5.1–7 >7 may help to correlate the cycle outcome with quantitative
Conc. 0 26 70 67 41 parameter rather than endometrial thickness.9 A study by
Non Conc. 20 132 78 42 24 Raga et al.29 shows pregnancy and implantation rates were
Total 20 158 148 109 65 significantly lower when endometrial volume less than 2 ml,
(Conc., conceived cases; non conc., nonconceived cases) while no pregnancy was achieved when endometrial volume
was less than 1 ml. Study by Kupesic et al. also shows no
Decline in conception rates at endometrial volumes pregnancy when endometrial volume was less than 2 ml,
of more than 7 cc is seen. This can be explained by or when exceeded 8 ml.30 For the same calculated volume,
pathological increase in endometrial thickness and volume histogram is switched on and it calculates the
volume like hyperplasia or large polyps that significantly endometrial VI, FI and VFI (Figs 21.19 and 21.20). In our
decrease the implantation rates. Endometrial volume by series8 the endometrial VI values were not very conclusive.
3D ultrasound volume calculation of the endometrium Endometrial FI when was less than 20, only 23% of patients
A B
Figures 21.20A and B Glass body mode of endometrial 3D power Doppler vascularity
Figure 21.21 Pre-hCG endometrial volume and 3D PD values
showed conception, between 20 and 40 it was almost 50% When endometrial VFI was greater than 20 the conception
but when FI was more than 40, 68% of patients showed occurred in 71.2% of patients and when VFI was less than
conception. 1.0 no conception was seen. Although between VFI 5 and
20 the percentage of conception was 49–56% (Fig. 21.21).
Endometrial FI (500 cases)
Endometrial VFI (500 cases)
Endo. FI < 20 20–30 30.1–40 > 40
Endo.VFI <2 2–5 5.1–12 12.1–20 >20
Conc. 37 68 75 34
Conc. 00 96 64 45 09
Non Conc. 125 76 68 17
Non Conc. 44 136 66 36 04
Total 162 144 143 51 Total 44 232 130 81 13
(Conc., conceived cases; non conc., nonconceived cases) (Conc., conceived cases; non conc., nonconceived cases)
A scoring system reported by Kupesic et al. 30 for
uterine receptivity done on the day of embryo transfer
shows that subendometrial FI less than 11 was a cut off
limit (subendometrial indices are calculated in the same
way from the endometrial volume as we calculate the
perifollicular indices from the follicular volume, i.e. by
shell volume of 2 mm thickness). No pregnancies occurred
when it was less than 11 and the conception group showed
its values of 13.2 ± 2.2. These values differ from our
values probably because we have done calculations on
whole endometrium as compared to the calculations made
for the subendometrial layers here, but is common in both
that higher FI values are associated with higher pregnancy
rates.
Whereas Ng et al.31 documented a low endometrial VI and
VFI in pregnant group on the day of oocyte retrieval and also
a nonsignificant trend of higher implantation and pregnancy
rates in patients with absent subendometrial and endometrial Figure 21.22 Maximum implantation point
flow. This probably can be explained on the basis that hCG
administration or LH peak causes increased uterine artery
resistance and hence decrease in endometrial perfusion Summary
also on the day of oocyte retrieval. This also correlates
Follicle Endometrium
with the observation made by Ng et al.32 which says that
subendometrial vascularization flow indices are significantly Size/thickness 16–18 mm 8–10 mm
lower in patients with uterine artery RI greater than or equal Morphology Thin wall, no internal Grade A/B
echoes, halo
to 0.95. They concluded that number of embryos replaced,
Vascualrity 3/4th circumference Zone 3–4
and endometrial VFI were the only two predictive factors
RI 0.4–0.48 <0.5
for pregnancy. Wu et al.33 reported that endometrial VFI was
more reliable than VI and FI, and best prediction rate was PSV >10 cm/sec -
achieved by VFI cutoff value of greater than 0.24. Uterine artery PI - <3.2
Volume 3–7 cc 3–7 cc
3D morphology Cumulus Intact endo-myo
Contractions and Maximum junction
Implantation Point 3D PD More symmetrical

the better
Higher the better
Apart from these criteria, there are another few that have
been worked upon in some studies. It has been shown Three-dimensional ultrasound is much accurate for volume
that uterine motility on the day of embryo transfer has an assessment both for follicle and the endometrium, and are much
more reliable parameters than follicular diameter or endometrial
impact on implantation rates. Number of uterine peristaltic thickness. The presence of cumulus can be confirmed by 3D
contractions is counted per minute in longitudinal scan ultrasound increases the surety of the presence of a mature
ovum in the follicle. The 3D power Doppler gives idea about the
of the uterus. More than 5 contractions per minute has
global vascularity of follicle and endometrium. Although still larger
considered as unfavorable sign and less than 3 has been studies and standardization of ultrasound parameters and settings
considered as a favorable sign for implantation.34 Point are required to establish more precise values for follicular and
endometrial VI, FI and VFI, the results are fairly promising. We
of maximum implantation also has been worked out. This can hope to understand the follicular and endometrial physiological
point is an intersection of two lines that are drawn parallel status better with these parameters and achieve better pregnancy
to both cornu on a mid-true coronal section of uterus35 rates with ART procedures and reduce the span of unexplained
infertility.
(Fig. 21.22).
References with endometriosis undergoing in vitro fertilization.

1. Kyei-Mensah A, Zaidi J, Pittrof R, et al. Transvaginal three 14. Vlaisavljevic V, Reljic M, Gavric Lovrec V, et al.
dimensional ultrasound: accuracy of follicular volume Measurement of perifollicular blood flow of the dominant
measurements. Fertil Steril. 1996;65:371-6. preovulatory follicle using three dimensional power
2. Jokubkeine L, Sladkevicius P, rovas L, et al. Assessment Doppler. Ultrasound Obstet Gynecol. 2003;22:520-6
of changes in volume and vascularity of ovaries during 15. Kupesic S, Kurjak A. Prediction of IVF outcome by three
the normal menstrual cycle using three dimensional power dimensional ultrasound. Hum Reprod. 2002;17:950-5.
Doppler ultrasound. Hum Reprod. 2006;21(10): 2661-8.
16. Merce LT. Ultrasound markers of implantation. Ultrasound
3. Chui D, Pugh N, Walker S, et al. Follicular vascularity—
Rev Obstet Gynecol. 2002;2:110-23.
the predictive value of transvaginal power Doppler
17. Merce LT, Barco MJ, Kupesic S, et al. 2D and 3D power
ultrasonography in an in vitrofertilization program: a
Doppler ultrasound from ovulation to implantation. In:
preliminary study. Hum Reprod. 1997;12(1):191-6.
Kurjak A, Chervenak F (Eds). Textbook of Perinatal
4. Kupesic S, Kurjak A.Uterine and ovarian perfusion during
Medicine. London: Parthenon Publishing; 2005.
the periovulatory period assessed by transvaginal colour
Doppler. Fertil Steril. 1993;3:439-43. 18. Kupesic S, Kurjak A, Vujisic S, et al. Luteal phase defect:
comparison between Doppler velocimetry, histological
5. Nargund G, Doyle PE, Bourne TH, et al. Ultrasound-deviced
and hormonal markers. Ultrasound Obstet Gynecology.
indices of follicular blood flow before hCG administration
1997;9:105-12.
and prediction of oocyte recovery and preimplantation
embryo quality. Hum Reprod. 1996;11:2512-7. 19. Smith et al., Porter R, Ahuja, K, et al. Ultrasonic assessment
6. Nargund G, Bourne TH, Doyle PE, et al. Association of endometrial changes in stimulated cycles in an in vitro
between ultrasound indices of follicular blood flow, oocyte fertilization and embryo transfer program. J in Vitro Fertil
recovery and preimplantation embryo quality. Hum Reprod. Embryo Transf. 1984:1:233-8.
1996;11:109-13. 20. Zaidi J, Campbell S, Pittrof R, et al. Endometrial thickness,
7. Blerkom V, Antezak M, Schrader R. The developmental morphology, vascular penetration and velocimetry in
potential of human oocyte is related to the dissolved predicting implantation in an in vitro fertilization program.
oxygen content of follicular fluid: association with vascular Ultrasound Obstet Gynecol. 1995;6:191-8.
endothelial growth factor levels and perifollicular blood 21. Applebaum M. The ‘steel’ or ‘teflon’ endometrium-
flow charecteristics. Hum Reprod. 1997;12(5):1047-55. ultrasound visualization of endometrial vascularity in IVF
8. Panchal SY, Nagori CB. Can 3D PD be a better tool patients and outcome. presented at the third World Congress
for assessing the pre hCG follicle and endometrium? A of Ultrasound in Obstetrics and Gyneacolgy. Ultrasound
randomized study of 500 cases. Presented at 16th World Obstet Gynecol. 1993;3(Suppl 2):10.
Congress on Ultrasound in Obstetrics and Gynecology, 2006, 22. Chein LW, Au HK, Chen PL, et al. Assessment of uterine
London. J Ultrasound Obstet Gynecol. 2006;28(4):504. receptivity by the endometrial-subendometrial blood flow
9. Wittmack FM, Kreger DO, Blasco L, et al. Effect of distribution pattern in women undergoing IVF-ET. Fertil-
follicular size on oocyte retrieval, fertilization, cleavage Steril. 2002;78:245-51.
and embryo quality in in vitro fertilization cycles: a 6 year 23. Steer CV, Campbell S, Tan SL, et al. The use of transvaginal
data collection. Fertil Steril. 1994;62:1205-10. colour flow imaging after in vitro fertilization to identify
10. Kyei-Mensah A, Zaidi J, Pittrof R, et al. Transvaginal optimum uterine conditions before embryo transfer. Fertil
three dimensional ultrasound reproducibility of ovarian Steril. 1992;57:372-6.
and endometrial volume measurements. Fertil Steril. 24. Zaidi J, Pittrof R, Shaker A, et al. Assessment of uterine
1996;66:718-22. artery blood flow on the day of human chorionic
11. Feichtinger W. Transvaginal three dimensional imaging for gonadotropin administration by transvaginal colour
evaluation and treatment of infertility. In: Merz E (Ed). 3D Doppler ultrasound in an in vitro fertilization program.
Ultrasound in Obstetrics and Gyneacology. Philadelphia: Fertil Steril. 1996;65:377-81.
Lipincott Williams & Wilkins; 1998. pp 37-43. 25. Coulam CB, Stern JJ, Soenksen DM, et al. Comparison of
12. Poehl M, Hohlagschwandtner M, Doerner V, et al. Cumulus pulsatility indexes on the day of oocyte retrieval and embryo
assessment by three dimensional ultrasound for in vitro transfer. Hum Reprod. 1995;10:82-4.
fertilization. Ultrasound Obstet Gynecol. 2000;16:251-3. 26. Tsai Y-C, Chang J-C, Tai M-J, et al. Relationship of uterine
13. Wu MH, Tsai SJ, Pan HA, et al. Three dimensional power perfusion to outcome of intrauterine insemination. J
Doppler imaging of ovarian stromal blood flow in women Ultrasound Med. 1996;15:633-6.
27. Cacciatore B, Simberg N, Fusaro P, et al. Transvaginal Doppler 32. Ng EH, Chan CC, Tang OS, et al. Relationship between
study of uterine artery blood flow in in vitro fertilization uterine blood flow and endometrial and subendometrial
embryo transfer cycles. Fertil Steril. 1996;66:130-4. blood flows during stimulated and natural cycles. Fertil
28. Kyei-Mensah A, Zaidi J, Pittrof R, et al. Transvaginal three Steril. 2006;85(3):721-7.
dimensional ultrasound: accuracy of follicular volume 33. Wu HM, Chiang CH, Huang HY, et al. Detection of
measurements. Fertil Steril. 1996;65:371-6. subendometrial vascularization flow index by three
29. Raga F, Bonilla-Musoles F, Casan EM, et al. Assessment of dimensional ultrasound may be useful for predicting
endometrial volume by three dimensional ultrasound prior pregnancy rate for patients undergoing in vitro fertilization-
to embryo transfer: clues to endometrial receptivity. Hum embryo transfer. Fertil Steril. 2003;79(3):507-11.
Reprod. 1999;14:2851-4.
34. Renato Fanchin1, Claudia Righini, Franҫois Olivennes,
30. Kupesic S, Bekavac I, Bjelos D, et al. Assessment of
et al. Uterine contractions at the time of embryo transfer
endometrial receptivity by transvaginal colour Doppler
alter pregnancy rates after in-vitro fertilization. Human
and three dimensional power Doppler ultrasonography
Reproduction. 1998;13(7):1968-74.
in patients undergoing in vitro fertilization procedures. J
Ultrasound Med. 2001;20:125-34. 35. Robert Z Gergely, Catherine Marin DeUgarte, Hal Danzer,
31. Ng EH, Chan CC, Tang OS, et al. The role of endometrial and et al. Three dimensional/four dimensional ultrasound-guided
subendometrial blood flows measured by three dimensional embryo transfer using the maximalimplantation potential
power Doppler ultrasound in prediction of pregnancy during point. Fertility and Sterility. 2005;84(2):500-3.
IVF treatment. Hum Reprod. 2006;21(1):164-70.
CHAPTER
22 Asymptomatic Simple Ovarian

Cyst in Postmenopausal Women:
Syndrome of “Visible Ovary“
Ivica Zalud, Raydeen Busse, Biserka Funduk Kurjak
Introduction There are a few studies that have looked at the prevalence
of simple ovarian cysts in asymptomatic postmenopausal
The performance of high-resolution ultrasound in the women. The general consensus is 5–17% (Table 22.1).5
postmenopausal female is becoming more commonplace in Wolf et al.6 performed transabdominal sonography (TAS)
modern medicine. The old adage of the “postmenopausal and transvaginal sonography (TVS) on 149 unselected,
palpable ovary syndrome” as described by H Barber et al. in self-referred asymptomatic female volunteers aged 50 years
19711 requiring surgical management is no longer the sole or older who were at least 1 year postmenopausal and had
issue in determining a normal or abnormal postmenopausal at least one ovary. Unilocular cysts ranged from 0.4 cm to
ovary. The new adage is “the visible ovary syndrome” and 4.7 cm in diameter in 22 (14.8%) women. Conway et al.7
the issues surrounding the management of these findings. performed TVS on 1,769 asymptomatic postmenopausal
Ovarian cancer deaths are the leading cause of women and found 116 (6.6%) simple ovarian cysts less than
gynecological malignancy mortality in the United States 5 cm in diameter. Andolf and Jorgensen8 performed TAS
causing more than 16,000 deaths projected in 2004.2 About on 534 postmenopausal women and found simple ovarian
1 in every 57 women in the United States will develop cysts ranging from 2 cm to 8 cm in size in 30 (5.6%) of
ovarian cancer; and most cases occur in women over the them. Aubert et al.9 performed TVS on 622 asymptomatic
age of 50. It is well-known that the overall 5-year survival postmenopausal women and found simple unilocular cysts
rate is 39%.3 This lends particular importance to the need to between 1 and 5 cm in diameter in 36 (5.7%) women.
know the natural history and prevalence of simple ovarian Bailey et al.10 performed TVS on 7,705 asymptomatic
cysts in the postmenopausal state and how it relates to postmenopausal women and found unilocular ovarian cystic
ovarian carcinoma, if at all. Our ignorance has led to an tumors in 256 (3.3%) of them. Of these, 231 (3%) of the
aggressive approach when an ovarian cyst is detected. It cysts were 5 cm or less in diameter, and 25 were 5–10 cm
is also well-known that the majority of ovarian cancers, in diameter.5
especially in older women, are diagnosed in the advanced Additional circumstances in which asymptomatic
stage and that the survival rate is the highest for stage I postmenopausal women have gynecological ultrasounds are
disease. This chapter covers the most up-to-date and best during tamoxifen use and postmenopausal hormone therapy.
evidence on this challenge of the simple ovarian cyst seen Kazandi et al.11 found that ovarian cysts are a common
in the postmenopausal patient.
Table 22.1 Prevalence of simple ovarian cysts in asymptomatic
Natural History of the postmenopausal women
Postmenopausal Ovary Authors Number of

women
Number of
cysts
Percentage
of women
with cysts
The menopausal ovary gets lighter and smaller as atrophy 6
Wolf et al. 149 22 14.8
of the graafian follicles and ova take place. Ultrasound 7
studies looking at the mean normal size of a postmenopausal Conway et al. 1,769 116 6.6
ovary show that, overall, the size should not exceed 2 × 3 Andolf and
8
534 30 5.6
Jorgensen
× 4 cm. Ovarian volume studies also done and show that 9
Aubert et al. 622 36 5.7
normal postmenopausal ovarian volumes range from 2.5 10
Bailey et al. 7,705 256 3.3
to 4.33 cu mm.4
Chapter 22  Asymptomatic Simple Ovarian Cyst in Postmenopausal Women: Syndrome of “Visible Ovary” 219
finding in postmenopausal breast cancer patients on cyst before developing cancer or developed cancer in the
tamoxifen with an incidence of 13.2%(5/38) and Seoud et contralateral ovary. No woman with an isolated unilocular
al.12 found an incidence of ovarian cysts to be 25%(18/72). cystic ovarian tumor had developed ovarian cancer in
In 1997, Bar-Hava et al.13 found that hormone replacement this population. Their conclusion was that the risk of
therapy is associated with a reduced prevalence of ovarian malignancy in unilocular ovarian cystic tumors less than 10
cysts (only) in the early postmenopause. cm in diameter in women 50 years old or older is extremely
The natural history of simple ovarian cysts that are low. The majority will resolve spontaneously. Shushan
followed by serial ultrasounds and possibly other test et al.18 in 1996 also noted that ovarian cysts are a common
methods has been described by numerous authors since side effect of tamoxifen and most of these cysts disappear
1986. Valentin et al.14 followed 134 patients with 160 cysts; after tamoxifen treatment is abandoned. Cohen et al.19 found
121 (76%) were unilocular and were followed at 3, 6 and 9.6% of 322 postmenopausal women with breast carcinoma
12 months. There was spontaneous resolution in 29% of under treatment with tamoxifen had simple ovarian cysts
patients and new cyst formation in 13%. There was no and that there was a statistically significant decrease in cyst
change in 49% and no malignancies detected in any cyst size over long-term follow-up.
from 3 mm to 80 mm in diameter. The authors stated that
women in whom cysts disappeared or developed were Pathology of Simple Cysts
younger and had passed the menopause more recently than
those in whom findings remained unchanged. They also A few studies have looked at the pathology of surgically
stated that the cysts in the older women with more stable removed simple ovarian cysts. In the Bailey study of 45
ultrasound findings are more likely to have been inclusion women who underwent oophorectomy, 32 (71%) had
cysts or neoplastic cysts. benign serous cystadenomas. Additional diagnoses were
Bailey et al.10 found unilocular cystic tumors less than 10 paratubal and paraovarian cysts, endometriotic cysts,
cm in diameter (90% less than 5 cm) in 256/7,705 (3.3%) mucinous cystadenomas, hydrosalpinx and peritoneal cyst
of patients and 125 (49%) resolved spontaneously and 131 in descending frequency.10 Goldstein et al.20 had similar
(51%) persisted. Forty-five of these patients had surgical results of 28 women who had undergone oophorectomy for
removal of the tumors and notably, there were no cases simple ovarian cysts; 16 (57%) were serous cysts; and in
of ovarian carcinoma in this group. Kroon and Andolf15 descending order of frequency, hydrosalpinges, paraovarian
followed 83 postmenopausal women with small, completely cysts, endometriotic cyst and mucinous cyst. Rodriguez et
anechoic, thin-walled cysts less than 5 cm, 43 underwent al.21 reported 3 out of 7 serous inclusion cysts, 2 paraovarian
surgery and 32 underwent serial observation (8 were lost to cysts, 1 mucinous inclusion cyst and 1 benign epithelial cyst.
follow-up) There were no ovarian cancers identified and 12 Conway et al.7 found 67% of cysts removed from 18 women
out of 32 cysts underwent spontaneous resolution. Levine16 were benign serous cystadenomas. Hall and McCarthy22
did a study on 184 asymptomatic postmenopausal women found 10 simple cysts out of 13 postmenopausal cysts ranging
and found 37 simple cysts and of these, 53% resolved in size from 1.5 to 10 cm; 7 were benign serous cysts; 1 was
spontaneously and out of 6 surgical interventions, there was a hydrosalpinx and 4 were benign cystadenomas.
one malignancy in a cyst that developed septations and an A more recent study by Ekerhovd et al.23 compared
abnormal Doppler study. ultrasonographic and macroscopic appearances of the
Modesitt et al.17 followed 15,106 asymptomatic women cysts with histopathologic diagnosis. The results for
from 1987 to 2002 who were at least 50 years old. They the postmenopausal population with cysts that were
found 2,763 (18%) with 3,259 (16.5%) unilocular ovarian characterized either as echo-free, without solid parts or
cyst less than 10 cm in diameter; 2,261 (69.4%) of these papillary formations showed 4 of 247 cysts (1.6%) proved
cysts resolved spontaneously; 537 (16.5%) developed to be borderline or malignant.
a septum; 189 (5.8%) developed a solid area and 220
(6.8%) persisted as an unilocular lesion. During this time, Sonography
27 women received a diagnosis of ovarian cancer, and 10
had been previously diagnosed with simple ovarian cysts. Simple cysts that are thin-walled, unilocular with smooth
All ten of these women, however, developed another walls are more likely to be benign than multiloculated cysts
morphologic abnormality, experienced resolution of the (Fig. 22.1). Most studies excluded cysts that were more
Figure 22.1 A small simple cyst in postmenopausal ovary Figure 22.2 Highly vascular ovary visualized by color Doppler
Box 22.1: Sonographic findings suggesting malignancy

• Diameter > 10 cm
• Multiple septations
• Thick septae
• Solid components
• Papillary projections
• Bilaterality
• Ascites/pelvic fluid
• Neovascularization
• Doppler resistance index < 0.4
than 5 cm in diameter even if they were simple. Findings

suggestive for malignancy are: diameter more than 10
cm, multiple septations, thick septae, solid components,
papillary projections, bilateralism, ascites/pelvic fluid and
neovascularization (Box 22.1). These findings do not point
toward conservative management, but strongly point toward Figure 22.3 Color and pulsed Doppler of ovarian blood flow
surgical exploration.5
Malignant tumors are frequently “vascular” and obtained a sensitivity of 96% and a specificity of 99% for
Doppler waveform analysis can separate high versus low distinguishing between benign and malignant neoplasms
resistance vessels (Figs 22.2 and 22.3). Low resistance when using a cutoff of 0.40 for the resistance index for
vessels tend to be new vessels; and new growth creates benign tumors. Conway’s study7 evaluated 116 simple
new vessels for nourishment. It is also known that solid cysts by TVS. There were no malignancies, and all of
tumors cannot grow more than 2–3 mm in diameter without the cysts exhibited normal or undetectable blood flow.
neovascularization.24 Color and pulsed Doppler sonography Other investigators have questioned the role of Doppler
can reveal the vascularity of an adnexal mass; thus, it in differentiating between benign and malignant masses
may help in determining which cysts are more likely to due to the significant overlap between Doppler values
be malignant. Malignant neoplasms often have bizarre for benign versus malignant cysts. It is clear that Doppler
architecture and are often associated with a low-resistance, analysis cannot be used as the sole measure of a growth’s
high-flow picture. Benign tumors usually have normal flow malignant potential. The role of Doppler, especially in light
patterns, demonstrating a high-resistance type of flow. of three-dimensional power Doppler imaging and tumor
Kurjak et al. 25 examined 680 premenopausal and angiogenesis is intriguing and the future may hold more
postmenopausal women with ovarian neoplasms and vascular parameters to analyze.
Chapter 22  Asymptomatic Simple Ovarian Cyst in Postmenopausal Women: Syndrome of “Visible Ovary” 221
Role of CA-125 3–6 months for up to 2 years with CA-125 measurements.
Patient compliance and having a scan performed by an
Many investigators have incorporated the level of CA-125 experienced sonographer are crucial. The indications
in their “scoring” of a woman’s risk of having an ovarian for surgical (preferably laparoscopically) removal of the
carcinoma when evaluating a postmenopausal woman ovary are as follows: increasing size, development of solid
with a simple ovarian cyst. CA-125 is a nonspecific tumor components, abnormal Doppler flow, CA-125 elevation and
marker that has been shown to be elevated in 80–90% of noncompliance with follow-up.
women with epithelial serous ovarian tumors. It can be Auslender’s study from the prior section26 supports
elevated in many gynecologic as well as nongynecologic the conservative management of small, simple cysts
medical conditions. When used in conjunction with an in the postmenopausal woman with repeat ultrasounds
abnormal sonographic finding, this nonspecific test can and CA-125. Kroon et al.15 in his 1995 study concluded
raise the suspicion for an ovarian malignancy. Auslender that nonpalpable ovarian cysts commonly detected by
et al.26 followed 34 postmenopausal women with CA-125 ultrasound in asymptomatic women have a low risk for
levels and vaginal ultrasound with simple ovarian cysts. The malignancy. They recommended ultrasound follow-up
cysts measured less than 5 cm in diameter and there were of stationary lesions and that surgery can be confined to
no cases of malignancy found. The CA-125 levels were all symptomatic cases of those with a family history of ovarian,
normal in these cases. Other investigators have found the breast or colon cancer.
combination of transvaginal ultrasound and CA-125 that
is useful in helping to distinguish between low-risk and Conclusion
high-risk adnexal masses. Simple cysts of the ovary are quite common, with a prevalence of
5–17%. Advances in the technology of ultrasound and the increasing
frequency of use of TVS has made it all the more important to
Management have knowledge of the natural history of simple asymptomatic
postmenopausal cysts. This knowledge impacts not only upon the
Now it is understood and accepted that simple management protocols and cost-analyses but also has psychosocial
impact and health implications on the patient, especially if managed
postmenopausal ovarian cysts, especially if they are less surgically. Previously, due to the paucity of data, postmenopausal
than 5 cm and have a normal CA-125 in an asymptomatic women with asymptomatic simple cysts were managed much
woman are nearly always benign, the next logical question too aggressively. Current available data now suggest a more
conservative approach with serial ultrasounds, Doppler evaluation
deals with management. Again, the old adage of the palpable and CA-125 levels. Further studies are needed in order to have
ovarian syndrome being a strong case for surgical removal definitive guidelines for the gynecologic practitioner.
and exploration begs updating. Conway et al.7 showed that
of the 1,769 postmenopausal patients that had persistent References
simple ovarian cysts (116 or 59.5%), 26% were surgically
managed and 74% were expectantly managed; 67% of those 1. B a r b e r H R , G r a b e r E A . T h e P M P O s y n d r o m e
(postmenopausal palpable ovary syndrome). Obstet
managed surgically were done laparoscopically and 33%
Gynecol. 1971;38(6):921-3.
had total abdominal hysterectomies with bilateral salpingo-
2. American Cancer Society. (2004). [online] Available from http://
oophorectomies. Again, the most common pathology
www.cancer.org/downloads/STT/CAFF2003PWSecured.pdf.
diagnosis was serous cystadenoma. There were no ovarian
3. Young RC, Walton LA, Ellenberg SS, et al. Adjuvant
malignancies. Their conclusion was that, with their findings
therapy in stage I and stage II epithelial ovarian cancer.
and additional support from the literature, simple ovarian
Results of two prospective randomized trials. N Engl J Med.
cysts, less than 5 cm in postmenopausal patients are very 1990;322(15):1021-7.
unlikely to be malignant and are capable of being followed
4. Ujevic B, Funduk-Kurjak B, Kurjak A. Ultrasound in
conservatively. In their study, a large number of surgical the postmenopause. In: Kurjak A, Chervenak F (Eds).
candidates (by previous standards) had spontaneous Donald School Textbook of Ultrasound in Obstetrics
resolution and thus no surgical intervention was needed. and Gynecology. New Delhi: Jaypee Brothers Medical
Furthermore, they concluded that for those opting for Publishers (P) Ltd; 2003. pp 726-46.
surgical intervention, the information presented illustrates 5. Oyelese Y, Kueck AS, Barter JF, et al. Asymptomatic
a role for laparoscopic approach. Of those followed postmenopausal simple ovarian cyst. Obstet Gynecol Surv.
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6. Wolf SI, Gosink BB, Feldesman MR, et al. Prevalence of 17. Modesitt SC, Pavlik EJ, Ueland FR, et al. Risk of malignancy
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7. Conway C, Zalud I, Dilena M, et al. Simple cyst in the 18. Shushan A, Peretz T, Uziely B, et al. Ovarian cysts
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Ultrasound Med. 1998;17(6):369-72. treated women with breast cancer. Am J Obstet Gynecol.
8. Andolf E, Jörgensen C. Simple adnexal cysts diagnosed by 1996;174(1 Pt 1):141-4.
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1988;16(5):301-3. cysts in postmenopausal patients with breast carcinoma
9. Aubert JM, Rombaut C, Argacha P, et al. Simple adnexal treated with tamoxifen: long-term follow-up. Radiology.
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10. Bailey CL, Ueland FR, Land GL, et al. The malignant postmenopausal cystic adnexal mass: the potential role of
potential of small cystic ovarian tumors in women over 50 ultrasound in conservative management. Obstet Gynecol.
years of age. Gynecol Oncol. 1998;69(1):3-7. 1989;73(1):8-10.
11. Kazandi M, Sendag F, Akercan F, et al. Ovarian cysts in 21. Rodriguez MH, Platt LD, Medearis AL, et al. The use of
postmenopausal tamoxifen-treated breast cancer patients transvaginal sonography for evaluation of postmenopausal
with endometrial thickening detected by transvaginal ovarian size and morphology. Am J Obstet Gynecol.
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13. Bar-Hava I, Orvieto R, Vardimon D, et al. Ovarian cysts and 23. Ekerhovd E, Wienerroith H, Staudach A, et al. Preoperative
assessment of unilocular adnexal cysts by transvaginal
cyclic hormone replacement therapy: is there an association?
ultrasonography: a comparison between ultrasonographic
Acta Obstet Gynecol Scand. 1997;76(6):563-6.
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14. Valentin L, Akrawi D. The natural history of adnexal cysts Obstet Gynecol. 2001;184(2):48-54.
incidentally detected at transvaginal ultrasound examination
24. Folkman J. A novel anti-vascular therapy for cancer. Cancer
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16. Levine D, Gosink BB, Wolf SI, et al. Simple adnexal cysts: 26. Auslender R, Atlas I, Lissak A, et al. Follow-up of small,
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CHAPTER
Evaluation of Functional
Ovarian Cysts
Ma Angela Pascual
Introduction Four parameters have been analyzed: (i) age of the

patient, (ii) size of the cyst, (iii) ultrasound pattern (taking
Ovarian tumoral pathology is comprised of a large variety account the presence of septal structures, proliferations,
of histological types including functioning cysts that do diffusion due to shadowing and if the pattern is solid
not require surgical intervention.1 The use of ultrasound, and/or heterogeneous), and (iv) vascularization. Also the
especially since the advent of vaginal transducers, permits parameters of the resistance index (RI) and the pulsatility
prediction of the histological type of an ovarian tumor with index (PI) were considered.
high levels of both sensitivity and specificity.2-15
All the ultrasound explorations were undertaken with a
However, it has been estimated that the incidence of real time sonograph with a vaginal probe of 6 MHz, with a
hospitalization due to functioning ovarian cysts is high.
sweeping angle of 150° and color Doppler (Toshiba SSA 270
One study, undertaken in the United States, calculated that
A, Toshiba SSA-370 A/E2 PowerVision and Toshiba SSA-
this rate was in the order of 500 per 100,000 women.16
700A Aplio). On the few occasions that the ultrasound was
In other studies, the presentation of luteinized unruptured
undertaken through the suprapubic zone of the abdomen,
follicle (LUF) was seen to vary between 6 and 47%.17-19
with the bladder being full, either for the entire ultrasound
It has been described that LUF could cause unexplained
test or for complementary testing, a transducer of 3.5 MHz
infertility and has also been associated with endometrial
processes.20-22 was used. Later on, three-dimensional (3D) ultrasound was
used in their practice (General Electric Voluson 5,300).
The aim of this chapter is to report on author’s own
efficiency in the diagnosis of functional ovarian cysts. The diagnostic efficiency of the vaginal ultrasound for
this diagnosis has been evaluated through the parameters of
sensitivity, specificity, the positive predictive value (PPV)
Barcelona Experience
and the negative predictive value (NPV).
Author’s study includes more than 10,000 gynecological The results are expressed as percentages or mean values.
ultrasounds undertaken at their unit. Of these, 854 diagnoses
To test differences in mean values, the Students T-test has
were made of some type of ovarian tumor.
been used, whilst the Chi-square test has been used to test
The study group is comprised of 117 (13.7%) patients qualitative or categorical variables. Fischer’s exact test was
with a diagnosis of functional ovarian cysts. The control
used when the expected frequencies were less than 5 in over
groups are made up of a group of 237 patients diagnosed
20% of the total. The level of significance was set at 5%.
with benign tumoral pathology (excluding functional cysts)
and a group of 24 patients with malignant cysts. For the The mean age of the patients was 38.6 years (± 10.16).
other patients, either follow-up was not available or they Of these, 11 women had reached menopause.
were treated in another center. No significant differences were seen for this parameter for
None of the patients in the study group were undergoing patients with non-functioning benign ovarian pathology (35.9
treatment to either induce or prevent ovulation. All patients ± 11.1 years), whilst those patients with malignant ovarian
included had spontaneous menstrual cycles. cysts were significantly older (47.45 ± 12.31; p < 0.001).
The diagnosis was confirmed by either ultrasound The mean size of the functioning ovarian cysts was 41.8
follow-up (vanish after menstruation) or by histopathology. mm (± 17.35). Significant differences were found between
this group and the other two groups: for nonfunctional (43.6%) than among those with non-functioning benign
benign pathology a mean size of 62.7 mm (± 69.5; pathology (58.2%) and those with malignant cysts (62.5%).
p < 0.001) was observed; and for the group of malignant Furthermore, the width of the septal structures was narrower
cysts, the mean size was 86.9 mm (± 48.6; p < 0.001). (< 3 mm) for the functioning cysts than for the other groups
(> 3 mm; p = 0.02).
A heterogeneous pattern (Figs 23.13 to 23.19) was more
Illustrative Examples frequent among the malignant cysts (79.2%) than among
The presence of diffuse images (Figs 23.1 to 23.8) due to the non-functioning benign cysts (42.2%) and relatively
shadowing was less frequent for functioning cysts than for rare among the functioning cysts (7.7%). The difference
the groups of nonfunctioning benign pathology or malignant in heterogeneity between the diagnostic groups was
cysts (38%, 72.2%, 54.2% respectively). This difference is statistically significant (p<0.001).
statistically significant (p < 0.001). The presence of proliferations (Figs 23.20 to 23.23) was
The presence of intracystic septal structures (Figs 23.9 frequent in the malignant cysts (58.3%), rare in the benign cysts
to 23.12) was less frequent among the functioning cysts (8.4%) and practically inexistent among the functioning cysts
Figure 23.1 Illustrative example of corpus luteum with diffuse echoes Figure 23.2 Corpus luteum, without diffuse echoes and peripheral
and peripheral vascularization vascularization “fire-ring”
Figure 23.3 Other example of corpus luteum. Fire-ring can be seen Figure 23.4 Corpus luteum, without color Doppler we can confuse
in this figure with endometriosis
Chapter 23  Transvaginal Sonography in Evaluation of Functional Ovarian Cysts 225
Figure 23.5 Luteal cyst in the pregnancy Figure 23.6 Functional cyst with septal structures and diffuse echoes
Figure 23.7 Functional cyst with hemorrhagic phenomena. Figure 23.8 Three-dimensional power Doppler of functional ovarian
Homogenous diffuse echoes can be seen in this figure cyst with diffuse echoes, we can confuse with endometrioma. Note
there is peripheral flow
Figure 23.9 Luteinized unruptured follicle (LUF) with diffuse internal Figure 23.10 Luteinized unruptured follicle with peripheral
echoes and thin septal structures vascularization and thin septae
Figure 23.11 Functional cyst. Thin septal structures can be seen in Figure 23.12 Functional ovarian cyst. The presence of thin septae
this figure is frequently seen
Figure 23.13 Functional cyst with extensive hemorrhage Figure 23.14 Heterogeneous pattern in a functional ovarian cyst
(0.9%) (p < 0.001). This same distribution was seen for the
presence of a solid pattern (malignant cysts = 58.3%; benign
cysts = 13.5%; functioning cysts = 0.9%; p < 0.001).
The characteristics of anechogenic pattern (Figs 23.24
to 23.26) was associated with the functional cyst in
approximately a half of these cases, whilst this was less
frequent in cases with either nonfunctional benign cysts
(15.4%) or malignant cysts (4.2%) (p < 0.001).
Vascular flow was obtained for 85 cases out of the 117
cases with functional cysts (Fig. 23.27), 23 out of the 24
cases with malignant cysts and for 146 out of the 237 cases
with benign organic cysts. The values of the RIs and PIs,
are given in Table 23.1.
Figure 23.15 Other example of functional ovarian cyst with A significant difference in the RI value between the
hemorrhagic phenomenon functioning cysts and the malignant cysts (p = 0.009) was
Figure 23.16 Heterogeneous pattern in a functional ovarian cyst. Figure 23.17 Functional ovarian cyst with a clot. Peripheral flow can
Diffuse echoes and hemorrhagic areas with peripheral vascularization be observed in this figure
can be seen in this figure
Figure 23.18 Three-dimensional power Doppler that shows a Figure 23.19 The same case as in Figure 23.18. The vessels in the
functional ovarian cyst with important hemorrhagic phenomena. periphery of dysfunctional ovarian cyst can be seen in this figure
Localized peripheral flow can be observed in this figure
observed, as was a difference in PI between these diseases of the ultrasound to rule out the presence of an ovarian
(p = 0.047). Furthermore, differences in these values (RI functioning cyst, i.e. its specificity, was observed to be
and PI) were detected between functioning cysts and the 99.2%.
benign organic cysts (p < 0.001) (Figs 23.28 and 23.29). The PPV of the transvaginal ultrasound (TVUS) for
Out of the 117 functioning cysts diagnosed through functioning cysts was seen to be 98% and the NPV was
ultrasound, 99 were confirmed by ultrasound follow-up seen to be 93.5%.
or by histopathology. Two cases were reclassified by
histopathology as having functioning cysts after having Some Conclusions from Author’s
been previously diagnosed as having nonfunctioning
benign cysts by ultrasound. This means that there were 18
Experience
false-positives and 2 false-negatives, indicating that the Ovarian functioning cysts make-up the most common type
capacity to detect ovarian functioning cysts by ultrasound, of ovarian tumor among women of fertile ages16,23 for whom
i.e. its sensitivity, was observed to be 84.6%. The capacity the majority do not require medical treatment.
Figure 23.20 An image of “proliferation” in a functional ovarian cyst Figure 23.21 This picture shows a functional ovarian cyst with
can be seen in this figure. We can observe there is not flow into the clot hemorrhage mimicking a solid area
Figure 23.22 Functional ovarian cyst with a clot, it seems that the Figure 23.23 Three-dimensional power Doppler shows the peripheral
flow is into the pseudopapillae; but the 3D study showing, it is in the flow in a functional ovarian cyst with hemorrhagic phenomena like a clot
periphery (see Fig. 23.23)
Out of all the women author studied, the percentage of ultrasound images; 2 out of 5 present within septal
functioning cysts showing the pattern of cystic disease of structures; less than 10% show a heterogeneous pattern;
the ovary was 13.7%. However, it must be remembered and that presentation with proliferation or solid areas is
that a majority spontaneously vanish with menstruation very rare.
and hence will escape medical attention and diagnosis. When this type of cyst presents with diffuse images
In one of the prospective studies undertaken over (38%), it raises the possibility of a differential diagnosis
10 years,24 it was observed that, in the absence of oral with an endometrial type cyst.11,25 Likewise, if its pattern
contraceptives, functioning cysts made up 66% of all is heterogeneous (7.7%), it raises the possibility of a
diagnosed ovarian cysts for whom three quarters were differential diagnosis with a hemorrhagic cyst, which can
fortuitously diagnosed as a result of other medical in turn be functioning cysts. These results hold-up what has
procedures. been published by other authors.5,24,26
From the results author has obtained, it can be concluded As has been seen in these results, a large proportion
that a third of the functioning cysts present with diffuse of these cysts are vascularized (72.6%) and present with
Figure 23.24 Three-dimensional sonography. A functional ovarian Figure 23.25 Functional ovarian cyst with an echogenic pattern
cyst with an echogenic pattern can be seen in this figure
Figure 23.26 The color Doppler shows poor peripheral flow Figure 23.27 Three-dimensional power Doppler, with mode niche we
can observe the vessels in the capsule of the cyst
Table 23.1 Results of color Doppler

Type of cyst n Flow (%) RI PI
Functional 117 85 (72.6) 0.57 ± 0.10 0.93 ± 0.33
Benign 237 146 (61.6) 0.65 ± 0.18** 1.16 ± 0.48**
Malignant 24 23 (95.80) 0.48 ± 0.14* 0.77 ± 0.37*
Total 378 254 (67.2)
*p < 0.05, **p < 0.001

(Abbreviations: RI, resistance index; PI, pulsatility index)
low RIs and PIs. Hence, it is of importance, and in fact

absolutely necessary, to undertake the ultrasound with color
Doppler in the first phase of the cycle in order to rule out
the presence of a functioning type cyst.27
Figure 23.28 Functional ovarian cyst with peripheral flow. The values
The diagnostic capacity of the ultrasound in the diagnosis
of the RI and PI are 0.58 and 0.93 respectively can be seen in this figure of a functioning cyst is clearly illustrated in Figure 23.30.
Figure 23.29 Functional ovarian cyst with some peripheral vessels. Figure 23.30 Functional ovarian cyst with diffused echoes and thin
The values of the RI and PI are 0.52 and 0.84, respectively septae. The color Doppler shows peripheral flow
Conclusion 7. Athey PA, Diment DD. The spectrum of sonographic findings

in endometriomas. J Ultrasound Med. 1989;8(9):487-91.
The results obtained allow us to conclude that there are two main
groups of functioning cysts: (i) the simple ultrasound cyst that 8. Sassone AM, Timor-Tritsch IE, Artner A, et al. Transvaginal
corresponds to a cyst or follicular persistence and (ii) the LUF that sonographic characterization of ovarian disease: evaluation
presents with thin septal structures (43.6%) which are in general of a new scoring system to predict ovarian malignancy.
highly vascularized and they spontaneously vanish confirming their
Obstet Gynecol. 1991;78(1):70-6.
functional origin.
The knowledge of the ultrasound characteristics of the functioning 9. Broussin B. Les kystes ovariens: confrontation écho-
cysts and their course is of great importance for the gynecologist, anatomique. Contracep Fertil Sex. 1991;19:223-30.
so that unnecessary interventions can be avoided and that some
10. Pascual MA, Carreras O, Hereter L, et al. Diagnostico
light can be shown on the phenomenon of unexplainable infertility.
Without any doubt, transvaginal sonography (TVS), two- ecografico del quiste dermoide de ovario. Progr Obstet
dimensional (2D) or 3D, together with conventional color Doppler Ginecol. 1993;36:508-12.
and 3D power Doppler is a powerful tool in accurate and reliable 11. Pascual MA, Carreras O, Hereter L, et al. Characterísticas
assessment of functional ovarian cyst.
ecográficas de los quistes endometriósicos. Progr Obstet
Ginecol. 1993;36:69-75.
References 12. Okai T, Kobayashi K, Ryo E, et al. Transvaginal sonographic
1. Hall DA. Sonographic appearance of the normal ovary, of appearance of hemorrhagic functional ovarian cysts
polycystic ovary disease, and of functional ovarian cysts. and their spontaneous regression. Int J Gynecol Obstet.
Semin Ultrasound. 1983;4:149-65. 1994;44(1):47-52.
2. Coulam CB, Hill LM, Breckle R. Ultrasonic evidence for 13. Pascual MA, Tresserra F, Grases PJ, et al. Borderline
luteinization of unruptured pre-ovulatory follicles. Fertil cystic tumors of the ovary: gray-scale and color Doppler
Steril. 1982;37(4):524-9. sonographic findings. J Clin Ultrasound. 2002;30(2):76-82.
3. Liukkonen S, Koskimies AL, Tenhunen A, et al. Diagnosis 14. Alcázar JL, Errasti T, Jurado M. Blood flow in functional
of luteinized unruptured follicle (LUF) syndrome by cysts and benign ovarian neoplasms in premenopausal
ultrasound. Fertil Steril. 1984;41(1):26-30. women. J Ultrasound Med. 1997;16(12):819-24.
4. Reynolds T, Hill MC, Glassamn LM. Sonography 15. Guerriero S, Mallarini G, Ajossa S, et al. Transvaginal
of hemorrhagic ovarian cysts. J Clin Ultrasound. ultrasound and computed tomography combined with
1986;14(6):449-53. clinical parameters and CA-125 determinations in the
5. Baltarovich OH, Kurtz AB. Pasto ME, et al. The spectrum differential diagnosis of persistent ovarian cysts in
of sonographic findings in hemorrhagic ovarian cysts. AJR premenopausal women. Ultrasound Obstet Gynecol.
Am J Roentgenol. 1987;148(5):901-5. 1997;9(5):339-43.
6. Timor-Tritsch IE, Rottem S, Thaler I. Review of transvaginal 16. Grimes DA, Hugues JM. Use multiphasic oral contraceptives
ultrasonography: a description with clinical application. and hospitalizations of women functional ovarian cysts in
Ultrasound Q. 1988;6:1-34. the United States. Obstet Gynecol. 1989;73(6):1037-45.
17. Marik J, Hulka J. Luteinized unruptured follicle syndrome: 23. Holt VL, Cushing-Haugen KL, Daling JR. Oral
a subtle cause of infertility. Fertil Steril. 1978;29(3):270-4. contraceptives, tubal sterilization, and functional ovarian
18. de Crespigny LH, O’Herlilhy C, Robinson HP. Ultrasonic cyst risk. Obstet Gynecol. 2003;102(2):252-8.
observation of the mechanism of human ovulation. Am J
24. Vessey M, Metacalfe A, Wells C, et al. Ovarian neoplasms,
Obstet Gynecol. 1981;139(6):636-9.
functional ovarian cysts, and oral contraceptives. Br Med J
19. Vanrell JA, Balasch J, Fuster JS, et al. Ovulation stigma in
(Clin Res Ed). 1987;294(6586):1518-20.
fertile women. Fertil Steril. 1982;37(5):712-3.
20. Brosens IA, Koninckx PR, Corvelyn PA. A study of plasma 25. Pascual MA, Tresserra F, López-Marín L, et al. Role of color
progesterone, oestradiol-17 beta, prolactin and LH levels, Doppler ultrasonography in the diagnosis of endometriotic
and of the luteal appearance of the ovaries in patients cyst. J Ultrasound Med. 2000;19(10):695-9.
with endometriosis and infertility. Br J Obstet Gynecol. 26. Pascual MA, Hereter L, Treserra F, et al. Transvaginal
1978;85(4):246-50. sonographic appearance of functional ovarian cysts. Hum
21. Dmowski WP, Rao R, Scommegna A. The luteinized
Reprod. 1997;12(6):1246-9.
unruptured follicle syndrome and endometriosis. Fertil
Steril. 1980;33(1):30-4. 27. Hamilton CJ, Evers JL, Hoogland HJ. Ovulatory disorders
22. Portuondo JA, Agustin A, Herran C, et al. The corpus luteum and inflammatory adnexal damage: a neglected cause of
in infertile patients found during laparoscopy. Fertil Steril. the failure of fertility microsurgery. Br J Obstet Gynecol.
1981;36(1):37-40. 1986;93(3):282-4.
CHAPTER
24 Baseline Scan and Ultrasound

Diagnosis of PCOS
Introduction being interrogated on pulse Doppler. Moreover, 3D US has

an advantage of storing the volumes and reproducing the
Success of any assisted reproductive technology (ART) images and measurements.
is chiefly dependent on two decisions: (i) selection of This scan is done to categorize ovary into one of the
correct stimulation protocol and (ii) correct timing of following four types: (i) normal ovaries, (ii) low reserve
human chorionic gonadotrophin (hCG). Selection of correct ovaries, (iii) poorly responding ovaries, and (iv) polycystic
stimulation protocol is based on prestimulation assessment ovaries (PCOs). Or in other words to predict the ovarian
of female to assess ovarian response and reserve. This can reserve and response that can guide to decide the stimulation
be done by assessment of baseline hormones, anti-müllerian protocols for ART.
hormone (AMH), follicle stimulation hormone (FSH) and
estradiol on the second to third day of the menstrual cycle.
But, this assessment can also be done by baseline ultrasound Techniques for Baseline
(US) scan before starting stimulation on the second to third Scan of Ovaries
day of the menstrual cycle. This scan can be also named B mode US assessment of the ovaries consists of assessment
as “Baseline scan”. of ovarian diameters and volume and counting of antral
follicles as quantitative assessment and qualitative
Baseline Scan assessment of stromal density.
This scan is done when hormonal levels are at baseline, Once ovary is located, the probe is rotated to find out
ovaries are silent and have no active follicle or corpus the longest diameter of ovary and is stored as one frame
luteum (CL). on a dual screen. Then probe is rotated 90° to get a true
Route of scan has to be transvaginal always. Using transverse axis of ovary. Measure the largest longitudinal,
transabdominal approach for ovarian assessment may transverse and anteroposterior (AP) diameter of the ovary
miss at least 42% of the ovarian anatomical details.1 All in centimeters, and ovarian volume can be calculated by
the scans are done using B mode US with color Doppler, the formula (x × y × z × 0.523) (Fig. 24.1).
pulse Doppler, three-dimensional (3D) US and 3D Number of antral follicles are counted in the longest
power Doppler. Using color Doppler in this assessment section of ovary, but are better counted in the whole ovary
is mandatory because a large number of biochemical by taking a 2D sweep across whole ovary. This method is
or hormonal changes occur during the menstrual cycle, very feasible and reliable when number of antral follicles
which reflect as vascular and morphological changes in the is approximately 10–15. But when number of follicles is
ovaries and uterus and vascular changes can be assessed much more as in PCOs, the calculation using B mode scroll
by Doppler. Three-dimensional US is especially useful for may be inaccurate.
volume measurements. Volumes, when calculated by 3D Stromal echogenicity is assessed against echogenicity
US using volume calculation (VOCAL) software, are much of myometrium, especially if ovary and uterus are at
more reliable than volumes calculated by 2D US. Three- almost same depth from probe. Normally ovarian stroma
dimensional power Doppler assessment has been found is hypoechoic or isoechoic to myometrium.
to be highly promising as it gives idea about the global Color or power Doppler box is now placed on the ovary,
vascularity of ovaries, instead of one or two selected vessels so that whole ovary in included in color box. Doppler is
Chapter 24  Baseline Scan and Ultrasound Diagnosis of PCOS 233
Figure 24.1 Longitudinal and transverse sections of ovary Figure 24.2 Measuring ovarian stromal flows
Figure 24.3 Three-dimensional power Doppler volume of ovary
used to see presence of vessels in ovarian stroma (Fig. 24.2). count, ovarian volume, stromal volume and blood flow
The vessel that is close to any of the follicles is not a in the ovary.2.Power Doppler box is set to include whole
stromal vessel. If vascularity is present, pulse Doppler is ovary and then 3D volume of ovary is acquired (Fig. 24.3).
used for quantitative assessment of the flows—intraovarian This volume of ovary is used to calculate ovarian volume,
resistance index (RI) and peak systolic velocity (PSV). stromal volume and to count number of antral follicles.
For color Doppler pulse repetition frequency (PRF) is set Global vascular indices [vascularity index (VI), flow index
at 0.3, wall filters lowest with optimum gains and balance (FI) and vascularity flow index (VFI)] may be calculated
settings. For pulse Doppler also lowest PRF and wall filters from the same ovarian volume.
are used as stromal flows at base line scan are low velocity Antral follicles can be counted by using inversion mode
flows. The vessel selected for interrogation is a vessel that rendering (Fig. 24.4) or using a software called Sono
is showed brightest color on color Doppler. automated volume calculation (Sono AVC) (Fig. 24.5).
After having completed the Doppler study, volume Region of interest (ROI) is selected to include the whole
studies are initiated. Three-dimensional US provides a new ovary in all three orthogonal planes on acquired ovarian
method for objective quantitative assessment of follicle volume. Sono AVC is based on inversion mode rendering,
Figure 24.4 Follicles as seen on inversion mode rendering
Figure 24.5 Antral follicles as seen on Sono AVC
but further color codes each follicle and also shows x, y and in a selected volume and VFI is a perfusion index. Applying
z diameters, mean diameter and volume of each follicle on threshold volume on the same VOCAL calculated volume will
result sheet (Fig. 24.6). define stromal volume when threshold is set to differentiate
A software called VOCAL is used to define ovarian follicles from rest of the ovarian tissue (Fig. 24.9).
volume (Fig. 24.7). The VOCAL calculates volume of any Based on the above described assessment of the ovaries,
structure by rotating it 180°. A rotating angle of 6–30° can they are categorized into normal, low reserve, poorly
be selected. A circumference is drawn around the structure responding or PCOs. This helps to decide the stimulation
of interest at every rotation and at the end of 180° total protocol and also to decide any additional or supportive
volume is calculated. On this calculated ovarian volume with therapy required for a particular patient.
power Doppler, applying volume histogram gives values
of 3D power Doppler indices, VI, FI and VFI (Fig. 24.8). Normal Ovaries
Vascularity index is an index for abundance of flow in the Normal ovaries are the ones that have a largest diameter of 2–3
selected volume, FI is an index for average intensity of flow cm, ovarian volume of 3–6.6 cc, antral follicle count (AFC)
Figure 24.6 Result sheet of Sono AVC
Figure 24.7 Ovarian volume calculated by VOCAL
per ovary of 5–12, isoechoic stroma (Fig. 24.10), stromal RI of number of antral follicles, less than 5 per ovary. As they
0.6–0.7, stromal PSV 5–10 cm/sec, stromal FI 11–14. Ovaries have less number of antral follicles they are also small in
with these features are categorized as normal ovaries because size (Fig. 24.11). They have a largest diameter of less than
they respond to standard stimulation protocols and produce 2 cm and volume less than 3 cc. As the reserve or AFC is
adequate follicles for the concerned ART. These standard low, these ovaries produce less number of follicles at the
protocols are 75 IU for intrauterine insemination (IUI) cycles end of stimulation.
and 150–225 IU for in vitro fertilization (IVF) cycles.
Poorly Responding Ovaries
Low Reserve Ovaries Poorly responding ovaries are the ones that respond poorly
Low reserve ovaries are the ones that have low reserve, to any stimulation. This means these ovaries require larger
and reserve in ovaries means number of reserve follicles doses of gonadotrophins for stimulation. This poor response
in ovary. Therefore, these are the ovaries that have less can be attributed to the poor blood flow to these ovaries.
Figure 24.8 Three-dimensional power Doppler volume histogram of ovary

(Abbreviations: MG, mean gray value; VI, vascularization index; FI, flow index; VFI,
vascularization flow index)
Figure 24.9 Stromal volume calculated using threshold volume after VOCAL of ovary
Measurement of ovarian stromal flow in early follicular produce those follicles. This means that any ovary would
phase is related to subsequent ovarian response in IVF be a permutation combination of one of the characteristics
treatment.3 Ovarian stromal PSV after pituitary suppression from each of these two groups: (i) normal response, poor
is predictive of ovarian responsiveness and outcome of IVF response and hyper-response and (ii) normal reserve,
treatment.4 These ovaries show high resistance (RI > 0.7), low reserve and high reserve or PCOs. It is therefore a
low velocity (PSV < 5 cm/sec) flow (Fig. 24.12). combination of findings like AFC and stromal flow: RI,
Low reserve and poorly responding ovaries are often PSV and FI that would ultimately decide the optimum
used as synonyms, but these are different entities. This is so stimulation protocol.
because reserve relates to AFC or ultimate yield of follicles/ Although before authors do that, let us discuss US for
ova at the end of stimulation, whereas response relates diagnosis and management of polycystic ovarian syndrome
to sensitivity of ovary to ovulation stimulating agents to (PCOS).
Figure 24.10 Normal ovaries
Figure 24.11 Low reserve ovaries: small size and less than 3 antral follicles
Polycystic Ovaries ÀÀ Oligo and/or anovulation

ÀÀ Hyperandrogenism: biochemical or clinical
Diagnosis of PCOS has been a controversial and always ÀÀ Polycystic ovaries on US: this means an ovary that is 10
a debatable issue. Earliest description of PCOs appears cc in volume and/or has more than 12 antral follicles.
to date from 1845 as “sclerocystic ovaries”. 5 Other “And enlarged spherical ovaries greater than 10 cc
names suggested are polyfollicular syndrome or ovarian have shown good correlation between US and diagnosis
dysmetabolic syndrome. Three major ways to diagnosis of polycystic morphology and histopathological criteria for
of PCOS: (i) clinical findings, (ii) laboratory testing, and PCOs.” 6 But, there are controversies regarding the ovarian
(iii) US findings. Approximately 20–30% of women in enlargement in PCO. Concerning the ovarian volume
reproductive age have PCOs and about half of these have setting the threshold at 7 cc offered the best compromise
signs and symptoms of PCOS. According to European between specificity (91.2%) and sensitivity (67.5%). In
Society of Human Reproduction and Embryology/ comparison, specificity and sensitivity were 98.2% and
American Society for Reproductive Medicine (ESHRE/ 45%, respectively with threshold at 10 cc.7 Ovarian volume
ASRM) consensus 2003 the diagnosis of PCOS consists 6.6 cc has shown 91% sensitivity and 91% specificity for
of at least two of the three following criteria: PCOS.8 Moreover according to S Kupesic, ovaries that are
hyperinsulinemia and/or other metabolic influence linked

to obesity.10 All these follicles do not become dominant.
This is so because there is partial conversion of androgen
to estrogen and there is also cumulative effect of minimal
estradiol production by multiple follicles leading to negative
feedback for FSH and positive feedback for luteinizing
hormone (LH). These factors lead to maturation arrest of
these follicles and premature luteinization leading to atresia.
These luteinized atretic follicles ultimately contribute to the
stroma leading to stromal abundance.
Antral Follicle Count in PCO and its

Hormonal Implications
Figure 24.12 Poor responding ovary: with little stromal flow Anti-müllerian hormone (AMH) is a biomarker that
predicts the number of antral follicles and is involved in
normal in volume can be polycystic as demonstrated by follicular arrest for women with PCOS. Antral follicle count
histological and biochemical studies (in 20%). Polycystic and ovarian volume showed significant correlation with
ovarian morphology (PCOM) has, therefore, been found AMH, total testosterone and free androgen index (FAI)
to be a better discriminator than ovarian volume between but not with age, body mass index (BMI) or homeostasis
PCOS and control women.9 This discussion indicates that model assessment of insulin resistance (HOMA-IR).
ovarian volume alone cannot be used as a parameter for Anti-müllerian hormone and total testosterone were main
diagnosis of PCOs. Therefore, morphological features of determinants for ovarian volume in stepwise regression
PCOs need consideration. model. Anti-müllerian hormone, obesity, insulin resistance
Morphological characteristics of PCOs consist of number (IR) and high androgen levels relates to large size of antral
and arrangement of antral follicles, stromal echogenicity follicle pool and ovarian volume on PCOS. Obesity and IR
and vascularity. may enhance follicular excess by dysregulation of AMH
through pathway of hyperandrogenemia.11
The mean FNPO of follicles 2–5 mm in size was
Antral Follicle Count significantly higher in PCOs than in controls, while
Antral follicle count of 12 or more (2–9 mm) has been it was similar within 6–9 mm range. Within 2–5 mm
used as a characteristic for PCOs according to Rotterdam range, significant relationship was found between FNPO
criteria. Setting the threshold at 12 for 2–9 mm follicle and androgens but FNPO in the range of 6–9 mm was
number per ovary (FNPO) offered the best compromise significantly and negatively related to BMI and fasting
between specificity (99%) and sensitivity (75%).10 Although serum insulin level.
polycystic histology and morphology has been found in This indicates that AFC and size of antral follicles can derive
ovaries having AFC between 5 and 15. Antral follicle count a lot of information about the biochemical status of the patient.
also thus cannot be used as the characteristic of PCOs.
At this stage, a short understanding of pathophysiology Arrangement of Follicles
and hormonal correlation of US findings may be helpful.
The antral and atretic follicles get arranged peripherally
or are dispersed in the stroma and thus may categorize
Pathophysiology PCO as peripheral cystic pattern (PCP) and general
Polycystic ovaries are a result of chronic anovulation. cystic pattern (GCP). In PCP there is typical garland like
Mildly raised androgen levels in early follicular phase in arrangement of follicles and in GCP, the follicles can
PCOS patients leads to recruitment of several follicles. be seen throughout the ovary 12 (Fig. 24.13). Although
It is believed that androgen leads to early follicular one school of thoughts believes that peripheral cystic
development but further progression is not normal due to POCs and generalized cystic PCOs have different
Figure 24.13 Generalized polycystic pattern and peripheral polycystic pattern
histopathological and endocrine bases,13 another theory is

different. According to this the ovary is multifollicular in
adolescence. Because of the pathophysiology explained
earlier, follicles that are less than 9 mm are exposed to LH
and undergo atresia and make stroma denser giving rise
to generalized cystic PCO. If at this stage the condition
is left untreated, gradually the follicles in the central part
of the ovary, in an effort and process of recruitment reach
the periphery or are pushed out to periphery by expanding
stroma and undergo atresia ultimately leading to peripheral
cysticPCO.14,15 So multicystic ovary to generalized cystic
PCO, to peripheral cystic PCO is a process of evolution
of the disease. This indicates that the patients who have
more severe form of disease or a long standing disease
have a PCP and evidently will have worse hormonal milieu Figure 24.14 Solid looking PCO
as compared to those who have generalized polycystic
pattern. Assessment of Stromal Abundance
Polycystic ovaries show a hyperechoic stroma but
Stromal Abundance
assessment of this hyperechogenicity is subjective not only
Hyperdense stroma and stromal abundance have been to the operator but also to equipment settings.16,17 Though
described with PCOs since the first definition of the ovarian stroma can be stamped as hyperechoic when it’s
syndrome by Stein-Leventhal. more echogenic than myometrium. This hyperechogenicity
Stromal abundance can present as increased echogenicity is especially useful for its differentiation from multicystic
because stroma is densely packed and increased stromal ovaries that are normally seen in adolescence and have
area or increased stromal volume in large ovary. Patients multiple follicles, of variable sizes and non-hyperechogenic
having long standing PCOS and long standing anovulation stroma. Increased stromal echogenicity for diagnosis of
have more dense stroma. Most severe form of stromal PCO has a sensitivity of 94% and specificity of 90%18
abundance, hyperthecosis, presents large ovaries with (Fig. 24.15).
almost absence of cystic lesions: solid looking ovaries But recent studies have shown that mean stromal
(Fig. 24.14). echogenicity or total ovarian echogenicity as measured by
Figure 24.15 Dense hyperechoic stroma of PCO
histogram are not different in controls and PCOS. But stromal indicated as a reliable marker for hyperandrogenism.
index (stromal echogenicity/total ovarian echogenicity) was Hyperandrogenic subjects showed higher values of stromal
significantly higher in PCOS than controls.19 area and S/A ratio, with no difference in ovarian volume and
Not only the echogenicity but total stromal volume is ovarian area.22 The S/A has also been found to be the best
also increased in PCOs. This can be measured on US as significant predictor of elevated androgen and testosterone
stromal area in the most longitudinal section of ovary on levels. This parameter may be used in routine clinical
2D US. As for echogenicity this also has been found to practice for improving US diagnosis of PCOS.21 Stromal to
be sensitive for diagnosis of polycystic ovarian disease ovarian ratio is lower in normal females. Stromal abundance
(PCOD). Stromal area: 4.6 cm2 has 91% sensitivity and 86% may be better assessed by stromal volume than with stromal
specificity for diagnosis of PCOS. The ovarian area can area. Stromal volume can be assessed by using threshold
also be measured in this same section. Ovarian area of 5.3 volume on vocal calculated ovarian volume.
cm2 has 93% sensitivity and 91% specificity for diagnosis Three-dimensional US provides a new method for
of PCOS.8 objective quantitative assessment of follicle count, ovarian
But the ratio of stromal area to ovarian area has been volume, stromal volume and blood flow in the ovary.14
found to be more reliable. The S/A ratio also has a strongest Ovarian volume calculation by 3D US has been found to
correlation with S. androgens especially testosterone and be useful over two-dimensional (2D) evaluation of ovarian
androstenedione and insulin.20 Stromal area/ovarian area long diameter or volume by 2D US (Table 24.1).
ratio of greater than 0.34 is diagnostic of PCOS and can be Right ovary is larger in PCOS patients, whereas left
correlated with S. androstenedione. ovary is larger in normal patients.
Theca cells of PCOS women hyper respond to
Sensitivity for diagnosis of PCOS: gonadotrophins (LH) and produce excess androgens.
ÀÀ Ovarian volume 13.21 cc 21% This is due to an escape of their normal down regulation
ÀÀ Ovarian area 7 cm2 4% to gonadotrophins. This dysregulation is linked to excess
2
ÀÀ Stromal area 1.95 cm 62% of insulin and insulin-like growth factor 1 (IGF-1).
ÀÀ Stromal/total area 0.34 100% Hyperinsulinemia is a key factor to the pathogenesis
Mean stromal area/mean ovarian area ratio of 0.34 and of PCOS. Insulin augments LH stimulated androgen
above also has a specificity of 100% in the same study.21 production by stromal cells. Androgen in turn causes
proliferation of stromal and theca cells. This leads to
Stromal Abundance in PCO and its Table 24.1 Ovarian volume calculation by 3D US
Hormonal Implications Ovarian volume Right (cc) Left (cc)
Normal 5.3 ± 2.0 5.7 ± 1.6
The proportion revealed between the stromal and the
PCOD 12.2 ± 4.7 10.5 ± 3.619
ovary surface in the median section (S/A ratio) had been
increase stroma in the PCO. Stromal volume was positively A similar study has also been done earlier. Study by Pache
correlated with serum androstenedione concentrations in et al. has shown that the degree of IR can be correlated with
patients with PCOS.23 Increased androstenedione secretion ovarian volume and stromal echogenicity.26 A retrospective
as shown earlier is due to hyperinsulinemia.24 observational study done with 50 PCOS patients showing
A prospective study of 50 PCOS patients with 50 non- correlation between ovarian volumes and stromal volumes
PCOS patients was done over a period of 6 months with with fasting and PP insulin levels. But in this study neither
clinical examination, baseline US scan with 2D and 3D US BMI nor age group were defined. In PCOS patients a strong
and fasting and postprandial (PP) insulin levels. Group A: and similar correlation was seen between ovarian volumes
fifty patients with normal ovulation, no hirsutism, normal and stromal volumes to fasting and PP insulin levels.
menstrual cycle and normal ovarian size and Group B: fifty
patients with PCOS, according to Rotterdam criteria. Age Stromal Vascularity
range of patients for both groups was between 25 and 35
with mean age for Group A was 30.4 years, mean age for Based on 3D US, women with PCOS have an increased
Group B was 29.7 years. Mean BMI in both the groups was stromal volume and vascularity. Even with same echogenicity,
28, range from 25 to 32 kg/m2. PCOS has more stromal flow. In PCOs even on third day of
Patients with BMI less than 25 kg/m2, proved diabetes the cycle intraovarian stromal flow is seen and they have
mellitus, any other endocrinological derangement. (thyroid, moderate to low resistance flow with RI of 0.50–0.58.27
adrenal, etc.), follicles larger than 9 mm or residual corpus Elevated LH levels may be responsible for increased
lutea on day 3 and ovarian mass lesions (cystic/solid) stromal vascularization due to neoangiogenesis,
were excluded from the study cohort. Ovarian volume and catecholaminergic stimulation and leukocyte and cytokine
stromal volume were calculated by applying threshold activation. This vascularity is inversely related to LH/
volume to the VOCAL calculated volume. The threshold FSH ratio. Tonic secretion of LH in early follicular phase
is set to differentiate follicles from stroma. Fasting and PP in PCOS is also associated with theca and stromal cell
insulin levels were checked for all on the same day. Insulin hyperplasia and consequent androgen production. This
estimation was done by Chemiluminescence method. For androgen hypersecretion is responsible for not only
PP insulin measurement patient was given 75 gm of glucose increased follicular recruitment but also for vasoconstrictive
after fasting blood sample and then blood sample for PP effect on the uterine arteries. This effect is thought to be
insulin was taken after 2 hours. Values of ovarian volumes, due to activation of specific receptors in arterial walls
stromal volumes and AFC were all averaged for both ovaries and collagen and elastin deposition in smooth muscle
in each patient. Two tailed Pearson correlation was checked cells. Uterine artery PI is greater than 3 and sometimes
for ovarian volume, stromal volume and stromal volume to the diastolic flow is absolutely absent. Even in later
ovarian volume ratio with fasting insulin and PP insulin level phases of the cycle this effect continues. This leads to
each. Ovarian volumes and stromal volumes were compared inadequate perfusion of the endometrium and is thought to
and correlated with both fasting and PP insulin levels. be responsible for blastocyst implantation failure and high
Positive correlation was seen between ovarian volumes, abortion rate in PCOS.
stromal volumes and fasting and PP insulin levels. With
Pearson correlation significance level of 0.01 (2 tailed) the Stromal Vascularity in PCO and its
correlation for: Hormonal Implications
À Ovarian volume to fasting insulin is 0.651
Looking to the hormonal correlation with the Doppler
À Ovarian volume to PP insulin is 0.409
findings, it is evident that in patients in whom the hormonal
À Stromal volume to fasting insulin is 0.736 milieu is worse the Doppler findings are more prominent. As
À Stromal volume to PP insulin is 0.428 discussed earlier the peripheral cystic PCO is an advanced
Stromal volumes, ovarian volumes and AFC correlated stage then GCP and so the intraovarian vascularity and
significantly well with the fasting insulin levels, more uterine artery resistance are more in peripheral cystic PCOs
than with PP insulin levels in obese PCOS patients. It is than in generalized cystic PCOs. In 22% of generalized
the stromal volume that can be best correlated with fasting cystic PCO intraovarian vessels are not recognized.28
insulin levels followed by ovarian volumes and AFC.25 Stromal vascularity is significantly higher in women with
PCOS who are hyperandrogenic and lean rather than Though their understanding of US findings has
normoandrogenic and obese.29 Fertile controls and PCOS substantially increased in the near past, certain controversies
women had similar total ovarian 3D power Doppler flow still need explanation:
indices. Normal weight PCOS women had significantly Low flow in PCO: Many of the PCO patients consume
higher total ovarian 3D power Doppler flow indices than large doses of gonadotropins. These are the patients who
their overweight counterparts.30 Higher age, obesity and on US do show multiple follicles, large ovaries and dense
amenorrhea as compared to young age, normal weight and stroma, and on Doppler they do have a moderate resistance
oligomenorrhea show higher uterine artery resistance and flow but have a low PSV. They may be grouped clinically
increased ovarian stromal flow. These are the patients who as resistant PCO.
also have higher LH and higher androstenedione levels
Moderate resistance in uterine arteries: Not all patients
and higher ovarian volumes. Uterine artery resistance
with PCOS have high androgen levels which are responsible
has also been found to be higher in obese than in lean
for high uterine artery resistance, this is especially so
patients and is also associated with hyperinsulinemia, high
in generalized cystic PCOS. Another cause of moderate
triglycerides, low high density lipids and higher hematocrit
resistance in uterine artery instead of high resistance is
values. Oligoanovulatory patients with PCO but without
adenomyosis or fibroid in the fibroid commonly associated
hyperandrogenic have mild endocrine and metabolic
with PCOS.
features of PCOS.31
But the results were different when 3D and 3D power Deciding Stimulation Protocol
Doppler were used. Women with PCOS had higher AFC
(median 16.3 vs 5.5 per ovary), ovarian volume (12.56 vs Predictors of ovarian response are:36
5.6 ml), stromal volume (10.79 vs 4.69 ml) and stromal À Number of antral follicles
vascularization (VI 3.85 vs 2.79% and VFI 1.27 vs 0.85). À Ovarian stromal FI
Though 2D power Doppler indices were not higher in PCOS À Total ovarian stromal area
than in controls. Ovarian stromal FI is higher (33.94 vs À Total ovarian volume.
29.30) in hirsute than in norm androgenic PCOS women. In that order of importance.
But in PCOS women with obesity the vascularity was lower Antral follicle count is a better marker than basal FSH for
than in normal weight women (VI 3.25 vs 4.51%, VFI 1.22 selection of older patients with acceptable pregnancy offer.12
vs 1.56).32 Comparing ovarian stromal blood flow and Antral follicle count and ovarian volume showed significant
serum vascular endothelial growth factor (VEGF) between correlation with AMH, total testosterone and FAI.37
fertile women with normal ovaries and infertile women Precise calculation of AFC therefore can help in predicting
with PCOS, it was found that both the groups had similar the ovarian response. This can be done on 2D US or by 3D
total ovarian VI, FI, and VFI values after controlling for with inversion mode rendering and Sono AVC as described
the age. Though VI, FI and VFI were significantly higher earlier. This method is more precise as there is least chance
in normal weight PCOS than in obese PCOS women.30 The of follicles being missed or being counted twice. But post-
vascularization indices (VI, FI and VFI) are significantly processing is required for accurate calculations. It takes
higher in PCOS than in normal females which explains longer to perform, because of the need for post-processing,
excessive response to gonadotropins in PCOS females. and obtains values that are lower than those obtained by
Three-dimensional vascularization quantification has the 2D-MPV (main portal vein) and 3D-MPV techniques.
been found to be more sensitive than 2D vascularization However, the AFC obtained by Sono AVC-PP is likely to
quantification.33 Though a study from Finland shows no be lower because this method measures and color codes
difference in VI, FI and VFI values in PCO and normal each follicle preventing recounting. Antral follicle when
ovaries. But in normal ovaries, FI was found to be higher counted by inversion mode: likely to get 60% of follicles
in left ovary.34 Total ovarian VI and VFI were significantly of the counted antral follicles in IVF cycles.38 Intraobserver
lower in women aged 41 or more. Antral follicle count has and interobserver reliability of automated AFCs made using
the best correlation with the age, followed by S. FSH and 3D US and Sono AVC a preferred method.39
ovarian 3D power Doppler indices. The rate of decline of It has been shown by Zaidi et al. that stomal blood flow
total ovarian VI was 0.18% per year.35 velocity after pituitary suppression was an independent
Table 24.2 Dose calculation 2. Lam PM, Raine-Fenning N. The role of three-dimensional
Increase the dose Decrease the dose ultrasonography in polycystic ovary syndrome. Hum
when when Reprod. 2006;21(9):2209-15.
Age >35 years <25 years 3. Zaidi J, Barber J, Kyei-Mensah A, et al. Relationship
of ovarian stromal blood flow at baseline ultrasound to
BMI >28 kg/m2 <20 kg/m2
subsequent follicular response in an in vitro fertilization
AFC <3 (FNPO) >12 (FNPO)
program. Obstet Gynecol. 1996;88(5):779-84.
Stromal RI >0.7 <0.5 4. Engmann L, Sladkevicius P, Agrawal R, et al. Value
Stromal PSV <5 cm/sec >10 cm/sec of ovarian stromal blood flow velocity measurement
Stromal FI <11 >15 after pituitary suppression in the prediction of ovarian
Ovarian volume <3 cc >10 cc responsiveness and outcome of in vitro fertilization
treatment. Fertil Steril. 1999;71(1):22-9.
(Abbreviations: BMI, body mass index; AFC, antral follicle count; RI, 5. Dr. Thatcher. Defining PCOS—a perspective. The American
resistance index; PSV, peak systolic velocity; FI, follow index; FNPO, Infertility Association News Letter, February 2001.
follicle number per ovary)
6. Takahashi K, Eda Y, Abu-Musa A, et al. Transvaginal
ultrasound imaging, histopathology and endocrinopathy in
predictor of ovarian response.3 Measurement of ovarian patients with polycystic ovarian syndrome. Hum Reprod.
stromal flow in early follicular phase is related to 1994;9(7):1231-6.
subsequent ovarian response in IVF treatment.4 Ovarian 7. Kyei-Mensah AA, Lin Tan S, Zaidi J, et al. Relationship of
stromal PSV after pituitary suppression is predictive of ovarian stromal volume to serum androgen concentrations
ovarian responsiveness and outcome of IVF treatment.36 in patients with polycystic ovary syndrome. Hum Reprod.
Kupesic has shown correlation in the ovarian stromal FI and 1998;13(6):1437-41.
8. Wu MH, Tang HH, Hsu CC, et al. The role of three-
number of mature oocytes retrieved in an IVF cycles and
dimensional ultrasonographic images in ovarian
pregnancy rates.36 Stromal FI [less than 11 low responder,
measurement. Fertil Steril. 1998;69(6):1152-5.
11–14 good, more than 15 risk of ovarian hyperstimulation 9. Legro RS, Gnatuk CL, Kunselman AR, et al. Changes in
syndrome (OHSS)]. glucose tolerance over time in women with polycystic ovary
Based on all these facts and findings we understand that syndrome: a controlled study. J Clin Endocrinol Metab.
ovaries that have high resistance, low velocity flow require 2005;90(6):3236-42.
higher doses of gonadotrophins for stimulation. Whereas 10. Jonard S, Robert Y, Cortet-Rudelli C, et al. Ultrasound
those with low resistance, high velocity flow require lower examination of polycystic ovaries: is it worth counting the
doses of gonadotrophins for stimulation. Number of antral follicles? Hum Reprod. 2003;18(3):598-603.
follicles decides the ultimate yield of mature follicles 11. Mei-Jou Chen, Wei-Shiung Yang, Chi-ling Chen, et al. The
at the end of stimulation. If number of antral follicles is relationship between anti-Müllerian hormones, androgen
high, it would be preferable to proceed with low doses of and insulin resistance on the number of antral follicles in
women with polycystic ovary syndrome. Hum Reprod.
gonadotrophins, whereas in ovaries that have low AFC, it
2008;23(4):952-57.
is preferable to start with high doses of gonadotrophins.
12. Matsunaga I, Hata T, Kitao M. Ultrasonographic
Patients with higher age and high BMI require higher doses identification of polycystic ovary. Asia Oceania J Obstet
for stimulation whereas those of young age and with low Gynecol. 1985;11(2):227-32.
BMI require lower doses for stimulation. 13. Takahashi K, Ozaki T, Okada M, et al. Relationship between
The final dose calculation can be based on the following ultrasonography and histopathological changes in polycystic
factors shown in Table 24.2 and would prefer to simplify it. ovarian syndrome. Hum Reprod. 1994;9(12):2255-8.
To select the correct stimulation protocol, doses are 14. Ardaens Y, Robert Y, Lemaitre L, et al. Polycystic ovarian
titrated depending on findings present in a particular patient disease: contribution of transvaginal endosonography and
from high dose table or low dose table. reassessment of ultrasonographic diagnosis. Fertil Steril.
1991;55(6):1062-8.
15. Robert Y, Dubrulle F, Gailandre L, et al. Ultrasound assessment
References of ovarian stroma hypertrophy in hyperandrogenism and
1. Hull MGR. Polycystic ovarian disease: clinical aspects and ovulation disorders: visual analysis versus computerized
prevalence. Res Clin Forums. 1989;11:21-34. quantification. Fertil Steril. 1995;64(2):307-12.
16. Pache TD, Wladimiroff JW, Hop WC, et al. How to 29. Ozkan S, Vural B, Calişkan E, et al. Color Doppler
discriminate between normal and polycystic ovaries— sonographic analysis of uterine and ovarian artery blood
transvaginal US study. Radiology. 1992;183(2):421-3. flow in women with polycystic ovarian syndrome. J Clin
17. Buckett WM, Bouzayen R, Watkin KL, et al. Ovarian Ultrasound. 2007;35(6):305-13.
stromal echogenicity in women with normal and polycystic 30. Ng EH, Chan CC, Yeung WS, et al. Comparison of
ovaries. Hum Reprod. 1999;14(3):618-21. ovarian stromal blood flow between fertile women with
18. Dewailly D, Robert Y, Helin I, et al. Ovarian stromal normal ovaries and infertile women with polycystic ovary
hypertrophy in hyperandrogenic women. Clin Endocrinol syndrome. Hum Reprod. 2005;20(7):1881-6.
(Oxf). 1994;41(5):557-62. 31. Dewailly D, Catteau-Jonard S, Reyss AC, et al. Oligoanovulation
19. Belosi C, Selvaggi L, Apa R, et al. Is the PCOS diagnosis with polycystic ovaries but not overt hyperandrogenism. J
solved by ESHRE/ASRM 2003 consensus or could it Clin Endocrinol Metab. 2006;91(10):3922-7.
include ultrasound examination of the ovarian stroma? Hum
32. Lam PM, Jhonson IR, Rainne-Fenning NJ. Three-
Reprod. 2006;21(12):3108-15.
dimensional ultrasound features of the polycystic ovary
20. Fulghesu AM, Ciampelli M, Belosi C, et al. A new
and the effect of different phenotypic expressions on these
ultrasound criterion for the diagnosis of polycystic ovary
parameters. Hum Reprod. 2007;22(12):3116-23.
syndrome: the ovarian stroma/total area ratio. Fertil Steril.
2001;76(2):326-31. 33. Pan HA, Wu MH, Cheng YC, et al. Quantification of
21. Fulghesu AM, Angioni S, Frau E, et al. Ultrasound in Doppler signal in polycystic ovary syndrome using three-
polycystic ovary syndrome—the measuring of ovarian dimensional power Doppler ultrasonography: a possible new
stroma and relationship with circulating androgens: results marker for diagnosis. Hum Reprod. 2002;17(1):201-6.
of multicentric study. Hum Reprod. 2007;22(9):2501-8. 34. Järvelä IY, Mason HD, Sladkevicius P, et al. Characterization
22. Jonard S, Robert Y, Dewailly D. Revisiting the ovarian of normal and polycystic ovaries using three-dimensional
volume as diagnostic criterion for polycystic ovaries. Hum power Doppler ultrasonography. J Assist Reprod Genet.
Reprod. 2005;20(10):2893-98. 2002;19(12):582-90.
23. Adam H Balen, et al. Polycystic ovary syndrome: a guide to 35. Ng EH, Chan CC, Yeung WS, et al. Effect of age on ovarian
clinical management. New York: Taylor & Francis; 2005. stromal flow measured by three-dimensional ultrasound with
24. Pache TD, de Jang FH, Hop WC, et al, Association power Doppler in Chinese women with proven fertility. Hum
between ovarian changes assessed by TVS and clinical and Reprod. 2004;19(9):2132-7.
endocrine signs of polycystic ovarian syndrome. Feril Steril.
36. Kupesic S, Kurjak A. Predictors of in vitro fertilization
1993;59(3):544-9.
outcome by three-dimensional ultrasound. Hum Reprod.
25. Nagori CB, Panchal SY, Assessing correlation between
2002;17(4):950-55.
ovarian and stromal volumes and fasting and postprandial
37. Klinkert ER, Broekmans FJ, Looman CW, et al. The
insulin levels in PCOS patients. Int Soc Ultrasound Obstet
antral follicle count is a better marker than basal follicle-
Gynecol. 2008;32:373.
stimulating hormone for the selection of older patients with
26. Pache TD, de Jong FH, Hop WC, et al. Association between
acceptable pregnancy prospects after in vitro fertilization.
ovarian changes assessed by transvaginal sonography and
Fertil Steril. 2005;83(3):811-4.
clinical and endocrine signs of polycystic ovary syndrome.
Fertil Steril. 1993;59(3):544-9. 38. Raine-Fenning NL, Lam PM. Assessment of ovarian reserve
27. Battalgia C, Artini PG, D’Ambrogio G, et al. The role of using the inversion mode. Ultrasound Obstet Gynecol.
color Doppler imaging in the diagnosis of polycystic ovarian 2006;27(1):104-6.
syndrome. Am J Obstet Gynecol. 1995;172(1 Pt 1):108-13. 39. Deb S, Jayaprakasan K, Campbell BK, et al. Intraobserver
28. Battalgia C, Artini PG, Salvatori M, et al. Ultrasonographic and interobserver reliability of automated antral follicle
patterns of polycystic ovaries: color Doppler and hormonal counts made using three-dimensional ultrasound and Sono
correlations. Ultrasound Obstet Gynecol. 1998;11(5):332-6. AVC. Ultrasound Obstet Gynecol. 2009;33(4):477-83.
CHAPTER
25 Hormone Replacement
Therapy: Ultrasound Role
Ivica Zalud, Deepika Deka, Anita Matai
Introduction repeated urinary tract infections. Osteoporosis is the result

of increased bone resorption that exceeds osteoblastic
“Menopause” is derived from the Greek word “men” activity. The average bone loss in women 5–15 years after
(month) and “pauo” (to stop) and this phenomenon of the menopause is 3% per annum, compared to about 1% in
cessation of menstruation was recognized since the men of the same age.5
time of Aristotle (384 to 322 BC).1 The WHO scientific Epidemiological studies have shown that, during the
group defines menopause as “no menstrual period for reproductive years, women are protected from coronary
12 consecutive months in the absence of any obvious artery disease, but postmenopausal women (PMW) are
cause such as pregnancy or lactation.”2 The median age at increased risk for cardiovascular (angina, myocardial
at menopause is 51 years, but for women who smoke, infarction, hypertension) and cerebrovascular (strokes)
it is 1–2 years earlier than nonsmokers.2,3 At the present pathology.6
time, approximately 90% of females live long enough
to experience the menopause in developed countries and
account for 30% of the female population. That menopause
Hormone Replacement Therapy
is not just cessation of menstruation and fertility, but is also During the last decade, evidence has accumulated that
associated with a number of symptoms was observed by hormone replacement therapy (HRT) relieves the acute
Leake as early as 1777.4 symptoms of estrogen deficiency; beneficially affects
some of the intermediate symptoms (urinary, genital) and
Physiology of Menopause and reduces the risk of long-term sequelae. Emerging trends
advocate that HRT should be offered to all symptomatic
Postmenopausal Symptoms perimenopausal and postmenopausal, and asymptomatic
Menopause occurs as a consequence of exhaustion of the PMW, as it increases life expectancy, reduces mortality by
stock of oocytes or primordial follicles in the ovary with 20–50%, and significantly improves the quality of life.7-9
subsequent fall in estrogen and progesterone secretion. The decision to take HRT should be made by the patient
Plasma follicle-stimulating hormone (FSH) and luteinizing (not by the physician) and only after full discussion of all
hormone (LH) levels rise due to increased gonadotropin- potential benefits and risks. The physician must take into
releasing hormone (GnRH) pulses.5 A large number of account many practical considerations and be aware of the
symptoms and physical changes have been attributed to impact that HRT can have on preexisting conditions or
the menopause, quite often even before (4–5 years) the diseases in these elderly women. Absolute contraindications
cessation of menopause—the perimenopause. Vasomotor are few, but most clinicians would consider women with
symptoms are often the earliest, consisting of hot flushes, abnormal vaginal bleeding, current endometrial and breast
sweating, palpitation, vertigo, feeling of weakness and cancer or venous thrombosis as unsuitable candidates for
anxiety. Estrogen receptors are found in the vagina, bladder, HRT. Relative gynecological contraindications requiring
urethra, pelvic floor muscles and even urogenital ligaments. closer follow-up are fibromyoma uterus, endometriosis.
Estrogen deficiency causes atrophic changes and decreased Ultrasound is the most common modality for imaging
vascularization, resulting in various genital symptoms such of the pelvic structures. Color Doppler can very accurately
as dryness, irritation, dyspareunia, dysuria, urgency and assess vascularity. Interpretation of ultrasound requires
thorough understanding of the pathophysiology of the metabolism. They may stimulate hepatic production of
menopause, the effect of various hormones, routes and renin substrate and angiotensin leading to an increased risk
regimen, on the PMW. Knowledge of normal anatomy will of vasoconstriction, hypertension and platelet aggregation.
enable the ultrasonologist and clinician to diagnose any Though current oral HRT does not appear to increase
subtle deviations from normal for prompt modifications in blood pressure in hypertensive women, on theoretical
HRT. grounds this route is avoided. Several studies implicate
oral estrogens as increasing coagulation activation, while
Hormones in Hormone Replacement others contradict the effect, especially when progesterone
Therapy Protocols is also taken. The transdermal route by virtue of bypassing
1. Estrogens are the mainstay of all HRT protocols; the the “first pass effect” appears to be more suitable. Oral
three most common estrogens in use are: (i) estradiol, estrogen therapy significantly elevates HDL lipoproteins,
(ii) estrone, and (iii) estriol. Conjugated equine estrogen lowers cholesterol and LDL lipoprotein. Serum triglyceride
(CEE) that has been available for nearly 4–5 decades is levels are elevated by oral therapy, but transdermal estradiol
composed of 50–60% estrone sulfate and the remainder causes a reduction. Hence, oral estrogens should be avoided
of equine estrogen. in women with hypertriglyceridemia. The transdermal route
Routes: is also preferable in smokers, because smoking reduces
– Oral: Conjugated estrone sulfate, CEE (0.625 mcg), circulating levels of estradiol and estrone in women taking
micronized estradiol, estradiol valerate oral HRT.
– Transdermal: Micronized 17β estradiol patches, 17 In women with severe osteoporosis, a better bone
β estradiol gel (1 mcg) density response is obtained by higher circulating levels
– Vaginal: Estriol, CEE cream, estradiol rings (Estrin of estradiol achieved by estradiol implants. Persistence of
3 monthly), tablet side effects of oral HRT indicates a non-oral route, and poor
– Subdermal implants: Pellets of crystalloid estradiol systemic absorption from oral/transdermal routes can be
(25,50,100 mcg monthly). managed by switching over to estradiol pellets. The vaginal
2. Progestogens are used in HRT to oppose the estrogenic route is specific to quicker relief of urogenital symptoms
effect on the endometrium, thereby protect against initially. Once the vaginal epithelium has achieved
endometrial hyperplasia and carcinoma. Various sufficient thickness and vascularity, systemic therapy can
compounds used are oral medroxyprogesterone acetate, be instituted.
dydrogesterone, norethisterone, newer progestins— In patients at risk for gallstone formation or on
desogestrel, gestodene and norgestimate. nonsurgical gallstone therapy, non-oral route of HRT is
Routes: a wiser option because oral estrogen increases the free
– Oral: 10–14 days or continuous cholesterol pool in hepatic cells, increasing cholesterol
– Transdermal: Matrix patch 28 day sequential regimen secretion into the bile. Transdermal estradiol seems to
(Nuvelle TS/Evorel sequi) or continuous combined have less effect on glucose metabolism than oral estrogens.
regimen (Evorel conti) About 5–100% populations have lactose intolerance that
– Vaginal: Pessary (Cyclogest) or gel (Crinone) causes gastrointestinal and some systemic side effects
– Intrauterine device (IUD): Continuous levonor when ingested as the bulking agent in oral pills. The
gestrel—Mirena. non-oral routes are devoid of this complication. Poor
3. Gonadomimetic therapy (tibolone) possesses estrogenic, response of improvement in libido with use of estrogen and
progestogenic and androgenic activity. progesterone indicates testosterone therapy in combination
4. Testosterone (100 mcg pellets). with estradiol.10
Effect of Route of Hormone Effects of Various Hormone

Replacement Therapy Replacement Therapy Regimens
There are some differences in the effects of the various Several regimens are presently available for estrogen (E)
routes available and hence, special indications in specific and progesterone (P) in HRT, and most women themselves
situations. Oral estrogens have greater impact on hepatic decide which one is suitable.
Chapter 25  Hormone Replacement Therapy: Ultrasound Role 247
Estrogen alone: In hysterectomized women, vaginal mean uterine volume is reported to be 4.2 cm3 and ovarian
application volume less than 2.5 cm3 (mean 1.3 ± 0.7 cm3).12,13
Cyclic sequential: E-day 1st to 25th/month, P-day 13th The risk of endometrial cancer increases in PMW;
to 25th/month therefore, a reliable, noninvasive method for pretreatment
Cyclic combined: E- and P-day 1st to 25th/month screening as well as monitoring during HRT is desirable.
Long cycle sequential: E-day 1st to 70th Office sampling including curettage and biopsy, aspiration,
P-day 71st to 85th/3 months brushing or washing of endometrial cavity and hysteroscopy
Continuous combined: E and P daily are all invasive. Ultrasound offers a noninvasive method for
Menopausal women are at increased risk for endometrial pretreatment screening, and follow-up, and the diagnosis
cancer. Studies in the early 1980s showed increased risk for of abnormal bleeding. Color Doppler ultrasound also helps
endometrial cancer in PMW taking estrogens alone, especially baseline assessment and in surveillance of benefits/risks of
when higher doses are taken and for longer duration.2 With HRT on systemic vessels cardiovascular and cerebral.
the use of progestins, the incidence of endometrial carcinoma
has decreased from 18% to less than 1%. The most common Transabdominal Ultrasound
side effects are breast tenderness, nipple sensitivity, leg The first careful correlation between transabdominal
cramps. Women also tend to worry a lot about breast cancer ultrasonic image of the endometrium and histopathology
risk, but meta-analysis reveals only a small excess in risk.10,11 was published in 1986 by Fleischer and colleagues.14 They
The major problem with HRT is withdrawal bleeding and made useful observations that provided the basis for the use
sometimes breakthrough bleeding. A large number of patients of ultrasound as the imaging method of choice for the uterus.
regard re-establishment of menstruation like withdrawal The range of sonographic endometrial thickness per wall in
bleeding with cyclic sequential HRT, a negative feature. Long PMW as observed by them was 2–3 mm (mean 2.8 mm), and
cycle HRT and continuous combined schedules are aimed at double-walled normal endometrium 6 mm. Comparison of
minimizing or avoiding bleeding altogether. gross and sonographic endometrial measurements was within
Continuous combined HRT induces endometrial atrophy 2 mm. But distortion by pathology or poor transabdominal
through the antiproliferative effect of the continuously images rendered eight measurements inaccurate. The
administered, low dose of progestogen. However, subendometrial or inner layer of dense myometrium, which
hypertrophy of the highly vascular stroma may be caused is seen in PMW as a hypoechoic halo around a relatively
by continuous progesterone therapy. Due to fluctuating echogenic endometrium, was described. Disruption of this
endogenous estrogen levels, 30–40% of women experience layer suggests a pathological extension of endometrium
erratic bleeding which may last for up to 6 months, after into the myometrium and vice versa (adenomyosis, invasive
which the goal of amenorrhea is usually achieved. The adenocarcinoma, myomata, sarcoma).
gonadomimetic and tibolone also have similar course. As imaging technology improved, sonologists continued
Therefore, it is recommended that sequential regimen be to demonstrate the measurable differences between
used in the first 1–5 years after the menopause and then normal and abnormal endometrium using transabdominal
switch to continuous regimen, to prevent discontinuation techniques. British investigators compared histology of
of treatment because of vaginal bleeding.10 curettings and ultrasound images in 85 untreated PMW, of
In long cycle HRT any endometrial hyperplasia that whom 63 were bleeding.15 Abdominal pelvic ultrasound
may arise, while estrogen is administered continuously is measurement of endometrial thickness reliably excluded
reversed by the addition of progesterone every 3rd month. significant pathology (as diagnosed by diagnostic curettage
and biopsy) 100% of the time. Single wall measurements
Ultrasound Role in “Pretreatment of 57 women, in whom inactive, atrophic or no endometrial
tissue was retrieved, were between 1.9 mm and 4.5 mm.
Assessment” Three endocervical polyps, seven endometrial cancers,
Prehormone replacement therapy assessment includes two pyometras with cervical carcinoma, nine polyps, three
a full medical, gynecological history, general physical cases of hyperplasia and one case of uterine carcinoma
examination and assessment of breast, abdominal, vaginal with a negative curettage and normal endometrium were
and pelvic status. In PMW, there is progressive atrophy of correctly predicted. Three small polyps were missed,
uterus and ovaries.5 This is better appreciated on ultrasound, rendering the sensitivity of the test as 91%. They concluded
that an endometrium measuring less than 5 mm in single Granberg et al. who first described transvaginal follicle
wall thickness invariably produced atrophic or insufficient aspiration in 1984, published their preliminary experience
tissue at surgery and suggested that sampling was not with 205 bleeding PMW in 1997.22 All 150 women with
necessary. This thickness (10 mm in total measurement) is endometrium measuring 5 mm or less in total thickness
too generous to be used as the cutoff value, as their later had atrophic or no endometrium on curettage; 7 cases with
study using transvaginal technique demonstrated.16 endometrial thickness between 6 mm and 15 mm were
also atrophic. Other investigators found no cancer in any
Transvaginal Ultrasound endometrium measuring 4 mm or less in thickness.23 Thus,
ultrasound finding of linear endometrial thickness 5 mm
With the exquisite resolution of endometrial image
or less can be used as a cutoff level and is a noninvasive,
allowed by high-frequency, near field imaging of vaginal
reliable screening test for endometrial carcinoma.
transducers, transvaginal sonography (TVS) years and form
Endometrial measurement has high sensitivity, but low
the basis of current management of menopause and HRT.17
specificity in screening for endometrial cancer.
Goldstein and colleagues performed suction curettage after
vaginal sonography in 30 bleeding PMW, 18 of whom
were on cyclic HRT.18 All 11 women with endometrium Progesterone Challenge Test and
measuring 5 mm or less had unstimulated or insufficient Ultrasonography
endometrium on biopsy, while 6 of 17 endometrium over
The progesterone challenge test (PCT) has been used to
6 mm had pathology: 3 had hyperplasia, 2 had polyps and
screen asymptomatic PMW for carcinoma endometrium,
1 had cancer. In the other women with thick endometrium,
along with ultrasonography before starting HRT.
2 biopsies showed atrophic endometrium and 9 showed
Medroxyprogesterone acetate 10–20 mcg daily for 10
hormonal effects. Notably, in two cases the endometrial
days is given orally. Absence of withdrawal bleeding
lining was distorted by myomata and could not be imaged
is associated with normal, atrophic endometrium and
well. The histopathology showed atrophy in one and
ultrasound in these patients that always show a thin linear
hyperplasia in the other.
1–3 mm endometrial echo.
Larger series demonstrating the significant lack of Presence of withdrawal bleeding suggests estrogen
pathology in endometrium measuring less than 5 mm prepared endometrium. Endometrial sampling is advisable
have repeatedly been reported in the literature. Nasri and to rule out pathology—hyperplasia or carcinoma. There
coworkers found that all 50 (of 90) bleeding women with is positive correlation between amount of bleeding and
an endometrium of 5 mm or less had atrophy on biopsy. thickness of endometrial wall.
The rest measured more than 5 mm and all had endometrial
pathology, including 6 cancers.19 Comparing aging to
endometrial thickness, it was seen that the thickness Color Doppler Ultrasound
was 0.31 cm in the group of patients with 1–5 years With color and pulsed Doppler ultrasound, it is possible
after menopause and 0.23 cm after 15 years or more of to analyze the quality of blood flow in the uterine artery
menopause, but this was not statistically significant.20 or any other pelvic vessel, giving valuable information on
Osmers et al. measured each endometrial wall separately pathophysiology (Fig. 25.1). In menopausal women, as
in 103 bleeding PMW.21 They concluded that endometrium years of postmenopause progressed, the resistance to blood
measuring less than or equal to 3 mm per wall (6 mm flow in uterine arteries remained same, but vascularity
in total) never harbored atypical hyperplasia or cancer. decreased.20 Other studies have shown high impedance to
Based on these findings, they biopsied only 76 of 283 flow and increased vascular tone as measured by pulsatility
asymptomatic women, rescanning the rest frequently to index and resistance index. Estrogen by virtue of its
detect endometrial growth: 12.6% of bleeding women effect on endothelial cells through release of nitric oxide
had cancer, while the prevalence in asymptomatic women and also by relaxation of vascular smooth muscle leads
was a surprisingly high 3.5%. Two cases of distorting to vasodilation.24 Deficiency of estrogen in menopause
myomata caused superthreshold measurements despite appears to be generalized on other vessels studied such
atrophic endometrium. All cases of endometrial cancers and as internal carotid artery, middle cerebral artery, coronary
hyperplasia had endometrial thickness of 8 mm or more. artery and peripheral arteries.25-27
in increase in uterine volume after HRT by all routes of
administration,18,29 although one study did not observe any
significant change in uterine/ovarian volume or endometrial
thickness after vaginal supplementation, especially with
estriol.12 Uterine volume was found to decrease in women
receiving sequential oral or transdermal HRT, probably, as a
result of progressive uterine atrophy in the study of Hanggi
(1997),30 although statistically significant increase in uterine
dimensions were observed by others.31,32
Effect of Hormone Replacement Therapy

on Endometrial Thickness
Irregular bleeding, fear of cancer are very important reasons
of patient noncompliance. Most patients do not remain on
Figure 25.1 High resistance blood flow in the uterine artery therapy beyond 2–3 years. Ultrasound can be of immense
help in allaying these fears, offering a sensitive, noninvasive
Sonohysterography surveillance schedule (Figs 25.2 and 25.3).
Saline infusion sonography provides better visualization of Monitoring of genital changes, especially endometrial
the endometrial cavity and reliably distinguishes patients thickness, to exclude endometrial hyperplasia or endometrial
with significant tissue. In difficult and doubtful cases, where carcinoma is necessary when a woman is on long-term
a simple ultrasound demonstrates a shaggy, heterogneous HRT.18,30 Screening for endometrial pathology should be
or even a thin endometrium, saline infusion into the uterus done in the days just following withdrawal of bleeding
can demonstrate polyps or endometrial carcinoma in women in cyclical therapy.33 With continuous combined regimen,
on HRT.28 Half the women on cyclic HRT regimens will the endometrium was found to be less than 8 mm in
have a total endometrial thickness between 5 and 8 mm; 85%of cases, while half of those on unopposed estrogen
and thus, one must consider the bleeding pattern and saline had endometrial thickness more than 8 mm.31 With cyclic
hysterosonography to determine if a biopsy is needed in regimen, ultrasound showed endometrium of fluctuating
these women. Women who bleed before the 11th day of thickness, which increases up to 8 mm, mimicking the
cyclic progestogen administration are at risk for hyperplasia. natural cycle.
Thickness of endometrium was larger in the groups with
Role of Ultrasound for “On Hormone HRT in comparison with the groups without HRT (p <
0.01) in our study.20 It was concluded that continuous HRT
Replacement Therapy Assessment” significantly influenced the thickness of postmenopausal
Traditionally, the first visit after starting HRT is after 3 endometrium, but not myometrium. The endometrial
months. Further, regular visits are advised every 12–18 thickness was also found to be increased after sequential
months or when a problem arises. At the on HRT check- oral and transdermal HRT after 24 months,33 although
up, bleeding patterns, any estrogenic/progestogenic side another study did not find any significant change in mean
effects must be asked. Specific inquiries for the presence of endometrial thickness after 6 months of continuous vaginal
gynecological symptom/signs such as offensive blood-stained CEE (0.625 mcg).12
vaginal discharge, postcoital bleeding should be made. In a study by Varner et al. the HRT regimen was
correlated with ultrasonographic measurement of
Effect of Hormone Replacement endometrial thickness in 27 women. 34 Eleven women
Therapy on Morphology of Uterus on cyclic regime had inactive, proliferative or secretory
endometrium with thickness ranging from 4 to 8 mm.
and Ovaries Thirteen of fourteen women on unspecified continuous
Hormone replacement therapy improves vascularity estrogen and progesterone therapy had endometrium less
and increases endometrial proliferation. 11 This results than 5 mm thick, one was 8 mm thick, and histopathology
Figure 25.2 Thickened endometrium in postmenopausal patient with Figure 25.3 Very thick endometrium in postmenopausal patient on
retroverted uterus hormone replacement therapy (anteverted uterus)
showed proliferative pattern. In two women on unopposed thickness is less than 5 mm, it suggests an atrophic or
estrogen therapy, the endometrium was 7–8 mm thick and “unstable” endometrium and is the most common cause of
hyperplasia was present. What action needs to be taken in abnormal bleeding on continuous HRT. This can be further
asymptomatic women when the endometrium is 5–8 mm confirmed by hysteroscopy.
thick is still controversial. A more than 5 mm thick or irregular and heterogeneous
Progesterone use causes endometrial shedding in endometrium or an irregularly thick endometrium with
cyclic regimen, the intensity and duration of withdrawal cystic spaces and sometimes fluid in the endometrial cavity
bleeding correlates very well with transvaginal sonographic suggests need for biopsy and hysteroscopy, as ultrasound
evaluation of endometrial thinning and shedding.29 has poor predictive value if endometrial thickness is greater
than 5 mm. It may be difficult to differentiate whether a
Role of Ultrasound in Special Conditions “thick” endometrium is caused by a polyp or any other
intrauterine structural abnormality. Endometrial polyps
Abnormal Vaginal Bleeding are found in 16.5% of women with postmenopausal
A number of studies have reported that TVS is helpful in the bleeding on HRT as compared to 10.8% in nonusers.35
diagnosis of the etiology of abnormal uterine bleeding.18,22 Endometrial polyps were the most common (54%) cause
In sequential HRT heavy or prolonged bleeding at the time of refractory bleeding in PMW on more than 6 months of
of cycle or breakthrough bleeding at any time may occur. In continuous therapy. Saline infusion sonography may help in
continuous regimen light spotting or “staining” occurring visualization of endometrial polyps which must be managed
beyond 6 months of treatment or bleeding recurring after by hysteroscopic resection, whereas “thick” endometrium
amenorrhea has been established is considered abnormal. alone can be managed by a lesser invasive dilation (or
Erratic bleeding suggests the presence of submucous dilatation) and curettage (D and C). Polyps are usually
fibroid, endometrial polyp or carcinoma. benign, but may rarely become malignant or be associated
Gynecological disorders include uterine, ovarian, with cancer endometrium.
cervical, vaginal and vulvar pathologies. Tests and Transvaginal sonography is also helpful in the diagnosis
investigations advised are clinical examination, ultrasound of endometrial hyperplasia which may occur in 30% of
(with or without saline infusion) and if required hysteroscopy women with unopposed estrogen use; 3–4% if progestogens
or endometrial sampling. are added for 7 days; 1–2% when progestogens are added
Ultrasound is of help in ascertaining the cause, and for 10 days and less than 1% when continuous combined
is used to assess endometrial thickness, endometrial regimen are used.36,37 Women on HRT have a thicker
and myometrial homogenicity or heterogenicity and endometrium, and different cut-off values (range 4–8 mm)
abnormalities of endometrial morphology. If endometrial have been proposed above which disease is more likely.38
When a thin endometrium is visualized on ultra Pulse and color Doppler can vividly describe changes
sonography (<4 mm), it can exclude those women who are in vascularity in different organ systems39 of significance
at very low risk for endometrial disease and need no further are the effect of hormone replacement therapy on the
investigation. This group comprises of half the women with cardiovascular and cerebrovascular systems. This is
irregular bleeding on HRT. of significant help in special conditions such as HRT
in patients with arterial disease, hypertriglyceridemia,
Use of Tamoxifen previous venous thromboembolism, diabetes (with lipid
abnormalities). Estrogens cause dilatation of blood vessels
Patients of breast cancer on tamoxifen may be prescribed
thereby improving vascular reactivity patterns, but addition
HRT if symptomatic. Irregular bleeding may occur
of progesterone partly attenuates this effect.40,41
in patients on long-term therapy caused by polyp or
carcinoma. Ultrasound with the help of saline infusion may
Uterine Vessels
help in displaying polyps; however, hysteroscopy directed
biopsy is warranted. Uterine artery flow velocity showed mean RI of 0.88 ±
0.04 in proliferative phase, which decreased to 0.84 ± 0.04
Breast Disease in luteal phase. High impedance values (RI 0.80–0.90)
are seen in PMW in both right and left uterine arteries.42
Benign breast disease is not a contraindication to HRT,
After continuous or sequential HRT, a significantly lower
although lobular and ductal hyperplasia with atypia increases
value of PI has been observed after 6 month to 1 year.43,44
risk of malignancy. Breast imaging by mammography or
Disappearance of uterine notch suggests decreasing vessel
ultrasound, along with clinical examination and fine-
compliance. In women taking HRT, the uterine notch
needle aspiration cytology are advised. Use of HRT in
persists or even reappears.33 With regards to route of
women on treatment for breast cancer is controversial, yet
administration of estrogen, a decrease in PI by 50% and
recommended for severe postmenopausal symptoms, using
40% with transdermal estrogen is reported.27,44 The effect of
lowest dose regimen, progestogen-only therapy or local
estrogen on vascular reactivity when given by transvaginal
vaginal creams. Follow-up with ultrasound of other breast
route is negligible and this may be related to minimal
and ovaries is helpful.
systemic absorption of estrogen through vaginal epithelium.
Fibroid Internal Carotid Artery and

Preexisting fibromyoma of uterus may increase in size with
HRT and may induce abnormal bleeding. Growth in size
Cerebrovascular System
can very precisely be monitored by clinical examination There are gender differences in cerebral blood flow related
and with the help of ultrasound on every 6 months. Sudden to estrogen. Until the menopause, cerebral blood flow
increase in size associated with pain and pressure may is greater in women than in men of the same age. After
suggest sarcomatous change. menopause, cerebral blood flow decreases in females and
is the same as in age-matched males.45 Epidemiological
Endometriosis studies indicate beneficial effect of postmenopausal
Estrogen replacement therapy in menopausal patients with estrogen use on stroke risk and mortality.46,47
previous severe endometriosis, and even after bilateral In a double blind placebo controlled trial, Jackson
oophorectomy carries a potential risk of recurrence of randomized 28 PMW into two groups receiving oral
disease, commonly at rectovaginal septum, cul-de-sac estradiol (2 mg daily) or placebo.48 The mean pulsatility
and vagina. Ten case reports of malignant transformation index in carotid artery decreased by –0.11 in 15 women who
are available in the literature (Dunn, 1993). Ultrasound received estradiol compared to 12 women who received
can help to diagnose any pelvic or adnexal mass. It is placebo (p = 0.006).
suggested that HRT should be started after 3–12 months Gangar evaluated blood flow characteristics in the internal
of surgery/menopause for spontaneous regression, or after carotid artery of 12 PMW, who were put on transdermal
3–6 months of danazol/GnRH therapy postoperatively. The estradiol 50 μ/day. The PI was measured at onset of study
most appropriate assessment is by laparoscopy. and then 4, 6, 9 and 22 weeks of therapy. They reported fall
in PI by 50% in uterine artery in 10 PMW put on continuous Effect of Hormone Replacement Therapy
transdermal estradiol and sequential oral norethisterone on Vascular Reactivity of Other Vessels
acetate. This fall in PI recorded rapidly within 6–10 weeks
Belfort using color Doppler ultrasonography determined
after estrogen supplementation by transdermal route.49
systolic, diastolic and mean velocity, as well as resistance
Penotti observed a significant fall (p < 0.001) in internal index in central retinal and ophthalmic arteries in 10
carotid artery PI and middle cerebral artery PI with 8 weeks PMW.25 The PMW were again studied at 2 months after
of transdermal estradiol therapy in 15 hysterectomized starting daily oral therapy with 2 mg of micronized
PMW. The PI decreased up to 6 months of therapy. After 17β estradiol. They observed that postmenopausal on
that no beneficial effects could be observed.26 HRT had a significantly (p<0.05) higher diastolic blood
Changes in cognitive or neuropsychologic function have flow velocity and lower resistance index in central
been associated with hormonal decline. Studies have shown retinal artery. Hata also investigated the effects of HRT
that the risk of dementia and Alzheimer’s disease decreased (conjugated estrogen, 0.625 mg/day and MPA 2.5 mg/day)
with increasing doses of estrogen and with increasing on ophthalmic arteries and found decrease in pulsatility
interval of use.46 Studies of the effect of HRT on cerebral index.53 They also observed a correlation of PI with serum
perfusion and cognition among PMW suggest that HRT estradiol level.
may ameliorate congnitive decline by improving cerebral Lau studied the PI of the peripheral arteries (brachial,
perfusion.50 It is suggested that cerebral autoregulation radial, dorsalis pedis and popliteal artery) in the PMW
and blood flow are highly dependent on the entry of on HRT and observed the beneficial effects in PI after 6
extracellular calcium. It is not surprising that estrogen, months.54
with its calcium channel blocking action should play an
important role in the control of cerebral perfusion.25 Conclusion
There are only a few reports addressing the issue of Ultrasound, pulsed and color Doppler can greatly help in the
effects of progesterone on vascular reactivity parameters. management of PMW on HRT. Transabdominal and especially
transvaginal sonography vividly images normal postmenopausal
Hillard observed a 13% higher uterine artery PI in estrogen- body changes and the beneficial effects of HRT not only on the
progesterone phase when compared with estrogen only urogenital tract but also on the vasculature of the heart and brain.
phase.51 Marsh observed that norethisterone increased the It is almost indispensable for pre-HRT assessment, on treatment
assessment and early diagnosis of any deviations from normal
mean uterine artery PI by 30%. They also observed that requiring further invasive work-up and therapy.
the effects of progesterone was short lived and subsided
within 4 days of cessation of the progesterone therapy.40
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measurements of Doppler-derived parameters of aortic flow.
42. Kurjak A, Kupesic S. Ovarian senescence and its
Am J Obstet Gynecol. 1991;164(3):806-12.
significance on uterine and ovarian perfusion. Fertil Steril.
1995;64(3):532-7. 53. Hata K, Hata T. Effects of oophorectomy and hormone
43. Delzanno G, Paoletti R, Demarchi A, et al. Variations in replacement therapy on ophthalmic artery blood flow
the pulsatile index of the uterine arteries in postmenopausal velocity waveforms. J Ultrasound Med. 1997;16(11):737-
women receiving hormone replacement therapy. Minerva 41.
Ginecol. 1996;48(1-2):11-3. 54. Lau TK, Wan D, Yim SF, et al. Prospective, randomized,
44. Bourne T, Hillard TC, Whitehead MI, et al. Oestrogens, controlled study of the effect of hormone replacement
arterial status, and postmenopausal women. Lancet. therapy on peripheral blood flow velocity in postmenopausal
1990;335(8703):1470-1. women. Fertil Steril. 1998;70(2):284-8.
CHAPTER
26
Ectopic Pregnancy
Sanja Kupesic Plavsic, Alenka Aksamija, Jose Bajo Arenas, Asim Kurjak
Introduction The main problem of ectopic pregnancy is clinical

presentation.17 Symptoms can vary from vaginal spotting
Ectopic pregnancy represents implantation of the fertilized to vasomotor shock with hematoperitoneum.18,19 The classic
ovum outside the uterine cavity. In 95% of the cases,
triad of delayed menses, irregular vaginal bleeding and
it is localized in the fallopian tube (95%), but sites like
abdominal pain is most commonly not encountered, but
abdominal cavity, ovary, intraligamentous location, cornual,
the exact frequency of clinical symptoms and signs is hard
intramural or cervical sites are not unusual.1-4 The exact
cause of blastocyst implantation and development outside to assess.1 Both typical and atypical clinical presentation
the endometrial cavity is not fully understood. Increased can mimic all kinds of diseases, which have no connection
incidence of ectopic pregnancy was found during the last with pathology of reproductive system, such as appendicitis,
decades5,6 mainly attributed to greater degree of socially diverticulitis, nonspecific mesenterial lymphadenitis or
acceptable sexual behavior, which led to increased incidence diseases of the urinary system. In most cases ectopic
of the pelvic inflammatory disease (PID). Fortunately, the pregnancy is confused with an early spontaneous abortion
fatal outcomes have been reduced up to 75% for the reason because of the similar symptoms in both processes
of early diagnosis and less invasive treatment techniques. (delayed menses, enlarged and softened uterus and
Mechanical factors predisposing pathomorphological site bleeding). Other conditions that should be considered in
of implantation are: low-grade pelvic infection (main cause differential diagnosis of ectopic pregnancy are normal
for the faulty implantation), peritubal adhesions (result intrauterine pregnancy, salpingitis, torsion or rupture of
of the previous PID) and salpingitis with the partial or the ovarian cyst, adnexal torsion, bleeding corpus luteum,
total destruction of the tubal mucosa. It has been reported endometriosis, appendicitis, gastroenteritis, diverticulitis,
that ectopic pregnancies do occur in totally normal tubes, conditions affecting urinary tract, etc. Therefore, early and
suggesting that abnormalities of the conceptus or maternal reliable diagnosis of ectopic pregnancy is major challenge
hormonal changes may act as etiological factors.7,8
for every clinician. Significance of early diagnosis lays in
Risk factors for ectopic pregnancy are sexually the possibility for application of the conservative methods
transmitted diseases-pelvic inflammatory disease, 9,10 of treatment, which are crucial for preserving further
assisted reproductive techniques, abnormalities of the
reproductive capability, and in severe cases the life itself.20
conceptus, maternal hormonal changes, surgical procedures
Diagnostic procedures are divided into two groups:
in pelvis,11 intrauterine device (IUD),12 previous ectopic
pregnancy, fibroids, uterine malformations, cigarette 1. Noninvasive: History, general, clinical and gynecological
smoking, etc. In addition to providing an accurate examinations, hormonal and other laboratory markers
description of the sites of implantation of ectopic pregnancy, and ultrasound diagnostics.
some authors showed that current IUD use “protects” 2. Invasive: Culdocenthesis,21 curettage,22 and laparoscopy.
against interstitial pregnancies, which are the most difficult
to manage and that subsequent fertility tends to be higher Role of Biochemical Markers in
in women with distal ectopic pregnancy.13 It is essential Ectopic Pregnancy
to identify the risk factors so that we can provide patients
with adequate information, diagnosis and treatment of an Beta human chorionic gonadotropin (hCG) is the
ectopic pregnancy early, and possibly to develop preventive glycoprotein hormone released into circulation by human
strategies.14-16 placental trophoblastic cells. From the 8th day after
conception, its concentration in blood rises 1.7 times every Transabdominal Ultrasound
day.23 As soon as implantation occurs the trophoblast starts The absence of gestational sac inside the intrauterine cavity
producing beta hCG. Common urine beta hCG tests react at 6 weeks of gestation raises the suspicion of an ectopic
at concentrations higher or equal to 1,000 IU/L of urine, pregnancy. Transabdominal ultrasonography cannot reliably
which means that they become positive in 10–14 days after diagnose ectopic pregnancy, except when a live fetus is
conception.1 Falsely-positive results are mainly obtained demonstrated in the abdominal cavity. In only 3–5% of
in the case of proteinuria, erythrocyturia, gynecological the cases an ectopic gestational sac with embryonic echoes
tumors, tubo-ovarian abscess24 or some drug intake (e.g. and clear heart activity can be demonstrated.32 Probe with
tranquilizers). Embryo in cases of an ectopic pregnancy frequency of 3.5 MHz and a large contact area is used for
usually disappears, gets resorbed and we normally visualize transabdominal ultrasonographic imaging, and full bladder
an empty gestational sac producing smaller amounts of plays a role of an acoustic window. Resolution of this probe
beta hCG. Normal levels of beta hCG could be found only is somewhat lower, but the penetration is much deeper than
in cases of a still living embryo, which occurs in 5–8% of one of the transvaginal probe.
ectopic pregnancies.23 For the reason of low concentrations The best results in confirming the intrauterine pregnancy
of hCG, only 40–60% of ectopic pregnancies have the are achieved using the following criteria:
positive urine test; therefore, more sensitive blood test
ÀÀ Normal size, shape and location of the gestational sac
should be performed, which becomes positive already
in the uterine cavity
10 days after conception.23 Absolute values of beta hCG
ÀÀ Double ring surrounding the gestational sac
levels in circulation are much lower than the levels of the
ÀÀ Embryonic parts with eventual heart action.
same hormone in normal intrauterine pregnancies of the
same gestational age.25,26 Dynamics of the titer show slower Signs for ectopic pregnancy could be divided into uterine
increase of circulating concentrations and prolongate the and extrauterine, some of them being diagnostic or just
time for doubling its values. The most important use of suggestive.
the quantitative beta hCG determination in conjunction ÀÀ Diagnostic signs include absence of the intrauterine
with ultrasonography is that of understanding the value gestational sac surrounded with double ring, absence of
of “discriminatory zone” of beta hCG. The discriminatory the yolk sac and/or fetal structures inside the gestational
zone represents the level of beta hCG above which all sac and presence of extraovarian adnexal structure
normal intrauterine chorionic sacs will be detected by ÀÀ Suggestive signs are uterine enlargement with thickened
ultrasound. There is now almost a consensus in considering endometrium and blood or coagulum in the retrouterine
the discriminatory zone to be about 1,000 mIU/ml with the space.32
use of transvaginal probe of at least 5 MHz.27-30 Low sensitivity, specificity, positive and negative
predictive values for detection of ectopic pregnancy are
Role of Ultrasound in the Diagnosis shortcomings of transabdominal ultrasound. 33,34 This
of Ectopic Pregnancy modality still has some value in successful detection of
a small proportion of ectopic pregnancies with bizarre
With recent technological development, ultrasonography
location, such as high in the pelvis.
(but more precisely, transvaginal sonography) has become
the “gold standard” diagnostic modality for the effective
and fast detection of ectopic pregnancy. An important
Transvaginal Ultrasound
advantage of most currently used transvaginal transducers In comparison with transabdominal approach, transvaginal
is the ability to perform simultaneous and spectral Doppler ultrasound enables much better image of the morphological
studies, allowing easy identification of the ectopic features in pelvis, thanks to higher frequencies and probe
peritrophoblastic flow. In comparison to transvaginal location in immediate vicinity of the examined area.
sonography, transabdominal ultrasound, as a method for Sensitivity of transvaginal sonography was found to be
detecting ectopic gestation, is restricted for a very small 96%, the specificity reached 88%, the positive predictive
number of oddly located ectopic pregnancies, mainly high value 89% and negative predictive value 95%.35 Intrauterine
up in the pelvis—outside the effective reach of 5 MHz gestational sac surrounded with double ring with clear
vaginal probe.31 embryonic echo is considered to be strong evidence
Chapter 26  Ectopic Pregnancy 257
against ectopic pregnancy because heterotopic pregnancy trying to distinguish tubal pregnancy from the ipsilateral
(intrauterine and ectopic) coincides rarely, but should not corpus luteum. Corpus luteum is found in the ovary and
be so easily ignored, especially in the patients undergoing its echogenicity is slightly (or at times even substantially)
some of the methods of assisted reproduction.36 lower than that of trophoblastic tissue of the tubal ring.
Intrauterine sonographic findings in women with ectopic Furthermore, hemorrhagic corpus luteum usually shows
pregnancy are variable. These include: a hypoechoic rather than a cystic central region.42 Other
ÀÀ Empty uterus, with or without increased endometrial three conditions that need to be correctly differentiated
thickness from an ectopic gestation are a thick-walled ovarian follicle,
ÀÀ Central hypoechoic area or a sac-like structure inside the small intestine and tubal pathology conditions such as
cavity—the so-called pseudogestational sac hydrosalpinx containing fluid.
ÀÀ Concurrent intrauterine pregnancy. Using the protocol of combination of clinical examination,
Early intrauterine pregnancy and recent spontaneous serum beta hCG assay and transvaginal ultrasound
abortion may present themselves on transvaginal sonography examination, it is possible to diagnose ectopic pregnancy
with empty uterus and endometrial layer variable in with a sensitivity of 100% and specificity of 99%.43
thickness.3 Therefore, they are considered to be suggestive Another problem in detection of an ectopic pregnancy
signs. Pseudogestational sac can be demonstrated in in adnexal region arises in patients who are undergoing
10–20% of patients with ectopic pregnancy3 as a mixed assisted reproductive procedures or simple hormonal
echo pattern of endometrium that results from a decidual superovulation. Besides the increased risk for ectopic
reaction, fluid or both. Careful examination of the uterine pregnancy in these patients, a large number of artificial
cavity usually allows a reliable distinction to be made corpora lutea will be seen that resemble the tubal ring of
between the pseudogestational sac and normal gestational an ectopic pregnancy. Sometimes cystic adnexal masses
sac. The pseudogestational sac is detected in the middle of (ovarian cystadenoma, cystadenofibroma, endometrioma,
the uterine cavity, its shape changes, owing to myometrial teratoma and pedunculated fibroids) may also raise
contractions. In differentiating a real gestational sac from differential diagnostic problems.
a pseudogestational one, transvaginal color and pulsed Free intraperitoneal fluid is seen in 40–83% women
Doppler ultrasound proved to be very useful. with ectopic pregnancy, but also in up to 20% of normal
intrauterine pregnancies. 38 In case of tubal abortion,
Adnexal sonographic findings in women with ectopic
echogenic echoes suggesting the presence of blood clots
pregnancy are variable. Gestational sac located inside
are demonstrated, while tubal rupture is associated with a
adnexa with clear embryonic echo and heart activity directly
homogeneous, hypoechoic retrouterine echo that represents
proves ectopic pregnancy, but is seen in only 15–28% of the
blood collection. The possibility of an ectopic pregnancy
cases. Less rare is visualization of an adnexal gestational
increases if the amount of fluid is moderate to large, but
sac with or without embryonic echo (without heart action).37
the absence of blood does not exclude its diagnosis.
Such a finding is detected in 46–71% of reported cases if
Serial serum beta hCG assay may raise a suspicion
the tube is unruptured,38 while the most common finding is
on ectopic pregnancy at a very early gestation, while
an unspecific adnexal tumor. Free fluid in the retrouterine transvaginal ultrasound scan may not be able to demonstrate
space is seen in 40–83% of cases. the site of pregnancy. Under these circumstances, sometimes,
Accurate ultrasound diagnosis of ectopic pregnancy it is necessary to perform laparoscopic examination to
depends strongly on examiner’s experience. Adnexal exclude the possibility of ectopic pregnancy. However,
abnormalities may be difficult to identify due to confusion even laparoscopic examination may not be able to achieve
with loops of bowel or other pelvic structures.39 a precise diagnosis, especially when the ectopic pregnancy
There are four adnexal structures that may resemble is very small or when there are coexisting pathologies such
an ectopic pregnancy and should be correctly identified.40 as hydrosalpinges, adhesions or fibroids. Some reports
One is the corpus luteum, which is eccentrically located demonstrated that laparoscopic ultrasound can facilitate the
within the ovary, surrounded by ovarian tissue and possibly diagnosis of the site of ectopic pregnancy intraoperatively,
creating the impression of a sac-like structure. About 85% even if it is as small as 3.9 mm.44 The number of negative
of ectopic pregnancies are formed on the same side as the laparoscopies can be decreased and repeat laparoscopy
corpus luteum.41 This is important to bear in mind while avoided. Therefore, laparoscopic ultrasound should be used
when the site of ectopic pregnancy cannot be determined The mean reduction of the RI on the side with ectopic
or is obscured by other pathologies during laparoscopic pregnancy compared to the opposite side was 15.5%.4 These
examination. changes appear to be due to trophoblastic invasion, and
showed no dependence on gestational age. Bright color on
Color Doppler Facility the screen, while using the pulsed Doppler facility, is due
Ultrasound machine with color Doppler facility is an to very high speed of the peritrophoblastic blood flow and
excellent guide in search for blood flow signals within low impedance (Fig. 26.5). It should be stressed out that
the entire pelvis. The color flow pattern associated with the patients with tubal abortion demonstrate significantly
ectopic pregnancy is variable. It usually presents randomly higher vascular impedance of peritrophoblastic flow (RI
dispersed multiple small vessels within the adnexa > 0.60), and less prominent color signals (Fig. 26.6).
(Fig. 26.1), showing high-velocity and low impedance The main diagnostic importance of transvaginal color
signals [resistance index (RI) = 0.36−0.45] clearly separated and pulsed Doppler is in differentiating the nature of
from the ovarian tissue and corpus luteum (Fig. 26.2). The nonspecific adnexal masses. Doppler blood flow indices
sensitivity of transvaginal color and pulsed Doppler in in the uterine, spiral arteries and corpus luteum arteries
diagnosis of ectopic pregnancy reported in several studies in ectopic and intrauterine pregnancies showed that
ranging from 73% to 96%, and specificity from 87% to the mean uterine and spiral artery RI decreased with
100%.3,8,38,45 increased gestational age of the intrauterine pregnancies,
Visualization of ipsilateral corpus luteum blood flow but remained constantly high in ectopic pregnancies.47
may aid in diagnosis of ectopic pregnancy (Fig. 26.3). The peak systolic blood flow velocity in the uterine artery
The RI of luteal flow in the cases of ectopic pregnancy increased with increasing gestational age in intrauterine
has been reported to be 0.48 ± 0.07, which is between the pregnancies, and the values were significantly higher than
values of the nonpregnant women (0.42 ± 0.12) and those in ectopic pregnancies.48 The difference in peak systolic
with normal early intrauterine pregnancy (0.53 ± 0.09).46 In velocity reflects a decreased blood supply to the ectopic
majority of patients with proven ectopic pregnancy, luteal pregnancy. Intrauterine gestational sac shows prominent
flow is detected on the same side as the ectopic pregnancy. peritrophoblastic vascular signals (RI = 0.44 – 0.45), while
This observation could be used as a guide in searching for pseudogestational sacs do not demonstrate increased blood
ectopic pregnancy (Fig. 26.4). flow (RI > 0.55). It has been suggested that velocities below
The between-side difference in tubal artery blood flow 21 cm/sec are diagnostic for pseudogestational sac and
was also documented. There was a significant increase in can successfully rule out trophoblastic flow of a normal
the tubal artery blood flow on the side of tubal gestation. intrauterine pregnancy.49
Figure 26.1 Transvaginal color Doppler scan of a small gestational sac Figure 26.2 The same patient as in Figure 26.1. Blood flow velocity
in the adnexal region measuring 8–10 mm. Note the dilated tubal vessels, waveforms depicted from the area of peritrophoblastic flow show high
indicating the pathophysiological site of the pregnancy (within the tube) velocity (23.3 cm/sec) and low vascular resistance (RI = 0.25)
Figure 26.3 The same patient as in the Figures 26.1 and 26.2. An Figure 26.4 Color Doppler facilitates visualization of randomly
ipsilateral corpus luteum is demonstrated laterally to the ectopic dispersed tubal arteries indicating prominent trophoblastic vitality and
gestational sac invasiveness. Note the ipsilateral corpus luteum
Figure 26.5 Transvaginal color Doppler imaging of a left-sided ectopic Figure 26.6 Gestational sac measuring 12 mm visualized in the left
pregnancy. Note the color signals indicative of invasive trophoblast adnexal region. Color Doppler depicts a small area of angiogenesis
(left). Pulsed Doppler waveform analysis (right) demonstrates low characterized by a high resistance index (RI = 0.73). This finding is
resistance index (RI = 0.43) indicative of tubal abortion
The intravascular ultrasound contrast agent has a lack of experience or patients’ noncompliance. The other
recognizable effect on Doppler ultrasonographic examination possibility of fault diagnosis is nonvascularized ectopic
of the adnexal circulation. It appears to be helpful when gestation, as these are associated with low beta hCG values.
the finding in color flow imaging is ambiguous. The use Some authors compared technical errors with improper
of the contrast agent may also facilitate localization of setting of color flow parameters.51 The color velocity scale,
trophoblastic tissue in hemorrhagic adnexal lesions.50 color priority, color gain, color sensitivity and color wall
As with other diagnostic methods, transvaginal color filter should be adjusted to optimize color flow information.
and pulsed Doppler studies include both false-positive and Technical errors may result in false diagnosis of ovarian
false-negative findings. A false-positive diagnosis arises torsion, malignancy and ectopic pregnancy.
predominantly from the corpus luteum; but in exceptional The diagnosis of ectopic pregnancy still remains a
cases, some adnexal lesions may mimic ectopic pregnancy. challenge to the clinician despite advances in ultrasound and
A false-negative result may arise from technical inadequacy, biochemical technology. Frequently, the diagnosis remains
uncertain until laparoscopy or dilatation and curettage (D A prospective follow-up study was conducted in
and C) are performed. With the increasing tendency toward order to evaluate the potential utility of 3D ultrasound to
conservative therapy, the distinction between ectopic differentiate the intrauterine from ectopic gestations.59 Fifty-
pregnancies that will resolve spontaneously and those four pregnancies with a gestational age less than 10 weeks
that will rupture is essential.52 Usually, patients without and with an intrauterine gestational sac less than 5 mm in
acute symptoms and with declining beta hCG values are diameter formed the study group. The configuration of the
treated conservatively.53 However, secondary ruptures endometrium in the frontal plane of the uterus was correlated
have been reported in patients with low initial beta hCG with pregnancy outcome. After exclusion of three patients
concentrations.54 The differentiation between viable ectopic with a poor 3D image quality, the endometrial shape was found
pregnancies with trophoblastic activity and dissolving tubal to be asymmetrical with regard to the median longitudinal
abortions could facilitate the decision to proceed with axis of the uterus in 84% of intrauterine pregnancies, whereas
conservative or operative treatment. endometrium showed symmetry in the frontal plane in 90%
After implantation in the mucosa of endosalpinx, the of ectopic pregnancies. Intrauterine fluid accumulation may
lamina propria and then the muscularis of the oviduct, the distort the uterine cavity, thus being responsible for false-
blastocyst grows mainly between the lumen of the tube and positive, as well as false-negative results. The evaluation
its peritoneal covering.55 Growth occurs both parallel to the of the endometrial shape in the frontal plane appeared to
long axis of the tube and circumferentially around it. As the be a useful additional mean of distinguishing intrauterine
trophoblast invades surrounding vessels, intensive blood from ectopic pregnancies, especially when a gestational sac
flow and/or intraperitoneal bleeding occur. The intensive was not clearly demonstrated with conventional ultrasound.
ring of vascular signals could be a criterion for viability of Similarly, preliminary data of other authors suggested that 3D
an ectopic pregnancy that can be determined rapidly and sonography is an effective procedure for early diagnosis of
easily, and seems to be independent of beta hCG values.56 ectopic pregnancy in asymptomatic patients before 6 weeks
In patients with a viable ectopic pregnancy who demand of amenorrhea.60
a conservative treatment, this method could provide an The possible use of 3D power Doppler is the monitoring
aid, in addition to beta hCG values; for supervising the of the vascularity of ectopic pregnancy. The hypoperfusion,
efficiency of treatment, especially in those cases where quantified by indices of vascularity (VI) and flow (FI),
beta hCG levels slowly normalize. In this way, duration of could indicate that the ectopic pregnancy is spontaneously
hospitalization could be shortened, the patients’ uncertainty being resolved, and that laparoscopy should be postponed.
diminished, and the cost of the treatment reduced. In cases This way, the conservative approach to ectopic pregnancy
of persisting high beta hCG levels after operative removal of would rely on more precise and easily obtainable data. Vice
the ectopic, color Doppler sonography can provide evidence versa, in case of hyperperfusion, the patients should be
for the presence of viable trophoblast remnants. On subjected to laparoscopy or medical treatment immediately.
contrary, in asymptomatic patients with hypoperfused and/ Shih and colleagues61 described the use of 3D color/
or avascular ectopic gestational sac and decreased values power angiography in two cases in which an arteriovenous
of beta hCG, expectative treatment can be established. malformation of mesosalpinx was diagnosed following
involution of an anembryonic ectopic gestation. The
Three-dimensional Ultrasound in the diagnosis of arteriovenous malformations has traditionally
Assessment of Tubal Ectopic Pregnancy been made by arteriography. Recently, it has also been
diagnosed by noninvasive methods such as contrast-
Three-dimensional (3D) ultrasound technology offers enhanced CT, MRI and color Doppler ultrasound. The
some advantages over conventional two-dimensional (2D) advantage of 3D reconstruction of color/power angiography
sonographic imaging.57,58 Modern systems are capable images is better spatial and anatomic orientation and quick
of generating surface and transparent views depicting demonstration of the vessels, usually within 1 minute,
sculpture-like reconstruction of surfaces or the transparent especially in the areas where complex structures are present.
images structure’s content. Therefore, unlike MRI, digital subtraction angiography or
Planar mode tomograms are helpful in distinguishing the contrast-enhanced CT, 3D color/power angiography allows
early intraendometrial gestational sac from a collection of the the physician to examine vascular anatomy immediately
fluid between the endometrial leaves (pseudogestational sac). and without radiation exposure.
Most tubal gestations are not ongoing viable gestations. Other Sites of Implantation
They are usually in the involutional phase of abortion within
a confined area, which results in the extrusion of products About 5% of ectopic pregnancies implant in sites other
of conception through a ruptured site or fimbriae. In the than the tubes.1 These are at times more difficult to detect
two reported cases, the serum assays of beta hCG in both and some, owing to strategic sites of implantation, may
patients increased to significant levels, which precluded cause rupture, significant bleeding and higher morbidity
intrauterine missed abortion.61 Besides, there were neither and mortality than the tubal gestations.
retained products of conception in utero nor heavy vaginal
bleeding (indicating process of abortion in progress) prior Interstitial Pregnancy
to the diagnosis of arteriovenous malformation. Therefore, Interstitial pregnancy occurs in 1.1–6.3% of all ectopic
authors speculated that there might be an ectopic gestation pregnancies.1,63 This location of ectopic pregnancy usually
occurring somewhere, although they could find only a occurs following in vitro fertilization (IVF) and previous
pelvic arteriovenous malformation rather than an adnexal salpingectomy,63 but in most cases there are no apparent
gestational sac. risk factors. Interstitial pregnancy clinically presents with
The major difference between uterine implantation abdominal pain and a tender asymmetrically enlarged
and tubal gestation is that endosalpingeal stroma usually uterus. The major problem of this location lies in late
faills to undergo decidualization. The chorionic villi of the diagnosis because it is commonly diagnosed after the
tubal implantation may then invade into the tubal wall and rupture of the cornu has occurred, and this may result in
mesentery (mesosalpinx) more directly and rapidly. The massive hemorrhage. Previously, interstitial pregnancies
vascularization within the ectopic pregnancy is an analog were diagnosed only at laparotomy following the rupture.
of placenta increta.62 In such situations cytotrophoblast may For the reason of major hemorrhage, hysterectomy rate
invade the contiguous artery and vein of mesosalpinx with was as high as 40%.60 In recent years, the routine use
destruction of these vessels’ walls, and thus may induce an of ultrasound for the assessment of women with early
arteriovenous malformation in situ or nearby. Possibly, the pregnancy complications has enabled a noninvasive
secretion of angiogenic factors (by trophoblast) and the diagnosis of interstitial pregnancy to be made. Earlier
increasing afterload of an arterioventricular shunt existing diagnosis made before serious complications allows the
in the tubal gestation can induce the rapid growth of a use of more conservative management, such as medical
small pre-existing congenital arteriovenous malformation. treatment or laparoscopic surgery.
However, two unusual cases of adnexal arteriovenous A viable interstitial pregnancy may occasionally
malformations associated with “vanishing” ectopic be misinterpreted as a normal intrauterine pregnancy.
gestation where congenital etiology seemed unlikely Therefore, it is important that strict diagnostic criteria are
have also been reported.61 B-mode ultrasound and color used in every case:64
Doppler provided information on the hemodynamics of the ÀÀ Empty uterine cavity
vascular tumor and led to the diagnosis of arteriovenous ÀÀ Chorionic sac that is seen separately and more than 1
malformation. Three-dimensional color/power angiography cm from the most lateral edge of the uterine cavity and
further improved understanding of the complex vascular surrounded by a thin myometrial layer.
anatomy and refined the diagnosis. It is worth to mention that approximately 15% of patients
Even though the exact role of 3D ultrasound in the with interstitial pregnancy have heterotopic pregnancy.64
pathology of early pregnancy is yet to be established, In these cases, intrauterine findings may be misleading
promising results of already published papers are and should be interpreted with caution, rather than being
encouraging. Unlimited numbers of sections are easily used as primary diagnostic criterion. Visualization of
obtained without the need for excessive manipulation the interstitial part of the tube in close proximity of the
with the probe. Additional progress has been made owing endometrium and depiction of the trophoblastic tissue
to the permanent possibility or repeated analysis of improves the diagnosis of interstitial pregnancy.65 It also
previous stored 3D volumes and Cartesian elimination of confirms that pregnancy is located outside the uterine
surrounding structures and artifacts. Three-dimensional cavity, facilitating the differential diagnosis between an
reconstruction of stored image without any degradation is interstitial pregnancy and unusual forms of intrauterine
the most impressive benefit of 3D scanning. pregnancy, such as angular pregnancy or pregnancy in the
for the increased effectiveness of local injection is in

higher concentration of therapeutic agent achieved in
the target tissue. Although absorption of methotrexate
into the circulation occurs after both local and systemic
administration, a lower dose of methotrexate is used locally,
leading to lower systemic levels and therefore, fewer side
effects.70 Color Doppler plays an extremely important role
providing an aid in approaching the cornual pregnancy from
the medial aspect and traversing the thicker myometrial
layer, so rupture or bleeding is less likely to occur.71 In
these cases, color Doppler guidance during the instillation
of methotrexate enables better visualization of blood vessels
and avoidance of intraprocedural complications.
Viable heterotopic/interstitial pregnancies are often
Figure 26.7 Transvaginal color Doppler scan of interstitial pregnancy. treated by local injection of potassium chloride, as this
Color signals facilitate early diagnosis of this ectopic pregnancy location
by exposing low resistance peritrophoblastic flow
is not teratogenic. All six reported cases of heterotopic
pregnancies in the literature were successfully treated in this
way, with three (50%) intrauterine pregnancies progressing
cornu of an anomalous uterus. This sign is particularly
normally to full term.4
helpful in women with small intramural fibroids located
Expectant management of the interstitial pregnancy
in vicinity of the interstitial part of the tube, which may be
has also been reported.64,66 All three nonviable interstitial
misinterpreted as a solid interstitial pregnancy.66 In women
pregnancies managed in this way were resolved
with fibroids, the intramural part of the tube is displaced and
spontaneously without any need for intervention. Expectant
can be visualized bypassing the mass, thus preventing the
false-positive diagnosis of the interstitial pregnancy. Color management can, therefore, be a useful option in selected
Doppler facilitates the diagnosis of a cornual pregnancy by cases.
exposing low resistance peritrophoblastic flow (Fig. 26.7).
Three-dimensional ultrasound has the advantage of Cervical Pregnancy
providing views of the uterus, which can rarely be obtained Cervical pregnancy is defined as the implantation of
by conventional 2D ultrasound scan.67 In the coronal conceptus below the level of internal os. It is the rare
section, the position of the interstitial pregnancy in relation condition that occurs in 1 in 50,000.4 Intrauterine adhesions,
to the uterine cavity can be studied in detail. Visualization of uterine anomalies, previous cesarean sections, fibroids,
the proximal section of the interstitial tube is also facilitated, previous therapeutic abortions and IVF treatment have all
which increases diagnostic confidence.65 It is believed that been associated with cervical implantation. Traditionally
3D ultrasound is a helpful diagnostic tool in women with the diagnosis of cervical pregnancy was based solely on
suspected interstitial pregnancy and should be considered clinical findings and history reports after hysterectomy.
in the cases where diagnosis is not certain on conventional Therefore, it is likely that only the most severe cases were
2D transvaginal ultrasound scan.68 diagnosed, and a number of cervical pregnancies went
Most cornual/interstitial ectopic pregnancies are treated undiagnosed or were treated as incomplete miscarriages.
by laparoscopy and laparotomy using various surgical In the past two decades, ultrasound has become the method
procedures (excision, suturing, etc.). Lately, transvaginal of choice for diagnosis of early pregnancy disorders and
sonographic puncture and local injection of methotrexate certainly contributed to the recent increase in number of
have been used to treat both viable and nonviable interstitial reported cervical pregnancies.
pregnancies.64,65 There have been very few reported side The diagnosis of cervical pregnancy can be made on the
effects after treatment with low-dose local injection of following criteria:
methotrexate.69 Data reported in the literature suggest the ÀÀ No evidence on intrauterine pregnancy
superiority of local therapy, with regard to both safety ÀÀ An hour glass uterine shape with ballooned cervical
aspect and the success rate. In general, a likely explanation canal
necessary to stress out the potential of 3D sonography in
diagnosis of cervical gestation and include better anatomic
orientation and multiplanar sections of the investigated area.
Local injection of methotrexate or potassium chloride
appears to be most effective way of treating an early
viable cervical pregnancy regardless of the gestational age.
There are no data on the use of local injection in nonviable
pregnancies, and it is uncertain whether the treatment
would be as effective as in viable pregnancies. Systemic
treatment in these cases is simple and highly effective and
local injection would offer a very little advantage.
The regimens and dosages of methotrexate used for
systemic therapy have varied considerably. There is no clear
correlation between the dose and the therapeutic success,
Figure 26.8 Transvaginal color Doppler scan of a cervical pregnancy. and it is, therefore, logical to use as little methotrexate as
Blood flow signals are derived from the fetal heart and demonstrate possible to minimize the side effects. The usual regimen
regular heart action
should be two intramuscular injections of 1 mg/kg
methotrexate followed by folic acid. For local injection, 25
ÀÀ Presence of a gestational sac or placental tissue within mg methotrexate into gestation sac appears to be sufficient.
the cervical canal Potassium chloride 3–5 mEq is equally successful and less
ÀÀ Closed internal os. likely to cause side effects.4
Early diagnosis may also explain the milder clinical The place of surgery should be limited to those cases
symptoms and better prognosis of cervical pregnancy today where medical treatment has failed. Dilatation and curettage
as compared to pre-ultrasound era. in combination with cervical cerclage or the insertion of a
Transvaginal ultrasound approach has become the Foley’s catheter is probably the best choice for a general
accepted standard for the examination of patients with gynecologist and is as effective as more complicated and
suspected early pregnancy abnormalities. Apart from expensive methods for the prevention of uncontrollable
providing superior images of pelvic anatomy, addition of hemorrhage.71
color Doppler enables simultaneous visualization of the
pelvic blood vessels (Fig. 26.8). The level of insertion of Ovarian Pregnancy
the uterine arteries should be used to identify the internal
The sonographic diagnosis of ovarian pregnancy is
os and thus facilitate the diagnosis of cervical pregnancy.71
extremely difficult to establish. It has been calculated that
The extensive vascular blood supply to the trophoblastic
ovarian pregnancy accounts for less than 3% of ectopic
tissue originating from the adjacent maternal arteries at the
pregnancies.1,2 The sonographic diagnosis is made upon
implantation site (within the cervix) is easily visualized by
the finding of a hyperechoic trophoblastic ring detected
transvaginal color Doppler. The products of conception in
within ovarian tissue, and the fact that it is impossible
transit through the cervix after the failure of a normally
to separate the ectopic gestational sac from the ovary by
implanted pregnancy are detached from their implantation
transabdominal pressure from either examiner’s hand or
site and maternal vascular supply. It is, therefore, impossible
transvaginal ultrasound probe.2 Color Doppler facilitates
to detect any peritrophoblastic blood flow in these cases.72
detection of the peritrophoblastic flow, which can speed
Conversely, even a small amount of placental tissue in a
up the entire diagnostic procedure.
true cervical pregnancy remains highly vascularized on
color Doppler examination.73 This facilitates the differential
diagnosis between the cervical pregnancy and incomplete Intra-abdominal Pregnancy
miscarriage. Color Doppler analysis may also improve Intra-abdominal pregnancy is a rare condition, constituting
selection of the patients for primary surgical removal of only 1% of all ectopic gestations. 74 Its complications,
cervical pregnancy and assist in planning dilatation and however, can be devastating. These include massive
curettage (D and C) following medical treatment. It is hemorrhage due to disseminated intravascular coagulation
and placental separation complicating fetal demise or Although there are no available data on the use of
infection with abscess formation. The outlook for the fetus color Doppler and 3D ultrasound in this field, we believe
is even worse, and perinatal mortality may reach 75% that these modalities may add additional information on
with up to 90% of the surviving infants having serious the implantation site and attachment of the placenta to
malformations.75 The diagnosis of the abdominal pregnancy surrounding structures.
is not easy, especially in the early stages. Characteristically,
patients present with abdominal pain, vaginal bleeding and Therapy
gastrointestinal complaints. Ultrasonography together with
beta hCG estimations have made early diagnosis easier. The Throughout the years, the treatment of ectopic pregnancy
problem still exists, however, as a patient subgroup with an has been emergency laparotomy, including salpingectomy.
ambiguous presentation remains.76 In order to preserve fertility, alternatives to laparotomy and
Ultrasound seems to be the most valuable diagnostic salpingectomy include observation, laparoscopic removal of
tool to localize this rare type of ectopic pregnancy. 2 ectopic pregnancy and systemic or local use of methotrexate
Primary abdominal pregnancy is a condition where or other feticidal agents. As medical therapy for ectopic
fertilized egg implants itself directly into the peritoneal pregnancy becomes a common practice, familiarity with
surface of abdominal cavity. If, however, an early tubal its side effects may lead to greater success rates. The
pregnancy dislodges and aborts into the pelvis, adhering to decision to abandon medical treatment and proceed with
peritoneal surface, it is termed as a secondary abdominal surgery should be based on defined guidelines, such as
pregnancy through the secondary nidation. The sonographic development of peritoneal signs, decreasing hemoglobin
presentation of abdominal pregnancy is no different from levels or hemodynamic instability.79
any other ectopic pregnancy, i.e. showing a hyperechoic Methotrexate may be administered systemically, 80
ectopic gestational sac containing embryonic/fetal locally81,82 or in combination. Local application is performed
structures and extraembryonic structures with or without either laparoscopically or transvaginally under ultrasound
active heart beats. Oligohydramnios is the rule, and there needle puncture.40 In the latter approach, methotrexate is
is no uterine mantle around the fetus. injected directly into the gestational sac. The success rate of
Surgery is a time-honored treatment for abdominal systemic, single-dose methotrexate (83–96%) is similar to
pregnancy following its diagnosis, with placenta left in that of local administration under laparoscopic guidance (89–
situ. This is mainly because, in many instances, the placenta 100%), but the success rate of methotrexate under ultrasound
is attached to the vital organs or vascular sites, which guidance seems to be lower (70–83%).83 Local injection of
could be seriously damaged during placental separation. methotrexate under control of color Doppler imaging may
No serious complications occur when it is left in situ.77 increase the success rate.4 The use of color and pulsed Doppler
An additional important factor is that most abdominal enables visualization of the trophoblastic adnexal flow with
pregnancies are diagnosed relatively late in pregnancy high-velocity and low impedance pulsed Doppler (RI < 0.40).
when the placenta and its area of attachment are larger. The needle can be inserted into the area of maximum color
Recently, abdominal pregnancies have been diagnosed signal, which marks trophoblastic invasiveness and vitality.
earlier and in one case the diagnosis was made at 6 weeks Pharmacological management of an unruptured, size-
of amenorrhea.74 This made it possible for these pregnancies appropriate ectopic pregnancy is now an established
to be removed laparoscopically. The possible advantages standard of care. The present protocol recommends
of such therapeutic approach include lower morbidity and systemic use of methotrexate in a single-dose.84 This form of
mortality, as well as better fertility outcome. However, only methotrexate has proven to be successful and cost-effective
a limited number of cases of abdominal pregnancy have alternative to traditional surgical management of ectopic
been reported early in pregnancy and the safety of operative pregnancy.85 In view of the risk of standard therapy and
laparoscopy can be guaranteed only in appropriately patients desire for fertility, methotrexate treatment may be a
selected cases.74 Similar cases demonstrate further the therapeutic alternative in cervical pregnancy as well. Recent
importance of first-trimester ultrasound examination in reports have affirmed that ectopic pregnancy has become a
diagnosing early pregnancy complications. The importance medical rather than a surgical disease.2,4,69,72,79,83,84,86
of sonographic imaging in cases of acute abdomen in Puncture injections are valid and reasonable alternative
pregnancy cannot be overstressed.78 to a traditional surgical approach, especially in patients with
an interstitial, cervical or heterotopic pregnancy. In these Contd...
particular cases, puncture procedures guided by transvaginal pregnancy. It is expected that increased sensitivity of the serum
ultrasound can efficiently replace surgical treatment and beta hCG immunoassay and the quality of transvaginal B-mode,
color Doppler ultrasound and more recently 3D with color and power
save the patient from unnecessary hysterectomy. Doppler facilities will allow even earlier detection and conservative
Early diagnosis is the key to effective nonsurgical management of ectopic pregnancies. Furthermore, it seems that
fertility outcomes and number of women attempting to conceive
treatment. Diagnostic algorithms using serial beta hCG after ectopic pregnancy will further increase.
measurements and transvaginal ultrasound examinations
make definitive diagnosis possible without laparoscopy. As References
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CHAPTER
27 Female Pelvic Floor: Descriptive

Anatomy and Clinical Exploration by
Transvaginal Ultrasound Echography
Juan M Troyano Luque, MT Clavijo, P Hernández-Ponz, I Martinez-Wallin, OY Marco, PS Casas,
L Martinez-Cortés, Luis T Mercé, Jose Bajo Arenas, Biserka Funduk Kurjak
Introduction transperineal or transrectal,2-4 but they pose a number of

drawbacks contrasted below with those of TVU.
In order to assess the state and pathology of the woman’s
pelvis minor, a number of methods are commonly used Transabdominal Echography
among practitioners, encompassing clinical exploration,
Transabdominal ultrasound echography (TAU) supplies the
radiology, magnetic resonance neurography (MRN),
practitioner with valuable records of the vesical base (when
urodynamics, endoscopy and echography.
full) but is rather opaque to the Retzius’ space and to all the
Echography has been poorly used in clinical pelvic
organs supporting the pelvic floor, particularly in obese women.
exploration and its reliability is actually a matter of
Furthermore, the manipulation of the woman’s abdomen by
controversy.1 However, echographic surveys can provide
means of the TAU transducer may induce unnoticed anatomic
with valuable gynecological data on the state and pathologies
changes and thus distort images which may be inaccurate for
of the soft pelvis, within the genital regions or even going
comparison among different explorations.5
beyond them, i.e. the rectal channel, bladder, urethra, anus,
In a gynecological context, TAU is fairly accurate to
vascular plexuses and all of their supporting tissues.
estimate the degree of descensus of the bladder neck in
At authors’ research unit, they have been long employing
response to the Valsalva’s maneuver, and so it is a valid
transvaginal ultrasound echography (TVU) in conjunction
method to diagnose urinary stress incontinences (Fig. 27.1).
with other pelvis-focused methods in order to study
different kinds of pelvic alterations. The TVU has proven
to be user-friendly, fast, harmless and inexpensive, allowing
serial explorations and producing high-quality dynamic
images (loop-cinema, video-tape). Furthermore, this
method is fairly aseptic in that the occurrence of feces in
the rectal ampulla is not a nuisance but a bonus in tracking
the contours of the rectum walls and other topographical
features which would be otherwise difficult to survey.
A complete pelvic floor TVU may add no longer than
5−8 minutes to a routine gynecological examination, can
be implemented by the general gynecologist and generates
data than can be further studied by the appropriate specialist
for a more insightful evaluation.2
Echography Use in Pelvic Diagnosis

Figure 27.1 Transabdominal echography. Measurement of
The TVU is mostly inadequate for patients with a complete anteroposterior bladder neck displacement following the Valsalva’s
1
hymen, although this event occurs in only 2% of the cases maneuver (a) Calibrator pointing to the bladder neck in resting position
(b) Second row of arrows traces the total displacement of the bladder
presenting pelvic floor pathologies. Alternatively, other 2
neck after the Valsalva’s maneuver. The difference between distance
echographic tracks are possible, namely transabdominal, (1) and distance (2) amounts to the bladder neck displacement
Transperineal Echography in some patients. The method provides the practitioner with
Transperineal echography was first described by Lewin good records of the vesicourethral anatomy and internal
et al.2 in patients presenting cervical pathologies or placenta genitals, notwithstanding of that the rectum walls may
previa, and was further implemented by Yeanty (1984)6 who go distended at the contact with some sort of probes (i.e.
used it to measure the posterior angle between the urethra standard, sectorial and multifrequency types), leading to
and the bladder following the Valsalva’s maneuver. In the inaccurate estimates for wall thickness and for the degree of
latter situation, a convex or linear probe is required and plexus vascularization; moreover, the rectal ampulla must be
operated effectively, however, full the bladder is.7 emptied prior to exploration. Furthermore, the exploration
The probe must be inserted in the intervulvar sulcus from via transrectal echography may be delayed to a greater or
which only sagittal planes can be recorded. The method is lesser extent by a number of factors, like using narrowly
inappropriate for transversal scanning, while the presence focused probes or endocavitary probes with a 360º rotation
of air in the vagina and/or the rectum may blur the position range, or the unavoidable distention of the anal channel
of the posterior pelvis and so the location and structure of occurring while the exploration takes place. On the other
the pelvic floor. Unreliable records may also occur during hand, the internal genitals, bladder and pelvic floor muscles
the cutaneous vulvoperineal period and in situations of high are outside the scope of this method9 (Fig. 27.3).
muscular sound resistance (Fig. 27.2).
Transvaginal Echography
Transrectal Echography The TVU has been extensively used in the study of the
Nishikawa and Perkash pioneered the use of transrectal internal genitals.10-12 However, little has been done with it
echography in the study of pelvic floor and urinary to explore extragenital areas which may complement the
pathologies.8 Their approach was useful to monitor the data withdrawn from genital surveys. Such double-fold
dynamics of the urethrovesical joint and the state of the target expands the potential applications of TVU and, as
vesical base proper, both in resting and in stress conditions, discussed above, adds no longer than 5−8 minutes to a
and featured high sensitivity to diagnose urethrovesical routine gynecological exploration.2
dyssynergia. Basically, TVU contributes with thorough insights into
A common drawback of this method is that, albeit the anatomy and functionality of the pelvic floor, the anal
bearable, the introduction of the probe may cause malaise sphincter and the rectal channel. This information is of
Figure 27.2 Transperineal echography. Only sagittal sections are possible to scan. Exploration can be impaired by the presence of air in the
rectum or the vagina
Chapter 27  Female Pelvic Floor: Descriptive Anatomy and Clinical Exploration by Transvaginal Ultrasound Echography 271
Figure 27.3 Transvaginal ultrasound echography. Images correspond to the anal sphincter and rectal channel and contrast transvaginal ultrasound
echography (rotational, 360°) with transrectal echography records. The narrow focus of the latter provides views only of the region neighboring
the echographic probe. 1. External sphincter, 2. Internal sphincter, 3. Mucosa
great potential in diagnosing heavy pathologies such as true À The TVU probe approach must be perpendicular to the
urinary stress/fecal incontinence and miction impresiona, vaginal axis and transverse along the perineal apex. To
or cystocele, archocele, anal sphincter tearing or the kind start with, this will ensure close-up records of the vaginal
of further dysfunctions resulting in vaginal wall descensus. mucosa, anal sphincter and pelvic floor musculature, as
In particular, rectography can be straightforwardly well as scan the former region for the location and size
assessed by means of TVU focusing on the vascular flow of the hemorrhoid plexuses (Figs 27.6A and B).
of the anal sphincter and channel, and on the anatomy and À Once the study area is located, the probe must be rotated
location of the hemorrhoid plexus. Thus, the extent of rectal 90º and slided from the introitus toward the bottom of the
failures, and associated pathologies entailing neoplasia or Douglas’ bag so as to get a sagittal view of the rectum
local chronic inflammation, can be detected and evaluated through the straight vaginal wall. This maneuver should
(Fig. 27.4). warrant access to the rectal mucosa and muscularis,
Among the advantages of the TVU echography identification of the two largest local vascular plexuses
against the other kind of echographic methods, it should and evaluation of a possible descensus of the Park’s
be underlined that TVU is innocuous, versatile in its ligament (Figs 27.7A and B).
ÀÀ From the latter position, the probe must be further rotated
explorative scope (encompassing the survey of the pelvic
muscular floor, Fig. 27.5), benefits from the presence of 180º as to be perpendicular to the longitudinal axis of the
rectal feces in delimiting the contours of the rectal ampulla, urethra, and then moved on from the urethra neck to its
and guides manual explorations to locate anorectal regions meatus. This move would be favored if the urethra contains
of interest. a good deal of material, which in turn would accentuate the
detrusor echographic records (Figs 27.8A and B).
The diversity of TVU applications in the exploration of
À Finally, a transverse view of the urethral diameter and
the pelvic floor can be seen in Table 27.1.
walls can be now gained, along with images of the pubic
The manipulation of TVU probes in pelvic floor surveying symphysis, pubourethral ligament, Retzius’ space, and
differs from that in routine gynecological exploration in the paraurethral and Santorini vascularization networks
following aspects: (Figs 27.9A and B).
Figure 27.4 Transvaginal echography. Scanned images of the Figure 27.5 Transvaginal echography. Scanned images of the rectal
anus showing disperse vascularization regions embodied in anal channel (sagittal view), where the presence of feces gives an echogenic
mucosa signal delimiting the intestinal space
Table 27.1 Transvaginal echography: applications in pelvic floor exploration

Posterior pelvic area
• Characterization and evaluation of normal/pathological anatomy in the levator muscle
• Survey of sphincteral area in anus and post-parturition monitoring
• Survey of anal mucosa
• Survey of rectal channel and characterization of rectal wall, mucosa and muscles
• Survey of topography and blood flow in hemorrhoid plexus
• Detection of areas suffering from abnormal hemodynamic activity
• General anorectal pathology
Anterior pelvic area
• Measurement and evaluation of posterior vesicourethral angles
• Survey of bladder neck
• Survey of pubourethral ligament and pubic symphysis
• Measurement of bladder neck descensus in prolapse simultaneous with urinary incontinence
• Urethral dyssynergia (neck opening and mictional delay by color Doppler)
• Measurement of bladder content and residual urine volumes
• Dynamic tests by color Doppler on:
– Unstable bladder
– Urethral mictional flow
– Ureteral mictional flow
– Bonney´s test
Echography and Anatomy of the Pelvis the weight of and pressure from the set of endopelvic visca,
Minor and the Pelvic Floor (Correlation) and regulates the activity of the urethral, vaginal and anal
In gynecological surveys, a correct correspondence between sphincters and the circulation of materials through the latter
TVU echographic records and the location of particular even against gravity forces.
structures can only be achieved by a detailed knowledge of The interplay between the endopelvic fascia and the anal
the anatomy of two target areas, i.e. the pelvic region and levator muscle is one of the most important events taking
its neighboring extragenital area. place in the pelvic floor. The endopelvic fascia comprises a
The pelvic floor represents a supporting structure structural complex including the parametrium, paracolpium,
attached to the internal face of the pelvis ossea and is made and uterosacral and round ligaments, and protects the
up with muscles and fascia. As such, the pelvic floor bears morphology of urethrovaginal structures and their position
A B
Figures 27.6A and B Transvaginal ultrasound echography exploration 1st stage: record of the anal sphincter. The probe is placed perpendicular
to the vaginal axis and transverse along the perineal furcula
A B
Figures 27.7A and B Transvaginal ultrasound echography exploration 2nd stage: record of the rectal channel. Sagittal views are obtained by
rotating the probe a further 90° (see Figure 27.6) in relation to the horizontal axis. (A) Rectovaginal wall; (B) Rectosigma border
relative to the pelvis ossea. In turn, the anal levator muscle narrows to merge in one central muscular band which runs
modulates the movements of the endopelvic fascia. backward to join the coax (Fig. 27.11).
The anal levator muscle is an elastic double muscular bed The anterior central portion of the pubococcygeal muscle
and looks like an inverted vault in a caudal direction. On one comprises the puborectal and pubococcygeal retinacula, that
hand, the pubococcygeal muscle connects each of the two pubic surround the rectum, and acts as a supporting hiatus.13,14
branches with each of the two anterior sacrococcygeal ligaments A full gynecological exploration of the anterior
and so forms a symmetric X-shaped set (Figs 27.10A and B). pelvic region should mainly monitor and categorize any
From an anterior and cranial view, the action of this muscle pathological sign in the bladder, urethra, pubourethral
creates a central space, the so-called arcade of the levator ligament, paraurethral vascularization and the Retzius’
muscle, which constitutes the urethrogenital and anal hiatuses. space as observed through the Santorini plexus. Likewise,
On the other hand, the iliococcygeal muscle resembles a pair of post-surgery recovery from urinary incontinence
butterfly wings; this muscle attaches to both tendinous arches pathologies should also be assessed in the exploration
emerging from each of the two pubic branches and gradually (Fig. 27.12).
A B
Figures 27.8A and B Transvaginal ultrasound echography exploration 3rd stage: record of the bladder. The probe is directed toward the abdominal
wall so scanning the bladder across, as well as including its neck (inverted view) (Abbreviations: U, urethra; N, bladder neck; B, bladder proper;
S, symphysis; R, retzius’ space)
1
2
3 4
A B
Figures 27.9A and B Transvaginal ultrasound echography exploration 4th stage: record of the anal sphincter. Transversal views of the urethra
and the bladder are gained. 1. Pubic branches and pubourethral ligament, 2. Inferior border of the pubic symphysis, 3. Santorini plexus (Retzius’
space), 4. Paraurethral vascularization and urethra
A B
Figures 27.10A and B (A) Echographic records of the pubococcygeal muscle and the anal levator muscle. The most obvious area corresponds
to the urogenital and anal hiatuses. (Abbreviations: IS, Internal sphincter; ES, external sphincter; M, mucosa; EA, anal levator muscle). (B) Anal
sphincter disruption and funneling of the urogenital hiatus is associated with the weak state of the pubococcygeal muscle
Figure 27.11 Echographic record of the anal levator muscle (iliococcygeal region), with contours slightly blurred but overall structure well defined
Ecoanatomy of the Rectal Channel – The artery pudendum, which attaches to the whole
external face of the iliac bone and forms a distal
Sagittal views of the rectal channel gained by a TVU survey
anastomosis with the inferior rectal artery
displays from a top to a bottom are position, the following
●À Inferior rectal artery (Fig. 27.14)
are anatomic and vascular structures.
ÀÀ Venous structures (hemorrhoid plexuses):
À Anatomic structures: ●À External hemorrhoid plexus, consisting of three
●À Rectal longitudinal muscle branches irrigating the inferior rectal vein which in
●À Rectal circular muscle turn derives from the inferior cava vein
●À Intersphincteric regions ●À Internal hemorrhoid plexus, directly irrigating the
●À Muscular layer underneath the anal submucosa

inferior mesenteric vein which branches off from the
portal area
●À Internal hemorrhoid plexus
A further two venous structures comprise of the following:
●À Longitudinal muscular complex ÀÀ An anastomosis connecting the external and internal
●À Morgagni columns hemorrhoid plexuses
●À Submucosa space ÀÀ An anastomosis connecting the inferior and median
●À Anal sinus rectal veins.
●À Dentate line
The former venous complex constitutes a fairly
hydrodynamic network feeding with blood the portal vein
●À External sphincter (deepest region)
and the inferior cava (Fig. 27.15).
●À Internal sphincter
Most commonly, a total of three external hemorrhoids
●À Park ligament can be found, forming two anterior plexuses symmetrically
●À External sphincter (subcutaneous region) located on both sides of the raphe of perineum, and one
●À External hemorrhoid plexus single posterior plexus located to the left side of this rectal
●À Skin and anal borders (Fig. 27.13)
region (Fig. 27.16A). A further fourth plexus may occur
although rarely (Fig. 27.16B).
À Arterial structures:
●À Superior rectal artery (double artery system), i.e. a
branch from the mesenteric inferior artery
Pathologies of the Posterior
●À Internal iliac artery bifurcating into two branches: Pelvic Region
– The median rectal artery, which irrigates the It has been shown so far that TVU echography is a
median portion of the rectal channel useful tool for the study of the morphology and, to some
1 2
3 4
Figure 27.12 Echographic record of a number of areas in the anterior pelvis, namely: 1. Paraurethral vascularization
and Retzius’ space, 2. Urethral channel and paraurethral vessels, 3. Pubic symphysis (transversal and sagittal views)
and pubourethral ligament, 4. Rich vascularization in the Retzius’ space, which is characteristic of healthy endopelvic
fascia and further supporting tissues. 5. Typical vascularization in Santorini vascular plexus, physiological flow profile and
transverse ligament (green arrows)
Figure 27.13 Transvaginal ultrasound echography record (sagittal view) showing the following structures: 1. Feces and recto-sigma boundary,

2. Rectal longitudinal muscle, 3. Anal levator muscle, 4. Park’s ligament, 5. Internal sphincter, 6. External sphincter, 7. Anal papillae
extent, functionality of both the pelvic floor and the final ÀÀ Serose: Most common in hemorrhoid processes and
third portion of the rectal channel and anal sphincter, in prolapses, although neoplasia should not be ruled out
pathological states detected (e.g. cystorectocele and feces ÀÀ Purulent: Often originated from fistula, abscesses and
incontinence) or unnoticed (e.g. rectorrhaphy and anal sexually transmitted diseases
secretion) during gynecological exploration. ÀÀ Fecal-like: Mostly combined with sphincter incontinence.
Pain-triggering pathologies in the posterior pelvic region
can also be subjected to diagnosis by TVU, mainly in the Severe Hemorrhoid Syndrome
following cases. Hemorrhoid processes can manifest themselves in the anal
À Severe hemorrhoid syndrome mucosa or be hidden for long periods of time in the form
À Loss of hemorrhoid structure and depression of vascular of varicose structures growing in the internal plexuses.
flow (thrombosis) Nevertheless, both recurrent pain and rectorrhaphy
À Hemorrhoid prolapse problems help the practitioner to detect this pathology. A
À Anal fistula
direct exploration suffices to detect hemorrhoid outbreaks,
but the extent of anal mucosa affected and the occurrence of
À Abscess
related internal syndromes can be best assessed by means
À Chronic inflammation (i.e. Crohn’s disease) of color Doppler surveys (Fig. 27.17).
À Carcinoma Internal hemorrhoid hemodynamics are caused by an
À Endometriosis. overdistention of the arteriovenous network, as a result of
The practitioner may be guided to trace the latter which drainage venous systems may overflow and precapilar
pathologies by the fact that they often display various sphincters may experience anomalous contractions, all
associated signs like rectorrhaphy and/or anal secretion. together triggering local venous hyperpressure.
Such anal secretion may show up in different states Transvaginal ultrasound echography exploration is very
including: successful in recording hemodynamic profiles, both arterial
Figure 27.14 Arterial organization in the anal and rectal channels
and venous, that enable the practitioner to detect internal infection, which originate from hemorrhoid processes or from
hemorrhoid processes, which may otherwise go unnoticed pathologies much more severe than the latter. Such anoperineal
(Fig. 27.18). fistula usually develop purulent or fecaloid secretions.
Likewise, when external hemorrhoids display no signs of By swinging the TVU probe on the perineal furcula, the
venous overflow, with or without arterial hypercirculation, observer can gain visual access to the mucosa morphology, so
it must be ascertained whether thrombotic syndromes have detecting possible malformations and their continuity along
taken place, particularly if local pain is intense (Fig. 27.19). the external and the internal sphincter regions (Fig. 27.21).
The diagnosis of hemorrhoid prolapse is fairly
straightforward in routine gynecological exploration, Perineal Abscess
but again TVU profiles can give an insight into possible Albeit this phenomenon has an easy diagnosis in routine
drainage failures deriving from upper rectum thrombosis or explorations, TVU surveying gives estimates for the area
anal sphincter stenosis, which are associated with increased affected and, in heavy abscesses, for possible effects on
vascular circulation in the rectal mucosa (Fig. 27.20). other anal structures and the pelvic floor (Fig. 27.22).
Anal Fistula Chronic Inflammatory Disease

The joint occurrence of episodic rectorrhaphy and painful Any inflammatory process involves increased
defecation may be indicative of mucosa outbreaks and local vascularization around some kind of local damage, e.g.
Figure 27.15 Venous organization in the hemorrhoid plexuses
A B
Figures 27.16A and B Physiological appearance of the hemorrhoid plexuses: they are usually three and rarely four
Figures 27.17 Severe hemorrhoid syndrome. Echographic records found mucosa vascularization related with damage in the internal sphincter
Figure 27.18 Color Doppler mapping showing a notably increased blood flow in both the median rectal and superior arteries, in combination with

telediastolic restriction as a result of vascular hyperpressure
rectitis. However, severe rectal inflammation featuring of materials, are confined to the area under stress as shown
episodic outbreaks may magnify the size and shape of a by TVU. This pattern often suggests the occurrence of a
typical inflammation-triggered vascularization pattern. In neoplasia or a chronic inflammation of major importance.
these chronic cases, large dark patches around apparently Notwithstanding any hemodynamic source beyond a normal
normal rectal structures can be found in color Doppler profile should be investigated by the proctologist (Figs
records (Fig. 27.23). 27.25A and B).
Along with the latter pattern, endometriosis can also Traumatic pathologies in the pelvic floor are one of the
result in Doppler records showing blurred anatomic main diagnosis areas benefited from TVU exploration.
contours, low echo feedback and low vascularization, This field encompasses pathologies, like tocurgia,
particularly from the local mucosa which usually displays difficult parturition, fetal macrostomy and iatrogenic
increased peripheral vascularization (Fig. 27.24). traumatisms occasioned by perineal surgery and extensive
Vascularization patterns in carcinoma, and further episiotomies having damaged anus levator muscles and
pathologies stuffing the rectal channel with different kinds even impaired motor nerves. It is striking that these
associated with descensus of the vaginal walls or tearing
of the anal sphincter. Urinary and gas incontinence occurs
in 25% of the cases during the first month after parturition,
while urinary incontinence and urgent miction occurs in
over 30% of the cases within the first 3−4 post-parturition
months.15-17 However, perineal tone and sphincter control
are recovered by 75% of the women in the first puerperium
month (Table 27.2).
Patients who have experienced difficult and traumatic
parturition (e.g. forceps-aided, perineal tearing, etc.) should
be subjected to TVU exploration, preferably in two rounds
48 hours and 2−3 months after childbirth in order to estimate
the recovery of the anatomical structure and functionality
of the pelvic floor.18 Wherever structural and, especially,
Figure 27.19 Reconstructive neovascularization following perineal functional alterations have been detected and studied by
damage (e.g. episiotomy) or heavy thrombosis, whereby the vascular the general gynecologist, thorough explorations should be
plexuses grow in size to reach the perineal region
followed on by the relevant specialist (Fig. 27.26).
problems have maintained the same rate of occurrence for
over a century. They were first experienced by our mothers Pathologies of
due to inadequate home medical care, but they are still a
the Anterior Pelvic Region
modern problem for the XX and XXI women facing faulty
iatrogenic tocurgia. Echographic exploration is one of the most promising
Pelvic floor pathologies can be identified by a number methods in urogynecology, offering many advantages
of combined pathognomic symptoms, mainly urinary, against very few drawbacks as commented so far in
gas and fecal incontinences, which may be or may not be this paper. In the study of urinary stress incontinence
Figure 27.20 Disrupted anal sphincter showing increased, disperse vascularization, commonly resulting from obstruction or thrombosis problems

taking place in the upper parts of the study area
Figure 27.21 Distribution of rectoperineal fistula
In abdominal hyperpressure conditions, Angio-Doppler

records from the transurethral flow provide with data on the
volume, sequence and rate of urinary incontinence release.
This enables the practitioner to differentiate urine release
modes caused by detrusor instability (delay >15 seconds after
Valsalva’s maneuver, with relatively fast but small volume
release) from those caused by proper/urgent incontinence
(synchronized with abdominal pressure applications, with
relatively slow but large volume release) (Figs 27.27A and B).
Inadequate manipulation of the TVU probe, i.e.
overpressing the womb or the bladder, may produce faulty
records of both functional and morphological states.
However, it must be noted that if the bladder and its neck
need to be lifted and so their length increased, overpressure
Figure 27.22 Perineal abscess co-occurring with the fistula of Figure may be unavoidable and cause urine release by altering the
27.21 posterior vesicourethral angle in cystocele, which then turns
out to be a Bonney’s test modified by the TVU probe.
problems, TVU echography achieves a complete view
Despite that computer-based methods such as
of any urogynecological structure, allows to monitor
urethrocystography have improved our knowledge on
normal-against-pathological morphologies on the basis of
incontinence physiopathologies, they are not yet definitive
intended abdominal pressure movements, and complements
to diagnose urinary stress incontinences.
data from other urodynamic methods. However, the TVU
approach is not yet widely spread among practitioners in Cystourethrocele associated with urinary incontinences
the field, so that future research, sound methodological that have been triggered by abdominal overpressure may
systematization and biometric validation are needed. experience three main anatomic changes over time, namely
In any echography-based urogynecological survey, the an increase in the urethrovesical angle by 40%, while the
bladder must be full prior to exploration so as to get an bladder neck may on one hand slide and rotate along the
overall perspective not only of urogynecological structures edge of the pubic symphysis; and on the other hand; move
but also of their functional behavior and changes as caused from resting position to an anterioposterior position (Figs
by the Valsalva’s maneuver, cough and intended abdominal 27.28A and B, Table 27.3).
pressure which may be either triggered by the very patient The former bladder neck changes may occur in cases of
or aided with the TVU probe as in the Bonney’s test. urinary incontinence involving no obvious anatomic shifts,
Figure 27.23 Crohn’s disease. Increased vascularization in the Figure 27.24 Endometriosis. Increased peripheral vascularization
superior rectal artery can be noted along with anomalous vascular can be seen around the local mucosa under stress. Sometimes
distribution in the mucosa pseudodiverticular structures can be observed penetrating the
muscularis. This pathology is often painful and develops recurrent
rectorrhaphy
A B
Figures 27.25A and B Intestine adenocarcinoma showing loss of vascular morphology and anomalous, massive distribution of rectal vessels
Table 27.2 Types and degree of pelvic floor dysfunctions caused

by tocurgic-related damage. Dysfunctions remain symptomatic in
25% of the cases following reconstructive surgery, particularly after
perineal tearing
Post-parturition clinico-functional state of the pelvic floor
Parturition Dysfunction Post- Percentage

mode parturition
(tocurgia) period
Normal + 1 month 75
Forceps-aided +++ 1 year 25
Perineal +++ Persistent 85

tearing
Nerve +++ Persistent 15

pudendum
damaged Figure 27.26 Pattern of reconstructive neovascularization, one month
after parturition, following tearing of the external and internal anal
sphincters due to central episiotomy
1 2
A B
Figures 27.27A and B (A) Angio-Doppler survey of the mictional flow transurethral in a patient with urinary stress incontinence. The flow is
relatively voluminous, slow and synchronous with abdominal pressure application. (B) Different mictional flow through ureter: 1 and 2 in Detrusor
slack, 3 jet in ureter stenosis
A B
Figures 27.28A and B Transvaginal ultrasound echography survey of urethrovesical changes following the Valsalva’s maneuver in a patient
with urinary stress incontinence, namely 1. Increase in the posterior urethrovescial angle by over 40%, 2. Anteroposterior displacement of the
bladder neck by over 3 cm, 3. Craniocaudal displacement of the bladder neck by over 1.5 cm
Table 27.3 Changes in three parameters indicator for urinary symphysis is one of those landmarks valid for exploring
stress incontinence pathologies displacements of the bladder neck. Alternatively, bladder
Posterior urethrovesical angle neck displacements before and after the Valsalva’s maneuver
Rest Valsalva’s Urodynamic can be marked on echographic records through the TVU
maneuver state calibrator, and represent the most sensitive and specific
Invariable Invariable Continent landmark such that a distance greater than or equal to 30
Invariable 40% increase Incontinent mm is the pathological threshold (Displacement threshold,
Anteroposterior bladder neck displacement Troyano and Clavijo) over which urinary stress incontinence
30 ± 5 mm Stress incontinence pathologies can be ascertained (100% sensitivity, 96%
110% 96% specificity), in combination with echography-detected
Craniocaudal bladder neck displacement changes in morphology. The assessment of these arrays of
15 ± 2 mm Stress incontinence factors may call for surgery by colposuspension or the like
< 10 mm Continent in pathological situations.
(multipara women) Urinary incontinence pathologies can also be detected
when the urethrovesical angle increases as a result of
and can be so used in designing adequate strategies for rotational displacements of the bladder proximal region and
surgery and ensuing therapy, specifically for those surgical neck. However, this feature shows high variability among
methods entailing the elevation of the bladder neck by patients hence little diagnostic specificity (Fig. 27.29).
means of urethral anchorage or suspension. From authors’ experience, the craniocaudal displacement
As a complementary method, TVU echography of the bladder neck is a better diagnostic feature for urinary
can have a major contribution to studying urinary incontinence problems.2
incontinence physiopathologies and their surgery, and Color Doppler surveys, as a complement to routine
especially to monitoring recovery following surgery. But gynecological explorations, guarantee the collection of
urethrovesicoechographies should be never combined morphological and quantitative data on transurethral urinary
with other complementary invasive methods (e.g. incontinence rates and on time lags between the occurrence
urethrocystography, urethrocystomanometry, cinema- of mictional flows and the application of abdominal
urethrocystography, etc.) which may cause morphological pressure. At the same time, the latter lags may help the
shifts and so bias echographic records. practitioner tell urinary stress incontinence from detrusor
Morphological landmarks are useful in the study of dyssynergia19 (Fig. 27.30). In urinary stress incontinence
anterior pelvic pathologies. The posterior edge of the pubic pathologies, bladder contractile waves and intended
abdominal pressure are simultaneous with urine release, but

the former precedes the latter by at least 15 seconds when
detrusor dyssynergia occurs (Table 27.4).
Asymptomatic, continent nullipara women experience
zero bladder neck displacement in response to the Valsalva’s
maneuver. This results from dilation in a double bracket
pattern of the bladder neck which remains closed or
invariable during exploration (Figs 27.31A to D).
In 85% of the continent multipara women bladder neck
displacements reach up to 10 mm.
To sum up, key features in TVU echography exploring
urinary incontinence problems are:
À Craniocaudal displacement of the bladder neck fitting
into an inverted-arch shape pattern
Figure 27.29 Craniocaudal displacement of the bladder neck in À Increase in the posterior urethrovesical angle by 40% in
response to the Valsalva’s maneuver as assessed by the echographic
calibrator. Distance greater than 15 mm between landmarks 1 and 2 response to the Valsalva’s maneuver
corresponds to an increase in the posterior urethrovesical angle by À Bladder neck opening in response to the Valsalva’s
over 40°
maneuver
Figure 27.30 Mictional flow caused by detrusor dyssynergia. Delays greater than or equal to 15 seconds after the Valsalva’s maneuver, with

urine flow being relatively small but fairly fast (mictional jet). The bladder is never filled up and the flow experiences unpredictable release
Table 27.4 Changes in detrusor dyssynergia as observed by ÀÀ More than 15 seconds delay from Valsalva’s maneuver
transvaginal ultrasound echography to urine release
Mictional jet delay following the Valsalva’s maneuver ÀÀ Bladder neck opening
Valsalva’s Mictional time Urodynamic ÀÀ Urine release faster but less voluminous than that of
maneuver delay state
urinary stress incontinence pathologies, as shown by
++++ 15 seconds Detrusor
dyssynergia color Doppler records (jet miction).19
++++ 15−20 seconds Further etiologies: Three-dimensional echography does not offer at present
• Neurogen bladder substantial merits over 2D echography. On the contrary, the
• Urethral polyps
• Other obstructive causes
so-called 3D dynamic application (wrongly called after 4D)
only supports edition rates of 80 images per second and is thus
unable to keep pace with temporal changes in morphology
À Transurethral urine release simultaneous with the of the study areas triggered by the Valsalva’s maneuver. Yet
Valsalva’s maneuver, slower but more voluminous than 3D echographies have been valid to assess the morphology
that deriving from detrusor dyssynergia. of the rectal and anal sphincters20 (Figs 27.32A and B).
Urinary incontinence observations caused by detrusor Further research is needed into 3D echography and
dyssynergia are characterized by: color Doppler methods in the study of mictional dynamics
A B
2
1
C D
Figures 27.31A to D (A) Opening of the vesical neck in a patient with urinary stress incontinence. (B) Morphological changes are negligible in
the bladder with no neck deformation (continent women). (C) Sagittal view of the bladder following abdominal pressure application (continent
women). (D) Cytoscopy: 1. Opening of the bladder neck in response to the Valsalva’s maneuver. 2. Shutting of the bladder neck (continent women)
A B
Figures 27.32A and B 3D volumetric echography. (A) Volumetric section of the anal channel showing the mucosa, longitudinal muscle and part
of the external sphincter. (B) Transversal volumetric section of the anal sphincter
and morphological changes caused by urinary and fecal 10. Goldstein SR. Incorporating endovaginal ultrasonography
incontinences, with a focus on achieving scanning speeds into the overall gynaecologic examination. Am J Obstet
simultaneous with anatomical moves. Gynecol. 1990;162:625-30.
11. Kurjak A, Zarker D, Kupesic S. Normal Pelvic Blood Flow:
Transvaginal Color Doppler. Parthenon Publishing Group;
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1. Kornhuber HH, Widder D, Christ K. The measurement of 12. Williams PM, Warwick R. Gray’s Anatomy. The Urinary
residual urine by means of ultrasound (sonocystography) Organs. Churchil Livingstone; 1980; pp. 1387-423.
in neurogenic bladder disturbances. Arch Psychiatr 13. Netter FH, Gaines JA, Hingson RA, et al. Anatomía normal
Nervenkrank. 1980;228:1-6. del tracto genital femenino y sus relaciones funcionales.
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del canal rectal y área esfintertiana mediante ecografía Ed. SA; 1977.pp.89-123.
tansvaginal. XXVI. Congreso Español de Ginecología y 14. Putz R, Pabst R. Vísceras abdominals y pelvianas. Atlas de
Obstetricia. Valencia Junio, 2001. Anatomía Humana. Sobotta, 20th edition. Editorial Médica
3. Schaer GN, Koechli OR, Schuessler B, et al. Perineal Panamericana; 1993.pp.226-7.
ultrasound for evaluating the bladder neck in urinary stress 15. Gainey HL. Post-partum observation of pelvis tissue
incontinence. Obstet Gynecol. 1995;85:220-4. damage. Am J Obstet Gynecol. 1943;45:457-66.
4. Sultan AH, Kamm MA, Hudson CN, et al. Effect of 16. Richardson AC, Edmonds PB, Williams NL. Treatment of
pregnancy on anal sphincter morphology and function. Int urinary stress incontinence due to paravaginal fascial defect.
J Colored Dis. 1993;8:206-9. Obstet Gynecol. 1981;57:357-62.
5. Rageth JC, Langer K. Ultrasound assessment of residual 17. De Lancey JOL. Structural support of the urethra as it relates
bladder volume. Urol Res. 1986;10:57-60. to urinary stress incontinence: the hammock hypothesis. Am
6. Grischke EM, Dietz HP, Jeanty P, et al. Eine neue J Obstet Gynecol. 1994;170:1713-23.
Untersuchungsmethode: perinael scan in der Geburtshilfe 18. Rockner G, Jonasson A, Olund A. The effect of mediolateral
und Gynäkologie. Ultraschall. 1986;7:154-61. episiotomy at delivery on pelvic floor muscle strench
7. K ohorn EI, Scioscia AL, Jeanty P. U ltras ound evaluated with vaginal cones. Acta Obstet Gynecol Scand.
cystourethrography by perineal scanning for the assessment 1991;70:51-4.
of female urinary stress incontinence. Obstet Gynecol. 19. Quinn MJ, Beynon J, Mortensen NM, et al. Transvaginal
1986;68:269-72. endosonography in the assessment of urinary stress
8. Nishizawa O, Harada T, Takada H, et al. A new synchronous incontinence. Br J Urol. 1988;62:414-8.
videourodynamics. Tohoku J Exp Med. 1982;136:349-50. 20. Dietz HP, Steensma AB, Hastings R. Three-dimensional
9. Sultan AH, Kamm MA, Hudson CN, et al. Anal-sphincter ultrasound imaging of the pelvic floor: the effect of
disruption during vaginal delivery. N Engl J Med. parturition on paravaginal support structures. Ultr in Obstet
1993;329:1905-11. and Gynecol. 2003;21:595-9.
CHAPTER
28 Sonography of
the Pelvic Infection
Introduction Table 28.2 Stages of PID
Stage I Acute salpingitis

It is well known how pelvic inflammatory disease (PID)
applied to every inflammation or infection inside the pelvis, Stage II Acute salpingitis with
pelviperitonitis
which, by general rule, affects the genital organs and is
Stage III Formation of abscesses: Tubal
hereditary. According to the Center for Disease Control (pyosalpinx), ovarian, tubo-
and Prevention (CDC) in the United States, one condition ovarian or pelvic abscess
concerning PID would be the absence of the relationship Stage IV Rupture of the abscess
with pregnancy or surgery.
Depending on the affected organs, the disease has Laparoscopy has been, until this moment, the most
received distinct names, which appear in Table 28.1; but precise diagnostic method to diagnose a case of salpingitis,
in this day and age, the most utilized term for the disease is classifying the findings according to Table 28.2. But, its
PID. With the exception of numerous occasions, it is very utilization is not always available or justified, especially
difficult to individualize these cases and when the disease in those cases with acute symptoms. In addition, the
is initiated, it will affect progressively some of the organs laparoscope does not detect cases of endometritis and
or others. The biggest protagonists are the fallopian tubes, cannot detect cases of acute salpingitis.
who always find themselves involved.
The disease begins with an acute case of salpingitis (often Stage I: Acute Phase (Salpingitis)
silent), although if treated well, results without relapses; but Normal uterian fallopian tubes are not visible in standard
in a case that it is not treated or is done so inadequately, the condition. It is assumed that the fallopian tubes are normal
disease could evolve into a more serious form, toward the in the absence of adnexal out-of-ovary images; but not being
absence of any localizations (tubal, pyosalpinx, ovarian, able to visualize, the fallopian tube does not mean that you
tubo-ovarian, pelvic). If the process is stopped and cured can assume its permeability.
in this stage, relapses are always discarded. A normal fallopian tube can be seen by means of a
From the first visit to the clinic, the most used transvaginal sonogram if free liquid exists in the bottom
classification is the Monif (Table 28.2), which is the one of the Douglas pouch (Fig. 28.1). And so, a portion of the
that we will refer to for the sonographic findings. ampulla can be seen, including the fimbrias (Figs 28.2 and
28.3). If the liquid surrounds the fimbria, more extension
Table 28.1 Terminology of the tube can be seen (Fig. 28.4), but it is difficult to see
Affected organs Names all of its length.
Uterus Endometritis, myometritis The diagnosis of initial acute PID (acute salpingitis) begins
Fallopian tube Salpingitis, tubal abscess with a challenge for the doctor, due to the little sensibility of
Ovary Oopheritis, ovarican abscess the clinic’s criteria. According to L Jacobson and L Westrom,
Parametritis Parametritis, pelvic cellulitis
the probability of fulfilling all of the major criteria is at 16.1%,
Peritoneum Pelviperitonitis
the probability of fulfilling all of the major criteria and one
minor is at 28.3% and the probability of fulfilling all of the
Vessel Thrombophlebitis, lymphadenitis
major criteria and two minor is at 38.7%.
Figure 28.1 The existence of interabdominal liquid permits a visual Figure 28.2 Fallopian tube with liquid in the abdominal cavity
of the fallopian tube
Figure 28.3 Tubal fimbrias: the surrounding liquid permits a visual of Figure 28.4 Tubal tract: this image alone shows the presence of free
the outline of the fallopian tube liquid
It is difficult to diagnose a disease that includes an acute the empirical treatment of those women who suspect PID
state and especially with these minimum findings that can and present the major diagnostic criteria, but this procedure
cause relapses like infertility and complications like an allows us to use treatment processes that do not correspond
ectopic pregnancy. with PID, with the morbidity that supposes an inadequate
For this reason, the necessity arises to identify those signs treatment.
in the ultrasonograms that create suspicion of salpingitis The sonographic diagnosis of salpingitis is a threat for a
and that could direct us toward a more precise diagnosis, sonographer. Acute salpingitis can begin with a diagnosis
mainly in those cases of atypical pain and in those cases the moment in which the liquid is accumulated in the
where the absence of treatment could provoke chronic pain interior of the fallopian tube (Fig. 28.5) and is dilated (Fig.
or cases of sterility that had been possible to avoid in the 28.6), signs that we can now detect with vaginal probe. In
diagnosis and treatment processes. The CDC recommends this moment, the restoration of suitable treatment can allow
Chapter 28  Sonography of the Pelvic Infection 291
Figure 28.5 Initial acute salpingitis: the fallopian tube can be seen Figure 28.6 Acute salpingitis: the fallopian tube with liquid in the
when, due to inflammation, liquid is accumulated in the interior interior and dilated
the case to be cured or to regress, with or without relapses, 2. Cogwheel: The fallopian tube appears dilated with
and already this inevitably is always unexpected. irregular excrescencies, and already disorganized, that
are projected toward the interior light. They are signs of
Stage II: Salpingitis with Pelviperitonitis important destruction inside the fallopian tube with large
Two events mark the passage into this stage: (i) the obvious contents of pus (Figs 28.11 to 28.13).
engrossment of the fallopian tube and (ii) the free liquid 3. Incomplete septa: It is an image of the pseudothin
inside the cavity. The fallopian tube is inflamed by the wall that does not arrive to occlude the complete tubal
accumulation of the liquid in the interior, transudate in the light. When the affected area reaches the ampule, the
tubal light (Fig. 28.7), or by the pronounced engrossment fimbrias can close the fallopian tubes. The exudate that
of all of the anatomy (Fig. 28.8). In both cases there is is accumulated in the light can reach dilation of the
liquid in the peritoneal cavity. It is the image observed by fallopian tube in such a method that this folds over the
the sonograph as sonolucence and the clinic translates it as same (Figs 28.14 to 28.16).
Blumberg positive. 4. Wall thickness: It is important to distinguish if the
thickness of the tubal wall is larger or smaller than 5 mm.
Stage III: Tubal, Ovarian, Tubo-ovarian or The result of the thick wall follows the acute process,
Pelvic Abscess in those processes that are frequently present in the
The accumulation of pus inside the fallopian tube gives tubular edema (Figs 28.17 and 28.18). On the contrary,
a location for the tubaric abscess or pyosalpinx, whose the finding of a thin wall can suggest tubal fibrosis.
characteristic signal is the presence of purulent material in 5. Tubal contents: In the pyosalpinx, there frequently is
considerable quantities and is obviously visible by means a mixed echogenicity or refringent due to the purulent
of a sonograph inside the tubal light. But, in addition, there material (Fig. 28.19).
exists a series of characteristic signs that advise us. 6. Tubo-ovarian complex: It is possible to recognize the
1. Beads-on-a-string: The fallopian tube appears to be fallopian tube and the ovary, but it is not possible to
dilated, with excretions that project toward the interior separate when we intend to differentiate the two with a
of the light, of the same size and distribution. They are vaginal probe. This could be due to the fibrous deposits
the expression of the destruction of the tubal mucus, that are formed during the inflammatory process, which
whose folds leave a mold and they are perfectly visible surrounds the fallopian tubes and attaches to the ovary
by means of the vaginal sonograph (Figs 28.9 and 28.10). (Figs 28.20 and 28.21).
Figure 28.7 Salpingitis with pelviperitonitis (Stage II): liquid in the Figure 28.8 Salpingitis with pelviperitonitis (Stage II): engrossed
interior and in the exterior of the fallopian tube fallopian tube with liquid in the exterior, inside the pelvis
Figure 28.9 Sonographic sign of “beads-on-a-string”, evidence of a Figure 28.10 Sonographic sign of “beads-on-a-string”. Two side views
thin wall with a few excretions of mucus in the interior of the fallopian tube where the mucal excretions appear
According to our experience, the sign of incomplete although it manifests pain in the adnexal exploration of the
septum and tubal contents of mixed echorefringence are the vaginal probe. If salpingitis is really acute, the fallopian
most characteristic findings of pyosalpinx and tubo-ovarian tube dilates, providing evidence of an edematized, a thin
abscess. In Table 28.3 authors have shown the frequency of wall is confirmed (a sign of “cogwheel”), and it fulfills
those signs in thier series, including the rare cases that they the generally mixed contents. If it evolves to tubo-ovarian
had on occasion to contrast the diagnosis for laparoscopy abscess, the fallopian tubes are seen as very dilated and
or laparotomy. elongated to the ovary, which is badly defined with the
Authors believe that acute salpingitis generally runs signs of incomplete septa, mixed contents with levels and
without trouble or difficulty to the sonographic signs free liquids in the pouch of Douglas (Table 28.4).
Figure 28.11 Pyosalpinx. Sign of the “cogwheel”. The excretions are Figure 28.12 Pyosalpinx. Sign of “cogwheel”. Sonographic contents
distributed in irregular forms. Also, it has an image of a pseudothin wall of pus
Figure 28.13 Pyosalpinx. Sign of “cogwheel”. Irregular excretions Figure 28.14 Pyosalpinx. Septa inside the fallopian tube that in reality
inside the tubal light is not, without a fold in the fallopian tube
The color Doppler also contributes to the diagnosis that prevent us from obtaining the sensibility and actual
defines the inflammation that is characteristic of the acute specificality of the sonograph.
process, but more irritation exists. Therefore, it detects more Ultrasonography is very illustrative in the serious
color signals in which the process already freezes (Figs cases, and in the cases that are very acute, we put aside the
28.22 and 28.23). processes with similar symptoms. The ability to explore
The fact that no control group is used, due to the with a vaginal probe attached permits us to perform a
characteristics of the disease and the impossibility to directed exploration, reaffirming the origin of the directed
visualize the normal fallopian tubes sonographically, pain. It is important to recognize that acute appendicitis
Figure 28.15 Pyosalpinx. Incomplete septa. When the fallopian Figure 28.16 Pyosalpinx. Incomplete septa. A sonographic sign of
tube is dilated and is doubled, the wall provokes a sonographic sign incomplete septa is important to identify the tubal origin of the complex
of incomplete septa. Echo-refringent material in the interior of the anexial mass. Observe the destruction of the tubal wall
fallopian tube
Figure 28.17 Pyosalpinx. Engrossment of the tubal wall that is Figure 28.18 Pyosalpinx. Engrossment of the tubal wall that ends in
characteristic of the acute process. Refringent material in its interior the cul-de-sac through distal stenosis of the fallopian tube
that indicates pus. The color map shows intense inflammation
(Fig. 28.24) can have some symptoms and sonographic is because the periodic menstrual descamation most likely
signs similar to those of acute salpingitis. protects this organ. Obviously, this is not always the case and
sometimes the uterus can be seen wrapped up in the process,
producing endometritis and less frequently, myometritis.
Endometritis Since this point can be seen from the sonographic view, the
It has been confirmed that PID is an infection inside the infection of the uterus can be manifested in two forms:
pelvis that affects the feminine genital organs. It should be 1. The presence of refringent spotting that passes through
added that this occurs, generally, outside of the uterus. This all of the endometrial line (Fig. 28.25).
Figure 28.19 Pyosalpinx. All signs. Refringent contents, pseudothin Figure 28.20 Tubo-ovarian abscess. Complex attachment in which we
wall, excretions. Engrossment of the tubal wall find the fallopian tubes surrounded as much as the ovary
Figure 28.21 Tubo-ovarian abscess. Tubo-ovarian complex in which Figure 28.22 Sign of color Doppler throughout the tube which suggests
it is difficult to distinguish between the borders of the ovary and the acute infection
dilated fallopian tube
Table 28.3 Laparoscopic classification of PID Table 28.4 Sonographic findings of pelvic inflammatory disease
Acute Erythema and edema of the PID n = 17 False-positive n = 3

fallopian tube Thin wall of 5 mm 5 (29.4%) 0
Moderate Fallopian tubes with purulent Cogwheel 5 (29.4%) 0
excess
Beads-on-a-string 5 (29.4%) 0
Severe Pyosalpinx, tubo-ovarian Incomplete septa 6 (35.2%) 1
abscess, tumor, inflammation
Sonolucence 4 (23.4%) 2
contents
Mixed contents 7 (41.1%) 2
Tubo-ovarian 4 (23.4%) 1
complex
Figure 28.23 Abundant map color in the tubal wall, with a very dilated Figure 28.24 Acute appendicitis. Inflamed and engrossed appendix,
fallopian tube. Suggestive of acute infection with Doppler sign
Figure 28.25 Endometriosis Figure 28.26 Endometriosis (accumulation of liquid in the cavity)
2. The accumulation of liquid, translated in the sonolucence germs and anaerobic causes of the disease. If acute
inside of the uterus cavity (Fig. 28.26). salpingitis is treated, it can evolve with restitutio ad
integrum, but immediately the disease finds itself a little
more advanced, and concerning all the cases in stage III,
Hydrosalpinx
this is not possible and we find our collections of liquid with
It is the most frequent result of PID. After an acute germs inside the fallopian tube. This condition is known
inflammatory or infectious process in any previous phase as hydrosalpinx. From the point of view of the sonograph,
described, and with the adequate medical treatment, the the lengthened tubal structure is identified (Figs 28.27 and
process can be cured with the elimination of the aerobic 28.28), with a fine wall of mucus atrophic (Fig. 28.29)
Figure 28.27 Hydrosalpinx (longitudinal view) Figure 28.28 Hydrosalpinx (sonolucent contents)
Figure 28.29 Hydrosalpinx. Sonolucent contents. Tubal wall very Figure 28.30 Hydrosalpinx. Sonolucent contents. Few Doppler signs
thinned in the wall of the fallopian tube
and containing sonolucent (a typical characteristic) (Fig. Hysterosalpingosonography

28.30). The lesions of tubal mucus will depend on the
gravity of the process, but the contained sonolucent creates The principal proposal of hysterosalpingosonography
an acoustic window that permits a visual, even better, the concerning the tubal pathologies could be the substitution
signs described earlier, like the projected cases on the of hysterosalpingography in the analysis of the fallopian
internal edge of hydrosalpinx (a sign of the “beads-on-a- tubes. The published results are interesting and include
string”) (Figs 28.31 and 28.32) or if the dilated fallopian authors like Goldstein and Yarali who have complemented
tube reaches a sufficient size or is doubled in size (a sign their work with the use of the Doppler. Nevertheless, the
of incomplete septa) (Figs 28.33 and 28.34). sonographic technology will provide less information
Figure 28.31 Hydrosalpinx. It remains a sign of “beads-on-a-string”. Figure 28.32 Hydrosalpinx. Sonolucent formation. Sign of “beads-on-
There is no activity in the wall. Practically no sign in the Doppler a-string”. Few Doppler signs
Figure 28.33 Hydrosalpinx. Sonolucent formation. Pseudothin wall Figure 28.34 Hydrosalpinx. Sonolucent. Detail of the pseudothin wall.
Tubal mucus destroyed
about the morphology of the fallopian tube, its internal permeable. However, its utilization has not been reached,
structure and the location of obstruction. The analysis because it will not provide the information of how passage
of the latest articles about hysterosonography makes it occurs and, therefore, hysterosalpingography cannot be
obvious that, in reality, the majority of the authors who use substituted as a method of reference to validate the tubal
this technology in their analysis of intracavity pathology, pathology.
still appeal to hysterosonography and chromopertubation
like the specified technology to demonstrate the tubal Sonographic Drainage as a Guide to
permeability. To verify this last claim, it has to be assumed
the introduction of a liquid (serum saline or contrast
Pelvic Abscess Perforation
sonograph) through the cervix (hysterosonography). By Traditionally, obstetricians and gynecologists, including
using this procedure, the passage of opposition or the free those before the arrival of sonography, became accustomed
liquid in the peritoneal cavity can be visualized, if it is to draining the pelvic abscesses that bulge convexly toward
the vagina through the pouch of Douglas, it became a route quicker recuperation and reduced the hospital stay, with
with which we were familiarizing ourselves and with the statistically proven differences. Similarly, in the study group
intention to alleviate the pus. Afterwards, we have come to a smaller number of laparotomies were necessary to provide
project this same idea with sonography on how to give a a motive to use this process. Recently, this pathology,
guide to perforation. In this prospective study published in whose incidences have diminished, begins a new as they
1996, in which we randomly selected 40 patients with pelvic are found in the clinics, perhaps the product of promiscuity
abscess to administer medical treatment with antibiotics and with attention to the emigrant populations, for whom
without further procedure or with medical treatment in we believe that they have the technology that could result
addition to abscess perforation by route of the vaginal tract beneficially that is simple to perform and pose inherent
with sonography. We found the latter method shared a much few complications.
CHAPTER
29
Sonohysterography
Takashi Murakami, Kunihiro Okamura
Introduction
Recent technical progress in the design of ultrasound
devices has greatly improved the accuracy of diagnosing
gynecological disorders. Transvaginal sonography (TVS)
has allowed uterine and adnexal lesions to be visualized
more clearly.
To increase the precision of diagnostic ultrasound
procedures, abdominal sonography with saline instillation
was developed by Beyth. 1 Parsons then applied this
method to TVS and called it sonohysterography (SHG).2
The negative contrast produced through the use of a
physiological saline solution allows a lining of endometrium
to grind distinctly, causing the shadow of an intrauterine
mass to stand out. Thus, saline-infusion SHG is an
Figure 29.1 A longitudinal scan of the uterus in a patient with
extremely useful and easy-to-use technique, which has postmenopausal bleeding before SHG. Thickness of hyperechoic
become a standard test in gynecological outpatient facilities. endometrium is found about 9 mm
with an endometrial thickness of more than 10 mm had

Indications
endometrial cancer,3 whereas the probability of malignancy
Abnormal Uterine Bleeding in postmenopausal patients with an endometrial thickness
The SHG is commonly used in cases of abnormal uterine of less than 5 mm was much lower.4,5 However, TVS
bleeding in premenopausal and postmenopausal women. measurements of endometrial thickness alone cannot rule
This is important as intrauterine abnormalities often cause out endometrial cancer, and endometrial biopsy might be
metrorrhagia and/or hypermenorrhea. Standard TVS is able necessary.
to show endometrial thickness, distortion of the endometrial Since SHG has a potential to distinguish between
lining and abnormal constructions, whilst SHG allows diffuse endometrial thickening and focal intracavitary
the details of intrauterine abnormalities to be visualized lesions,6 SHG is useful in determining whether subsequent
(Figs 29.1 and 29.2). In addition, SHG can be used to hysteroscopic biopsy is necessary.7 If a focal lesion is
provide a clinical diagnosis, such as endometrial polyps, observed using SHG, even if the imaging features suggest
submucosal leiomyoma or endometrial carcinoma, thus that it is benign, tissue diagnosis should be carried out.8
enabling further strategies to be devised.
Patients with postmenopausal bleeding should be Tamoxifen-exposed Patients
carefully examined because of the possibility of malignancy. Tamoxifen, which is one of the selective estrogen-receptor
In the Nordic multicenter study, the percentage of women modulators, has been used as an adjuvant treatment for
with endometrial cancer increased in a linear fashion breast cancer. Tamoxifen decreases the risk of recurrence
with increasing endometrial thickness: 35% of patients and death from breast cancer, but increases endometrial
Chapter 29  Sonohysterography 301
It is important to carry out an assessment of the uterine
cavity before commencing treatment using assisted
reproductive technology, such as in vitro fertilization (IVF).
Sonohysterography has a diagnostic accuracy equal to
hysteroscopy in the detection of uterine cavity diseases17,18
and is a cheaper and less painful technique. Thus, the use of
SHG is recommended as a screening test before embarking
on an IVF program.20
Recurrent Pregnancy Loss

A high percentage of patients that repeatedly suffer
pregnancy loss have either uterine anatomic disorders (for
example, congenital Müllerian anomalies) or acquired
defects (for example, uterine leiomyoma and uterine
Figure 29.2 The longitudinal scan of the patient seen in Figure synechia). Consequently, the uterine cavity is the primary
29.1 during SHG. An endometrial polyp is visualized on the fundus. focus of anatomical screening in patients suffering recurrent
Placement of a balloon is in the lower uterine cavity
miscarriage. Hysterosalpingography produces a silhouette
of the uterine cavity, and hysteroscopy shows an internal
view of the uterus. Both techniques are clearly limited, as
thickness and the risk of the formation of endometrial
they do not allow assessment of the outer uterine contour
lesions, including carcinoma.
and discrimination between septate and bicorunate uteri.21
Hence, it is recommended that women taking tamoxifen
However, SHG allows the examination of both the outer and
should have a gynecological examination at least once
the inner uterine bodies at the same time, and thus provides
every year.9 However, screening for endometrial cancer
a more sensitive assessment.
with routine TVS or biopsy has not been effective in
In cases of severe synechia, SHG cannot assess the
asymptomatic women using this agent.10 The SHG provides
uterine cavity as precisely as hysteroscopy; however, it
additional information about endometrial contours and
remains a highly sensitive, specific and accurate screening
has been used to detect subendometrial sonolucencies11 or
tool for the evaluation of uterine-cavity defects that are
occult endometrial polyps in tamoxifen-treated patients.12-14
associated with recurrent pregnancy loss.22
Endometrial cancer has also been detected in two cases from
asymptomatic patients.15 Hence, SHG might be a useful
technique in the assessment of endometrial pathologies in Technique
asymptomatic women taking tamoxifen. In practice, the necessity of carrying out SHG is determined
by the complaint as well as the results of an internal
Infertility examination and TVS.
The SHG is widely used in the treatment of infertility, as In premenopausal cases, SHG should be performed in the
it is necessary to check intrauterine abnormality and tubal follicular phase of the menstrual cycle, after menstruation
patency during treatment. Hysterosalpingography (HSG) is is completed. During the secretory phase, endometria will
routinely used to perform an initial investigation, but this appear lobular in SHG. It is necessary to perform SHG in
method has disadvantages compared with SHG.16-18 Firstly, the early proliferative phase to ensure accurate diagnosis. In
HSG requires the use of an iodinated contrast medium, postmenopausal patients with considerable hemorrhaging,
which risks exposing the patient to ionizing radiation or SHG should be avoided and the examination should not be
inducing an allergic reaction. Secondly, HSG generally carried out until after the hemorrhaging has stopped.
shows only the anterior-posterior view; it might, therefore, The administration of Buscopan or nonsteroidal
be hard to get optimal results in the case of anteverted or anti-inflammatory agents 30−60 minutes before SHG is
retroverted uteri. Although HSG is useful for the evaluation recommended to reduce discomfort.21 In addition, standard
of both tubal patencies, SHG has greater potential as a transvaginal ultrasound should be carried out to assess the
screening test for infertility.19 endometrial lining and/or adnexal pathology before SHG.
A speculum is inserted into the vagina after removal of the whilst moving it up and down, rotating the probe 90 degrees
transvaginal transducer, and the cervix is visualized. After counter-clockwise (Fig. 29.4). If necessary, tubal flow and
checking vaginal discharge, the external os of the cervix effusion into the cul-de-sac pouch can be observed. At the
is cleansed fully with antiseptic solution and a catheter is end of the procedure, the cervical canal and lower uterine
then inserted into the external cervical os, taking care not segment are checked while deflating the balloon.
to grasp the cervix. Images can be recorded in realtime using photographic
An assessment of the instruments used in SHG was or video equipment. After the examination, it is important
carried out by Dessole et al.23 By comparing six different that the operator records all biometric and anatomic data
types of catheter, they showed that a catheter with an immediately.9
introducer is easiest to insert, and that a catheter without
a balloon is less painful for patients. However, the type Findings
without a balloon allows high backflow into the vagina, and
the assessment of the uterine cavity and/or tubal patency Endometrial Polyps
might be insufficient using this technique. Therefore, we Endometrial polyps are the most common focal lesions
generally use a catheter with a balloon and an introducer. occurring in uterine cavities. In the clinical diagnosis of
A catheter is introduced into the uterine cavity beyond endometrial polyps, SHG performs better than standard
the internal cervical os and the balloon is filled with as TVS and HSG.7,16,17 Most cases show high echogenic
little air or fluid as possible to prevent a counter-current of shadow and endometrial thickness in standard TVS;
normal saline infusion. It is common to place the balloon however, it can be difficult to detect these phenomena
just beyond the internal cervical os; however, intracervical distinctly. Figure 29.5 shows a typical endometrial polyp
placement of the balloon is less painful for the patient and image produced by SHG. Saline infusion visualizes the
allows observation of the lower part of the uterus.24 After the endometrial polyps as homogeneous echogenic solid lesions
placement of the catheter, the inner introducer is removed. A with narrow peduncles. Using SHG, the shape, position and
syringe containing warm saline is connected to the catheter number of endometrial polyps are easily clarified, and this
and the transvaginal transducer is reinserted to verify the information is useful in subsequent operative hysteroscopy.
position of the catheter. A large endometrial polyp is difficult to distinguish
The standard position of the transvaginal transducer is from a small pedunculated leiomyoma using SHG. It has
sagittal (Fig. 29.3) After the air is released from the catheter, been reported that color Doppler SHG might be useful
saline is injected slowly. The uterine cavity is observed in distinguishing polyps from submucosal fibroids based
initially whilst moving the probe from right to left, and then, on the vascularity of the lesions; that is, polyps typically
Figure 29.3 Sagittal view of a normal uterus at day 11 of menstrual Figure 29.4 A transverse view of the same case as in Figure 29.3.
cycle. Endometrium is 8 mm in thickness and shows clear leaf pattern After saline infusion, the endometrium of proliferative phase shows the
before saline infusion. A balloon is placed in the cervical canal thin, hypoechoic and homogeneous appearance
Figure 29.5 A transverse view of a typical endometrial polyp during Figure 29.6 A longitudinal view of a uterus of a premenopausal
SHG. The lesion has homogeneously echogenic appearance and a woman with hypermenorrhea and dysmenorrhea. A heterogeneous
narrow pedunculated attachment echogenic tumor with distorted endometrial lining suggests submucosal
leiomyoma
contain a single feeding vessel, whereas fibroids have

several vessels. 25 However, there is no change in the
treatment of hysteroscopic resection in either. The SHG
alone is not sufficient for pathological diagnosis and
additional studies are necessary for a complete diagnosis.26
Submucosal Leiomyoma
Uterine leiomyoma is a common disease in women, and
submucosal leiomyoma causes menstrual and reproductive
disorders. Leiomyoma is visualized as a low echogenic
shadow using TVS, whereas SHG reveals the contours of
the leiomyoma (Figs 29.6 and 29.7). A systematic review
has demonstrated that SHG and hysteroscopy show high
accuracy in diagnosing submucosal fibroids.27
When deciding on an operative strategy, it is important Figure 29.7 After saline infusion view of the same case as in Figure
to determine the size, location and rate of protrusion of 29.6. The submucosal leiomyoma have a sessile attachment to the
posterior uterine wall
the fibroid into the uterine cavity before operating. It is
especially difficult to perform the hysteroscopic removal
of a fibroid with an intracavitary portion below 50%. detected. Several techniques are available for the detection
Sonohysterography can give a preoperative assessment of of tubal patency. These include the use of agitated saline,
the submucosal grading; that is, the measurement of the ultrasound-contrast medium, saline with air, saline after air
degree of intracavitary development.28 and color Doppler flow.
The methods that employ agitated saline29 and ultrasound-
Tubal Patency contrast medium30,31 are similar. Agitated saline is prepared
An intact fallopian tube is a poor sonic reflector, and by shaking the syringe containing saline and air before
both the detection and evaluation of the healthy tube is infusion. This induces the formation of microbubbles that
difficult using standard TVS. In SHG, the effusion of produce bright scintillating echoes on ultrasound, thus
normal saline into the cul-de-sac space is a good indicator enabling visualization of the flow that passes through the
of tubal patency; however, each tubal patency is not easily fallopian tubes, as same as contrast medium. The Sion test,
which involves pushing approximately 20 ml of saline

and air through the catheter, also allows the observation
of tubal patency.32 It is reported that the flow of saline and
micrometer-sized air bubbles is observed in transverse
section.
Injection of air through the catheter, followed by saline,
is another technique.33 In this method, when air is injected,
the lumen of the fallopian tube is visualized as a continuous
or dotted hyperechoic thin line. Next, when saline is
injected, air bubbles are disturbed and move rapidly through
the solution. Then, when the whole course of the tube can
no longer be visualized, the tubal patency can be evaluated
through the detection of air bubbles moving around the
ipsilateral ovary.
The SHG using color Doppler sonography is also Figure 29.8 A long-axis view of a patient with postmenopausal
bleeding. Hyperechoic endometrial thickness is about 5 mm
performed in the assessment of tubal patency.34-37 It is
thought that the forward flow of saline for at least 5 seconds
between the pars intramuralis and isthmus tubae without
interruption and hydrosalpinx formation, and/or fimbrial
turbulence to the cul-de-sac, indicates the presence of
tubal patency.38 Color flow is easier to visualize than
contrast flow, and thus there is a lower risk of error in the
interpretation of results.
Hyperplasia and Cancer

The SHG is more sensitive than hysteroscopy in detecting
hyperplasia. 39 The typical appearance of endometrial
hyperplasia in SHG is irregular echogenic endometrial
thickening, which is often distributed diffusely and
occasionally distributed locally. When only local thickening
is observed, the lesion should be sampled hysteroscopically Figure 29.9 Same view as Figure 29.8. A focal lesion with highly
to avoid the possibility of sampling error during office reflective irregular surface is shown. Histological diagnosis is
biopsy.8 endometrioid adenocarcinoma, G1
The SHG findings of endometrial cancer are diverse.

with SHG appears to be lower than that associated with
The lesions are generally hyperechoic and have irregular
hysteroscopy for small volume and low pressure, the risk
surfaces; however, size and shape can vary widely
of the dissemination of malignant cells still exists. It would,
(Figs 29.8 and 29.9). The SHG might also have a role
therefore, be prudent to perform SHG for all patients with
in preoperative staging by visualizing distortion of the
endometrial cancer.
endometrial-myometrial interface that suggests myometrial
invasions.40
In the case of cancer, there is a potential risk that saline
Complications
infusion might transport malignant cells into the peritoneal There are no major complications in SHG; however,
cavity during the SHG procedure. According to cytological patients should be counseled about the possibility of
analyses of the fluid spilled from the fimbrial ends during infection. The risk of intracavitary infection after SHG is
10−20 ml saline infusion into the uterine cavity at the time reported to be slightly over 1%.42
of laparotomy, malignant cells were present in the spilled Genital infections, such as vaginitis, adnexitis and
fluid in only 1 case out of 14.41 Although the risk associated pelvic inflammatory disease, are contraindications of
this procedure. If necessary, SHG can be used after the 7. Dubinsky TJ, Parvey HR, Gormaz G, et al. Transvaginal
inflammation is cured. Prophylactic antibiotics or cervical hysterosonography in the evaluation of small endoluminal
culture can be administered before SHG is performed. masses. J Ultrasound Med. 1995;14:1-6.
The exclusion of patients with mucopurulent discharge is 8. O’Neill MJ. Sonohysterography. Radiol Clin N Am.
another method to avoid the development of an infectious 2003;41:781-97.
complication without prophylactic antibiotics.43 9. Tamoxifen and endometrial cancer: American College of
Obstetricians and Gynecologists Committee Opinion 169.
To avoid intracavitary infection, all procedures should
Washington, DC: ACOG; 2000.
be performed under strictly aseptic conditions. To ensure
10. Bertelli G, Venturini M, Del Mastro L, et al. Tamoxifen and
safety, the American College of Obstetics and Gynecology
endometrium: findings of pelvic ultrasound examination and
(ACOG) assessment recommends that endovaginal endometrial biopsy in asymptomatic breast cancer patients.
transducers undergo appropriate antimicrobial and antiviral Breast Cancer Res Treat. 1998;47:41-6.
cleansing between patients.26 11. Goldstein SR. Unusual ultrasonographic appearance of the
uterus in patients receiving tamoxifen. Am J Obstet Gynecol.
Comments 1994;170:447-51.
The SHG has proved to be a useful tool in the clinical gynecological 12. Bourne TH, Lawton F, Leather A, et al. Use of intracavity
field, and appears to be a simple and easy procedure to use after saline instillation and transvaginal ultrasonography to detect
TVS in outpatient clinics. However, as with most procedures, SHG
is subject to a learning curve.44 Careless performance and indiscrete tamoxifen-associated endometrial polyps. Ultrasound Obstet
judgment can lead to misdiagnosis through either false-positive or Gynecol. 1994;4:73-5.
false-negative results. The injection of air bubbles, shearing the 13. Achiron R, Lipitz S, Sivan E, et al. Sonohysterography for
endometrium by rough catheter insertion, and shadowing of the
ultrasonographic evaluation of tamoxifen-associated cystic
catheter and balloon can produce iatrogenic effects that might
cause false-positive results. The presence of a blood clot might thickened endometrium. J Ultrasound Med. 1995;14:685-8.
also lead to an incorrect diagnosis.45 To avoid misdiagnoses, careful 14. Tepper R, Beyth Y, Altras MM, et al. Value of
operations and thoughtful interpretations are required. Furthermore, sonohysterography in asymptomatic postmenopausal
making a diagnosis of tubal patency demands considerable
technical skill. Adequate training is, therefore, essential in order to
tamoxifen-treated patients. Gynecol Oncol. 1997;64:386-91.
become fully competent in the use of SHG. 15. Look K, Sanders B, Eastlund M, et al. Detection of
endometrial adenocarcinoma in two asymptomatic
postmenopausal women receiving tamoxifen. J Reprod Med.
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1. Beyth Y, Beller U, Yarkoni S. A simple technique for 16. Gaucherand P, Piacenza JM, Salle B, et al. Sonohysterography
visualization of the uterine cavity and its pathology during of the uterine cavity: preliminary investigations. J Clin
ultrasound scanning. Isr J Med Sci. 1982;18:817-8. Ultrasound. 1995;23:339-48.
2. Parsons AK, Lense JJ. Sonohysterography for endometrial 17. Goldberg JM, Falcone T, Attaran M. Sonohysterographic
abnormalities: preliminary results. J Clin Ultrasound. evaluation of uterine abnormalities noted on
1993;21:87-95. hysterosalpingography. Hum Reprod. 1997;12:2151-3.
3. Karlsson B, Granberg S, Wiklans M, et al. Transvaginal 18. Soares SR, Barbosa dos Reis MMB, Camargos AF.
ultrasonography of the endometrium in women with Diagnostic accuracy of sonohysterography, transvaginal
postmenopausal bleeding—a Nordic multicenter study. Am sonography, and hysterosalpingography in patients with
J Obstet Gynecol. 1995;172:1488-94. uterine cavity diseases. Fertil Steril. 2000;73:406-11.
4. Gupta JK, Chien PFW, Voit D, et al. Ultrasonographic 19. Case AM, Pierson RA. Clinical use of sonohysterography
endometrial thickness for diagnosing endometrial pathology in the evaluation of infertility. J Obstet Gynecol Can.
in women with postmenopausal bleeding: a meta-analysis. 2003;25:641-8.
Acta Obstet Gynecol Scand. 2002;81:799-816. 20. Kim AH, McKay H, Keltz MD, et al. Sonohysterographic
5. Gull B, Carlsson SA, Karlsson B, et al. Transvaginal screening before in vitro fertilization. Fertil Steril.
ultrasonography of the endometrium in women with 1998;69:841-4.
postmenopausal bleeding: is it always necessary to perform an 21. L i n d h e i m S R , A d s u a r N , K u s h n e r D M , e t a l .
endometrial biopsy? Am J Obstet Gyneol. 2001;182:509-15. Sonohysterography: a valuable tool in evaluating the female
6. Cohen JR, Luxman D, Sagi J, et al. Sonohysterography for pelvis. Obstet Gynecol Surv. 2003;58(11):770-84.
distinguishing endometrial thickening from endometrial 22. Keltz MD, Olive DL, Kim AH, et al. Sonohysterography
polyps in postmenopausal bleeding. Ultrasound Obstet for screening in recurrent pregnancy loss. Fertil Steril.
Gynecol. 1994;4:227-30. 1997;67:670-4.
23. Dessole S, Farina M, Capobianco G, et al. Determining 35. Stern J, Peter AJ, Coulam CB. Color Doppler ultrasonography
the best catheter for sonohysterography. Fertil Steril. assessment of tubal patency: a comparison study with
2001;76:605-9. traditional techniques. Fertil Steril. 1992;58:897-900.
24. Keltz MD, Arici A, Duleba A, et al. A technique 36. Kleinkauf-Houcken A, Hüneke B, Lindner Ch, et al.
sonohysterographic evaluation of the endometrial cavity Combining B-mode ultrasound with pulsed wave Doppler
and tubal patency. J Gynecol Tech. 1995;1:213-8. for the assessment of tubal patency. Hum Reprod.
25. F l e i s c h e r A C , S h a p p e l l H W. C o l o r D o p p l e r 1997;12:2457-60.
sonohysterography of endometrial polyps and submucosal 37. Boudghene FP, Bazot M, Robert Y, et al. Assessment of
myoma. J Ultrasound Med. 2003;22:601-4. fallopian tube patency by HyCoSy: comparison of a positive
26. Breitkopf D, Goldstein SR, Seeds JW, et al. ACOG contrast agent with saline solution. Ultrasound Obstet
technology assessment in obstetrics and gynecology No. Gynecol. 2001;18:525-30.
3. Saline infusion sonohysterography. Obstet Gynecol.
38. Tüfekçi EC, Durmusoglu F, Girit S, et al. Evaluation of tubal
2003;102:659-62.
patency by transvaginal sonosalpingography. Fertil Steril.
27. Farquhar C, Exeroma A, Furness S, et al. A systematic
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review of transvaginal ultrasonography, sonohysterography
39. Widrich T, Bradley LD, Mitchinison AR, et al. Comparison
and hysteroscopy for the investigation of abnormal uterine
of saline infusion sonography with office hysteroscopy for
bleeding in premenopausal women. Acta Obstet Gynecol
the evaluation of the endometrium. Am J Obstet Gynecol.
Scand. 2003;82:493-504.
1996;174:1327-34.
28. Leone FPG, Lanzani C, Ferrazzi E. Use of strict
sonohysterographic methods for preoperative assessment 40. Valenzano M, Podesta M, Giannesi A, et al. The role of
of submucous myomas. Fertil Steril. 2003;79:998-1002. transvaginal ultrasound and sonohysterography in the
29. Chenia F, Hofmeyr GJ, Moolla S, et al. Sonographic diagnosis and staging of endometrial adenocarcinoma.
hydrotubation using agitated saline: a new technique Radiol Med. 2001;101:365-70.
for improving fallopian tube visualization. Br J Radiol. 41. Alcazar JL, Errasti T, Zornoza A. Saline infusion
1997;70:833-6. sonohysterography in endometrial cancer: assessment of
30. Balen FG, Allen CM, Siddle NC, et al. Ultrasound contrast malignant cells dissemination risk. Acta Obstet Gynecol
hysterosalpingography—evaluation as an outpatient Scand. 2000;79:321-2.
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31. Aylda G, Harris P, Kennedy S, et al. Hysterosalpingo- a prospective survey of results and complications in 81
contrast sonography (HyCoSy) using Echovist®-200 in the patients. Obstet Gynecol. 2002;102:42-7.
outpatient investigation of infertility patients. Br J Radiol. 43. Alatas C, Aksoy E, Akarsu C, et al. Evaluation of intrauterine
1996;69:910-3. abnormalities in infertile patients by sonohysterography.
32. Allahbadia GN, Nalawade YV, Patkar VD, et al. The Sion Hum Reprod. 1997;12:487-90.
test. Aust NZ J Obstet Gynecol. 1992;32:67-70. 44. Epstein E, Ramirez A, Skoog L, et al. Transvaginal
33. Volpi E, Zuccaro G, Patriarca A, et al. Transvaginal sonography, saline contrast sonohysterography and
sonographic tubal patency testing using air and saline hysteroscopy for the investigation of women with
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setting. Ultrasound Obstet Gynecol. 1996;7:43-8. Ultrasound Obstet Gynecol. 2001;18:157-62.
34. Peter AJ, Coulam CB. Hysterosalpingography with 45. Lindheim SR, Morales AJ. Comparison of sonohysterography
color Doppler ultrasonography. Am J Obstet Gynecol. and hysteroscopy: lessons learned and avoiding pitfalls. J
1991;164:1530-4. Am Assoc Gynecol Laparosc. 2002;9:223-31.
CHAPTER
Postmenopausal Women
Kuldeep Singh, Narendra Malhotra
Introduction
With the increase in life expectancy, the menopausal
population is on the rise and this has confronted the
gynecologist with a host of new gynecological pelvic
pathologies.
The ultrasound (US) technology, which is presently
available, offers a unique insight into the anatomical,
physiological and pathological states of the women in the
menopausal age group.
The images offered by modern-day transabdominal
ultrasound (TAUS) and transvaginal ultrasound (TVUS)
transducers with facilities for high frequency, color flow
mapping, duplex Doppler studies and three-dimensional
(3D) reconstruction, have revolutionized the approach to the Figure 30.1 The endometrium atrophies in menopause and appears
clinical problems of a woman beyond her reproductive years. on the ultrasound as a “pencil-line” echogenicity
Normal Endometrium in Menopause

The atrophic endometrium appears on US as a “pencil-
line” echogenicity which represents the thickness of tissues
between two sides of the atrophic basal endometrium (Fig.
30.1). The measurement on a US scan should definitely
include the maximum anteroposterior (AP) thickness
in the sagittal long axis view (Fig. 30.2). 1 Whenever
a fluid collection is present in the endometrium, the
depth of the collection should be excluded from the
total thickness (Fig. 30.3). The correlation of thickness
measurements, altered echotexture and sensitivity and
specificity considerations is discussed in the section on
postmenopausal bleeding. Figure 30.2 The measurement of the endometrial thickness on an
Hormone replacement therapy tends to increase the ultrasound scan should include the maximum anteroposterior thickness
in the sagittal long axis view
endometrial thickness of about 1–1.5 mm for continuous
estrogen or progesterone therapy and of about 3 mm The cut-off level of the endometrial thickness for
for sequential therapy2 regime (Box 30.1). Women on detection of endometrial disease should also be based on
sequential therapy have more variations in thickness in each the length of time since menopause. A 03 mm cutoff limit
month at different duration, with the thinnest endometrium after 5 years or more since menopause5 greatly improves
following progesterone withdrawal.3,4 the specificity and also the false-positive rate.
Endometrial measurements by transvaginal scanning

in women with postmenopausal bleeding can be used
to differentiate between a pathological and a normal
endometrium.
Karlsson and associates11 evaluated 1,168 postmenopausal
patients with bleeding by TVUS and curettage. They
confirmed the cutoff value of 05 mm, below which the
risk of endometrial abnormality is low (5.5%). They also
suggested refraining from curettage when the endometrial
thickness measurement was less than 05 mm.
Sheikh and Khurana1 in their study found that focal
increased echogenicity, diffuse increased echogenicity and
diffuse inhomogeneity definitely increase the predictability
of pathologic findings. In addition, these findings, even in
Figure 30.3 Uterine cavity with a fluid collection and debris. The an endometrium which is thinner than the cutoff values of
collection depth should be excluded from the total thickness
normal postmenopausal endometrium, are indicators for
inclusion in the group for invasive endometrial sampling.
Box 30.1: Remember
This study added the dimension of abnormal echogenicity
• The endometrium to be measured should include the maximum of the endometrium to the currently followed criterion of
anteroposterior thickness in the sagittal long axis view
• If a fluid collection is present in the endometrium, the depth endometrial thickness with a view to enhance accuracy
should be excluded from the total thickness (Figs 30.4 to 30.11), both for a better prediction of atrophy
and a higher prediction for endometrial cancer. Expectant
Box 30.2: Parameters to evaluate the endometrium management can be offered to patients with a homogeneous
• Thickness endometrium which is 6 mm thick or less. Aggressive
• Echo pattern evaluation for a malignancy must be made if there is a focal
• Time since menopausal
• Any HRT
increased echogenicity or a diffuse inhomogeneity even in
• Any antihypertensive drugs a thin endometrium.
• Sonohysterography for focal lesions as screening test Recent studies12 have concurred with these conclusions
made at the end of the last century and have highlighted
Endometrial thickness is usually greater in asymptomatic, the utility of saline infusion SHG,13 color Doppler14 and
hypertensive postmenopausal women receiving 3D techniques15 in further enhancing US-histopathology
antihypertensive drugs than in untreated hypertensive and
normotensive patients:6 6.2 mm compared to 4.3 mm and
3.6 mm.
Transvaginal sonohysterography (SHG) after a saline
infusion improves the detection rate of focal abnormalities.7
Similar improvement of results has been reported with 3D
US studies (Box 30.2).8
Postmenopausal Bleeding
Atrophic endometrium (estrogen deficient) is prone to
superficial ulceration and is the most common cause
of postmenopausal bleeding. 9 Approximately 80% of
endometrial cancers occur in postmenopausal women and
because these patients commonly present with vaginal
bleeding; it has been a dilemma in gynecologic practice to Figure 30.4 Diffuse inhomogeneity in a 05 mm thick endometrium.
sample such an endometrium.10 Scanty curettings but the histopathology showed an endometrial cancer
Chapter 30  Transvaginal Sonography in Postmenopausal Women 309
Figure 30.5 Focal increased echogenicity (solid line) in a 06–07 mm Figure 30.6 Irregularly thickened hyperechoic endometrium. This
thick endometrium. Postprocedure showed a malignant change should always prompt sampling irrespective of the thickness
Figure 30.7 Homogeneous 05–06 mm thick endometrium. Curettings Figure 30.8 Diffusely inhomogeneous 18 mm thick endometrium
showed an atrophic endometrium
Figure 30.9 Diffusely inhomogeneous 24 mm thick endometrium Figure 30.10 Homogeneous 14 mm thick endometrium. Sampling was
done and was positive for malignancy
Figure 30.11 Echogenic endometrial fluid collection with a mass in Figure 30.12 Polyp seen on a transvaginal scan which was even better
the posterior aspect. Curettings and aspirate both positive for cancer demarcated on a saline infusion sonohysterography
correlation and differentiate more reliably between

patients who need an endometrial sampling and those
who could be offered prudent expectant management
(Figs 30.12 to 30.15).
Endometrial Fluid Collections

Fluid collections in the endometrium in many postmenopausal
women mostly represent transudates associated with cervical
stenosis. One needs to check the endometrial layer peripheral
to the fluid collection. If it is 03 mm or less, the endometrium
is usually inactive. If the peripheral endometrium is 04 mm
or thicker, sampling is essential.16
Myometrium in Menopause Figure 30.13 Endometrial polyp (solid line) in a 14 mm thick

endometrium
The myometrium also atrophies during and after menopause
resulting in a reduction of uterine size but no appreciable in a menstruating female. Almost every ovary can, however,
change in echo pattern (Figs 30.16 and 30.17). Arcuate be visualized depending on the equipment resolution and
arteries may calcify, particularly in the diabetic patient experience of the observer.17 What one needs to remember is
and show as a speckled pattern in a small uterus. Fibroids that nonvisualization of the ovary is never an indication that
undergo a reduction in size after menopause and variably the ovary is normal. Ovarian volume shows a progressive
shrink and calcify. decrease from 8.6 ± 2.3 ml in the first menopausal year to 2.2
± 1.4 ml after more than 15 years after menopause.18
Normal Atrophic Ovary
The ovary lacks follicles after menopause and, therefore,
Ovary and Ovarian Cancer Screening
looks like an area of nonspecific solid echoes (Fig. 30.18) More than two-thirds of the cases of ovarian cancer are
making it more difficult to identify on US scans. More so the diagnosed when they reach Stage III or IV. In Stage I,
problem is compounded by the presence of overlapping bowel women have a 3 in 4 five-year survival, whereas advanced
segments and the relatively increased distance of the shrunken disease shows a 9–28% survival only. Eighty percent of
ovary from the iliac vessels which doctors use as landmarks ovarian cancers occur in women 50 years or older. The
Figure 30.14 With combined morphological and power Doppler evaluation, the sensitivity for diagnosis of endometrial carcinoma is increased
Figure 30.15 Power Doppler evaluation for endometrial and subendometrial vascularization and the nature of vascularization diagnosis and
expectant management for endometrial cancer patients can be planned
Figure 30.16 Fibroid with degeneration Figure 30.17 Multiple interstitial and subserous fibroids
Figure 30.18 Normal atrophic ovaries in a postmenopausal patient Figure 30.19 Thin-walled clear simple cyst seen in the left ovary
Figure 30.20 Thin-walled clear paraovarian cyst Figure 30.21 Left extraovarian adnexal tubular mass. Always check
the walls and any irregular thickening or masses within the tube before
labeling it as plain hydrosalpinx and leaving it alone
need to evaluate the menopausal woman for cancer is and para-aortic lymph node enlargement, ascites, suprarenal
therefore obvious. Even though screen positives are high and liver metastases and pleural effusions can be elucidated
and the cost-effectiveness and the cost efficiency are poor, by TAUS. Color flow and 3D vascular reconstruction criteria
the dramatically better quality of life after an early versus include abnormal calibration of vessels, dichotomous branches,
a late diagnosis in a single patient justifies this so-called elongation, coiling, aneurysms, vascular lakes, arteriovenous
inefficient screening. (AV) anastomoses and venovenous (VV) anastomoses.
An annual pelvic examination, tumor marker levels and Low resistive and pulsatility indices are inadequately wide
gray-scale ultrasonography (GSUS) with color Doppler and range to be reliable. These criteria and conclusions of other
3D reconstruction of tumor vascularity have emerged as a workers suggest that a cystic structure20 less than 30 mm in
reliable ovarian cancer screen when used together.19 size, unilateral, unilocular and with no internal echoes, solid
The criteria for diagnosis remain the same as in the areas or nodules, which is avascular on color flow mapping
premenopausal age group. These include gray-scale may be re-evaluated 6 and 12 weeks later and then annually
observations of a solid mass, a cystic mass with solid areas, if it does not increase or change in morphology or vascularity.
focal or diffusely thick walls or septations, mural nodules and Any mass with abnormal vascularity and all masses more
heterogeneous internal echoes (Figs 30.19 to 30.25). Pelvic than 50 mm in size warrant surgical evaluation. Aspirates
Figure 30.22 Irregular thickening of the cyst wall with septations and Figure 30.23 Eccentric nodule in an ovarian cyst
dense internal echoes within an ovarian cyst
Figure 30.24 Color flow and 3D vascular reconstruction of ovarian masses should include abnormal calibration of vessels, dichotomous branches,
elongation, coiling, aneurysms, vascular lakes, arteriovenous anastomoses and venovenous anastomoses. Low resistive and pulsatility indices
are inadequately wide range to be reliable
obtained even under US guidance do not contain an adequate Conclusion

representation of cells from the tissue of origin to justify the High technology implementations both in their cheaper and
technique. All masses associated with a rising Ca-125 level expensive top of the line avatars improve disease detection in the
warrant surgical evaluation. It must be remembered that not all postmenopausal women. Awareness of the imaging armamentarium
and appropriate referrals in the context of time, place and expertise
adnexal cysts are ovarian in origin and that the demonstration will continue to enhance the quality of life in this group of patients.
of an atrophied ovary separate from the cyst should bring It is suggested for efficient screening for ovarian and endometrial
into consideration the possibilities of peritoneal inclusion disease in the perimenopausal and menopausal age groups a routine
transvaginal scan with color flow mapping should be done along with
cysts, residual post-inflammatory cysts, tubal lesions and a Pap smear examination every year. This will ensure an effective
post-endometriosis residual fluid loculi. These entire lesions screening and early detection of malignancies and improve the health
are avascular on color flow mapping and may be seen in up of menopausal age group women.
to a fifth of postmenopausal women.

tumors: comparison with conventional transvaginal

sonography, hysterosalpingography, and hysteroscopy.
Gynecol Oncol. 1997;65(2):245-52.
9. Osmers R, Volksen M, Schauer A. Vaginosonography
for early detection of endometrial carcinoma? Lancet.
1990;335(8705):1569-71.
10. Goldstein SR, Nachtigall M, Synder JR, et al. Endometrial
assessment by vaginal ultrasonography before endometrial
sampling in patients with postmenopausal bleeding. Am J
Obstet Gynecol. 1990;163 (1 Pt 1):119-23.
11. Karlsson B, Granberg S, Wikland M, et al. Transvaginal
ultrasonography of the endometrium in women with
postmenopausal bleeding—a Nordic multicenter study. Am
J Obstet Gynecol. 1995;172(5):1488-94.
Figure 30.25 Inhomogeneous mass in the cervix
12. Randelzhofer B, Prömpeler HJ, Sauerbrei W, et al. Value of
sonomorphological criteria of the endometrium in women
with postmenopausal bleeding: a multivariate analysis.
References Ultrasound Obstet Gynecol. 2002;19(1):62-8.
1. Sheikh M, Sawhney S, Khurana A, et al. Alteration of 13. Epstein E, Ramirez A, Skoog L, et al. Transvaginal sonograph,
sonographic texture of the endometrium in postmenopausal saline contrast sonohysterography and hysteroscopy for the
bleeding: a guide to further management. Acta Obstet investigation of women with postmenopausal bleeding
Gynecol Scand. 2000;79(11):1006-10. and endometrium >5 mm. Ultrasound Obstet Gynecol.
2. Chanler IW, Davie MW. Low dose continuous combined 2001;18(2):157-62.
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effect on endometrium. J Ultrasound Med. 2000;19(1):33-8. of color Doppler ultrasound in patients with endometrial
3. Levine D, Gosnik BB, Johnson LA. Change in endometrial hyperplasia and carcinoma. Cancer. 2002;94(3):700-6.
thickness in postmenopausal women undergoing hormone 15. Gruboeck K, Jurkovic D, Lawton F, et al. The diagnostic
replacement therapy. Radiology. 1995;197(3):603-8. value of endometrial thickness and volume measurements by
4. Affinito P, Palomba S, Sammartino A, et al. Ultrasonographic three-dimensional ultrasound in patients with postmenopausal
endometrial monitoring during continuous-sequential bleeding. Ultrasound Obstet Gynecol. 1996;8(4):272-6.
hormonal replacement therapy regimen in postmenopausal
16. Perrot N, Guyot B, Antoine M, et al. The effects of tamoxifen on
women. Maturitas. 2001;39(3):239-44.
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5. Tsuda H, Kawabata M, Kawabata K, et al. Improvement
17. Rodriquez MH, Platt LD, Medeoris AL, et al. The use of
of diagnostic accuracy of transvaginal ultrasound for
transvaginal sonography for evaluation of postmenopausal
identification of endometrial malignancies by using cutoff
size and morphology. Am J Obstet Gynecol. 1988;159:810-4.
level of endometrial thickness based on length of time since
menopause. Gynecol Oncol. 1997;64(1):35-7. 18. Tepper R, Zalel Y, Markov S, et al. Ovarian volume in
6. Alcázar JL. Endometrial sonographic findings in postmenopausal women—suggestions to an ovarian size
asymptomatic, hypertensive postmenopausal women. J nomogram for menopausal age. Acta Obstet Gynecol Scand.
Clin Ultrasound. 2000;28(4):175-8. 1995;74(3):208-11.
7. Neele SJ, Marchien van Baal W, Van der Mooren MJ, et 19. Strigini FA, Gadducci A, Del Bravo B, et al. Differential
al. Ultrasound assessment of the endometrium in healthy, diagnosis of adnexal masses with transvaginal sonography,
asymptomatic early postmenopausal women: saline color flow imaging, and serum CA-125 assay in pre- and
infusion sonohysterography versus transvaginal ultrasound. postmenopausal women. Gynecol Oncol. 1996;61(1):68-72.
Ultrasound Obstet Gynecol. 2000;16(3):254-9. 20. Goldstein SR. Postmenopausal adnexal cysts: how
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dimensional hysterosonography for the study of endometrial 1996;175(6):1498-501.
CHAPTER
31 Use of Different Ultrasound

Techniques in the Field
of Urogynecology
Vaneesha Vallabh-Patel, Sanja Kupesic Plavsic
Introduction Other factors also associated with this dysfunction include

obesity, estrogen deficiency, chronic increase in intra-
Due to wide availability, low cost and lack of ionizing abdominal pressure, large birth weights and previous pelvic
radiation ultrasound has become an integral part of surgery to include a hysterectomy.
evaluation of the pelvic floor. In this chapter, the authors
The female pelvis is a very complex unit of muscles,
have discussed the uses of different sonographic methods
nerves, vessels and bones which are all integrated to form
[two-dimensional (2D), three-dimensional (3D) and color
the functional pelvis. Due to its complexity, the authors
Doppler ultrasound] and approaches (transabdominal,
have divided the pelvis into different compartments to
transperineal, introital, transvaginal and rectal) to depict
better explain anatomy and function associated with each
the lower urinary tract and pelvic floor.
compartment. They feel that this will give their readers a
better understanding of the pelvis and also how ultrasound
Pelvic Organ Prolapse can be used in each aspect.
Pelvic organ prolapse (POP) is defined as a protrusion of
pelvic organs to or beyond the hymenal ring of the vagina, Pelvic Anatomy
diagnosed during a gynecological pelvic exam. Pelvic organ
prolapse is currently described using two international
Bones of the Pelvis
systems, the Baden-Walker system and the Pelvic Organ The female pelvic skeleton is the anchor for all pelvic
Prolapse-Quantification (POP-Q) system. structures. The skeleton consists of the hip bones which
The Baden-Walker system was first described by Baden are made up of the ilium, ischium and pubis (Fig. 31.1).
in 1968.1 The system is based on interobserver reliability The ilium is the superior part of the hip described as a
to describe the most dependant position of pelvic organs fan-shaped flattened bone. The ischium can be described
during the time of relaxation and Valsalva. Points are in two parts: (1) body and (2) ramus. The body forms part
predetermined based on the landmarks in the female pelvis of the acetabulum of the hip and the ramus helps form the
and the correlation to POP to these sites. obturator foramen. The ischium also consists of an ischial
The POP-Q system was first introduced in 1996 as tuberosity and spine and helps to form the lesser sciatic
a standard classification system to better communicate notch and greater sciatic notch.
internationally the degree of POP described when examining The pubis is described in three parts: superior ramus,
a patient. It has proven to show both intraobserver and inferior ramus and body. The superior ramus forms part of
interobserver reliability when tested among various the acetabulum and has an oblique ridge named the pectin
physicians.2 The system is based on various qualitative pubis. The inferior ramus in conjunction with the ischium
measurement points to determine anterior, apical and forms the obturator foramen. The body of the pubis can
posterior vaginal prolapse predetermined by a standard map be further divided into the anterior pubic crest and a more
of the female pelvis. lateral structure called the pubic tubercle. The pubic arch is
Pelvic organ prolapse has an 11% lifetime risk for formed by the junction of the pubic rami and the ischium.
women to undergo corrective surgery in the United States.3 The rami also meet to form the pubic symphysis and the
The most important risk factor identified by Kearney et al. subpubic angle, which is known to be wider in female
is damage to the pelvic floor secondary to vaginal births.4 subjects compared to male subjects.
Figure 31.1 Bones of the female pelvis Figure 31.2 Muscles of the pelvic floor
The pelvis can further be divided into the greater and lesser Posterior Pelvic Wall
pelvis. The lesser pelvis has a greater role in the structures,
The posterior wall is covered posterolaterally by the
which affects the urogynecological problems that have
piriformis muscle (Fig. 31.2). The proximal attachment of
been described in this chapter. The lesser pelvis is between
this muscle is the pelvic surface of the second and fourth
the pelvic inlet and outlet. It is the location of the urinary
sacral segment, superior margin of the greater sciatic notch
bladder and reproductive organs. This structure is of major
and sacrotuberous ligament. The muscle then courses
obstetrics and gynecology significance.5 The design of
through the greater sciatic foramen and distally attaches
the pelvis allows the weight of the female to be dispersed
to the greater trochanter of the femur. Like the obturator
evenly among the pelvic structures and toward the femur.
internus muscle, it also laterally rotates the thigh and assists
in holding the femur head to the acetabulum. In addition,
Muscles of the Pelvis the piriformis muscle abducts the thigh. This muscle is
The levator ani and coccygeus muscles attached to the inner primarily innervated by the ventral rami of S1 and S2.
surface of the small pelvis form the muscular floor of the
pelvis (Fig. 31.2). For didactic purposed, the authors have Pelvic Floor
divided it into the anterior, lateral and posterior group.
The pelvic floor consists of two groups of muscles: (1)
Anterior Pelvic Wall levator ani and (2) the coccygeus. These two groups
of muscles, along with the fascial covering, form the
The anterior pelvic wall is comprised mostly of the rami funnel-shaped pelvic diaphragm that is critical to central
of the pubic bones and the pubic symphysis. There is no compartment dysfunction. There is an interactive role of the
significant musculature in this area. levator ani and endopelvic fascia in maintaining continence
and pelvic support.
Lateral Pelvic Wall
The levator ani muscles are made up of three separate
The lateral pelvic wall is mainly covered by the obturator muscles: (1) pubococcygeus, (2) puborectalis and (3)
internus muscles. The proximal attachment of this muscle iliococcygues. The pubococcygeus is the main component
is the pelvic surfaces of the ilium, ischium and obturator of the levator ani group. The proximal attachment is the
membrane. The muscle passes through the lesser sciatic posterior aspect of the body of the pubis and attaches distally
foramen and distally attaches to the greater trochanter of to the midline annococcygeal raphe and anterolateral
the femur. The function of the obturator internus muscle is border of the coccyx.1 The puborectalis muscle proximally
to rotate the thigh laterally and assist in holding the head attaches to the posterior inferior pubic rami and arcus
of the femur acetabulum. This muscle is innervated by the tendineus levator ani. It then courses posteriorly forming a
nerve to the obturator internus (L5, S1, S2). U-shaped structure around the vagina, rectum and perineal
Chapter 31  Use of Different Ultrasound Techniques in the Field of Urogynecology 317
body. This structure is very important when diagnosing outer longitudinal layer. The bladder base is known as the
fecal incontinence. The final muscle of the group is the trigone. This area is formed by three orifices: two ureteral
iliococcygeus muscle. This muscle is the posterior part of orifices approximately 3 cm apart and an internal urethral
the levator ani group and attaches proximally to the arcus orifice. The deep muscles of the trigone are innervated
tendineus levator ani from the pubis to the ischial spine.1 mainly by parasympathetic nerves and a sparse number of
It then courses distally and attaches to the anococcygeal sympathetic nerve fibers.1 The superficial musculature has
raphe to form the levator plate (Fig. 31.2). the opposite pairing in nerve fibers.
As a group, the levator ani muscles support the The female urethra originates in the bladder, then passes
abdominopelvic viscera and help to resist increases in intra- through the retropubic space and extends in the vestibule
abdominal pressure. The group is innervated by the nerve directly above the vaginal opening. The average length of
to levator ani (S4), inferior anal nerve and the coccygeal the urethra is approximately 4 cm, with a 6 mm diameter.
plexus. This muscular group is essential in compressing the The urethral smooth muscle and the detrusor muscle form
abdominal pelvic contents in such activities as coughing, the intrinsic urethral sphincter mechanism. This mechanism
sneezing, vomiting, urinating and defecating. When helps with urethral resistance to outflow at rest. The striated
dysfunctions in these muscles occur, symptoms include urethral and periurethral muscles form the external urethral
urinary and fecal incontinence in conjunction with loss of sphincter mechanism. This mechanism in conjunction
uterine support. with the striated urogenital sphincter (sphincter urethrae,
The coccygeous muscle attaches proximally to the ischial compressor urethrae, urethrovaginal sphincter) works as
spine and distally to the inferior end of the sacrum. It forms a unit to control the voluntary interruption of the urinary
a smaller part of the pelvic diaphragm which supports the stream and control urethral closure with associated stress.
pelvic viscera. The muscle is innervated by S4 and S5. The musculature of the pelvis is complex as a defect in one
Orientation in the cross-sectional anatomy of the female area can produce mechanical problems in various areas.
pelvis is crucial for better understanding of the relationship Urethral support is a good example. In an anatomically
between the pelvic structures (Fig. 31.3). normal female pelvis, the vagina supports both the urethra
and the bladder. When there is a defect in the pubourethral
Urinary Bladder ligament, the perineal membrane or the pelvic floor muscles
The urinary bladder contains three different muscular support to the bladder and the urethra are lost. This can
layers: (1) inner longitudinal, (2) middle circular and (3) cause symptoms of stress urinary incontinence (SUI) or
anatomical defect such as cystocele.
On transabdominal ultrasound the bladder may appear
square due to the pelvic musculature and bones. The bladder
wall is equally hyperechogenic, and has uniform thickness
(Figs 31.4A and B). Ultrasound assessment can precisely
estimate the amount of residual urine.
Color Doppler ultrasound enables visualization of
movement of fluid (Fig. 31.5).
Transvaginal ultrasound scanning enables more precise
evaluation of the trigone, posterior bladder wall and urethra.
The qualitative assessment includes assessment of the
urethra’s height (the distance between the bladder neck and
line through the lower edge of the pubic symphysis).
Figure 31.6 presents transvaginal ultrasound of the
urethra. Symphysis pubis is marked by dashed line.
Bladder neck mobility is assessed by height measurement
(yellow arrow), and is determined at rest and during
Valsalva maneuver. Figure 31.7 demonstrates posterior
Figure 31.3 A female pelvis in cross-section. Note the pelvic structures urethrovesical angle, which is also determined at rest and
and their relationship within the pelvic cavity during Valsalva maneuver. It is believed that 3D ultrasound
A B
Figures 31.4A and B (A) Transabdominal ultrasound of the urinary bladder (transverse plane); (B) Longitudinal transabdominal sonogram of
the urinary bladder. On the right side of the image note the ureteric orifice pointed by an arrow
Figure 31.5 Color Doppler enables visualization of the ureteric jets Figure 31.6 Transvaginal ultrasound of the urethra. Height
that represent the inflow of the urine from the ureters into the bladder measurement of the urethra is marked by yellow arrow. Dashed, white
line represents symphysis pubis
and tomographic ultrasound imaging may further improve works as a unit with the puborectal muscle. The etiology
noninvasive assessment of the urogynecologic disorders of fecal incontinence stems from defects with innervation
(Figs 31.8 and 31.9). to these muscles.
Rectum Anterior Compartment

Cystocele
The muscles of the rectum consist of the inner circular layer
and the outer longitudinal layer. The rectum is described as The prevalence of cystocele (anterior wall prolapse) is
the junction with the sigmoid colon extending to the anal estimated to be up to 34% in the US.5 Cystocele is defined
orifice.1 The internal anal sphincter (IAS) is formed by the as a herniation of the bladder into the vaginal opening. This
inner circular layer at the perineal flexure of the rectum. defect can be due to a paravaginal defect, which accounts
The external anal sphincter (EAS) is formed by striated for 80% of cystoceles. Other causes include transverse
muscle which remains mainly contracted. This sphincter defect, which accounts for up to 15% of cystoceles. A
ÀÀ Position of each structure should be measured relative
to the inferoposterior margin of the symphysis pubis.
Interpretation of the results:
A study performed by Dietz et al. has shown that most
nulliparous women show evidence of intact paravaginal
support structures.10 Tenting occurred in women with
widely varying bladder neck descent (BND), demonstrating
an association between excessive bladder neck mobility and
increased fascial compliance. Dietz et al. also demonstrated
that the descent of the bladder to greater than 10 mm below
the symphysis pubis is strongly associated with symptoms
of anterior compartment prolapse.
A similar study demonstrated that the use of translabial
ultrasound may be a less crude quantification method when
Figure 31.7 Transvaginal ultrasound assessment of the posterior compared to the traditional POP-Q.9 Ultrasound allowed for
urethrovesical angle
better imaging of all three pelvic compartments and was as
effective as the International Continence Society Prolapse
third type of cystocele is due to a midline defect which
assessment.
accounts for up to 5% of all cystoceles.6 Risk factors for the
development of a cystocele include trauma due to childbirth, Magnetic resonance imaging (MRI) has been used to
aging, prior hysterectomy, decreased estrogen levels and determine anterior compartment prolapse. However, due to
genetic predisposition.7 the dynamic nature of the pelvic organs, it has been questioned
Common symptoms associated with cystocele include to whether the MRI is able to produce reproducible images.10
bulging at the vaginal opening, vaginal pressure when Magnetic resonance imaging is also a much more expensive
bearing down, urinary incontinence, recurrent urinary tract imaging system compared to ultrasound.
infections, incomplete bladder emptying and dyspareunia.8
Stress Urinary Incontinence
Cystocele is commonly diagnosed using both physical
examination and a cystourethrogram. Physical examination The prevalence of SUI has been estimated to be between 4%
findings are based on a simple grading system. Grade and 35%.11 Stress urinary incontinence is defined as urinary
1 indicates the bladder falling only a short way into the leakage without associated detrusor contraction due to an
vagina, whereas Grade 2 shows the bladder reaching the incompetent urethral closure mechanism, associated with
hymenal ring. Grade 3 represents the bladder bulging increased intra-abdominal pressure.
through the vaginal opening.1 Risk factors for SUI are multifactorial and include
Figure 31.10 illustrates cystocele. Note the protrusion trauma to the levator muscles, prolonged second stage of
or the prolapse of the urinary bladder into the anterior wall labor, forceps delivery, older age and prior pelvic surgery.
of the vagina. Symptoms of the disorder consist of urinary leakage when
The protocol for the use of transperineal ultrasound intra-abdominal pressure exceeds urethral pressure such as
(TPUS) technique for visualization of cystocele is as with coughing, laughing, exercise or change in position.
follows:9 Currently physical examination includes the “Q-tip test”
ÀÀ Patient is placed in a supine position after voiding to test for urethral hypermobility. The test is performed by a
ÀÀ Ultrasound is performed with an empty bladder to clinician placing the cotton end of the Q-tip in the urethra to
maximize pelvic organ descent the level of the urethrovesical junction.10 Valsalva maneuver
ÀÀ Probe is placed on the perineum in a sagittal direction is then initiated; the change in angle from rest to Valsalva
ÀÀ Patient is asked to cough or strain is then measured using a goniometer. An angle of greater
ÀÀ When maximal descent is achieved, images of the than 30° above the horizontal is associated with urethral
bladder neck, leading edge of the cystocele, the cervix, hypermobility. Other diagnostic urodynamic evaluations
cul-de-sac and rectum should be taken. Care should be include uroflowmetry, resting and stress urethral pressure
taken to minimize pressure on these structures profilometry and subtracted water cystometry.
Figure 31.8 Three-dimensional ultrasound of the urethra
Figure 31.9 Tomographic ultrasound imaging of the urethra

Pregazzi et al. showed that a urethral angle of greater than
14° by ultrasound is representative of hypermobility. 13
A BN-S greater than 26 mm indicated stress urinary
incontinence. It was shown that when comparing urethral
angles to bladder neck mobility there is a greater sensitivity
(96% vs 87%) and specificity (92% vs 68%).
Studies have demonstrated the importance of BND in the
diagnosis of SUI.12 Although a standard normal measurement
for BND has yet to be defined, evidence suggests that BND
measurements greater than 15 mm correlate well with
hypermobility. Funneling is a characteristic entity to SUI
Figure 31.10 Medical illustration of cystocele but is not pathognomonic as it can also be demonstrated in
Source: Plavsic SK (Ed). Color Doppler, 3D and 4D Ultrasound in
Obstetrics, Gynecology and Infertility. New Delhi: Jaypee Brothers;
urge incontinence.
2011 (Medical illustration by Dr Patham and Dr Subramanya).
Central Compartment
A less invasive radiological technique is transvaginal and Levator ani complex is best assessed by transvaginal
transperineal ultrasonography.12 Sonographic assessment is ultrasonography using the following protocol:14
less invasive, highly reproducible, and leads to decreased ÀÀ Patient should be placed in a supine position
overall cost to the patient. Major disadvantages include length ÀÀ The scanning angle should be 360° in a plane
of time for the procedure to be completed and inability to perpendicular to the axis of the probe
complete a study if severe POP or procidentia is present. ÀÀ The probe is inserted into the vagina, paying attention
Protocol for introital ultrasound is as follows:13: not to exert the pressure on the pelvic floor muscles. The
ÀÀ Patient is placed in a dorsal lithotomy position with a prolapse should be reduced before insertion of the probe
full bladder ÀÀ Axial plane images of the pelvic floor are obtained along
ÀÀ The ultrasound probe is placed on the intralabial region the vagina using the pubic symphysis as a guide at the
of the vulva in a sagittal orientation. This enables the top of the screen and adjusting the probe, so symmetrical
sonographer to view the symphysis pubis, bladder and images can be obtained
urethra in one view ÀÀ By tilting the probe cranially or caudally, the pubococcygeus
ÀÀ The following measurements are performed first at muscle “sling” can be imaged in its entirety with its muscle
rest, at maximal straining and at maximal pelvic floor fibers running parallel to each other
contraction: ÀÀ The pubococcygeus muscle thickness should be
• Bladder neck-symphysis (BN-S) distance: The measured at the level of the posterior vaginal wall
distance from the bladder neck to the lowest point of ÀÀ The hiatal area should be measured by outlining the
the symphysis pubis inferior border of the symphysis pubis anteriorly and
• Alpha angle: The angle between the BN-S and the the inner boundary of the pubococcygeus muscle using
midline of the symphysis pubis, and a cursor. Alterations in the morphology, such as the
• Beta angle: The angle between the proximal mobile presence of mixed echogenicity and trauma, should be
aspect and distal immobile aspect of the urethra. noted on each side
ÀÀ Funneling of the internal urethral meatus is also noted ÀÀ At a higher scanning plane, the obturator internus muscle
during Valsalva and occasionally during the resting can be visualized as a hypoechogenic structure on the
phase. This is due to the rotational descent of the internal lateral pelvic sidewall. The hyperechoic line overlying the
meatus rotating around the pubic symphysis. A change in obturator internus muscle represents the obturator fascia
the retrovesicular angle is the cause of funneling (normal ÀÀ The origin of the iliococcygeus is clearly visible from
retrovesical angle is 90–120°). Funneling is associated the obturator fascia at a higher cephalad level.
with an angle of 160–180°. Multiple studies have been performed to better
ÀÀ In B-mode real time imaging, streaming can be noted understand the role that pelvic floor muscles play in women
and appears as two linear echoes. with diagnosed urogenital prolapse. The majority of these
studies focus on the use of pelvic ultrasound versus MR to into the wall of vagina. Risk factors include weakening of
obtain the best images to better assist with the recognition the pelvic floor structure due to pregnancy and childbirth,
of the extent of the prolapse.15-17 Until recently, MR was the increasing age, prior pelvic surgery, obesity and chronic
imaging modality of choice because it was the only method cough. Other factors include genetics, Hispanic and Asian
available for assessing the levator ani complex in vivo.18 race and family history of POP.11,25 Common symptoms
However, due to the advent of 3D ultrasound, this novel include abdominal pain, low back pain relieved with lying
technique can be used to equally demonstrate anatomical down, feeling of pelvic pressure and fullness, a bulge in the
structures of the pelvic floor. As mentioned previously, the vagina, dyspareunia and a pulling sensation in the pelvis.25,26
advantages include lower costs and wide availability.9,18,19 A major advantage of translabial ultrasound is due to the
Athanasiou et al. have prospectively evaluated women different characteristics and location of an enterocele in relation
using 2D ultrasound to compare the pelvic anatomy of to a rectocele. An enterocele is represented by the peritoneal
females with urogenital prolapse versus a control group to sac or loops of bowel anterior to the anorectal junction12
better understand the nature of prolapse.14 Specifically, the (Fig. 31.11). Enterocele can also be easily diagnosed with
levator ani muscle of women with POP were evaluated using TPUS with Valsalva due to the downward displacement of
real-time 2D ultrasound. The study showed that morphology abdominal contents anterior to the anorectal junction.
and hiatal area could be reliably imaged using 2D ultrasound, A pilot study performed by Beer-Gabel et al. showed
and noted that POP was related to a change in the pelvic floor that using transperineal imaging to define the infralevator
morphology and increased levator hiatal area. viscera, soft tissues and margins of the puborectalis muscle,
Childbirth has long been identified as a risk factor for a dynamic measurement of enteroceles was possible.27 It
POP, especially due to the trauma caused by fetal head was shown that transverse images of the anal sphincter were
during delivery.1,2,4,20,21 A study by DeLancey et al. was comparable to those using endoanal ultrasonography. The
performed to evaluate the difference in the levator ani advantages include noninvasive nature and reproducibility
complex in nulliparous women versus women who had when diagnosing patients with evacuatory disorders and
a history of vaginal delivery using MR as the imaging pelvic floor dysfunction.
modality of choice.22 The results revealed that 20% of A prospective observational study with POP patients by
primiparous women have a visible defect in the levator Steensma et al. assessed proctography versus 3D TPUS.28
ani muscle where most defects were visualized within the The study revealed that the Cohen’s Kappa Index for
pubovisceral muscle. an enterocele was 0.65 (good), and for a rectocele was
A similar study using four-dimensional (4D) translabial 0.55 (moderate), respectively. The results showed a good
ultrasound was used to estimate the risk of prolapse associated agreement between 3D TPUS and evacuation proctography
with levator avulsion injury in the urogynecological (EP) for the detection of enterocele and rectocele.
population. Nine hundred thirty-four women were evaluated A similar study by Perniola et al. revealed that translabial
using the POP-Q and results were compared to the images ultrasound was a good initial tool to use for defecatory
obtained using 4D labial ultrasound. The study concluded disorders as it was better tolerated by patients when compared
that levator avulsion defects were twice as likely to show to a defecation proctography.29 However, contrary to a previous
POP at stage II or higher.23 The advantage of using 4D study by Steensma et al., there was poor agreement between
ultrasound was high reproducibility of the results. The these two modalities when measuring qualitative parameters.
diagnosis of levator avulsion was demonstrated by lack
of continuity between the inferior pubic ramus and the Rectocele
puborectalis muscle. This is made evident as a V-shaped
loop defining the plane of minimal hiatal dimensions.23,24 Rectocele is defined as a fascial defect, which causes a
herniation of the anterior rectal wall in to the vagina.1 As
discussed previously, the prevalence between rectocele and
Posterior Compartment
enterocele cannot be divided into subgroups. The combined
Enterocele prevalence of the two groups ranges between 20 and 80%.15,30
Enteroceles are usually found in conjunction with Risk factors associated with rectocele include genetics,
rectoceles, limiting the ability to assess the prevalence.15 aging, obesity and connective tissue disorders.3,26,31 It was
An enterocele is defined as a herniation of the small bowel previously thought that trauma associated with childbirth
Figure 31.11 Medical illustration of enterocele. Figure 31.12 Medical illustration of rectocele.
Source: Plavsic SK (Ed). Color Doppler, 3D and 4D Ultrasound in Source: Plavsic SK (Ed). Color Doppler, 3D and 4D Ultrasound in
Obstetrics, Gynecology and Infertility. New Delhi: Jaypee Brothers; Obstetrics, Gynecology and Infertility. New Delhi: Jaypee Brothers;
2011 (Medical illustration by Dr Patham and Dr Subramanya) 2011 (Medical illustration by Dr Patham and Dr Subramanya)
was a risk factor for rectoceles, however, recently using 3D

ultrasound, less than 15% of nulliparous women show a
defect of the rectovaginal septum.32 Translabial ultrasound
and 3D ultrasound technology have shown that one-third
of clinical rectoceles were not seen sonographically.30
Symptoms of a rectocele depend on the severity of out
pouching. Patients may be asymptomatic or may present
with vaginal bulging, defecation problems, rectal pressure/
fullness and difficulty with intercourse.3,20,31 Figure 31.12
presents schematic illustration of rectocele.
Translabial ultrasound using 3D modality is performed

as follows:30
ÀÀ Patient is examined in a supine position after voiding
ÀÀ In the sagittal plane, measure posterior floor volume in Figure 31.13 Intact anal sphincter on the transverse section using
three phases: (i) at rest, (ii) with levator ani contraction the lower plane. Note “mucosal star” appearance, indicative of normal
anatomy.
and (iii) with maximal Valsalva. All measurements are
Source: Ahmed B, Andonotopo W, Khenyab N, et al. Assessment of
to be taken in 2D imaging. the anal sphincter in female patients using transvaginal sonography.
Ultrasound Rev Obstet Gynecol. 2005;5:1-10.
Downward displacement of a rectocele on valsalva inferior symphyseal margin. It should be noted that these
or displacement of rectal contents can be used to findings are only valid if no fascial defects are noted.
quantify posterior compartment prolapse. If the posterior Another imaging modality which has been used to
compartment herniation measures greater than 10 mm diagnose posterior compartment prolapse is MRI. A study
in depth along with findings of a sharp discontinuity in by Kruger et al. compared the use of 3D multiplanar MRI
the ventral contour of the anorectal muscularis, it can be to 3D translabial ultrasound when measuring pelvic floor
concluded that a rectovaginal defect is present.30 However, function by examining the levator hiatal dimensions of
this displacement should not be confused with perineal asymptomatic nulliparous females.33 It was shown that
hypermobility which is shown by the displacement of there was a moderate to substantial agreement between
ampullary contents below a reference line through the both modalities for all testing parameters.
A
B
C D
Figures 31.14A to D Three-dimensional ultrasound technique for visualization of the anal sphincter. (A) Transverse section; (B)
Longitudinal section; (C) Frontal section; (D) Three-dimensional reconstruction imaging.
Source: Ahmed B, Andonotopo W, Khenyab N, et al. Assessment of the anal sphincter in female patients using transvaginal
sonography. Ultrasound Rev Obstet Gynecol. 2005;5:1-10
Anal Incontinence
The definition of anal incontinence is the inability to
control ones bowel movement leading to leaking from
the rectum.34-37 The prevalence of both anal and fecal
incontinence ranges from 11 to 18%.30 Risk factors for fecal
incontinence include increased age, nerve damage due to
trauma, neurological diseases and diabetes mellitus.38-41
The most common symptoms of fecal incontinence
include the inability to make it to the restroom in a timely
fashion and the loss of sphincter control.1,40,41
Techniques for endoanal ultrasound42-44 are as follows:
ÀÀ The participant is placed in a left lateral decubitus
position
ÀÀ Endoanal probe is placed to the rectum, and rotated so
that the 12 o’clock position is anterior Figure 31.15 Three-dimensional niche mode demonstration of three
ÀÀ Withdraw probe until you are able to visualize the orthogonal planes of the anal sphincter seen in a stereoscopic view.
Source: Ahmed B, Andonotopo W, Khenyab N, et al. Assessment of
V-shaped puborectalis muscle. The most superior aspect the anal sphincter in female patients using transvaginal sonography.
of this is the anal sphincter Ultrasound Rev Obstet Gynecol. 2005 5:1-10
Table 31.1 Advantages of ultrasound imaging in urogynecology
Type of ultrasound Advantages Disadvantages
All ultrasound techniques • Can be performed at the bedside47-49 • Images dependent on body habitus49
• Inexpensive47-49 • Images are operator dependent47
• Real-time imaging without the need to
sedate patient47-49
• No exposure to radiation47
• Widely available
Transabdominal • Bladder can be easily visualized49 • Difficult imaging if bowel-gas is present

• Noninvasive due to obscured view47,49,50
• Suitable for all ages50 • Requires a full bladder for optimal imaging50,51
• Low probe frequency50
Transvaginal • High probe frequency which means better • Invasive

image quality50 • Not suitable for all patients
• Not dependent on body habitus
• Performed with an empty bladder52
• Provides a panoramic view of the true
pelvis52
• Can easily identify pelvic masses
Translabial • Superior to MRI for detection of mesh and • Inability to assess mesh erosion into the
other synthetic material after pelvic organ vagina, bladder or urethra12
prolapse surgery12
• Ability to perform dynamic evaluation12
• Ability to image the whole levator hiatus,
anal canal, anal sphincter, urethra and
bladder base43,53,
• Rectoceles can easily be distinguished
when compared to enteroceles54
• Funneling present with stress urinary
incontinence13
Endoanal • Accurately defines the external anal • Poor definition of atrophy55

sphincter and internal anal sphincter • Limited in assessment of suprasphincter
defects55 disease55
• Learning curve interpretation43
Color Doppler • Ability to record streaming in urinary

incontinence13
Three-dimensional • Increased accuracy of volume

measurements47,48
• Accurate anatomical details which can
potentially aid in surgical planning48
• Compatible with both transabdominal and
transvaginal data measurement48
• Excellent pelvic muscle floor definition
Table 31.2 Advantages and limitations of magnetic resonance imaging in urogynecology

Advantages Limitations
• Higher accuracy compared to endoanal ultrasound55 • Limited accuracy in internal anal sphincter defects55
• Standard to define external anal sphincter atrophy55 • Expensive43
• Excellent pelvic muscle floor definition43 • Not widely available
• More accurate for diagnosing fistulas43 • High false-positive rate of sphincter defects when fibrosis is
present43
Table 31.3 Key sonographic finding associated with each ultrasound modality
Type of ultrasound Urogynecologic disorder Ultrasound findings
Transperineal/translabial ultrasound Stress urinary incontinence • The mean values of the gamma angle are
smaller than 40°56
• Reduced mobility of the urethrovesical
junction53,56
• Bladder neck funneling present13,53
• No pelvic floor reactivity57
Urge incontinence • Thickness of the urinary bladder wall will be
greater than 5 mm56,57
Cystocele • Bladder neck descent of greater than 2 cm
with straining50
• Posterior urethrovesical angle of less than
140° with straining50
Transvaginal/transperineal ultrasound Levator ani complex • Levator avulsion is diagnosed by the
detachment of muscle from the pelvic side
wall58
• Atrophy is diagnosed if there is a marked
asymmetrical thinning (>50%) of the
muscle58
• The hyperechoic line overlying the
obturator internus muscle represents the
obturator fascia14
Endoanal ultrasound Enterocele • Herniation of the pouch of Douglas
containing loops of small bowel protruding
into the vagina during the Valsalva
maneuver31,59
Rectocele • A rectovaginal septum with a sharp
discontinuity in the ventral contour of
the anorectal muscularis resulting in a
herniation measuring greater than 10 mm
in depth30
• On 3D ultrasound the presence of a
hyperechoic layer between the hypoechoic
vaginal muscularis and the internal anal
sphincter/anorectal muscularis60
Anal Sphincter defect • Internal anal sphincter greater than 5 mm:
hereditary myopathy
• Local thickness: leiomyoma
• Internal anal sphincter less than 2 mm:
Muscular atrophy, anal incontinence, and
trauma42-44
ÀÀ The internal anal sphincter (IAS) can be described as • The EAS should be evaluated specifically for the
a concentric hypoechoic band surrounding the anal following:
mucosa: – Loss of continuity
• The IAS should be measured for its thickness. The – Partial or complete muscle tears: Trauma to the
following abnormalities may be noted: sphincter can be described as interruption of the
– Internal anal sphincter more than 5 mm, suggestive fibrillar echotexture of the sphincter, and
of hereditary myopathy – Change in echo density which may signify
– Increased local thickness, suggestive of leiomyoma hematoma, calcification or sphincter atrophy.
– Internal anal sphincter less than 2 mm, suggestive When loss of normal architecture is noted this
of muscular atrophy, anal incontinence and trauma can be due to scarring. It may present as low
ÀÀ The external anal sphincter (EAS) can be identified reflectiveness.
lateral to the IAS as a concentric band of mixed Currently both ultrasound and MRI have been used to
echogenicity: evaluate the extent of damage to the anal sphincter. Many
times such results are important to ascertain prior to surgical 4. Kearney R, Miller JM, Ashton-Miller JA, et al. Obstetric
management to ensure that the complete defect is identified factors associated with levator ani muscle injury after
so that a successful surgery can take place. Study by Rociu vaginal birth. Obstet Gynecol. 2006;107:144-9.
et al. evaluated MRI versus ultrasound in relation to surgical 5. Moore Keith, Dalley Arthur. Clinically Oriented Anatomy,
findings.43 Magnetic resonance imaging was more accurate 4th edition. Lippincott Williams & Wilkins; 1999. pp 332-62.
6. Armstrong PA, Pazona JF, Schaeffer AJ. In: Raz S,
than ultrasound for identifying sphincter lesions and
Rodriguez LV (Eds). Female Urology, 3rd edition.
allowed for higher spatial resolution and imaging contrast
Philadelphia: Saunder Elsevier; 2008. pp 847-56.
compared to US. However, US was noted to be superior and 7. Lentz GM. Anatomic defects of the abdominal wall and
more precise when measuring and describing the extent of pelvic floor. In: Katz VL (Ed). Comprehensive Gynecology,
a lesion, which overall was more helpful from the surgical 5th edition. Philadelphia PA: Mosby; 2007.
prospective. 8. Abed H, Rogers RJ. Urinary incontinence and pelvic organ
Richter et al. evaluated endoanal ultrasound to determine prolapse: diagnosis and treatment for the primary care
the correlation between symptom severity and the extent of physician. Med Clin North Am. 2008;92:1273-93.
sphincter damage.42 The results of the study revealed that 9. Dietz HP, Haylen BT, Broome J. Ultrasound in the
anal sphincter gaps were more prevalent in postpartum quantification of female pelvic organ prolapse. Ultrasound
primiparous women with increased severity of symptoms.
10. Dietz HP, Steenma AB, Hastings R. Three dimensional
This study further validates that one of the major risk factors
ultrasound imaging of the pelvic floor: the effect of
for anal incontinence is sphincter trauma.44,45 parturition on paravaginal support structures. Ultrasound
Figures 31.13 to 31.15 illustrate the assessment of anal Obstet Gynecol. 2003;21:589-95.
sphincter using 3D ultrasound.46. 11. Hughes D. Pelvic organ prolapse. In: Schorge JO, Schaffer
JI, Halvorson LM (Eds). Williams Gynecology. New York,
Summary NY: McGraw-Hill Medical; 2008.
Advantages and disadvantages of ultrasound and MR imaging are 12. Dietz HP, Hoyte L, Steensma A. Atlas of pelvic floor
presented in Tables 31.1 to 31.3. ultrasound. London: Springer-Verlag London Ltd; 2008.
13. Roberto P, Andrea S, Paolo B. Perineal ultrasound evaluation
of the uretral angle and bladder neck mobility in women
Conclusion
with stress urinary incontinence. BJOG. 2002;109:821-7.
The authors hope that this chapter has demonstrated the ease 14. Athanasiou S, Chaliha C, Toozs-Hobson P, et al. Direct
at which different ultrasound modalities can be used to evaluate imaging of the pelvic floor muscles using two-dimensional
patients with pelvic floor abnormalities. Although, as demonstrated,
MR is still the modality of choice for in vivo examination, the authors ultrasound: a comparison of women with urogenital prolapse
believe that, with the advances in 3D and 4D ultrasound and the verses controls. BJOG. 2007;114:882-8.
various approaches (transabdominal, transvaginal, translabial, 15. DeLancey JO. In: Cardozo L, Khoury S (Eds). Textbook of
transperineal, endoanal), ultrasound may become a method of Female Urology and Urogynecology. London: Isis Medical
choice for the dynamic assessment of pelvic floor disorders.
Media; 2001. pp 351-8.
16. Christensen LL, Djurhuus JC, Lewis MT, et al. MRI
of voluntary pelvic floor contraction in healthy female
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Section 4
DOPPLER SONOGRAPHY
¯¯ Physical Principles of the Doppler Effect and its Application in Medicine
¯¯ Use of Ultrasound in the Field of Infertility
¯¯ Chorionic Volume and Intervillous Blood Flow in Normal First Trimester Pregnancies Assessed by 3D
Power Doppler Ultrasound
¯¯ Doppler Evaluation of the Ovary: Clinical Applications and Challenges
CHAPTER
32 Physical Principles of the Doppler

Effect and its Application in Medicine
Branko Breyer
Introduction
Doppler technique has been used in medicine for many
years but only in the last decade this diagnostic modality
has gained practical importance in obstetrics and
gynecology. B-mode ultrasound (US) gives information
about morphology. Doppler US gives information about
blood flow.
One must bear in mind that Doppler techniques and
instruments are highly complex, additional education
and knowledge of pelvic hemodynamics is needed for
correct usage and many Doppler measurements are not
standardized. Additional complications are the cost-benefit
issues (Doppler machines are usually very expensive), the
question whether Doppler should be used as a screening
tool or as a secondary or even tertiary test, interpretation
of results, time-consuming procedure and the question of
safety in early pregnancy. Figure 32.1 Illustration of Doppler effect: change of frequency due to
the movement of the reflector
For intelligent and successful application of the technique
to medical diagnosis, an understanding of Doppler physics,
its possibilities and limitations is necessary. Flow can
case that the reflector moves away (case C) from the
be detected even in vessels that are too small to image.
transceiver, the received frequency f1 will be lower than
Doppler US can determine the presence or absence of flow,
the transmitted f0. This frequency change ∆f (called the
flow direction and flow character. One of the fundamental
Doppler shift) is proportional to the velocity V of the
limitations of flow information provided by the Doppler
reflector movement.
effects is that it is angle dependent. Furthermore, artifacts in
In practice this means that doctors need an apparatus
Doppler US can be confusing and lead to misinterpretation
that transmits US waves into the body and receives
of flow information. These problems have been addressed
their reflections from the body. The apparatus must then
in this chapter.
measure the difference between the transmitted and the
received frequency. The frequency difference (Doppler
Doppler Effect shift expressed in Hz) is proportional to the velocity of the
Basic principle of Doppler effect for the case when the movement along the line that connects the wave transceiver
waves reflect from a reflector is illustrated in Figure 32.1. and the moving reflector.
If the reflector does not move (case A), the frequency of In medical applications the Doppler effect is usually
the reflected wave f1 is equal to the transmitted frequency used by insonating the moving blood and assessment of the
f0. If the reflector moves toward the transceiver, the reflected Doppler shift of US scattered on erythrocytes (Fig. 32.2).
frequency will be higher than the transmitted, while in Single erythrocytes reflect (retransmit) US in various
334 Section 4  Doppler Sonography
Figure 32.2 Scattering of ultrasound yields multiple back-scattered Figure 32.3 Relation between ultrasound beam and the flow
wavelets
directions, but the total back-scattered energy is sufficient flow profile is parabolic, that is, the velocity in the center
for velocity assessment. is the fastest and slows down as doctors approach the
The general method of measurement consists of walls. The law by which this changes is approximately a
transmission of bundled US into the body at a general angle parabola (Fig. 32.4). If there is an obstacle in the blood
α to the flow. In this case the following equation of Doppler vessel (a plaque, a branching, etc.), the profile deviates
shift is valid to sufficient approximation. from parabolic and can become turbulent. In any case, at
any instance at any cross section the blood flows at many
2f 0 V
∆f = cos (α ) different velocities at the same time, i.e there is a full
C
spectrum of flow velocities.
It is important to note that in this approximation the Doppler The results are usually shown as Doppler shift spectra
shift for α = 90° equals zero. in real-time according as is shown in Figure 32.5.
A more detailed theory1 shows that for wave beams The ordinate is the Doppler shift (Figs 32.5 and 32.6) and
the Doppler shift is not exactly zero at α = 90o, but the the abscissa is the running time. Doppler shift measured in
shift is small and not used in the present commercial hertz (Hz) is proportional to flow velocity and if the angle α
instrumentation. Thus, the plane wave approximation from is known, one can put velocities onto the ordinate by using
the above equation is valid for the normal practice. the equation for velocity calculation.
The upper spectrum (ART) has the typical shape of an
From the above Doppler shift formula, the velocity V
arterial spectrum. It is pulsatile. The peripheral venous
can be calculated by the following equation:
spectrum (VEN) in the lower part of Figure 32.5 is not
∆f × c pulsatile. Venous flow is not pulsatile in peripheral blood
V= ( m / s)
2 f 0 c cos α vessels but can be very pulsatile as the vessels approach
the heart. Since the blood flows at each instance at different
with c = US propagation speed, Df = Doppler shift, f0 = velocities, the spectra are generally filled-in. The lowest
transmitted wave frequency and α is the angle among the frequencies are cutoff with special high-pass filters, the so-
US beam and flow direction (Fig. 32.3). called, wall filters (wf). The filter was originally designed
The flow in blood vessels depends on the quality of their to eliminate the artifacts from moving blood vessel walls.
walls and vessel dimensions. If the flow is laminar (when Apart from absolute velocity measurement, one can
the walls are even and blood vessel is large enough), the define relative indices, which are particularly useful for
Chapter 32  Physical Principles of the Doppler Effect and its Application in Medicine 335
Three indices are in common use, (i) the systolic/diastolic
ratio (S/D ratio), (ii) the pulsatility index (PI) also called
the impedance index, and (iii) the resistance index (RI) also
called the Pourcelot ratio. If doctors designate the peak
systolic Doppler shift with S and the maximal diastolic
Doppler shift with D, simple indices can be defined that
Figure 32.4 Real-time Doppler spectrum. Ordinate is the Doppler shift; roughly describe some properties of the spectra (Fig. 32.6).
abscissa is the real time The S/D ratio is the simplest, but it is irrelevant when
diastolic velocities are absent, and the ratio becomes
infinite. Values above 8.0 are considered “extremely high”.
Definitions of RI and PI are as follows:
S− D
Resistance index (RI) =
S
S−D
Pulsatility index (PI) =
Mean
The RI is moderately complicated but has the appeal of

approaching 1.00 when diastolic velocities are abnormally
low and does, therefore, reflect the relative impairment
of flow by high resistance. These indices are ratios,
independent of the angle between the US beam and the
Figure 32.5 Illustrative arterial (ART) and venous (VEN) flow Doppler
spectra insonated blood vessel, and therefore not dependent on
absolute measurement of true velocity.
The PI requires computer-assisted calculation of mean
velocity, which still may be subject to very large experimental
error. In a normal pregnancy, neither the S/D ratio nor PI is
normally distributed across all gestational ages.
Pourcelot and Gossling initially derived the indices for
their statistically demonstrated association with adverse
clinical findings. However, the RI must not be considered
independent of changes in physiologic variables such
as heart rate, cardiac contractility, blood pressure and
the many other determinants of flow. This information
does not depend on the measurement angle since all the
parts of the spectrum change proportionally when angle
Figure 32.6 Spectrum parts used in the calculation of RI and PI α changes. However, as the angle approaches 90° the
measurement error increases drastically. In practice is the
best compromise between the resolution of B-mode image
flow evaluation without known angle between the flow and
resolution and accuracy of Doppler spectroscopy is obtained
the US beam.
at angles between 30° and 60°.
The three indices are highly correlated.2,3 There are
Doppler Indices intrinsic errors in all that have been quantified and lie
Due to inherent difficulties in quantitatively evaluating between 10 and 20%. There may be advantages to the RI or
blood flow, the blood flow velocity waveform has commonly PI where flow is markedly abnormal or in early pregnancy,
been interpreted to distinguish patterns associated with high when a very low end-diastolic velocity can be a normal
and low resistance in the distal vascular tree (Fig. 32.6). finding.
Instrumentation for Doppler artifact is shown in Figure 32.9. The top of the pulsatile
spectrum (highest velocities) are shown as negative (reverse
Measurements flow). If the spectrum is simple like in Figure 32.9, the
There are two basic technological methods for application recognition of the aliasing artifact is easy. In complex
of the Doppler effect in medicine (Fig. 32.7). It is possible spectra this can be hard. In such cases, it may be useful to
to transmit and receive US waves continuously with a probe have a combined PW and CW system or a high pulse rate
that contains a transmission transducer and a reception frequency (HPRF) system. The HPRF system has such a
transducer [continuous wave (CW) in Figure 32.7]. Another pulse rate that it violates the sampling theorem and thus
possibility is to transmit in the form of pulses whose yields mathematically ambiguous results. In the screen
Doppler shift is measured after the time necessary for US this is usually shown as multiple sampling volumes (spots,
to reach a defined depth in the body [pulse wave (PW) in cursors). Such a system measures at multiple spots at a time.
Figure 32.7]. If the operator can recognize the spots with dominant flow
These two systems have different properties. or positions the cursors in such a way that only one of them
The CW system has no depth resolution so that the hits flow, the system achieves a better performance for high
measurement results of all flows along the line-of-sight add velocity flow measurement.
together and mix. On the other hand, this system measures
all (fast and slow) velocities well. If there is only one blood
vessel along the line-of-sight or one flow is dominant, the
CW system is very good for practice.
If, however, one must measure the flow in a single blood
vessel, the PW system can measure within a well-defined
sensitive volume. The sensitive volume has a length that
depends on the pulse length (in time) and a width that
depends on the beam width (and focusing) (shown as
sensitive volume in Figure 32.8). The disadvantage of
such a pulse Doppler system is that it cannot measure high
velocities deep in the body. The reason for this is that a PW
system only occasionally looks at the flow so that it cannot
convey all the information at enough high throughput.
The phenomenon can mathematically be described by the Figure 32.8 Aliasing
sampling theorem, which results in the so-called aliasing,
i.e. reverse indication of flow that is too fast. The resulting
Figure 32.7 Continuous wave (CW) and pulse wave (PW) Doppler Figure 32.9 Two-dimensional flow mapping
Data Acquisition consists of comparing the transmitter carrier frequencies of
the transducer’s output, to reflected echoes. The so-called
The computerized generation of the flow velocity waveform quadrature detector separates the demodulated signal in two
is not a simple task. In addition to the modification of channels, that is, flow toward the transducer is represented
returned frequencies by scattering and tissue attenuation, a as positive Doppler shift and flow away from the transducer
number of computer-based steps are required to eliminate is represented as negative Doppler shift. The flow data are
low-frequency noise generated by tissues vibrating in represented in real-time.
response to the US beam and by non-US-based movement The spectral analysis is done with an algorithm called the
of tissues. fast Fourier transform, which makes a fast and approximate
Several processing mechanisms are used to modify and Fourier analysis of the signal.
adjust the returned frequencies.
Both excessive low and high frequencies are filtered-out Flow versus Velocity
(band pass).
High-pass filtering (allowing only frequencies above The actual display is Doppler shift versus time. If the angle
a set minimum to be shown) removes unwanted low- between the US beam and the flow is known, one can
frequency signals. Thus, interference from vessel wall display velocity versus time. The actual measurement of
vibration, or other tissue movement, is eliminated—but this the Doppler angle is often difficult. In some disciplines the
mechanism will also remove low velocities representing practice is to ignore the angle and speak about “velocities”
low flow. High-pass filtering, therefore, is capable of (TCD, sometimes fetal echocardiography). The nature of
erroneously suggesting absent flow in diastole. The operator the flow (pulsatile or steady, regular or turbulent, single
can usually adjust this filter. or branching, parabolic or plug) impacts significantly on
Sample volume or “range gate” limits the area the frequencies returned. Thus, although volume blood
(depthwise) to be analyzed. In duplex scanning the range flow can be calculated as the product of mean blood flow
gate is adjustable for length and for position. Range gating velocity and vessel area, this is fraught with variation in
assumes a standard time interval between pulse emission practical terms.
and echo return that is based on the standard tissue transmit The cross-sectional area of the vessel measured from the
time from the depth set by the operator. The receiving gate gray-scale image is very susceptible to error. Additionally,
is open only for the anticipated moment of echo return, the volume flow depends on the fourth power of the
thus restricting information received to what is “expected” vessel diameter so that any measurement error is grossly
from the area designated by the calipers on the screen. amplified.4,5 Even the thickness of the distance measurement
The sample volume should be larger than the vessel, and cursor plays a major role in measurement accuracy in blood
positioned to span it completely if doctors wish to have vessels of a few millimeters in diameter.
complete data on the flow within the vessel. If it is set Another major problem in measuring flow is the
too large, extraneous signals may be included. If it is set variation of blood velocity across the vessel cross section.
much smaller than the blood vessel diameter, the resulting Since the overall flow rate is the sum of the contributions
spectrum will be narrow (i.e. it will have a “window”) made by the blood at every point on the cross section, it is
unless the flow is grossly turbulent. necessary to average the velocity profile (mean blood flow
These mechanisms, therefore, restrict the information velocity). Various approaches to this have been described.
that is returned and analyzed, in an effort to present an The calculation is different when the velocity profile is
acceptable image. Such editing can discard some desirable measured (with multigated pulsed Doppler) and averaged or
data on (usually low) velocities. if it is averaged using a large sample volume to encompass
the whole vessel. Volume blood flow has been expressed as
milliliters per minute. In fettle applications the result may be
Signal Processing normalized to the fetal weight. Estimating the fetal weight
Since the pressure of the reflected US wave from blood is by US measurement formulae is also error-prone. It is
about a hundred times smaller than from the surrounding clear, to allow accurate or even vaguely useful volume flow
structures, a substantially higher amplification is required. measurement, that Doppler interrogation must be limited to
The data are then filtered and demodulated. Demodulation large vessels, with meticulous attention to methodology.
Figure 32.9 is an illustration of the aliasing effect on

an arterial spectrum where the peak velocities have been
too fast to measure with the particular pulse repetition
frequency (PRF) of a pulsed Doppler system.
Two-dimensional Flow Measurement:

Two-dimensional Color Doppler Display
The flow can be shown in two-dimensions (2D). In principle,
comparison or subtraction of successive 2D images can
achieve this. Only echoes from moving structures stay in
such images. The final result is a 2D display of moving
structures, mainly blood flowing through blood vessels.
The directions and speeds are color coded. Movements
toward the probe are shown in different shades of 1 color,
Figure 32.10 Doppler angiography or power Doppler
e.g. red, and away from the probe in shades of another color,
e.g. blue. The different shades signify relative velocity.
One must always bear in mind that this system shows Power Doppler Ultrasound
the component of velocity projected onto the probing US The shortcomings of the 2D directional Doppler (color
beam. This makes the display semiquantitative. One can Doppler) are many. Above all, the sensitivity to direction is
display the multiple Doppler shift measurement variances. a mixed blessing. It does give the much-valued information
In the red-blue combination code, the variance is usually about the direction of flow, but suffers from not-very-
shown in green. The larger the measurement variance—the high sensitivity and direction artifacts. Now, in many
more green. This gives an indication of turbulence. Flow cases the directional information is very valuable, like in
at 90° to the US beam is not shown (in the image they are echocardiography. However, there are many instances when
the only relevant question is “Where are the blood vessels?” or
shown black, i.e. as if it were not there). The color code
“How many blood vessels are there?” or “What is the perfusion
is arbitrary and in the majority of machines can be chosen
of this area?” The direction may be of little importance or
from a number of different possibilities. Since the 2D color determinable with a built-in Doppler spectrometer. Basically,
Doppler is semiquantitative, it is as a rule combined with color Doppler yields that information. However, it is not
a PW Doppler spectrometer. The 2D display helps in fast uncommon to find a clear Doppler spectrum signal from an
finding of the points where doctors wish to analyze the flow area that is completely without any color signal or where (if
by spectrometry. In this way, the 2D system reduces the doctors are lucky) the color appears occasionally. The reason
duration of Doppler examinations. Sometimes, however, the for this is that the directional information is evaluated from a
2D map is characteristic enough to help with the diagnosis. number of subsequent frames and ambiguous and low signals
The limitations of the method are equal to the pulse Doppler average out to zero.
technique and so doctors got the now ubiquitous “color All these considerations led the instrumentation researchers
Doppler”. As with any new method, the first amazement to take a step backward and develop a 2D system which just
yielded its place to systematic and often controversial, but detects and displays movement; any movement, in 2D. The
result is an instrument, which displays areas with moving
always tedious evaluation in clinical medicine. Since many
structures in color. The color means that there is flow in the
of the most feared illnesses develop on a long-time scale,
area and the brightness of the color qualitatively indicates
the method is still under scrutiny but is already accepted as the quantity of moving erythrocytes.6
a useful tool. Every normal color Doppler system has the basic
A particular form of 2D flow mapping is the, so-called, capability for “power Doppler” or “Doppler Anglo”.
power Doppler (Fig. 32.10). Actually, the power Doppler is a mode of operation in
which any signal which shows a Doppler shift (change in measurement error tends asymptotically toward infinity
frequency) is tagged with color. So the direction becomes when the angle approaches 90°. The raw result of the
irrelevant. Unlike color Doppler where a symmetrical measurement is a spectrum which illustrates the general
turbulence shows a poor signal, in power Doppler the signal behavior well, but has the data on velocity hidden by an
will be as strong as any. The reason for this is that when additional unknown factor—the angle. However, even
directional information is displayed, the zero mean velocity with the angle α known, data like mean velocity can be
is not displayed; while in the case when the total reflection calculated only by way of a fairly complicated numerical
from any moving structure is displayed, a turbulent flow is integral of the weighted spectrum. The automation which
as indicative as any. picks up the respective weights of single velocities within
The decision as to what is flow and what is not is taken by the spectrum at each instant operates fairly autonomously,
looking at the frequency spectra and high enough frequency usually without intervention of the operator. The
shifts are considered to represent blood flow. The color intervention by way of changing measurement sensitivity
coding is made proportional in brightness to the total power can change the result of the calculation. One must
of reflected US from moving structures. Structures which continuously bear in mind that doctors measure Doppler
do not move, or move slowly are not color coded. shift only, while the rest of the data is derived from it.
The displayed color indicates the quantity of moving The accuracy of assessment of the Doppler shift really
blood, but not the volume flow of blood per unit time. depends on the knowledge and control of the frequency
Actually, the virtue of this display mode is that it shows content of the US pulses. This is often not well controlled.
about equally fast and slow flow so that doctors can get An exception is operation with CW Doppler systems
a feeling of the general blood perfusion in some area. where the measurement can be made more accurate
However, if actual blood velocity or volume per unit time ÀÀ Color Doppler itself is not designed as an accurate
is of any interest, doctors must revert to other display and measurement method, but mainly a semi-quantitative
measurement modes. guiding method for Doppler shift spectroscopy. In
The returned signal depends, in addition, on the spite of this, the significance of different colors must
attenuation of US in the intervening tissue. This means that be known, and in particular one must carefully adjust
the flow in deeper blood vessels or the flow in the same the baseline shift since this can essentially change the
blood vessel that changes the depth will be shown with velocity-color map.
different brightness, depending on the depth. The density There exists, however, a possibility to extract the accurate
of the moving blood cells depends on the concentration of data on the Doppler shift by using a cursor which helps in
blood cells and local flow situation. The sampling volume reading the frequency shift from the computer memory.
depends on the length of US pulse and beam width. If
Fourier power spectra, where available, give quantitative
the sampling volume is larger than the blood vessel, the
data but are often not well understood. This spectrum is
average number of red blood cells in it will be smaller and
the returned signal will be thus relatively weaker, showing not a real-time spectrum but a graph with Doppler shift
a dimmer color on the display. on the abscissa and the energy in frequency range on the
ordinate. Its width and symmetry properties contain ample
information about the nature of the flow (which is harder
Basic Limitations of Doppler
to read from a usual real-time spectrum). One should not
Examinations confuse this power spectrum with the “power Doppler”
In Doppler measurements one encounters problems of ÀÀ Power Doppler display method has a slightly better
accuracy, precision and artifacts like in any measurement geometrical accuracy in showing the blood vessel lumen
and imaging method. The peculiarities of this method are than the normal “color Doppler”. This happens at the
as follows: cost of image repetition rate.
Accuracy Precision
ÀÀ Doppler spectrometry operates adequately for angles ÀÀ Thequantitative functional dependence of the velocity
between US beam and flow less than 60°. The theoretical measurement error on the knowledge of the angle α is
known. However, the usual method of measurement of Artifacts

the angle is very crude and thus one should try to avoid
using absolute values whenever possible Several artifacts are encountered in Doppler US.7–12 These
ÀÀ Since the color map scale is virtually continuous,
are incorrect presentation of Doppler flow information
there is only marginal accuracy in the judgment of (Table 32.1). The most common of these is aliasing.
the velocity by way of color assessment. However, However, others occur, including range ambiguity,
the variance map, although not accurately assessable, spectrum mirror image, location mirror image, speckle and
gives a very useful clue as to where one ought to do electromagnetic interference.
spectroscopic measurements. Again, the Fourier power
spectra capability enables a precise variance calculation Aliasing
and the power Doppler modality increases observation Aliasing is the most common artifact encountered in
sensitivity at the cost of losing directional information. Doppler US (Fig. 32.9).
There is an upper limit to Doppler shift that can be
Contrast Media detected by pulsed instruments. If the Doppler shift
frequency exceeds one-half the PRF, aliasing occurs and
The energy reflected (scattered) back from the erythrocytes improper Doppler shift information (wrong direction and
is about 10,000 times smaller than the energy reflected from wrong value) results. An analogous optical form of aliasing
the blood vessel walls. This presents serious technological occurs in motion pictures when wagon wheels appear to
sensitivity problems. One of the possibilities to increase the rotate in reverse direction (this happens here because the
sensitivity is to use contrast particles as scatters instead of number of pictures per second is insufficient to correctly
erythrocytes. The contrast media are basically composed of show the rotation speed). Higher PRFs permit higher
bubbles of gas or liquid enclosed in thin, non-toxic, usually Doppler shifts to be detected but also increase the chance
organic, membranes. Such bubbles are of well-defined size of the range ambiguity artifact. Continuous-wave Doppler
and stable enough to stay in the circulation long enough to instruments do not have this limitation but neither do they
make the required Doppler measurements before dissolving provide depth resolution.
and disappearing from the circulation. They reflect US Aliasing can be eliminated by increasing PRF, increasing
much better than erythrocytes proper and thus alleviate
Doppler angle (which decreases the Doppler shift for
much of the sensitivity problems.
a given flow), or by baseline shifting. The latter is an
In addition to help Doppler measurements, the contrast
media can modify and enhance normal echographic images. electronic “cut and paste” technique that moves the
A concentrated effort in research is underway to make misplaced aliasing peaks over to their proper location. It
various parameters of the contrast media more specific, e.g. is a successful technique as long as there are no legitimate
resonant at specific frequencies, or with biologically active Doppler shifts in the region of the aliasing. If there are, they
membranes. will get moved over to an inappropriate location along with
Table 32.1 Summary of Doppler artifacts
Error Cause Effect
Aliasing High flow exceeds 0.5 PRF Velocity peaks switch direction: Information
Doppler angle moving lost
Biphasic flow wave
Double image Doppler angle near 90° Wave duplicated in both directions
Mirror image Strong reflector adjacent (e.g. pelvic side Inappropriate gate location
wall or bone) Loss of Doppler information
Range ambiguity Tissue layers (e.g. large cyst) change beam Aberrant depth resolution
velocity Incorrect gate location
Beam deflection Tissue layers change Doppler angle Reduced lateral spatial
Incorrect gate location
Clipping Excessive wall filter Loss of low velocity, misperception of high
Gate inside vessel resistance
the aliasing peaks. Other approaches to eliminating aliasing Turbulent flow measured with a small sample volume
include changing to a lower frequency Doppler transducer can yield a symmetrical spectrum as well.
or changing to a continuous-wave instrument, which is Occasionally, a spectral trace can show one or more
often built-in into specialized cardiologic units. Aliasing straight lines adjacent to and parallel to the baseline, often
can occur in a pulse system since it is a sampling system on both sides.
which cannot yield a correct result unless it samples often This is due to any electrical noise operating at multiples
enough, that is twice the highest Doppler shift frequency. or whole fractions of the monitor image repetition including
This is called the Nyquist limit (of the sampling theorem). 50 Hz interference from power lines or power supply. It can
make determination of low or absent diastolic flow difficult.
Increasing the PRF can reduce the aliasing problem.
Electromagnetic interference from power lines and nearby
However, this can cause localization ambiguity. This
occurs when a pulse is emitted before all the echoes from equipment can also cloud the spectral display with lines
the previous pulse have returned. When this happens, early or “snow”. Improper PRF settings can ultimately cause
echoes from the last pulse are simultaneously received with erroneous diagnosis of an absent diastolic blood flow.
late echoes from the previous pulse. This causes difficulty In Figure 32.5 “WI” indicates the “window”—an empty
with the ranging process. In effect, multiple gates or sample space in the real-time spectrum. Strictly speaking, this
volumes are operating at different depths. Multiple sample space ought never to be empty, but in the case of parabolic
gates are shown on the display to indicate this condition. flow and somewhat reduced sensitivity the space will not
Range ambiguity in color-flow Doppler, as in sonography, fill in with measurement results. This logic applies if the
places echoes (color Doppler shifts in this case) that have sensitive volume takes up the whole blood vessel cross
come from deep locations after a subsequent pulse was section. However, if doctors reduce the sensitive volume
emitted in shallow locations where they do not belong. As so as to take-up only a small part of the blood vessel, a
already said, the HPRF systems intentionally introduce this “window” will appear even at fairly irregular flows. This
ambiguity for spectrometry, requiring sound judgment by does not influence much the assessment of RI and PI, but
the operator as to whether the results are correct or not. disturbs our assessment of the turbulence. Very turbulent
The mirror image artifact can also occur with Doppler flow will show at the same time positive (toward probe)
systems. This means that an image of a vessel and a source and negative (away from probe) flow spectrum. However, a
of Doppler shifted echoes can be duplicated on the opposite similar spectrum appearance can be expected if doctors put
side of a strong reflector (such as a bone). The duplicated the measurement angle near 90°. Therefore, doctors must
vessel containing flow could be misinterpreted as an always interpret the cause of the apparent synchronous flow
additional vessel. It will have a spectrum similar to that for in opposite directions.
the real vessel. A mirror image of a Doppler spectrum can Inadvertent change of the “wf” can cutoff the diastolic
appear on the opposite side of the baseline when, indeed,
part of arterial Doppler spectrum and lead to wrong clinical
flow is unidirectional and should appear only on one side of
diagnosis.13,14
the baseline. This is an electronic duplication of the spectral
information. It can occur when receiver gain is set too high
How to Reduce Problems?
(causing overloading in the receiver and cross talk between
the two flow channels) or with low gain (where the receiver Use the sensitivity with caution (use as low sensitivity as
has difficulty in determining the sign of the Doppler shift). practical).
It can also occur when Doppler angle is near 90°. Here the Start examination with the standard symmetrical color
duplication is usually legitimate. This is because beams are map and then gradually change it to nonsymmetrical types
focused and not cylindrical in shape. Thus, some portions of if needed.
the beam can experience flow toward, while other portions Be aware of the depth and increased aliasing probability
can experience flow away. An additional possibility is to fit at deeper structures and higher velocities.
a bend of a small blood vessel in the same sample volume Use all the three modes (B-mode, spectrum, color) for
which then yields opposite flows in the two parts of the survey, but use single modality to obtain the best quality
“hook” as opposite, nearly symmetrical spectra. of each of them (Table 32.2).
Table 32.2 Comparison of different Doppler instruments

Type Advantage Disadvantage Other
SPECTROMETERS
Pulsed wave (PW) Has depth resolution Poorly measures high velocities Higher price
deep in the body
High pulse rate frequency PW system which can measure Ambiguous measurement Requires more caution from
(HPRF) system fast flows (multiple sensitive volumes) operator
Continuous wave (CW) Measures all velocities Has no depth resolution— Lower price
mixes flows along the US beam
2D DOPPLER SYSTEMS
“Color Doppler” Yields the directional flow map Does not measure at 90°, Less Quite sensitive to wrong
and indication of turbulence, can sensitive than spectrometer, manipulation
show fast flow changes Prone to aliasing
“Power Doppler” Sensitive to small flows, does not Poorly follows fast flow Insufficient clinical experience
confuse the operator with unclear changes, Color dependent on
direction data depth, No aliasing, Gives little
clue about the type of flow (slow
image repetition)
Acknowledgment 7. Zalud I, Kurjak A. Artifacts and pitfalls. In: Kurjak A (Ed).

Transvaginal Color Doppler, 2nd edition. London-New
In writing this chapter some materials provided by Ivica Zalud, York: Parthenon Publishing; 1994. pp 353-8.
MD, PhD, have been used and this is kindly acknowledged. 8. Derchi LE, Giannoni M, Crespi G, et al. Artifacts in echo-
Doppler and color-Doppler. Radiol Med. 1992;83(4):
References 340-52.
9. Jaffe R. Color Doppler imaging: a new interpretation of the
1. Censor D, Newhouse VL, Vontz T, et al. Theory of Doppler effect. In: Jaffe R, Warsof SL (Eds). Color Doppler
ultrasound Doppler-spectra velocimetry for arbitrary beam Imaging in Obstetrics and Gynecology. New York: McGraw-
and flow configurations. IEEE Trans on Biomed Eng. Hill; 1992. pp 17-34.
1988;35(9):740-51. 10. Winkler P, Helmke K, Mahl M. Major pitfalls in Doppler
2. Burns PN. Principles of Doppler and color flow. Radiol investigations. Part II: low flow velocity and color Doppler
Med. 1993;85(5):3-16. application. Pediatr Radiol. 1990;20(5):304-10.
3. Taylor KJ, Holland S. Doppler ultrasound. Part I: basic 11. Suchet IB. Color-flow Doppler artifacts in anechoic soft-
principles, instrumentation and pitfalls. Radiology. tissue masses of infants. Can Assoc Radiol J. 1994;45(3):
1990;174(2):297-307. 201-3.
4. Mitchell DG. Color Doppler imaging: principles, limitations 12. Pozniak MA, Zagzebski JA, Scanlan KA. Spectral and color
and artifacts. Radiology. 1990;177(1):1-10. Doppler artifacts. Radiographics. 1992;12(1):35-44.
5. Kremkau FW. Doppler color imaging: principles and 13. Maulik D. Biosafety of diagnostic Doppler ultrasonography.
instrumentation. Clin Diagn Ultrasound. 1992;27:7-60. In: Maulik D (Ed). Doppler Ultrasound in Obstetrics and
6. Chen JF, Fowlkes JB, Carson PL, et al. Auto-correlation Gynecology. New York: Springer; 1997. pp 88-106.
of integrated power Doppler signals and its application. 14. Duck F, Zauhar G. Report on experiments by Starrit H,
Ultrasound Med and Biol. 1996;22(8):1053-7. Zauhar G, Duck F in Bath, Autumn. 1996.
CHAPTER
33 Use of Ultrasound in
the Field of Infertility
Sanja Kupesic Plavsic, Maria Larrazaleta
Introduction of the cycle in which the estrogen level is relatively low

and progesterone is not yet present. It was reported that
Infertility is defined as the failure to conceive a desired FSH is the best predictor of the ovarian function once the
pregnancy after 12 months of unprotected intercourse, age, etiology of infertility and semen quality had been
and affects 10% of married couples.1 More than any considered.2 The combined use of parameters such as age
other new method, ultrasound has made significant and basal FSH in counseling patients improves the accuracy
improvements in the modern management of female of prognosis and may serve as an index of functional
infertility. Transvaginal sonography (TVS) provides the ovarian reserve (ovarian age).
reproductive endocrinologist with a tool that can not only
As the estrogen level of the blood rises to the point where
evaluate normal and stimulated cycles but also assists in
release of FSH is reduced and release of luteinizing hormone
follicle aspiration and subsequent transfer of the embryo.
(LH) is increased, ovulation occurs.3,4 Progesterone, the
The addition of color Doppler capabilities to transvaginal
concentration of which rises in blood as the corpus luteum
probes permits visualization of small intraovarian and
(CL) blooms, inhibits further secretion of LH, leading to the
endometrial vessels, allowing depiction of normal and
deterioration of the CL. When that occurs, the levels of both
abnormal physiologic changes in the ovary and uterus.1
estrogen and progesterone fall, starting the chain of events
It may help in prediction of ovulation and detection of
that result in menstruation and repeated release of FSH.
certain ovulatory disorders and the luteal phase defect
Follicular inhibins and activins are also important in the
(LPD). Doppler investigation of ovarian blood flow may
control of FSH secretion and in the regulation of androgen
improve the early diagnosis of ovarian hyperstimulation
production in the ovary. The role of these compounds in
syndrome (OHSS) in patients with ovulation induction.
the menstrual cycle is gradually being understood, but more
Initial impressions concerning the usefulness of blood
research is needed to elucidate it completely. The periodicity
flow studies in infertile patients have been confirmed by
of the pituitary gonadotropic function is, therefore, only
numerous studies during the last two decades.
partly governed by the quantity of estrogen in blood. The
hypothalamic pituitary unit stimulates estrogen production
Cyclic Changes in the theca interna of the ovarian follicle, and progesterone
The mystery of human reproduction lies in cyclic production in the CL. When the progesterone level rises
changes in two anatomic entities: (i) the uterus and and inhibits the hypothalamic-pituitary unit, the CL
(ii) the ovaries. These histologically, embryologically and disintegrates and menstruation occurs.5
functionally different organs are united by cyclic changes
of the menstrual cycle. The rhythmic ovarian changes are Transvaginal Sonography of the Uterus
regulated by the hypothalamic gonadotropin-releasing
and Ovaries During the Menstrual Cycle
hormone (GnRH) and by the gonadotropic hormones of
the anterior pituitary gland.1 The use of high-frequency transvaginal probes has enabled
The studies of the hypothalamo-pituitary function better visualization of pelvic organs. This is achieved by
show that the highest concentration of released follicle placing the transducer in close proximity to the observed
stimulating hormone (FSH) prevails between 6 and 9 area which automatically enhances the resolution. Patients
days after the onset of the menstrual flow, i.e. in the phase prefer this approach to the transabdominal one because
it eliminates discomfort caused by the full bladder. are essential parts of this mechanism. The increased coiling
Transvaginal ultrasound is particularly suitable for the of the spiral arterioles caused by the shrinkage of the
infertility patients, since they are often submitted to endometrium, creates circulatory stasis, leading to tissue
many diagnostic and follow-up procedures, in particular ischemia. Vasoconstriction of the spiral arterioles and
the follicular assessment. Owing to their technical necrosis of their walls result in bleeding.5 Sonographically,
characteristics, transvaginal transducers enable visualization the uterine cavity is seen as heterogeneous area with
of the endometrial cavity during the entire menstrual cycle, sonolucent and hyperechoic components. Table 33.1
which is important when measuring endometrial thickness demonstrates ovarian and endometrial changes for each
and echogenicity. Transvaginal ultrasound is also suitable phase of the menstrual cycle.
for the follow-up of the follicular growth in patients with
spontaneous and stimulated cycles. Follicular/Proliferative Phase
The menstrual cycle is divided into three phases: (i) the With regression of the CL from the previous menstrual
menstruation phase, (ii) the proliferative phase, also called cycle, the level of ovarian steroids drops, inhibition of the
the follicular or preovulatory phase, and (iii) the secretory hypothalamic-pituitary unit is reduced and an increasing
phase, also called the luteal or postovulatory phase. quantity of FSH becomes available to stimulate the growth
of a new cohort of the ovarian follicles.6 The theca interna of
Menstruation the follicles begins to secrete estrogen under the influence
The menstruation phase of the cycle in normal fertile of trace values of LH that always accompany the release
women is characterized by disintegration and exfoliation of FSH. Estrogen stimulates regrowth of the endometrial
of the two layers of the functional layer: (i) pars compacta patches, while other portions of the endometrial tissue are
and (ii) pars spongiosa. The basal layer, from which the still shedding. The preovulatory peak of blood estrogen
endometrial mucosa regenerates, remains intact. Hormonal inhibits the release of FSH, and at the same time causes
deprivation and alterations in the spiral arteriolar system the release of LH in a larger quantity.3
Table 33.1 Ovarian and endometrial changes during menstrual cycle
Phase of the menstrual Hormonal changes Endometrium Endometrial Ovarian sonography

cycle microscopy sonography
Proliferative phase Gradual increase of FSH Straight to slightly coiled, Narrow hyperechoic One or more follicles
and estradiol (E2) tubular glands, lined by border with central echo size 2–3 mm identified
pseudostratified columnar and hypoechoic functional sonographically as a
epithelium layer round, echo free zones
Day 8–12: recruitment of
the dominant follicle
Ovulation LH surge (10–12 hours Numerous glands Triple line Preovulatory follicle
before ovulation) 10–14 mm 20–22 mm
Progesterone increases Increase in alkaline Sonolucent halo
phosphatase and surrounding the follicle
ribonucleoprotein Cumulus oophorus
Early secretory phase Progesterone increases Coiled glands with wide Hyperechogenic basal Echogenic areas within
LH and FSH decrease diameter, lined by simple layers the follicle
columnar epithelium with Irregular borders
subnuclear vacuoles “Endometrial ring” sign Accumulation of fluid in
the cul-de-sac
Late secretory phase FSH and LH decrease Dilated glands with intra- Homogeneously Solid, cystic or complex
E2 and progesterone luminal secretion lined by hyperechogenic appearance of the CL
decrease short columnar cells
Menstrual phase Initially low FSH, LH, E2 Fragmented endometrium Progressively decreased Quiescent ovaries
and progesterone with condensed stroma endometrial thickness
and glands with secretory Intracavitary blood and
Gradual increase of FSH vacuoles in a background heterogeneous material
and E2 of blood
(
(Abbreviations: FSH, follicle stimulating hormone; LH, luteinizing hormone; CL, corpus luteum)
Chapter 33  Use of Ultrasound in the Field of Infertility 345
The proliferative phase of the menstrual cycle occurs reflectivity and thickness, change progressively throughout
during the period of follicular growth. By means of TVS, the follicular preovulatory phase.15
follicles can be observed when measuring only 2–3 mm Endometrial thickness of less than 5 mm is usually
in diameter, whereas transabdominal sonography (TAS) associated with the early follicular phase. Endometrial
depicts the follicles measuring 5 mm or more in diameter.7 glands, lined by moderately low columnar cells are narrow
The onset of follicular growth is a continuous process which and tubular. Mitotic figures become numerous and blood
is independent of gonadotropin stimulation. Gonadotropin- vessels begin to run upward from the basal layer toward
independent growth proceeds until the follicle reaches the surface of the endometrium, where a capillary network
5 mm. 8 Further growth of the follicles is, however, develops. Ultrasonically, the endometrium appears thin and
impossible in the absence of appropriate gonadotropin slightly more echogenic than the surrounding myometrium.
level.9 Selection of the dominant follicle from the cohort At the beginning of the second week, the inner part of
of developing follicles occurs normally between day 5 and the endometrium is hypoechogenic, and consists of two
7 of the menstrual cycle, but its dominance is not apparent endometrial layers touching each other and forming a
sonographically until cycle day 8–12. A decline in the FSH, hyper-reflective line in between. The borderline between the
which occurs in the late follicular phase, is responsible for endometrium and the hypoechogenic myometrium is seen
the selection of a single, most mature follicle.10 Follicles as a bright band. The hypoechogenic part of the endometrial
with fewer FSH receptors on their surfaces become atretic. layer is probably caused by edema. The hypoechogenic zone
These subordinate antral follicles rarely reach more than between the intermediate echo and the lining corresponds to
14 mm in diameter and therefore, any follicle exceeding 14 the pars functionalis and should not be confused with their
mm is usually the dominant follicle. relatively hypoechogenic halo surrounding the basal layer.
The rate of growth of the dominant follicle is linear The halo corresponds histologically to a vascular network
from day 5 to the ovulation, averaging 2–3 mm/day, and between the endometrium and the myometrium.
the follicle reaches 18–24 mm in diameter by the time
of ovulation.11 Sometimes follicles can be confused with
Periovulatory Phase
other pelvic structures, mainly large-caliber blood vessels
such as the hypogastric vein. They can be differentiated by Size alone is not a good predictor of impending ovulation,
rotating the transducer by 90º into the perpendicular plane. but careful sonographic visualization of the maturing
If the structure is a vessel, it will elongate on the screen follicle may show the development of a sonolucent halo
and appear tubular. With use of the color Doppler function, around the follicle, which reflects the preovulatory change
the blood flow within the vessels will be easily visualized, in response to the LH surge and is seen within 24 hours
differentiating vessels from the follicles. At this point, it is before ovulation. Detection of the cumulus oophorus within
important to stress the importance of follicular monitoring the follicle is also strong evidence of imminent ovulation
and understand how important it is to detect subtle changes (Figs 33.1A and B).
of the follicular growth and development. Success of As the endometrium grows the thickness of the hypodense
ovarian stimulation depends on careful ultrasound follow- endometrium layers increases in correlation with the rise
up and good timing. This is why women undergoing of estradiol.16 Endometrial growth is similar in hormonally
ovulation induction procedures are subjected to numerous stimulated cycles and spontaneous cycles.17,18 As ovulation
ultrasound examinations. Transvaginal ultrasound is a approaches, the glands become more numerous and the
method of choice for serial follicular assessment, because expected endometrial thickness is about 10–14 mm. An
it does not require full bladder, which makes it easier to increase in alkaline phosphatase and ribonucleoprotein
schedule the examination.12-14 parallels the morphological changes.
Endometrial regeneration and growth can also be Several studies attempted to correlate the endometrial
documented by using TVS. Sonographic appearance of thickness and the sonographic appearance with the
the endometrium is a result of dynamic, histological and possibility of predicting implantation and pregnancy.19,20
physiological changes. The sonographic appearance of the The thickness of the endometrium was found to be a
endometrium can be divided into four types: (i) proliferative reliable, predictive parameter for implantation in patients
type, (ii) periovulatory type, (iii) secretory type I, and undergoing in vitro fertilization/embryo transfer (IVF/
(iv) secretory type II. Two aspects of the endometrium, ET), since no pregnancy occurred when the endometrial
Figure 33.1A Three-dimensional (multiplanar) image of preovulatory follicle
thickness was less than 6 mm on the day before ovum and the fluid is collected in the cul-de-sac. Echogenic areas
retrieval.19 In these studies, the texture of the endometrium within the follicle, blurred follicular contours (Fig. 33.3)
was graded according to its reflectivity.20 and accumulation of the fluid in the cul-de-sac are ultrasonic
Three types of endometrium were defined: signs of ovulation. At that time luteinized theca, granulosa-
1. Type A: An entirely homogeneous hyperechogenic lutein cells and capillary tufts from the vessels of the theca
endometrium. interna form the CL, the hallmark of the secretory phase.21
2. Type B: An intermediate isoechogenic pattern. The endometrium undergoes secretory changes and each
3. Type C: A multilayered endometrium (Fig. 33.2) glandular cell increases in size, develops vacuoles and
consisting of prominent outer and central hyperechogenic bulges with secretion. During the secretory phase, there is a
lines with inner hypoechogenic or sonolucent regions.20 significant increase of glycogen, acid phosphatase and lipids
Significantly, more patients had a multilayered in the endometrium. At the beginning of the luteal phase,
endometrium on the day of oocyte retrieval in the group the intermediate echo and the lining start to disappear, while
who conceived than in the group who did not. endometrium becomes increasingly echogenic. Increase of
the echogenicity starts in the area of the lining and continues
Luteal/Secretory Phase toward the uterine cavity; a distinct hypoechogenic area,
Following ovulation the corpus hemorrhagicum can be however, can still be recognized. These changes have been
detected as the follicle area is filled with echogenic material described as the “endometrial ring sign” (Fig. 33.4).
Figure 33.1B Surface rendering of preovulatory follicle. Note cumulus Figure 33.2 Transvaginal ultrasound of triple line endometrium, typical
oophorus pointed by arrow for follicular and periovulatory phase of the menstrual cycle
Figure 33.3 Irregular contours of the ruptured follicle and accumulation Figure 33.4 Early secretory transformation of the endometrium. Note
of free fluid in the posterior cul-de-sac are signs of ovulation hyperechogenicity of the basal endometrial layers
During the late luteal phase, the endometrium is Transvaginal Color Doppler Assessment
homogeneously hyperechoic (Fig. 33.5). The endometrial
growth differs individually: endometrial thickness
of Ovarian and Uterine Blood Flow
decreases in the postovulatory phase and then increases in Ovarian Circulation
the luteal phase, or it continuously increases exceeding the The cyclic changes of the ovarian circulation are manifested
periovulatory maximum and lasts until the late secretory most intensively in the intrinsic (intraovarian) vascular
phase.15 system.22,23 The ovary receives its arterial vascularization
The histological pattern of secretory endometrium from two sources: (i) the ovarian artery and (ii) the utero-
includes remarkably increased vascularization. These ovarian branch of the uterine artery. 24 These arteries
changes reflect the anticipated reception and maintenance anastomose, forming an arch parallel to the ovarian hilus.
of a blastocyst. If no blastocyst is present, chorionic The vessels sprouting from the arcade run through the
gonadotropin is not available to support the CL, which central medullary part of the stroma toward the periphery
undergoes regression. i.e. the ovarian cortex. In the ovarian cortex, the vessels form
Figure 33.5 Secretory transformed endometrium visualized by Figure 33.6 Transvaginal color Doppler scan demonstrating dominant
transvaginal ultrasound follicle with ring of angiogenesis
vascular arcades in the stroma, surrounding the follicles. In Table 33.2 Ovarian B-mode and Doppler findings in preovulatory,
the development of an ovarian follicle during the menstrual ovulatory, and early postovulatory phase
cycle, a rich capillary plexus is progressively formed in the Phase of the cycle Ovarian B-mode and Doppler findings
connective tissue layer or theca surrounding the avascular Follicular phase • Linear growth of the follicle (2–3 mm
daily)
granulosa cell layer of the ovarian follicle (Fig. 33.6). These • RI = 0.54 ± 0.04
vessels can be seen by color Doppler ultrasound during the
Preovulatory phase • Preovulatory follicle measures 18–24 mm
follicular phase of the menstrual cycle. Several hours before in diameter
ovulation, vessels penetrate the granulosa cell layer. • Drop of the vascular impedance
• Increased flow velocity of the follicular
Table 33.2 illustrates ovarian B mode and Doppler
capillaries is the sign of impending
findings in preovulatory, ovulatory and early postovulatory ovulation
phases of the menstrual cycle. Ovulation • Follicular rupture
Color Doppler facilitates the detection of small vascular • RI = 0.44 ± 0.04
• Various appearances of the corpus
areas at the periphery of the follicle and/or CL.25 Blood flow
hemorrhagicum and CL (echogenic, solid,
velocity waveforms from the follicle can be seen when the complex, etc.)
follicle reaches 10 mm in diameter, and may be used as Luteal/ • Increase in flow velocity during the early LP
a hemodynamic parameter of its growth, maturation and Postovulatory • RI = 0.43 ± 0.06
ovulation. The resistance index (RI) is approximately 0.54 ± phase • RI remains the same for 4–5 days,
afterward it starts rising again (0.50 ± 0.04)
0.04 until ovulation approaches (Table 33.2). A decline
begins 2 days prior to ovulation and reaches its nadir at (Abbreviations: RI, resistance index; CL, corpus luteum)
ovulation (0.44 ± 0.04).26 Vascular changes at the time of

impending ovulation include increased vascularity of the remains at the same level for 4–5 days after the ovulation,
inner wall of the follicle and a coincident surge in blood and then gradually rises to 0.50 ± 0.04, still lower than the
velocity just prior to eruption (Fig. 33.7). This may be one measured in the proliferative phase (Table 33.2).
caused by the dilation of new vessels that have developed Following ovulation, there is proliferation of the vessels
between the relatively vascular theca cell layer and the of the theca to further vascularize the granulosa cell layer as
normally hypoxic granulosa cell layer of the follicle.27 it and the theca merge to form the CL. Within 3 or 4 days
These vascular changes intensify the effect of the oxygen after the follicular rupture, the CL is supplied with a dense,
concentration across the follicular epithelium. The multilayered network of sinusoidal capillaries which are
intrafollicular blood velocity increases 24 hours before the drained by numerous superficial venules. By means of color
time of follicular rupture and continues for at least 72 hours Doppler, the blood supply to the CL can be clearly seen as
after the formation of the corpus hemorrhagicum.28 The RI a bright colored ring surrounding the CL (Fig. 33.8).
Figure 33.7 Transvaginal color Doppler scan of a dominant follicle. Figure 33.8 Demonstration of increased intraovarian vascularity during
The pulsed Doppler waveform analysis of the follicular vessels shows the luteal phase of the menstrual cycle, as seen by transvaginal color
a resistance index of 0.45. Note that there is a decrease in vascular Doppler ultrasound
resistance as ovulation approaches
Data from the literature indicate that the changes in PI pulsatility index (PI), could be a sign of follicle maturity
observed from the wall of the dominant follicle and CL and impending ovulation.33 Recently, several groups have
were less marked than the changes in blood velocity.28 tried to utilize those findings and have used color Doppler
Intraovarian blood flow is significantly higher on dominant ultrasound to determine oocyte quality in stimulated
side.29,30 Higher blood flow velocity and lower impedance cycles. They found a strong correlation between follicular
detected in the vessels of the dominant ovary in the late dimensions and peak systolic blood flow velocity.34 In both
follicular and early luteal phase indicate increased blood small and large follicles, administration of hCG resulted
flow to the dominant ovary. The increased blood supply in a rapid increase in peak velocities. In another study, the
to the ovary containing the dominant follicle and CL is maximum peak systolic velocity in both ovaries before
necessary for delivery of steroid precursors to the ovary oocyte recovery was compared in women who subsequently
and the removal of progesterone (Fig. 33.9). become pregnant and those who did not.35 Semi-quantitative
Some experimental studies showed that the blood flow perifollicular vascularity index, defined as the ratio of the
to the dominant ovary decreased dramatically during the total number of follicles to the number of follicles with
late luteal phase of the cycle.30,31 The Doppler technique and demonstrable pulsatile vascularity, highly correlated with
uptake of radioactive microspheres by the ovary in ewes oocyte recovery. Higher oocyte recovery rate was achieved
demonstrated a threefold to sevenfold increase in blood in patients with increased perifollicular flow assessed by
flow during the luteal phase.32 Therefore, in both uterine color Doppler prior to the administration of hCG.36
and ovarian vessels, changes in flow velocity occur before More recent studies reported a very strong relationship
ovulation, implying that these changes are complex and between peak systolic velocities, collection rates, embryo
not purely secondary to progesterone action. Undoubtedly, development and implantation rates.37,38 Harvesting oocytes
many other vasoactive compounds, such as prostaglandins, from the follicles with a peak systolic velocity of greater
are involved in the regulation of the ovarian circulation. than or equal to 10 cm/s was significantly more likely to
Although the diameter of the follicle is a relatively good result in obtaining grade I embryos, which in turn were more
predictor of oocyte maturity it is not a perfect indicator likely to implant. These findings were supported recently
of oocyte quality. It would, therefore, be beneficial to by another study in which follicles were divided arbitrarily
have an additional test of oocyte quality available before according to the percentage of vascularized surface.39 In
human chorionic gonadotropin (hCG) administration. A conclusion, oocytes obtained from highly vascularized
marked increase in the peak systolic blood flow velocity follicles had higher quality and were more likely to fertilize
around the follicle, in the presence of a relatively constant and result in pregnancy.
In the absence of estrogen production by the ovary,

uterine arteries have a high degree of vascular resistance,
expressed by narrow systolic Doppler flow waves and high
values of the PI and resistive index (RI).49 Interestingly,
multiparous women have persistent diastolic flow during
the early follicular phase more often than nulliparous
women, and therefore have significantly lower PI and
RI.50 A profound modification of the Doppler flow pattern,
suggesting a marked decrease in vascular resistance, was
detected after the transdermal administration of estradiol
(0.1–0.4 mg/day).49 This observation is in accordance with
the hypothesis that the decrease in vascular resistance
observed at the time of ovulation is mediated by estradiol.51
Because estrogen receptors have been identified in the
Figure 33.9 A high blood flow velocity and low vascular resistance
walls of the uterine arteries, it is likely that the effect of
(RI of 0.50) represent typical flow pattern of a CL estradiol on the uterine waveforms is direct. Therefore it
is postulated that the estrogenic effect on the uterine artery
vascular resistance is directly related to the plasma level of
Uterine Circulation biologically active estrogens and that a direct dose-effect
The majority of the blood supply to the uterus is from the relationship exists.52
uterine arteries, with minor contribution from the ovarian Blood flow in the main pelvic vessels can be easily
arteries. The uterine arteries give rise to the arcuate arteries visualized and recognized. The color Doppler signals from
which are oriented circumferentially in the outer third of the the main uterine vessels can be observed as lateral to the
myometrium. These vessels give rise to the radial arteries cervix at the level of the cervicocorporal junction of the
which, after crossing the myometrium-endometrium border uterus.53 Waveform analysis shows high to moderate flow
branch and give rise to the basal arteries and the spiral velocity. The RI depends on age, phase of the menstrual
arteries. The basal arteries, which are relatively short, cycle and special conditions (e.g. presence of the pregnancy
terminate in a capillary bed that serves the basal layer of or uterine fibroid). In most women, there is a small
the endometrium. The spiral arteries project further into the amount of end-diastolic flow in the uterine arteries in the
endometrium and terminate in a vast capillary network that proliferative phase.25 The RI is about 0.88 ± 0.04 until day
serves the functional layer of the endometrium. 13 of the 28-days menstrual cycle (Fig. 33.10).
Color Doppler studies demonstrated that only the spiral Doppler studies reported that diastolic flow in the uterine
arteries undergo substantial anatomical changes during arteries disappeared during the day of ovulation,54 and
the menstrual cycle.40 At the time of menstruation, due an increasing RI and systolic/diastolic ratio was noticed
to decreasing estrogen and progesterone levels, the spiral during the postovulatory drop in the serum estradiol
arteries constrict, producing local hypoxia and ischemia concentration.55 Increased uterine artery impedance was
of the endometrium. The distal portions of the arteriolar reported 3 days after the LH peak, with the highest PI value
system, the capillary and venous beds are then shed with in the uterine arteries on cycle day 16.56 These findings
the functional layer. may be explained by increased uterine contractility and
Rhythmic changes in uterine blood flow during the compression of the vessels traversing the uterine wall that
estrous cycle in different species are temporally associated decrease their diameter and cause consequently higher
with the daily ratio of estrogen to progesterone in systemic resistance to flow.57 During the normal menstrual cycle
blood.41-43 The higher the estrogen-progesterone ratio, the there is a sharp increase in end-diastolic velocities between
greater the quantity of blood flow is detected through the the proliferative and secretory phases of the menstrual
uterine vascular bed.44-46 It has been demonstrated that cycle. It is interesting that the lowest blood flow impedance
progesterone antagonizes the uterine vasodilatory effect of occurs during the time of peak luteal function, during which
estrogen,47,48 and the magnitude of this inhibition is related implantation is most likely to occur.25 Doppler studies
to the ratio of the two steroids.49 detected that the uterine vascular supply is highest in mid
Figure 33.10 Pulsed Doppler waveform analysis of the uterine artery Figure 33.11 Power Doppler assessment of spiral artery perfusion
and late luteal phases.54,55,58 The persistently lower RI in

the luteal phase suggests that the relaxation effects on the
uterine arteries persist until the onset of menstruation.
In anovulatory cycles these changes are not present, and
a continuous increase in the RI is seen.25 More recently,
Doppler studies discovered existence of a circadian rhythm
in uterine artery blood flow during the periovulatory period
which appears to be independent from hormonal changes.59
Clearly, the increased endometrial vascularity is highly
dependent upon the uterine, arcuate and radial artery
blood flow (Fig. 33.11). Blood flow velocity waveform
changes in the spiral arteries during normal ovulatory
Figure 33.12 Changes in the uterine artery blood flow in ovulatory
cycles are characterized by lower velocity (P < 0.05) and and anovulatory cycles
lower impedance to blood flow than are those observed in
the uterine arteries, with a larger diameter.14 The features
of endometrial blood flow may be used to predict the pregnancy failures.61 No pregnancy occurred when the PI
implantation success rate and reveal unexplained infertility of the ascending branch of the uterine arteries on the day
problems more precisely than evaluation of the main uterine of hCG administration was more than 3.0.62 The fecundity
artery alone. rate was 18% when the pulsatility was less than 2 and was
19.8% when the PI was between 2 and 3. These data suggest
that the measurement of uterine perfusion on the day of
Uterine Perfusion in Infertile Patients hCG administration may have predictive value regarding
Transvaginal color and pulsed Doppler sonography was fecundity in patients undergoing intrauterine insemination.
established as an additional tool in the management of The ageing process and its influence on the uterus has
infertile patients. In anovulatory cycles, a continuous increase already been widely documented.63-65 It is reported that
of the uterine artery RI has been detected25,53 (Fig. 33.12). endometrial and myometrial thickness changes with the
Moreover, in some infertile patients, an end-diastolic years of postmenopause. Myometrial thickness after the
flow is absent.60 Therefore, the uterine artery blood flow menopause changes less than endometrial thickness, which
could be potentially used to predict a hostile uterine may suggest that myometrial changes are more dynamic.
environment prior to embryo transfer. A mean PI of more Resistance to blood flow increases in both the uterine and
than 3.0 before the transfer can predict up to 35% of the radial arteries as the years of postmenopause progress.62,63
In infertile women uterine artery pulsatility indices endometrial pattern does not appear to be influenced by the
measured in mid-luteal phase of unstimulated cycles type of ovarian stimulation and it is of prognostic value in
correlate inversely with endometrial thickness,66 suggesting both fresh IVF, as well as frozen embryo transfer cycles.
a direct effect of uterine perfusion on endometrial growth.17 However, if subendometrial blood flow is detectable
Furthermore, PI correlates directly with the age of the (Fig. 33.11), the endometrial morphology seems to be less
patients,60 suggesting a detrimental effect of age on uterine important than previously described and it may be that the
perfusion.67 absence of blood flow is more significant than morphologic
A high prevalence of increased uterine artery impedance appearance of the endometrium.74
among infertile patients with the diagnosis of endometriosis
has also been reported. These evidences, although gained Three-dimensional and 3D Power
in different settings, seem to suggest an adverse effect
of endometriosis on uterine perfusion. That could be
Doppler Ultrasound Markers of
another way endometriosis compromises woman’s fertility Implantation
potential. Whether this is due to mechanical effects on the Endometrial thickness obtained by two-dimensional
pelvic vessels as a result of adhesions or is mediated by (2D) sonography is considered an important parameter
production of agents with vasoactive properties remains of endometrial growth. However, this parameter does not
to be explained.1 include the total volume of the endometrium. Retarded
endometrial development may be associated with primary
Endometrial Thickness and Vascularity infertility, and, therefore, endometrial volume assessment
by 3D ultrasound may be a clinically relevant parameter.
The question of a correlation between endometrial thickness
Three-dimensional ultrasound is applied in the same
and the likelihood of conception, in the context of assisted
manner as 2D vaginal ultrasound, and therefore, does not
conception, remains a contentious issue. However, a very
cause additional patients’ discomfort. Quantification of
thin endometrium (< 7 mm) seems to be accepted as a
the endometrial volume by 3D ultrasound in combination
reliable sign of sub-optimal implantation potential. A
with blood flow studies may be the best way to predict the
systemic review of 2,665 assisted conception cycles from
pregnancy rates in patients undergoing medically assisted
25 reports found interesting results.68 The difference in
reproduction (Fig. 33.13).
the mean endometrial thickness of conception and non-
conception cycles was statistically significant in eight Data from the literature indicate that neither the
studies, while 17 reports found no significant difference.68 volume, nor the thickness of the endometrium on the day
The authors concluded that results from various trials are of embryo transfer had a predictive value for conception
conflicting and that insufficient data exist describing a
linear correlation between endometrial thickness and the
probability of conception. The main advantage of measuring
endometrial thickness lies in its high negative predictive
value in cases with minimal endometrial thickness.69 In a
group of oocyte recipients, no pregnancies were reported
in women who had an endometrial thickness of less than 5
mm, whereas several pregnancies occurred in patients with
an endometrium thinner than 7.5 mm.70,71
Endometrial pattern is defined as the relative echogenicity
of the endometrium and the adjacent myometrium as
demonstrated on a longitudinal ultrasound scan. In this
respect, multilayered pattern on the day of oocyte retrieval
seems to be more predictive of implantation than any other
parameter measured.72,73 Thirteen studies examined the
value of endometrial pattern in predicting pregnancy, of Figure 33.13 Three-dimensional ultrasound assessment of the uterine
which only four failed to confirm its predictive value. The cavity using “shell” imaging
during IVF cycles.75 Patients who became pregnant were endometrial hypoxia, leading to detrimental effect on
characterized by a significantly lower RI (0.53 ± 0.04 vs implantation potential. In normal spontaneous menstrual
0.64 ± 0.04), obtained from the subendometrial vessels cycles, endometrial vascular indices increase progressively
by transvaginal color Doppler ultrasonography and a during the course of the luteal phase. Endometrial and
significantly higher flow index (FI) (13.2 ± 2.2 vs 11.9 ± subendometrial perfusion is negatively affected by serum
2.4), as measured by a 3D power Doppler histogram. No estradiol concentrations, which can explain why patients
difference was found in the predictive value of scoring with hyperstimulation have lower endometrial and
systems analyzing endometrial thickness and volume, subendometrial blood flow during the early luteal phase.
endometrial morphology and subendometrial perfusion Three-dimentional power Doppler implantation markers
by color Doppler ultrasonography and 3D power Doppler seem to be crucial for planning a single embryo transfer
ultrasonography. However, a high degree of endometrial in order to select the most suitable cycle for transfer of a
perfusion illustrated by both techniques on the day of single cryopreserved embryo.76
embryo transfer indicated a more favorable endometrial Ultrasound is also used for the diagnosis of ovarian,
milieu for successful implantation (Fig. 33.14). uterine, and tubal causes of infertility (Table 33.3).
Endometrial 3D power Doppler indices change
significantly during the normal menstrual cycle. 75 Ovarian Causes of Infertility
Vascularity indices of the endometrial vessels and As illustrated before, TVS is considered the most reliable
subendometrial vessels increase throughout the proliferative method for monitoring the follicular growth. It enables
phase of the menstrual cycle, reaching a maximum accurate prediction of ovulation and detection of the
value 2–3 days prior to ovulation. From this peak, ovulation abnormalities. The success of IVF treatment
vascularity indices decrease and reach a nadir 2–5 days is dependent on the ability of the ovary to respond to
after ovulation. Reduced endometrial perfusion assessed controlled stimulation by gonadotropins and develop
by 3D power Doppler ultrasound is most likely related to a reasonable number of mature follicles and oocytes
increased uterine contractility. If prolonged, it may cause simultaneously. Failure to respond is associated with
Figure 33.14 Endometrial perfusion and subendometrial perfusion demonstrated by 3D power

Doppler ultrasound. Increased vascularity indicates normal uterine receptivity
Table 33.3 Causes of infertility
Ovarian Uterine Tubal

Polycystic ovarian syndrome Congenital uterine anomalies Pelvic inflammatory disease (PID)
Luteinized unruptured follicle Endometrial polyps Adhesions
Luteal phase defect Submucosal leiomyoma History of ruptured appendix
Endometriosis Adenomyosis History of ectopic pregnancy
Endometritis History of tubal surgery
Intrauterine adhesions (Asherman’s
syndrome)
cancellation of the cycle or poor outcome of the treatment. follicles, but not in ellipsoid ones. 79,80 Round follicles
Prior prediction of the likelihood of optimal ovarian were most prevalent in patients with the fewest follicles.
response is therefore essential in identifying the patients Patients selected for this study have produced fewer
who are most likely to benefit from an IVF treatment. follicles than normal, and therefore represent the group in
Doppler studies demonstrated a clear relationship between which the conventional technique was likely to be most
ovarian stromal blood flow velocity and ovarian follicular accurate. However, 3D assessment of the follicular volume
response. Increased ovarian stromal blood flow velocity produced a more accurate reflection of the true volume,
was detected in polycystic ovaries (PCOs), in combination especially in the patients with explosive response.81 This is
with a relatively unchanged impedance to blood flow. This because 3D measurement is not affected by the follicular
may reflect increased intraovarian perfusion and thus a shape, since the changing contours are outlined serially to
greater delivery of gonadotropins to the granulosa-theca obtain the specific volume measurement. The disparity in
cell complex, resulting in greater number of follicles accuracy between 3D assessment of the follicular volume
being produced. This mechanism may help to explain why and conventional 2D ultrasound is likely to increase
patients with PCOs tend to respond excessively to the significantly if there is a florid multifollicular ovarian
administration of gonadotropins, and may possibly explain response, because the conventional formula is less precise
their increased risk of OHSS.77 with ellipsoid follicles, which are likely to predominate in
Documentation of ovarian stromal vascularity at these cases. One limitation of 3D volume assessment is that
the initial baseline scan is important and may provide follicles with a mean diameter of less than 10 mm cannot
useful information for assisted reproduction techniques be assessed accurately because the limits of agreement are
(Fig. 33.15). Measurement of the ovarian stromal blood too wide in this range.
flow in the early follicular phase may be related to It has been reported that 3D ultrasound may be useful for
subsequent ovarian responsiveness in IVF treatment.77,78 distinction of the ovarian cysts from the ovarian follicles.80
This is very important since the ovarian age (capacity of Since both the ovarian cysts and follicles demonstrate an
the ovary to produce fertilizable oocytes) and chronological elevation of the serum estradiol levels, it is difficult to
age are not always synchronous, which leads to a degree of distinguish these two entities by estradiol (E2) assay alone.
unpredictability in the number of developing follicles and For the purpose of the prospective observational study the
collected oocytes. authors evaluated 50 IVF patients after ovulation induction.
Certainly, if an inadequate dose of gonadotropins is used Three-dimensional ultrasound was used to search for the
there may be a relatively poor response, which reduces the presence of cumuli in follicles greater than 15 mm. Only
number of the oocytes retrieved, whereas if an excessive dose cumuli demonstrable in all three planes by multiplanar
is used, there may be an increased risk of OHSS (Fig. 33.16). imaging predicted mature oocytes recovery. Follicles
The shape and number of the follicles influence the without visualization of the cumulus in all three planes
reliability of the standard 2D ultrasound technique of were not likely to contain mature fertilizable oocytes.
follicular volume measurement. Measurement of the Our group designed a study to evaluate whether the
follicular diameter may be difficult when its shape is ovarian antral follicle number, ovarian volume, stromal
distorted because of compression by adjacent follicles. It area, and ovarian stromal blood flow are predictive of
has been demonstrated that the mean follicular diameter ovarian response and IVF outcome.77 Total ovarian antral
accurately predicted volume in round and polygonal follicle number, total ovarian volume, and total stromal
Figure 33.15 Three-dimensional power Doppler assessment of the ovarian stromal blood
flow in early follicular phase
antral follicles achieved the best predictive value for a

favorable IVF outcome, followed by ovarian stromal FI,
total ovarian stromal area and total ovarian volume.77
In another study authors evaluated whether ovarian
antral follicle number, ovarian volume and ovarian stromal
blood flow changed with a women’s age and if they are
predictive of ovarian response and IVF outcome.78 Total
ovarian antral follicle number, ovarian volume and mean FI
of the ovarian stromal blood flow were determined by 3D
and power Doppler ultrasound after pituitary suppression.
Patients were separated into the three groups based upon
age and in each group the median values of 3D ultrasound
parameters (total ovarian antral follicle number, total
ovarian volume and mean ovarian stromal vascularity)
Figure 33.16 Transvaginal power Doppler of hyperstimulated ovary were measured and recorded. Pre-treatment 3D ultrasound
after gonadotropin induction ovarian measurements were compared with a subsequent
ovulation induction parameter (number of the oocytes)
area and mean FI of the ovarian stromal blood flow were and a cycle outcome (fertilization and pregnancy rates).
determined by 3D and power Doppler ultrasound after Increasing age was associated with poor ovarian response,
pituitary suppression. Pre-treatment 3D ultrasound ovarian smaller ovarian volume, lower antral follicle count and
measurements were compared with subsequent ovulation poor stromal vascularity.78 Similar studies performed more
induction parameters (peak estradiol on hCG administration recently indicated that there is a place for 3D ultrasound in
day and number of the oocytes), and the cycle outcome the assessment of the ovaries prior to ovulation induction
(fertilization and pregnancy rates). The total number of and with medically assisted reproduction.
Polycystic Ovarian Syndrome and that the PCP and GCP appearances reflect specific
Polycystic ovarian syndrome (PCOS) is one of the causes endocrine polycystic ovary syndrome (PCOS) patterns.84
of anovulation and amenorrhea. In its classic form it Another parameter considered in the diagnosis of PCOs
is characterized by infertility, oligo- and amenorrhea, is the ovarian volume. However, the wide volume overlaps
hirsutism, acne and obesity. In 1986 Adams et al. defined the between normal and PCOS patients suggesting that the
criteria for ultrasonographic diagnosis of PCOs: multiple discriminative capacity of ovarian volume alone is not
(n >10), small (2 – 8 mm) peripheral cysts around a dense sufficient for ultrasound diagnosis of PCOS.85 The role
core of stroma in enlarged (≥ 10 ml) ovaries.82 However, of visualization of a hyperechogenic ovarian stroma was
ovaries which are normal in volume may also be polycystic, emphasized, which is absolutely subjective and may be
as demonstrated by histological and biochemical studies. differently interpreted by the operator.86,87
The number of follicles necessary to establish the diagnosis Three-dimensional ultrasonography allows precise
of PCOs by ultrasonography has been reported varies measurement of the ovarian stroma, which is obtained
between five and fifteen. In many reports the highest number after subtracting the sum area of the ovarian follicles
of atretic follicles obtained in normal control patients was from the total ovarian area. Also, 3D ultrasound obtains
ten per ovary, so it was conventionally established that in a more accurate volume data by outlining the contour of
PCOs the number of atretic follicles per ovary would be the ovary, which is more accurate than the traditional 2D
at least ten (≥10).82 There are two types of PCOs on the ultrasonographic calculation using the ellipsoid formula
basis of ultrasonographic follicular distribution: (i) the (height × width × thickness × 0.523).
peripheral cystic pattern (PCP) and (ii) the general cystic Hence, 3D ultrasonography can complement 2D
pattern (GCP).83 In the PCP, small cysts are distributed in ultrasonography for the diagnosis of PCOS. It allows
the sub-capsular region of the ovary, whereas in the GCP excellent spatial evaluation of the PCOs, measurement of
they are scattered through the entire ovarian parenchyma the ovarian volume, and assessment of the follicular and
(Fig. 33.17). It was demonstrated that these two different stromal areas. Apart from the morphological and volume
ovarian morphologies reflect histopathologic differences, assessment of the ovaries, Doppler evaluation of the
Figure 33.17 Three-dimensional ultrasound of polycystic ovaries

hemodynamic parameters may be added to the traditional stimulation. These patients develop more follicles of all
endocrinologic and ultrasonographic parameters clinically sizes, in particular small and medium sized follicles, and
used for diagnosis and evaluation of the patients with are at greater risk of OHSS.89 This suggests that patients
PCOS. with PCOS are more sensitive to gonadotropin stimulation
Polycystic ovaries are characterized with prominent (Fig. 33.19).
intraovarian flow and low vascular impedance as early The exact mechanism is unknown, although it is possible
as day 3–5 of the 28-day cycle85 (Fig. 33.18). This blood that the increased ovarian stromal blood flow velocity, in
flow pattern was associated with typical PCOS hormonal combination with a relatively unchanged impedance to
parameters, and is inversely correlated with the LH/FSH blood flow, may reflect increased intraovarian perfusion
ratio. Tonic hypersecretion of LH during the follicular leading to a greater delivery of gonadotropins to the
phase of the menstrual cycle occurs in PCOS and is granulosa cells of the developing follicles.90 Polycystic
associated with theca cells and stromal hyperplasia with ovary syndrome patients have significantly increased
consequent androgen overproduction.88 Elevated LH levels blood flow velocity within the ovarian stroma detected by
may be responsible for increased stromal vascularization transvaginal color Doppler ultrasound, which may explain
by different mechanisms that may act individually or in a the excessive ovarian response when they are administered
cumulative way such as neoangiogenesis, catecholaminergic gonadotropins. Increased stromal blood flow velocity
stimulation, and leukocyte and cytokine activation. In the on color, power and pulsed Doppler ultrasound may be
same study the PCOS patients showed higher uterine PI an additional marker in the diagnosis of PCOS. It seems
values than non-hirsute normally menstruating women.88 that evaluation of the ovarian stromal vascularity by 3D
This finding was correlated with androstenedione levels, power Doppler may further increase our knowledge on this
confirming a possible direct androgen vasoconstrictive enigmatic syndrome.
effect due to activation of specific receptors in the arterial
vessel walls, and collagen and elastin deposition in smooth Luteinized Unruptured Follicle Syndrome
muscle cells. The above condition, by reducing the uterine Luteinized unruptured follicle (LUF) syndrome is
perfusion, has been theorized as the cause that prevents characterized by regular menses and presumptive ovulation,
blastocyst implantation, and increases the incidence of suggested by a cyclic hormonal profile, similar to that seen
miscarriages in PCOS patients. in normal ovulatory women, but without release of the
Patients with PCOS undergoing ovulation induction for oocyte. Although LUF was first diagnosed at laparoscopy
IVF are more likely to develop a greater number of follicles by the absence of an ovulation signs and demonstration
and generate more oocytes compared with women who have of the lower concentrations of estradiol and progesterone
normal ovaries even though they require less gonadotropin in peritoneal fluid compared with normal ovulatory
cycles, diagnosis is most commonly made on ultrasound
examination, due to the persistence of the ovarian follicle
with progressive loss of its typical echo-free cystic
appearance and accumulation of internal echogenicity.1 The
precise etiology of LUF remains uncertain, but impairment
of the mid-cycle LH surge, the absence of the preovulatory
progesterone rise, abnormalities of prostaglandin synthesis
and a primary abnormality of the oocyte have been
suggested as possible causes.91
In patients with LUF syndrome color Doppler studies
did not observe any decrease in perifollicular intraovarian
resistance after the LH peak.91,92 The so-called “luteal
conversion” did not take place in patients with LUF
syndrome, indicating that the perifollicular angiogenesis
was altered, probably because of follicular failure. The
Figure 33.18 Transvaginal color Doppler of polycystic ovary. Note reduction in perifollicular blood flow velocity has also been
increased intraovarian flow reported in a patient with drug-associated LUF syndrome.93
Figure 33.19 Three-dimensional ultrasound of the hyperstimulated ovary in a PCOS patient

after ovulation induction. Follicles of different sizes are color coded in different colors
Additional Doppler studies and biochemical research are no difference between the groups during the proliferative
needed to clarify the causes and consequences of LUF phase. A significant decline of the RI occurred in the control
syndrome. group for the day of the LH peak (RI = 0.45 ± 0.04), with a
return to the follicular phase level of 0.49 ± 0.02 during the
Luteal Phase Defect second phase of the menstrual cycle. The mean intraovarian
“Luteal conversion” is a term describing intraovarian Doppler RI for the LPD group (RI = 0.58 ± 0.04) was significantly
findings obtained during the luteal phase. Increased turbulence higher than in the control group throughout the luteal phase.
of the blood flow with low vascular impedance is a typical Patients in the control group had a significantly lower RI in
sign of CL angiogenesis. Doppler studies demonstrated the dominant than in the nondominant ovary, whereas LPD
that in patients with LPD, the dominant and nondominant patients had the almost same RI in both ovaries. Spiral arteries
ovaries demonstrate similar RI values, and there are no in the control group demonstrated mean RI of 0.53 ± 0.04
significant differences in intraovarian vascularity between during the periovulatory phase, and RI values of 0.50 ± 0.02
the follicular and luteal phases of the menstrual cycle.94 and 0.51 ± 0.04 were obtained during the mid-luteal and late
Our study correlating Doppler velocimetry, histological and luteal phase, respectively. Higher impedance values during
hormonal markers documented that mean progesterone levels the periovulatory phase (RI = 0.70 ± 0.06, p < 0.001), mid-
were significantly lower in the group with an LPD (10.2 ± luteal phase (RI = 0.72 ± 0.06, p < 0.001) and late luteal phase
4.3 ng/ml) than in control group (21 ± 4.2 ng/ml). The FSH/ (RI = 0.72 ± 0.04, p < 0.001) were obtained from the spiral
LH ratio was significantly lower in the group with a delayed arteries in the LPD group. Salim et al.95 correlated luteal blood
endometrial pattern compared to normal subjects during the in normal and abnormal pregnancies. Their study proved the
follicular and periovulatory phases (0.70 vs 1.24; 0.58 vs 0.75, hypothesis that an absence of luteal flow cannot coexist with
respectively). There was a close correlation between estradiol normal pregnancy. Impedance to intraovarian blood flow was
levels and the mean diameter of the dominant follicle from significantly higher in patients with abnormal early pregnancy
days –5 to –1 relative to the days of sonographically observed (missed, incomplete and threatened abortion) than in women
ovulation.94 Intraovarian blood flow resistance showed with normal pregnancy outcome. However, this was not
Figure 33.20 Three-dimensional ultrasound of the normal uterine cavity. Note secretory
appearance of the endometrium and triangular shape of the uterine cavity in frontal reformatted
section (low left image)
confirmed in patients with blighted ovum, molar and ectopic Three-dimensional ultrasound is highly sensitive
pregnancy. In these groups of patients the luteal blood flow and specific in diagnosis of major congenital uterine
was almost the same as in normal pregnancy. This difference anomalies.100-102 The uterine cavity can be precisely explored
among the subgroups of an abnormal early pregnancy may in digital reconstruction of the coronal plane (Fig. 33.20).
be a consequence of a different natural history of the disease. Three-dimensional ultrasound enables planar reformatted
Missed and incomplete abortions are manifested as failed sections through the uterus, which allows a precise
early pregnancy with no prospects for further development. evaluation of the fundal indentation and the length of the
Whether a decreased CL blood flow is a potential cause or a uterine septum (Fig. 33.21).
consequence of the event remains unclear. Our group analyzed the incidence of surgically
correctable uterine abnormalities (congenital uterine
Uterine Causes of Infertility anomalies, submucous leiomyoma, endometrial polyps
and intrauterine synechiae) in the infertile population
Congenital Uterine Anomalies attending a tertiary infertility clinic.102 All the infertile
Congenital uterine anomalies are variable in frequency patients enrolled in the study were evaluated by 3D
and are usually estimated to represent 3–4%, although ultrasound. Another objective was to assess the pregnancy
less than half have clinical symptoms.96-98 The respective rates before and after operative hysteroscopy in patients
frequency of symptomatic malformations is dominated by affected by uterine causes of infertility. The prevalence
a septate uterus.98,99 During the first trimester of pregnancy, of uterine abnormalities in their study was 7.9%. 102
the risk of spontaneous abortion in this group of patients is The most common uterine abnormality accounting
between 28 and 45%, while during the second trimester the for 77.1% of the uterine causes of infertility was the
frequency of late spontaneous abortions is approximately septate uterus. Out of 310 patients who were followed-
5%.98 Premature deliveries, abnormal fetal presentations, up during the course of 2 years, 225 (72.6%) patients
irregular uterine activity and dystocia at delivery are likely achieved pregnancy after hysteroscopic metroplasty for
to prevail in cases of a septate uterus. an intrauterine septum.
Figure 33.21 Three-dimensional ultrasound of a septate uterus. Note clear division of the
uterine cavity in lower images (coronal plane and surface reconstruction)
Endometrial Polyp smooth muscle and connective tissue, leading to a variety

The presence of significant intracavitary lesion can of sonographic features. Sonographic texture ranges
decrease the likelihood of implantation. Endometrial polyp from hypoechoic to echogenic, depending on the amount
appears as a focal thickening of the endometrium. Using of smooth muscle and connective tissue. Fibroids can
saline infusion sonography (SIS) an intracavitary polyp is contribute to infertility in different ways: by distorting the
visualized as hyperechoic lesion surrounded by sonolucent uterine cavity, interfering with uterine and endometrial flow
fluid (Fig. 33.22). When ultrasound examination is and preventing implantation.1
performed during the early postmenstrual and/or follicular
phase, the use of a distending medium may not be Adenomyosis
necessary to detect an abnormal endometrial thickening. Adenomyosis is characterized by in growing of the
However, during the periovulatory and secretory phase, endometrium into the superficial or deep myometrial
polyps are better visualized when outlined by intracavitary layer. In some patients it is asymptomatic, while in other
fluid. Using transvaginal color and pulsed Doppler it is associated with uterine bleeding, pain, and infertility.
minor arteries supplying the growth of an endometrial Patients with adenomyosis have a diffusely enlarged uterus
polyp can be visualized. Three-dimensional ultrasound with a heterogeneous myometrium, streaky lines with
allows a detailed analysis of the uterine cavity in frontal posterior shadowing and/or multiple small cysts within
reformatted sections, which enables clear demarcation of the myometrium.103 In severe cases there is disordered
the endometrial lesions.1 echogenicity of the middle and distal myometrial layers
(Fig. 33.23). Sensitivity and specificity of transvaginal
Submucosal Leiomyoma ultrasound in detection of this benign entity is 86% and
The diagnosis of a submucosal fibroid is based on the 50%, respectively.103 Color Doppler may reveal increased
distortion of the uterine contour, uterine enlargement and vascularity mainly characterized with moderate vascular
textural changes. Leiomyomas have a varying amount of resistance.
Figure 33.22 Saline infusion sonography demonstrating two Figure 33.23 Transvaginal ultrasound of adenomyosis. Note multiple
endometrial polyps surrounded by sonolucent fluid cystic structures within the proximal, middle and deep myometrial layer
Figure 33.24 Transvaginal ultrasound image of intrauterine adhesions Figure 33.25 Transvaginal color Doppler image of hydrosalpinx. Note
(pointed by an arrow) complex adnexal mass with complete and incomplete septations and
pseudopapillary projections
Asherman’s Syndrome distorted endometrial pattern with hyperechoic bridges.

Intrauterine synechiae do not present with increased
Destruction of the endometrium may result in scarring and
vascularity on color Doppler examination. In patients
development of the bands of the scar tissue, or synechiae,
with preserved menstrual function adhesions are better
within the uterine cavity. Asherman syndrome may result
visualized either during menstruation when the intracavitary
from postpartum or post-abortion surgical curettage,
fluid outlines them or following SIS. When a 3D ultrasound
pelvic inflammatory disease (PID), and uterine surgery
of the uterus visualizes a uterus with synechiae, it also
(cesarean section or myomectomy). Tuberculosis may
demonstrates a significant reduction of the endometrial
also cause uterine synechiae, but only in rare cases. 1
cavity volume in all reformatted sections.
Asherman’s syndrome is characterized by formation of
adhesive bands of different size with a subsequent partial
or total obliteration of the endometrial cavity (Fig. 33.24).
Tubal Causes of Infertility
Amenorrhea or hypomenorrhea are typical clinical patterns. The normal Fallopian tubes are narrow and usually not seen
Patients with endometrial adhesions typically have a by transabdominal ultrasound or transvaginal ultrasound
of diagnostic procedures has been developed.105-107 Three-

dimensional ultrasound technique offers simultaneous
visualization of the uterine cavity and the corresponding
Fallopian tube, shortens the procedure time and decreases the
discomfort of the patient.106 Transvaginal 3D examination
time is similar to 2D sonography, but has the advantage of
reviewing certain specific parts of the examination, such
as measurements, reconstruction of the planes of interest
or tomography and surface rendering at a later time and
off-line.107 Color and power Doppler imaging in 3D allows
simultaneous visualization of the uterine cavity and flow
of the contrast medium throughout the entire tubal length
(Fig. 33.26). Free spill of the contrast is clearly identified
in the majority of cases. The acquired volumes of the most
appropriate planes of interest are stored on a removable hard
Figure 33.26 Three-dimensional power Doppler hystero-contrast-
salpingography. Three-dimensional power Doppler enables disk for additional re-evaluations and documentation.106
simultaneous visualization of the uterine cavity and fallopian tube (on Table 33.4 demonstrates advantages and limitations of
the right)
hystero-contrast-salpingography.
Conclusion
unless they contain fluid within their lumina or are
surrounded by fluid. The motility and transport function of Transvaginal ultrasound, color Doppler and 3D ultrasound have
made a significant improvement in the assessment of infertility.
the oviducts are impaired during all stages of PID. First, in Sonography helps to diagnose ovulation and detect ovulatory
the acute phase, the tube becomes thick and edematous and disorders. Measurement of the uterine perfusion has a predictive
a large amount of purulent exudate fills the lumen. Later value regarding fecundity in patients undergoing different methods
of medically assisted reproduction. Absent subendometrial and
on, the inflammatory process may be organized to form intraendometrial vascularization on the day of hCG administration
a tubo-ovarian abscess, which will in most cases lead to is a useful predictor of failure of implantation in IVF cycles,
scarring and occlusion of the tube. Chronic hydrosalpinx irrespective of morphological appearance of the endometrium. In
some departments studies of spiral artery perfusion are used as
is the ultimate remnant of PID with a thin-walled, occluded noninvasive assays of uterine receptivity.
and fluid filled tube104 (Fig. 33.25). Different forms of sonography help in the diagnosis of anatomic
abnormalities, such as congenital uterine anomalies, submucosal
Infertility caused by tubal dysfunction is found in
leiomyoma and uterine adhesions. Sonography also aids in
approximately 35% of patients.1 History of PID, septic retrieving oocytes from the ovary and transferring the embryos in
abortion, ruptured appendix, tubal surgery or ectopic IVF/ET procedures.
Color Doppler and 3D hystero-contrast-salpingography are the
pregnancy should alert the physician to the possibility safe and efficacious methods for evaluation of the uterine cavity
of tubal damage (Table 33.3). Laparoscopy and X-ray and fallopian tube patency without exposure to radiation. These
hysterosalpingography are standard modalities for tubal procedures allow the physician to interpret the results immediately
on outpatient clinic basis and review them off-line, without the
investigation. With the development of transvaginal, presence of a patient.
color Doppler and 3D ultrasound, a totally new concept
Table 33.4 Advantages and limitations of hystero-contast-salpingography
Advantages Limitations
• Reproducible and reliable • Tubal spasm may lead to misdiagnosis of tubal occlusion
• Avoids radiation exposure • In hydrosalpinx, tubal flow may give a false impression of tubal
• Avoids allergic reactions to iodine contrast media patency
• Avoids general anesthesia • Inability to visualize the bowel and intrapelvic pathology
• Performed in an office setting • Requires a degree of technical competence
• Rapid • Around 10–20 investigations needed to acquire competency for
• Well tolerated: little discomfort and few adverse events this new technique
• Demonstrates tubal patency in “real time”
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comparison between Doppler velocimetry, histological and 103. Brosens JJ, de Souza NM, Barker FG, et al. Endovaginal
hormonal markers. Ultrasound Obstet Gynaecol. 1997; 9:1-8. ultrasonography in the diagnosis of adenomyosis uteri:
95. Salim A, Žalud I, Farmakides G, et al. Corpus luteum blood identifying the predictive characteristics. Br J Obstet
flow in normal and abnormal early pregnancy: evaluation Gynaecol. 1995;102(6):471.
with transvaginal color and pulsed Doppler sonography. J 104. Kupesic S, Kurjak A, Pasalic L, et al. The value of transvaginal
Ultrasound Med. 1994;13:971-5. color Doppler in the assessment of pelvic inflammatory
96. Ashton D, Amin HK, Richart RM, et al. The incidence of disease. Ultrasound Med Biol. 1995;21(6):733-8.
asymptomatic uterine anomalies in women undergoing 105. Kiyokawa K, Masuda H, Fuyuki T, et al. Three-dimensional
transcervical tubal sterilization. Obstet Gynecol. 1988;72:28-30. hysterosalpingo-contrast sonography (3D-HyCoSy) as an
97. Sorensen S. Estimated prevalence of mulerian anomalies. outpatient procedure to assess infertile women: a pilot study.
Acta Obstet Gynecol Scand. 1988;67:441-5. Ultrasound Obstet Gynecol. 2000;16(7):648-54.
98. Gaucherand P, Awada A, Rudigoz RC, et al. Obstetrical 106. Kupesic S, Plavsic MB. 2D and 3D hysterosalpingo-
prognosis of septate uterus: a plea for treatment of the contrast-sonography in the assessment of uterine cavity
septum. Eur J Obstet Gynecol Reprod Biol. 1994;54:109-12. and tubal patency. Eur J Obstet Gynecol Reprod Biol.
99. Fedele L, Arcaini L, Parazzini F, et al. Metroplastic 2007;133(1):64-9.
hysteroscopy and fertility. Fertil Steri. 1993;59:768-70. 107. Sladkevicius P, Ojha K, Campbell S, et al. Three-dimensional
100. Jurkovic D, Geipel A, Gruboeck K, et al. Three-dimensional power Doppler imaging in the assessment of Fallopian tube
ultrasound for the assessment of uterine anatomy and patency. Ultrasound Obstet Gynecol. 2000;16(7):644-7.
CHAPTER Chorionic Volume and Intervillous
34 Blood Flow in Normal First Trimester

Pregnancies Assessed by 3D Power
Doppler Ultrasound
Maria J Barco, Luis T Mercé, Rosa Sabatel, Jose Bajo Arenas
Introduction the outer layer of the trophoblast or syncytiotrophoblast

presents vacuoles that fuse to form large lacunae [lacunar
Human placentation is the development and differentiation stage (9th day of embryonic development or 23rd menstrual
of the trophoblast at the implantation site until the day)] particularly at the embryonic pole. As the syncytium
achievement of a definitive placental structure controlling penetrates the endometrium, it erodes the capillary walls
fetal-maternal exchanges. These exchanges take place by and the maternal blood enters the lacunar system, thus
blood flow, so they are mainly conditioned by the placental establishing the uteroplacental circulation (12th day of
vascular network and circulation. embryonic development or 26th menstrual day).14,15
Until recently, the in vivo assessment of the circulatory According to embryological studies, the uteroplacental
changes taking place at the uterochorionic level has been circulation is established around day 12 of the embryo
made through two-dimensional (2D) color or power development when maternal blood flows into the
Doppler ultrasound,1-7 being specially scarce those studies syncytiotrophoblast lacunae to fulfill the requirements
about intraplacental circulation.3,8-11 of the developing embryo.16-18 The true blood flow into
The advent of three-dimensional ultrasonography with the intervillous space (IVS) begins around days 14–15
power Doppler angiography (3D PDA) has allowed the of embryonic life (4 weeks of amenorrhea),19 and, in any
assessment of volumes and vascularization altogether,12,13 case, never later than 40 days (7 weeks and 5 days of
approaching at last the concept of placental perfusion. amenorrhea).20
Three-dimensional ultrasonography with power Doppler The inner layer of trophoblast or cytotrophoblast forms
angiography gives information about the number of cellular columns surrounded by syncytium that becomes the
vessels and the amount of blood flowing through them by placental primary villi (13th day of embryonic development
means of “vascularity indices.”13 This information is more or 27th menstrual day). During the 3rd week, mesodermal
precise than resistance Doppler indices in the evaluation cells enter the core of the villi to form the secondary
of placental perfusion. Furthermore, 3D volumetry offers villi. These cells begin a process of angiogenesis that
a more accurate measurement of chorionic volume and, for forms the villous capillary system and the villi become
the first time, its real whole volume. tertiary or definitive placental villi (21st day of embryonic
All the information about placental volume and development or 5th week of amenorrhea). They are bathed
vascularization seems promising for the in vivo assessment by maternal blood inside the IVS.
of the still poorly understood early pregnancy, which The capillaries in the tertiary villi make contact with
depends essentially on the blood supply. embryonic vessels through the connecting stalk. Then the
fetoplacental circulation begins and is effective with the
Current Knowledge about Early first heartbeat (4th week of embryonic development or
Placental Circulation 6th week of amenorrhea). The chorionic villi experience
progressive development and branching to become the
Anatomical Data definitive placenta.
After implantation, the placentation process begins, that is, After the uteroplacental circulation is established, the
the development and differentiation of the trophoblast. As cytotrophoblast continues the invasion of the implantation
the blastocyst is more deeply embedded in the endometrium, site as well of the interstitial tissues (interstitial invasion)
as of the maternal vessels (intra-arterial invasion). The Both features show the transformation of spiral arteries and,
trophoblast invasion takes place in two waves. The first to a lesser degree, the radial arteries into arteries of low
wave is superficial and affects the decidual and spiral impedance due to the trophoblast invasion. These changes
arteries, finishing by 10–12 weeks.21-23 The second wave take place only in one portion of the sac, precisely where the
advances more deeply into the myometrium to reach the chorion frondosum develops, predicting the site of placental
radial arteries, ending by 18–20 weeks of amenorrhea.22,23 insertion1 before its sonographical visualization.
All the changes produced by the trophoblastic invasion Retrochorionic flow velocity waveforms are character
on the uteroplacental arteries render them dilated vessels ized by a low-resistance pattern with an important
without muscular layer and very limited vascular reactivity. diastolic component (Fig. 34.1A). Retrochorionic blood
This allows the circulation of a greater and important flow increases progressively during the first trimester of
amount of blood flow to the IVS that guarantees the pregnancy as it is demonstrated by the evolution of the
fetomaternal interchange of oxygen and nutrients. velocimetric parameters related to gestational age.2
The intra-arterial trophoblast occludes the lumen of Kurjak 8 and Mercé 28 were the first to record the
the spiral arteries almost completely thus regulating the intervillous flow during early pregnancy by transvaginal
entrance of blood at a high pressure into the reduced IVS. color Doppler. A “venous-like” blood flow signal can be
Pressures and volumes adjust gradually as the trophoblastic registered from the chorionic ring at the implantation site
plugs disappear. This allows the increase of blood as early as 6 weeks of gestation, coinciding with the first
flowing into the IVS to fulfill the growing demands of the recording of the fetoplacental and umbilical circulation.2,27
fetoplacental unit. Two types of flow patterns were identified from the
intervillous color Doppler signal:5,9,29 (i) a pulsating arterial
Doppler Ultrasound Studies type and (ii) a continuous venous type (Fig. 34.1B).
The blood flow into the IVS is a dynamic process that can A progressive increase in the velocity of the IV flow
only be truly demonstrated in vivo. Until the advent of during the first trimester can be found from 6th week
Doppler only the Burchell’s study evaluated the intervillous onward, 30 although this finding is not supported by
circulation in vivo.24 He observed the arrival of angiographic all authors; they find the flow remaining unaltered5 or
contrast into the IVS from 6 weeks onward. increasing later from 11 weeks onward.9
Color or power Doppler is the perfect tool to perform a
noninvasive evaluation of the circulation into the IVS. It has Conflicting Data on Intervillous Circulation
been demonstrated that a good correlation exists between Despite the classical knowledge about the beginning of the
power Doppler intensity and blood flow either in vitro or intervillous circulation, in 1987 and 1988, it was suggested
in vivo.25 by Hustin31,32 and Schaaps33 that it was not established
Following implantation, the placentation process begins. before the second trimester. This concept was further
The uterine blood flow increases in all their branches, from supported by others.34-36
arcuate to radial and spiral arteries. The increase in color They performed ultrasound as well as in vivo
flow detection at the intrauterine circulation level has been hysteroscopic examinations and morphological and
reported as a sign of an early pregnancy,26 even before the radiological perfusion studies on hysterectomy specimens,
visualization of gestational sac.3 and they found no true circulation in the IVS during the
But the visualization of a gestational sac is essential normal first trimester of pregnancy. They concluded that it
to confirm that these color mapping changes are due to was caused by complete plugging of the spiral arteries by
the beginning of uteroplacental circulation. According to the trophoblast.
the authors’ results, the gestational sac can be detected on According to their findings, by 12–13 weeks the
average as early as on day 32 of amenorrhea when it has a intraplacental blood flow can be detected simultaneously
mean diameter of 3.8 mm.27 A color Doppler signal coming with umbilical artery pandiastolic flow and a sharp
from the periphery of the sac penetrates the endometrium increase in the uterine artery blood flow velocity. This fact
and the adjacent myometrium, in the way of a comet and so is attributed to the sudden loosening of the intra-arterial
could be called the “color comet” sign. Pulsed Doppler in trophoblastic plugs allowing the free entrance of maternal
this area demonstrates a low resistance velocity waveform. blood into the IVS.
Chapter 34  Chorionic Volume and Intervillous Blood Flow in Normal First Trimester Pregnancies 369
A B
Figures 34.1A and B Retrochorionic and intervillous color mapping and flow velocity waveforms at 6 weeks normal gestation. (A) Retrochorionic
flow velocity waveform is characterized by a low-resistance pattern with an important diastolic component; (B) Intervillous blood flow is identified
as a continuous venous type or a pulsating arterial type
Before that time, the IVS is occupied by a mixture of pregnancy. Moreover, the development of a complex fetal
plasma filtered fluid and endometrial glands secretions with cardiovascular system with a high heart rate connected
low oxygen content. This hypoxic environment would favor to another complex umbilicoplacental vascular network
the embryonic development during the sensitive period of would be nonsense if nutrition and oxygenation had to be
organogenesis.37 accomplished by diffusion only.40
Some studies about the placental oxygen content added
support to this hypothesis.38 Intervillous Blood Flow and Chorionic
In contrast to these data, a varying number of
authors2,3,5,8,10,15,29 report the detection of color and power Volume During the First Trimester
Doppler signals from the IVS as early as the 5th and Normal Pregnancies by 3D PDA
6th gestational weeks. Their results are supported by
Three-dimensional power Doppler ultrasound is a new
histological studies also5,21-23,39 demonstrating maternal red
technology to assess chorionic and/or placental perfusion
blood cells in the IVS from first trimester pregnancies.39
throughout the first trimester of pregnancy additionally to
Our current technology prevents us knowing the precise
conventional color Doppler. This technique provides the
components of the fluid circulating through the IVS or its
possibility to confirm or refuse our hypothesis about a very
oxygen or red blood cells content. But it is undeniable that
early establishment of the intervillous blood flow on the 1st
a true circulation from the retrochorionic arteries to the
weeks of placentation.
IVS begins with implantation as it is demonstrated by the
gradual reduction in vascular resistance and the augment in
blood flow velocity as well as the color or power Doppler Technical Aspects
map detection from the uterochorionic unit. This is a The application of 3D PDA to the assessment of placental
natural, continuous and progressive event without sudden vascularization has proven to be a sensitive tool to depict
changes in vascular resistance or the amount of blood flow all the vascular villous branches.41-44 It is a method more
as it could be expected from a physiologic process. specific than the subjective assessment of the color or power
It is also arguable that during the whole first trimester, Doppler map or even the velocimetric indices obtained from
the fetus could develop in a hypoxic environment. This the flow velocity waveforms. Besides the morphological
is an interesting hypothesis for the blastocyst evolution assessment of placental vascularization, 3D PDA allows
but not for further stages of embryo-fetal development. the calculation of vessel number, blood flow and tissue
The anaerobic vial does not seem to be the ideal source perfusion by the vascularity indices.13,45
to supply such a fast energy-consuming system as it The first trimester of pregnancy is a special case because
is the fetoplacental unit during the first 12 weeks of the reduced size of the chorion allows the acquisition of its
Figure 34.2 Technique to measure the chorionic volume and 3D Doppler indices during the
first trimester of pregnancy. Virtual organ computer-aided analysis program is used with a
manually defined contour
whole volume. In order to achieve this, we place the power (VFI) is the mean color value in all color and gray voxels
window over the chorion with the selected presets (pulse within the sample, and so it represents both vascularization
repetition frequency = 600 Hz, wall motion filter = 50 Hz). and flow, in other words, tissue perfusion.
After that, we adjust the volume box framing the region of The shape and size of the chorionic “cake” are similar to the
interest and start acquisition at an adequate angle to include endometrial volume. There are no studies validating the method
the whole chorion. of assessment of chorionic perfusion by 3D PDA, but there are
The chorionic volumes acquired this way are analyzed some works validating the method for endometrial perfusion.46
through the virtual organ computer-aided analysis In the same way, we can consider that the method is also valid
(VOCAL) program integrated in the sonography system. for the study of chorionic volume and vascularization.
When we generate manually the contours of the chorionic There is still controversy about the safety of Doppler
volume, we take special care to exclude the spiral arteries examination during the first trimester of pregnancy. In this
and the chorionic surface vessels (Fig. 34.2). respect, we are particularly concerned about not to include
Three-dimensional volume is integrated by units named embryonic parts inside the volume box, acquiring only the
“voxels”. Voxels contain all the information about color and chorionic tissue because the volume is constructed by the
gray scale using an intensity scale ranging from 0 to 100. integration of multiple tomograms. The exposition time for
According to these values, VOCAL automatically displays each of them takes only a fraction of second.47 This way,
three power Doppler indices expressing number of vessels, we further reduce the possibility of undesirable effects on
blood flow and tissue perfusion as well as the sample volume. the outcome of gestation.
The vascularization index (VI) measures the number
of color voxels in the sample volume, thus expressing Villous Vascular Tree
vascular density as a percentage. The flow index (FI) is the Three-dimensional power Doppler angiography allows the
mean color of all the color voxels, so it represents the mean morphological study of the villous vascular tree from its
intensity of blood flow. The vascularization flow index start at the chorionic plate with the fetoplacental vessels,
up to its branches from 1st order to 3rd order, and the of equal to three between correct gestational age in weeks
uteroplacental vessels.41-43 Power Doppler cannot detect and trophoblastic thickness in mm at the embryonic
vessels from the terminal villi, although the possibility to implantation site should be seen as an indication that closer
see the 4th order villous vessels with bi-dimensional power monitoring of the pregnancy is required, since this could
Doppler in normal pregnancies has been reported.41 mean a poor outcome.48
The subjective assessment of the villous vascular tree during In the authors’ cross-sectional study over 46 normal
the first trimester of normal gestation shows that only the vessels pregnancies from 5th week to 12th week, a physiological
from the chorionic and basal plates are usually registered. Our gradual linear increase of the chorionic thickness
method of study applies to the VOCAL program to select the (Fig. 34.4A) is detected along the normal first trimester that
precise contours of the chorionic volume and vascularization is significantly related to gestational age (Table 34.1). This
between the basal and chorionic plates. Therefore, the chorionic is in agreement with the placental growth and development
Doppler signals registered should belong exclusively to the showed on normal pregnancies.
intervillous flow because the villous vessels cannot be detected The measurement of the chorionic volume has not been
until the end of the first trimester (Figs 34.3A to F). This is in possible in such a precise way as it is now, thanks to the
agreement with the findings of the only report on placental 3D ultrasonography. In the authors’ study, they found a
vascularization assessed by 3D PDA during the first trimester.47 progressive and significant increase in chorionic volume
during the first trimester of gestation (Fig. 34.4B), which
Chorionic Thickness and Volume was significantly related to gestational age (Table 34.1).
Up to recent date, only the chorionic thickness measured The chorionic volume experiences an exponential increase
at the cord insertion, has been evaluated showing a high which is in accordance with the growing requirements of
predictive value of poor pregnancy outcome. A difference the embryo-chorionic unit.
A B C
D E F
Figures 34.3A to F Chorion or early placenta and intervillous blood flow at different weeks of the normal first trimester of pregnancy. (A) 6 weeks;
(B) 7 weeks; (C) 9 weeks; (D) 10 weeks; (E) 11 weeks; (F) 12 weeks. Three-dimensional ultrasonography with power Doppler angiography
mapping highlights a significant increase of intervillous blood flow
A B
Figures 34.4A and B (A) Chorionic thickness and (B) chorionic volume throughout the early normal pregnancy (see also Table 34.1)
Chorionic volume is a more precise and representative The VI prove a good correlation (r = 0.48, p < 0.001) and
measurement of the placental development than chorionic a linear increase with gestational age (Fig. 34.5A). Flow
thickness. Its exponential growth reveals the magnitude index shows the smaller regression coefficient (r = 0.40;
of the changes taking place at the embryo-chorionic p < 0.005), but with less scattering of values than the
unit. At the same time, the embryo also experiences an VI (Fig. 34.5B). Finally, the VFI representing chorionic
exponential increase in its volume,49 so the chorionic growth perfusion shows the best correlation (r = 0.51, p < 0.000)
accompanies the fetal evolution. (Fig. 34.5C). All 3D vascularity indices are significantly
The literature is scant on chorionic volume estimation related with gestational age (Table 34.1) but with some
during the first trimester of normal pregnancies47,50,51 and little variations.
their authors’ findings agree with ours about the exponential The authors’ findings reveal the progressive development
growth of the chorion. of the vascular IVS and the increasing amount of blood
Other intrauterine pregnancy contents, such as gestational flowing through it along the first trimester of gestation,
and yolk sac volumes, have been related to the pregnancy from the 5th week onward. These results confirm the early
outcome in terms of miscarriage, but there is no agreement establishment of intervillous flow during normal gestation
over its predictive value.52-57 and the gradual increase in its velocity as the authors
On the contrary, the studies about placental volume in previously observed by color Doppler.2
the first51,58 and second44,59 trimesters seem to have some Hafner et al. 47 got similar results with a positive
interesting predictive value about mid-term pregnancy correlation between vascularization and vascularization
complications. In that respect, Metzenbauer 51 finds flow indices and crown-rump length and chorionic volume.
a significantly lower placental volume in cases of
chromosomal anomalies.
Intervillous Blood Flow and Chorionic
Intervillous Blood Flow Volume in Abnormal Early Pregnancies
Despite some conflicting reports about intervillous A sound knowledge of the normal development of chorionic
flow detection on early pregnancy,11,31,33,35 the amazing vascularization and intervillous blood flow during the first
improvement of ultrasound equipment with more sensitive trimester of pregnancy is essential for the management of
color and power Doppler, and 3D methodology and the pathological cases. In other words, the validation of its
its rendering techniques allows a wide recognition of diagnostic, prognostic and predictive value may well have
intervillous flow from the 5th week onward. a useful clinical application.
By manual selection of the contours, the VOCAL program Since there is evidence of defective chorionic
allows differentiation of intrachorionic, i.e. intervillous flow development in early pregnancy wastage,60,61 fetal growth
from that of the basal and chorionic plates. Provided that restriction, preeclampsia62 and chromosomal anomalies,51
the authors took special care not to include spiral or surface it is essential to perform further investigations based on
vessels of the chorionic plate, their results speak precisely 3D PDA ultrasound of the early placenta. Until now,
about chorionic blood flow and vascularization. conventional Doppler results are contradictory although
A B
C
Figures 34.5A to C Intrachorionic three-dimensional Doppler indices throughout the early normal pregnancy. (A) Vascularization index; (B) Flow
index; (C) Vascularization flow index (see also Table 34.1)
Table 34.1 Relationships among ultrasound parameters and 3D

power Doppler and gestational age in 46 normal pregnancies during
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Biol. 2003;29:19-23. 2002;19:575-9.
46. Raine-Fenning NJ, Campbell BK, Clewes JS, et al. 56. Oh JS, Wright G, Coulam CB. Gestational sac diameter
The reliability of virtual organ computer-aided analysis in very early pregnancy as a predictor of fetal outcome.
(VOCAL) for the semiquantification of ovarian, endometrial Ultrasound Obstet Gynecol. 2002;20:267-9.
and subendometrial perfusion. Ultrasound Obstet Gynecol. 57. Figueras F, Torrents M, Muñoz A, et al. Three-dimensional
2003;22:633-9. yolk and gestational sac volume: a prospective study of
47. Hafner T, Kurjak A, Funduk-Kurjak B, et al. Assessment prognostic value. J Reprod Med. 2003;48:252-6.
of early chorionic circulation by three-dimensional power
58. Metzenbauer M, Hafner E, Hoefinger D, et al. Three-
Doppler. J Perinat Med. 2002;30:33-9.
dimensional ultrasound measurement of the placental
48. Bajo J, Moreno-Calvo FJ, Martinez-Cortés L, et al. Is
volume in early pregnancy: method and correlation with
trophoblastic thickness at the embryonic implantation site a
biochemical placental parameters. Placenta. 2001;22:602-5.
new sign of negative evolution in first trimester pregnancy?
59. Hafner E, Philipp T, Schuchter K, et al. Second-trimester
Hum Reprod. 2000;15:1629-33.
measurements of placental volume by three-dimensional
49. Kurjak A, Hafner T, Kupesic S, et al. Three-dimensional
ultrasound to predict small-for-gestational-age infants.
power Doppler in the study of embryonic vasculogenesis.
J Perinat Med. 2002;30:18-25.
50. Schuchter K, Metzenbauer M, Hafner E, et al. Uterine artery 60. Meegdes BH, Ingenhoes R, Peeters LL, et al. Early
Doppler and placental volume in the first trimester in the pregnancy wastage: relationship between chorionic
prediction of pregnancy complications. Ultrasound Obstet vascularization and embryonic development. Fertil Steril.
Gynecol. 2001;18:590-2. 1988;49:216-20.
51. Metzenbauer M, Hafner E, Schuchter K, et al. First trimester 61. Khong TY, Liddell HS, Robertson WB. Defective
placental volume as a marker for chromosomal anomalies: haemochorial placentation as a cause of miscarriage: a
preliminary results from an unselected population. preliminary study. Br J Obstet Gynaecol. 1987;94:649-55.
Ultrasound Obstet Gynecol. 2002;19:240-2. 62. Khong TY, De Wolf F, Robertson WB, et al. Inadequate
52. Steiner H, Gregg AR, Bogner G, et al. First trimester three- maternal vascular response to placentation in pregnancies
dimensional ultrasound volumetry of the gestational sac. complicated by pre-eclampsia and by small-for-gestational
Arch Gynecol Obstet. 1994;255:165-70. age infants. Br J Obstet Gynaecol. 1986;93:1049-59.
53. Kupesic S, Kurjak A. Volume and vascularity of the yolk 63. Mercé LT, Barco MJ, Bau S. Color Doppler sonography of
sac assessed by three-dimensional and power Doppler retrochorionic and intervillous circulation: predictive value
ultrasound. Early Pregnancy. 2001;5:40-1. in small gestational sacs. Med Imaging Int. 1997;7:16-9.
CHAPTER
35 Doppler Evaluation of the Ovary:

Clinical Applications and Challenges
Ivica Zalud
Introduction versus time. The major advantage of this analysis is angle

independence and there is no need for simultaneous vessel
The ovary is one of the most active organs in the female body. visualization and diameter measurements. More than 10
It progresses through many changes, including puberty, indices have been used for velocity waveform analysis.
pregnancy and menopause. It is complex in its embryology, The A/B ratio, resistance index and pulsatility index are
histology and steroidogenesis. Furthermore, it is made up predominantly used.
of germinal epithelium, germ cells of gonadal stroma and Doppler ultrasound has the potential to study patterns of
mesenchymal cells, each with their own potential to form ovarian blood flow and hence identify functional changes.
a tumor. The ovary is the site of origin for a larger variety The availability of pulsed Doppler instruments has made it
of primary cancers than any other organ. In addition, the possible to sample the signals at a chosen depth and thus to
ovary is unique in that it not only gives rise to a great variety direct flow in any selected deep pelvic vessel. Transvaginal
of malignancies but is also a favorite site for metastasis color Doppler is the system that uses pulsed Doppler that
from other organs. Furthermore, there are many clinical performs flow analysis at multiple points along each scan
entities in human medicine linked with ovarian changes, line of echo data. Flow information is then color coded
etiologically connected with abnormal quantity and quality and displayed on the entire corresponding anatomical
of the human genome. Ultrasound, more than any other image. The main advantage of this color Doppler system
modern technique, has enabled the direct assessment of is rapid and definitive determination of the position of the
many of the ovarian functions. Transvaginal sonography small vessel, accuracy of the measurements and precise
has revolutionized the morphological evaluation of the indication of flow direction and velocity. After simultaneous
ovary and its conditions, both benign and malignant. The visualization of morphological and blood flow information,
advancement and wider availability of therapies of assisted a pulsed Doppler gate is placed over the area of interests to
conception have occurred to a large extent as a result of provide flow velocity waveforms, which may be analyzed
developments in ultrasonography. Transvaginal color in a conventional fashion.
Doppler has opened up exciting new possibilities for the
better understanding of the physiology and pathophysiology Ovarian Doppler
of ovarian blood flow, resulting in a number of completely
The ovarian artery is a tributary of the upper aorta and reaches
new diagnostic parameters.
the lateral aspect of the ovary through the infundibulopelvic
ligament. In some patients, these vessels are not clearly
Technique of Doppler Study visualized and the sample volume should be moved across
Ultrasound imaging has provided a unique method for the ligament and then through the substance of the ovary
the noninvasive study of ovarian structural changes. The until the arterial signal is identified. Signals from the ovarian
measurements of blood flow velocity by ultrasound are artery are characterized by the low Doppler shifts of a small
based on the Doppler effect. This effect implies that the vessel with low velocity. The waveform shape varies with
frequency of a sound wave emitted from a stationary the state of activity of the ovary. Studies of ovarian artery
source and reflected from a moving interference changes blood flow show the difference in the vascular resistance
according to the velocity and direction of the moving between the two ovarian arteries depending on the presence
interface. Velocity waveform shows the frequency shift of the dominant follicle or corpus luteum. A longitudinal
Chapter 35  Doppler Evaluation of the Ovary: Clinical Applications and Challenges 377
study of the ovarian artery throughout the menstrual cycle morphological changes in the intraovarian vascular network
usually will show decreased pulsatility and resistance and appearance of numerous arteriovenous shunts during the
indices, reflecting vascular impedance and implying luteal phase. In summary, changes in the intraovarian blood
increased flow to the ovary containing the dominant follicle flow occur before ovulation, implying a complexity of these
or corpus luteum. The ovarian artery of the “inactive” ovary changes that may involve both angiogenesis and hormonal
in this cycle would show low end diastolic flow or absence factors, while postovulatory vascular accommodation is
of diastolic flow. A rise in end diastolic flow in “active potentially important in the luteal phase. Using transvaginal
ovary” is most obvious around day 21 and suggests that the color Doppler, corpus luteum blood flow, characterized by
corpus luteum acts as a low impedance shunt. The increased low impedance and high-flow requirements, can easily be
blood supply to the functioning corpus luteum is essential detected in normal early pregnancy, ectopic pregnancy and
for delivery of precursors involved in steroidogenesis and nonpregnant women.
for distribution of progesterone. It was long believed that simple dilatation of existing host
The ovarian artery is a high-pressure system with blood vessels accounted for increased tumor vascularity.
blood flow characteristics very different from intraovarian Tumor hyperemia could be related to new blood vessel
circulation (Fig. 35.1). Near the ovarian hilus, the growth. Angiogenesis and neovascularization are terms
penetrating vessels are coiled and tortuous. This type of that are entering the vocabulary of every ultrasonographer.
vascularity demonstrates high-resistance blood flow. Every Angiogenesis occurs during embryonic development and
month during the women’s reproductive life, one oocyte is during several physiological and pathological conditions in
released from the single mature follicle that has completed adult life. As mentioned before, angiogenesis is important
development. Increased vascularity on the innermost rim of in the process of ovulation and development of the corpus
the follicle may represent the dilatation of new vessels that luteum. It accompanies numerous nonmalignant diseases
have developed between the relatively vascular theca cell such as acute or chronic inflammation and ectopic
layer and the normally hypoxic granulosa cell layer of the pregnancy. However, tumor angiogenesis differs at least
follicle. It is hoped that information on ovarian perfusion in a temporal manner from other types of angiogenesis
may be used both to predict ovulation and to investigate described.1 In physiological conditions, angiogenesis is
ovulatory dysfunction. turned off once the process is completed. In nonmalignant
Color flow is more easily obtainable from ovarian tissue processes, angiogenesis is prolonged, but still self-limiting.
in the luteal phase (Figs 35.2 and 35.3). The qualitative In contrast, tumor angiogenesis is not self-limiting.
postovulatory changes in intraovarian blood flow are Malignant tumor microvasculature does not conform to the
characterized by increased turbulent flow accompanying vasculature of normal tissues. It contains giant capillaries
Figure 35.1 The ovarian artery color and pulsed Doppler. Note the Figure 35.2 Color Doppler image of the ovarian blood flow in the luteal
high resistance to blood flow part of the menstrual cycle
of functional cysts, follicle and corpus luteum cysts, are

benign and derived from either an unruptured follicle or
the cystic degeneration of a corpus luteum, respectively.
Typically, these cysts are unilateral and are less than 6 cm in
diameter, and during pelvic examination, they feel smooth
and cystic. On sonograms, the cysts appear unilocular
and fluid-filled, without evidence of solid components or
excrescences. It seems that transvaginal color Doppler is
helpful in differential diagnosis of different causes of acute
abdomen and detection of torsion of the functional cyst.2
Torsion affects blood supply to the ovary both from the
ovarian artery and the ovarian branch of the uterine artery.
Below a morphologically recognized point, no blood supply
was detected. Hemorrhage from a ruptured corpus luteum
cyst can be severe enough to be mistaken for a ruptured
Figure 35.3 Pulsed Doppler waveform analysis of the luteal blood ectopic pregnancy. This new technique enhances our ability
flow. Note the low resistance to blood flow
to distinguish between these two conditions, and select the
patients for surgical intervention when necessary.
and arteriovenous shunts without intervening capillaries. Mature teratomas (dermoid cysts) occur commonly in
Newly formed vessels contain no smooth muscle in their women of reproductive age. They contain elements of mature
walls, but instead contain only a small amount of fibrous adult structures derived from all three embryonic layers:
connective tissue. These vascular changes can be detected (i) endoderm, (ii) mesoderm, and (iii) peripherally ectoderm.
using color Doppler. Blood flow can be demonstrated These structures include hair, teeth, bone, skin and calcified
throughout diastole, reflecting significantly decreased components that give focal, high-amplitude reflectors with
impedance to flow distal to the point of sampling. Because acoustic shadowing. Unfortunately, these high-amplitude
very similar indices of impedance to blood flow are reflectors may simulate bowel gas; therefore, these lesions
seen from the preovulatory follicle and corpus luteum, may be camouflaged and sometimes even large lesions can
vascular information derived from the premenopausal go undetected on sonograms.
ovary must always be related to the patient’s menstrual Serous and mucinous cystadenomas are also common
cycle. Accordingly, physiological ovarian angiogenic lesions. Serous cystadenomas may be unilocular, but they
activity could be excluded by carrying out the examination are mostly multilocular, with or without papillary growth
during the early proliferative phase (from the 3rd to the into the cavity. Mucinous cystadenomas may attain a huge
l0th menstrual day). In ovarian lesions that demonstrate size, and several have been reported to weigh 45–90 kg.
low impedance and high diastolic flow, it is important Grossly, they present as rounded or ovoid masses with a
to determine whether the waveform has a diastolic smooth capsule that is usually translucent or bluish-whitish
notch. Existence of a notch indicates persistence of an gray. Mucinous cystadenomas are thin-walled and mostly
initial resistance from the muscular lining of preexisting multilocular. Papillary formations may be present, but they
arterioles, and is typical of benign tumors. Small vessels are less common than in serous cystadenomas. Sonographic
that feed growing ovarian tumors or metastases could evaluation whether alone or in combination with tumor
not be seen before the transvaginal application of color markers cannot determine the nature of the lesion before
Doppler. The clinical application of this new modality and Doppler assessment. This is not surprising, because it can
characterization of benign and malignant ovarian lesions on be difficult to distinguish a benign ovarian tumor from a
the basis of their vascularity have opened exciting avenues malignant or borderline one by macroscopic inspection of
in the field of gynecological oncology. the specimen or even by microscopic evaluation.
Fibromas, thecomas and Brenner’s tumors are solid, benign
Angiogenesis in Benign Ovarian Tumors tumors found in premenopausal and postmenopausal patients.
Functional cysts are the most common source of adnexal Small, solid tumors are difficult to detect on sonograms because
masses in women of reproductive age. The two main types they are similar in echo texture to the normal ovary. If a solid
lesion which is observed in the adnexa of a premenopausal collection with internal echoes that may have multiple
woman, it is more likely to be a pedunculated or broad ligament loculations. Occasionally, distinction from fluid-filled loops
leiomyoma than a solid ovarian neoplasm. Transvaginal of bowel may be difficult. In this instance, a water enema
color Doppler is useful in differentiating fibroids from solid may be helpful because the movement of water through the
ovarian masses on the basis of their vascularity. Within or on bowel will be observed on real time ultrasound. Because
the periphery of the uterine mass, even when it is out of the the inflammatory process in the ovary involves both
contour of the uterus, it is possible to detect waveform signals structural and vascular changes, color Doppler ultrasound
that are typical for the uterine vascular network. In such cases, can be a useful tool in its diagnosis and management. The
blood flow is usually similar to normal myometrial perfusion, early phase of the disease is characterized by edema of the
originating from terminal branches of the uterine artery. On the fallopian tubes and dilatation of the blood vessels in their
other hand, small vessels that feed a growing ovarian tumor are walls. The inflamed ovaries were enlarged and filled with
of ovarian vasculature origin. multiple cysts which represented infected follicles or corpus
luteum cysts. Intraovarian vessels could easily be identified
Endometriosis and show usually moderate resistance to blood flow.
Endometriosis is a condition in which abnormal growth of It is well known that the sonographic appearance of a
tissue, histologically resembling endometrial tissue occurs complex adnexal mass should be interpreted in the context
outside the uterus, including on the surfaces of the bowel, of the clinical setting. For example, in the febrile patient, a
bladder or abdominal wall. The ovary represents a relatively thick-walled mass containing echogenic fluid is likely to be
unique site of implantation, as the levels of steroids surpass an abscess. In this advanced and most severe form of pelvic
those in the circulation, and hence, this affords an ideal inflammatory disease (PID), it is difficult to identify the pelvic
environment for implantation of endometrial growth. It seems anatomy. Ovaries are usually adherent to the pelvic sidewall or
that the surface epithelium and the proximity of the tubal to the uterus, and the scarring process can alter their endocrine
ostia influence transplantation production. When endometrial function and circulation. Based on our experience, dynamic
cells enter the ovarian stroma, large endometrial cysts filled use of color Doppler ultrasound in patients affected with PID
with viscous chocolate-colored liquid may be formed. is important for accurate diagnosis, follow-up and evaluation
There is usually a well-demarcated separation between of the ovulatory function and ovarian perfusion.
the endometrial cyst wall and the normal adjacent ovarian Color Doppler ultrasound is a useful tool in the
stroma. The most prominent vascular area in these common diagnosis of PID. It helps to distinguish between dilated
benign cysts is at the level of the ovarian hilus. This type of vessels and a fluid-filled hydrosalpinx, and it can be
neovascularization was often seen with endometriomas. It useful in the differential diagnosis of tubo-ovarian abscess.
seems that low impedance/high diastolic flow is present when Measurements of the intraovarian resistance in the acute
there is a hemorrhage during the menstrual phase of the cycle. phase of the disease reveal the ovarian involvement and
Therefore, it is recommended to study ovarian endometrioma function, as these relate to the rapidly changing pattern of
vascularity during the late follicular phase. It is postulated the disease. An increased resistance to blood flow in the
that the effect of medical treatment is highly dependent chronic phase is probably related to the extensive scarring.
upon the metabolically active implants arriving via a blood This condition of reduced perfusion may have long-term
supplying network. Conservative treatment has encouraging effects on the endocrine function of the ovary.
potential and can be successfully used in patients with an
optimal vascular pattern. Surrounding inflammation and Infertility
fibrotic changes that may disturb this process can be detected The true possibilities of transvaginal color and pulsed
by transvaginal color Doppler. Based on some experience, Doppler sonography in research into the ovarian circulation,
avascular ovarian lesions could be best removed surgically. polycystic ovarian syndrome and corpus luteum function
are yet to be discovered. Ovarian blood flow velocity seems
Pelvic Inflammatory Disease to be the main determinant of follicular responsiveness
Ultrasonography is often used to exclude intrauterine and risk of ovarian hyperstimulation syndrome. Therefore,
and ectopic pregnancy or to document the presence of an ovarian stromal perfusion should be evaluated prior to in
adnexal mass. Sonography shows a predominantly cystic vitro fertilization (IVF) treatment, to identify patients with
an altered response to hormonal stimulation and those periphery of the tumor. New vessels are continually
with increased risk of hyperstimulation. It is hoped that produced on the periphery of the tumor, creating the
further research on promoters of angiogenesis will improve potential for its proliferation and growth. The second type of
ovarian responsiveness and IVF outcome in patients with signal, exhibiting little systolic-diastolic variation, is usually
diminished ovarian stromal blood flow.3,4 present in the central vessels within the malignant tumor.
This is most probably their response to the angiogenic
Angiogenesis in Borderline Tumors activity of tumor cells. These vessels have a relative paucity
of smooth muscle in their walls in comparison with their
Ultrasonography has been widely used to detect, characterize
caliber and ‘behave’ more like capillaries than true arteries
and evaluate ovarian tumors. The principle of the diagnostic
or arterioles. Vessels deficient in their muscular elements
imaging study is based on macropathology. Thick septae,
present diminished resistance to flow and thereby receive
irregular solid parts within a mass, indefinite margins and
a larger volume of flow than vessels with high impedance.
presence of ascites are regarded as malignant patterns. Some
It seems that distribution of the vessels and impedance to
authors have reported that ovarian tumors of low malignant
blood flow is dependent on tumor type and size. Tumors
potential presented the same patterns as malignant tumors.
gradually begin to compress their own blood vessels when
On the other hand, other authors mentioned that borderline
they continue growing beyond a certain size. The absence
tumors had an appearance similar to that of benign tumors
of functional lymphatic vessels in the tumor stroma, and the
and it was difficult to differentiate them from their benign
increase in cell mass and tumor vessel permeability, result
counterparts. Therefore, assessment of vascular changes and
in an increase in the interstitial pressure in the tumor core
the resistance to blood flow would be required in the ovarian
and lead to the occlusion of centrally located tumor vessels.
tumor presenting either benign or malignant features by
This causes prolonged cessation of flow in the center of
conventional ultrasound.5 Blood flow velocity waveforms
the tumor, followed by central necrosis. It seems that low
obtained from borderline tumors are relatively of high diastolic
resistance in centrally located vessels is a consequence of
flow and low resistance. Doppler features are extracted
a response to the angiogenic activity of the tumor cells and
from large arterioles or sinusoids with no muscles in their
to the differences in necrotic processes. Another important
walls. This is a possible hemodynamic response to the tumor
parameter for the assessment of tumor vascularity is the
angiogenesis factor produced from low malignant potential
vascular arrangement. Randomly dispersed vessels within
cells. Therefore, the preoperative assessment of the adnexal
the solid part of malignant tumors were seen four times
mass by ultrasonography would include the size, consistency
more than regularly separated vessels.
and blood flow to determine the likelihood of malignancy.6-8
Color and pulsed Doppler sonography demonstrates
the vascularity of an adnexal mass. Blood flow data
Angiogenesis in Malignant Ovarian Masses should be considered to indicate the angiogenic intensity
The advent of vaginal ultrasound screening methods for of a tumor, rather than indicating malignancy itself.10-12 It
ovarian cancer has made the ovaries more accessible.9 seems clear that initial attempts to classify ovarian tumors
Dramatic changes in ovarian tissue vascularity during solely on the basis of their impedance to blood flow have
oncogenesis are mediated by numerous angiogenic factors been too simplistic. This problem has been partly solved
and can be detected by using flow data from color Doppler. by the introduction of other ‘vascular parameters’ such as
Malignant tumor vessels are usually dilated, saccular blood vessel arrangement and location, shape of the pulsed
and tortuous, and may contain tumor cells within the Doppler waveform and appearance of an early diastolic
endothelial lining of the vessel wall. Other features include notch, as well as assessment of blood flow velocities.
the presence of arteriovenous shunting (large and direct However, the difference in flow parameters in benign
communications, or microscopic communications in the versus malignant lesions may not always be sufficient
tumor microcirculation) and bizarre thin-walled tortuous to form the basis of a firm diagnostic impression.13-16 A
vessels lined by tumor cells that end in amorphous spaces common criticism of color Doppler is that the operator is
constituting ‘tumor lakes’ with or without associated never blind to the B-mode image: there is a tendency to
necrosis. Arteriovenous shunts are remarkable because search harder for low impedance blood flow patterns in
of extreme velocities that occur at sites of high-pressure lesions with a malignant appearance rather than in simple
gradients. This type of vessel is usually situated on the adnexal cysts. However, when applied by expert operators
and in a disciplined fashion, it may significantly add to Doppler data. A change in color setting may lead to a totally
diagnostic information about an adnexal mass and its different three-dimensional vascular image and dissimilar
morphological appearance. If blood flow data are treated quantitative results. In addition, since now both color
as providing an insight into the pathology of a tumor, they and power Doppler can be combined with more complex
give reassurance when masses have a benign appearance, computing, the frame rate will be significantly reduced
while giving confirmation of malignancy in adnexal masses when the power/color Doppler mode is active. Therefore,
with suspicious morphological features. if a mechanical three-dimensional probe is used, some very
It is important to emphasize that the areas of overlap in small vessels may escape from image capture. The effects
benign versus malignant pelvic lesions tend to involve non- of ultrasound attenuation can sometimes cause different
neoplastic masses that contain vasodilated vessels, owing ‘power intensity’ and hence vessel detection between nearer
to local or general hormonal imbalances, whereas some and deeper parts of the tissue being explored.
malignant tumors elicit sparse angiogenesis and may appear Morphological analysis of the blood vessel system
avascular, and therefore benign, in terms of color Doppler represents another approach to tumor diagnosis that, so far,
sonography. Obese women and women with irregular cycles has not been extensively evaluated. Nevertheless, there is a
and hormonal disturbances may produce ovarian blood flow distinct impression from some reports that the distribution
patterns with typical low vascular resistance to blood flow. and branching pattern of blood vessels that supply fast-
Therefore, measurements of estradiol and progesterone growing tumors differ from those of the normal blood
serum levels on the day of the transvaginal color Doppler supply to normal organs. This means that the blood vessel
examination should be performed when low vascular distribution seems to carry additional information that is
impedance to blood flow is found. It is possible that, with missed by the present diagnostic approaches. However,
further improvement of color and pulsed Doppler sensitivity, describing branching structures such as the blood vessel tree
and in conjunction with clinical findings, grayscale ultrasound is a mathematically complicated task. Microvessel density
imaging and serum hormonal levels when necessary, a better in ovarian cancers has been correlated with the likelihood
distinction between malignant and benign pelvic tumors will of recurrence. The density (determined histologically) of
be made. Contrast agents are another possibility for enhancing microvessels, irrespective of their distribution, was found
both color and power Doppler examinations by increasing the also to have significant implications for recurrence. In color
detection rate of small vessels.17 Doppler studies the density can be determined by counting
the number of color spots in a tumor area.
Three-dimensional Ultrasound Different types of angiogenesis in different physiological
The three-dimensional capability has been extended to and pathological conditions have been described.
various diagnostic ultrasound modalities. In the case of Physiological angiogenesis is seen in folliculogenesis,
ovarian tumor vascularity, the three-dimensional display embryogenesis and implantation, chronic inflammation and
allows the physician to visualize multiple overlapping some benign neoplasms. According to some authors, the
vessels and to establish their relationship to other vessels luteal vessels are usually fewer and seldom have complicated
and tumors or other surrounding tissues. The implementation branching or encircle the cyst, in contrast to the findings in a
of the three-dimensional display permits the physician to malignant neoplasm. In simple cysts the vessels are usually
view structures in three dimensions interactively, rather straight and regularly branching, whereas in ‘chocolate’ cysts
than assembling the sectional images mentally. The three- vessels usually branch from a hilar vessel then run along the
dimensional power Doppler system may enable physicians surface of the tumor. Similar vascular anatomy is detected
to study the region of interest in more detail. Although power in dermoid cysts. In cases of malignant ovarian neoplasm
Doppler has several advantages over conventional color the tumor vessels are usually randomly dispersed within
Doppler ultrasound, it is still a kind of color Doppler imaging the stroma and periphery, and some of them form several
and, therefore, subject to some of the limitations of the tangles or coils around the surface. The course of the main
conventional technique. For example, various parameters of tumor vessel is usually irregular with more complicated
color Doppler ultrasound, such as pulse repetition frequency, branching. The diameter of these vessels is felt to be more
wall filter, priority, power gain, color persistence and frame uneven and ‘thorn-like’. These findings can be compared to
rate must be optimized for three-dimensional display, as well previous studies with conventional color Doppler ultrasound.
as for qualitative and quantitative analysis of these power However, the appeal of the three-dimensional display is that
it is more comprehensive and allows physicians to understand 5. Fleischer AC. New developments in the sonographic
the three-dimensional architecture of the microcirculation assessment of ovarian, uterine, and breast vascularity. Semin
interactively. In addition, the resolution of current power Ultrasound CT MR. 2001;22(1):42-9.
Doppler is sufficient to detect vessels of around 1 mm in 6. Kinkel K, Hricak H, Lu Y, et al. US characterization of ovarian
diameter. In an attempt to systematize the extent of perfusion, masses: a meta-analysis. Radiology. 2000;217(3):803-11.
7. Brown DL, Doubilet PM, Miller FH, et al. Benign
four regions of different perfusion states can be recognized:
and malignant ovarian masses: selection of the most
(i) a necrotic region (central portion); (ii) a seminecrotic
discriminating gray-scale and Doppler sonographic features.
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Different pathological types, tumors with different growth masses by transvaginal color ultrasound. J Ultrasound Med.
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The results reported in the recent literature on three- transvaginal sonographic screening in asymptomatic women
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4. Kurjak A, Kupesic S. An Atlas of Transvaginal Color dimensional power Doppler sonography: imaging and
Doppler, 2nd edition. New York, London: Parthenon quantifying blood flow and vascularization. Ultrasound
Publishing; 2000. Obstet Gynecol. 1999;14(2):139-43.
Section 5
3D AND 4D TRANSVAGINAL SONOGRAPHY
¯ Three-dimensional Sonoembryology
¯ Cesarean Scar Hysterotomy: Assessment by 3D Transvaginal Echography
¯ Assessment of Normal and Abnormal Ovaries by Transvaginal Sonography
¯ Screening for Ovarian Cancer by Different Modes of Transvaginal Sonography
¯ Four-dimensional Technical Aspects
¯ Fetal Upper Limb Movement in the First Half of Pregnancy Detected by Transvaginal 4D Ultrasound
¯ Advanced Sonographic Assessment of Benign Endometrial Disease
CHAPTER
36
Three-dimensional Sonoembryology
Guillermo Azumendi Pérez, Asim Kurjak, Wiku Andonotopo, Jose Bajo Arenas
Introduction A detailed sonogram of the fetus during the first trimester

can be obtained due to the large amount of amniotic fluid.
Three-dimensional (3D) sonography has obtained important Moreover, 3D sonography is absolutely superior to the
benefits among professionals interested in prenatal standard 2D sonography in assessment during the first
diagnostics. Although existing from the beginning in the trimester of pregnancy. Three-dimensional sonography
early 1980s,1,2 3D sonography has become fully established tremendously reduces the time of exposure of embryo to
in the last few years. This is mostly due to the exceptional the ultrasound beam. Volume acquisition takes only a few
development of computer processor technology essential seconds. Image processing and analysis is done off-line,
for 3D imaging systems. without any time limitations. Sonographers can choose
The main advantages of this new technology in between two principal modes of imaging: (i) the planar
obstetrics include improved assessment of complex mode and (ii) the full 3D image. In the planar mode the
anatomic structures, surface scan-analysis of minor defects, object is simultaneously projected onto three perpendicular
volumetric measurements of organs, spatial presentation planes (Fig. 36.1). There is no limit in object rotation or
of blood flow information and 3D examination of fetal in the number of tomograms of different sections of the
skeleton.3-8 Modern 3D systems are capable of generating analyzed object. Planar mode enables superb precision
surface and transparent views depicting the sculpture-like of measurement. Full 3D mode is particularly useful in
reconstruction of fetal surface structures or the X-ray- presenting the 3D interrelationship of different organs
like images of fetal skeletal anatomy. Operating in planar or the skeleton. Sonographers can change between
mode, 3D orientation of tomograms is unlimited, despite different modalities of image rendering, emphasizing the
limited probe manipulation or inadequate position of outer surface or presenting inner structures through the
fetal structures. These imaging capabilities are extremely transparent mode.
important during the first trimester of pregnancy when Three-dimensional sonography can improve accuracy
manipulation of the vaginal probe is restricted and and success rate of nuchal translucency (NT) measurement
obtainable ultrasound sections are limited.9 Additional in pregnancy between 10 and 14 weeks of gestation. In
progress is achieved owing to the permanent possibility a series of 120 pregnancies, Kurjak and Kupesic14 were
of repeated analysis of previously saved 3D volumes able to obtain the mid-sagittal section and measure NT in
and elimination of surrounding structures.1,10 It should 100% of cases using 3D transvaginal sonography. Using
be emphasized that in the field of prenatal diagnosis standard 2D sonography, this was possible in only 85% of
the 3D technique is complementary to the conventional cases. Due to the superb quality of images, 3D sonography
two-dimensional (2D) technique, rather than offering enables detection of developmental anomalies.15-21 Three-
an alternative. 11 However, 3D imaging is superior in dimensional sonography will certainly improve early
specific diagnostic problems. A comparison of 2D and 3D detection of fetal anomalies, and possibly become the
techniques shows that 3D provides a diagnostic gain in a screening method for them. In addition, 3D sonography
large percentage of cases. This is due to the possibility of produced better intraobserver reproducibility of results.
surface and transparent mode imaging that makes accurate Three-dimensional sonography with its potential for
topographic depiction of the desired image plane much complex and sophisticated postprocessing of images has
easier.1,12,13 proved to be a useful tool in experimental embryology.
386 Section 5  3D and 4D Transvaginal Sonography
Figure 36.1 Three section planes of 3D ultrasound. These three planes (frontal, transverse,
and midsagittal) are perpendicular to one another at the three axial center of rotation
Using a special off-line imaging computer device Blaas confirming gradual augmentation of the loci and intensity
et al.22 produced a series of ex vivo obtained images of the of the intervillous flow in pregnancies between 5 and 11
human embryo, emphasizing development of the brain gestational weeks.23,24
cavities during the first trimester. This new technology
has moved embryology from postmortem studies to in vivo Three-dimensional Ultrasound Findings
environment (Fig. 36.2). from Ovulation to Implantation
Developments on the ultrasound technology enabled
us to expand investigations of early placental vascular Uterus
supply. Three-dimensional power Doppler is a unique It is understood that normal early human development
instrument that enables assessment of vascular signals determined by uterine perfusion, implantation process and
within the whole investigated area. Hemodynamical chromosomal structure of the fetus. Insufficient implantation
changes included in the process of early placentation are and inadequate uterine blood flow can be noninvasively
one of the most exciting topics in investigation of early perceived by Doppler technique. Consequently, entire set
human development. This investigation was designed as of new undiscovered circumstances concerning this matter
an observational cross-sectional study. After acquiring the is accessible for research.
volume containing 3D power Doppler data of the pregnant After ovulation, there is a brief interval throughout which
uterus, the signals belonging to the chorion were isolated. endometrial receptivity is at its maximum. During these
Vascular 3D measurements were undertaken through few days, a blastocyst traveling to the uterine cavity can
3D power histogram and expressed by vascularization achieve a physical contact with the endothelial lining and
index (VI) and vascularization flow index (VFI). Volume eventually—implant. At the beginning of its attachment,
of the chorion increased exponentially throughout the the blastocyst is directed with the inner cell mass toward
observation period. The VI and VFI positively correlated the endometrium. Furthermore, the trophoblast produced
with the crown-rump length (CRL) and chorion volume action of the proteolysis enzymes which enabled penetration
(Fig. 36.3), and showed gradual increment through the and erosion of the uterine mucosa. During implantation,
investigation period. This investigation produced results the trophoblast erodes lying near maternal capillaries, and
Chapter 36  Three-dimensional Sonoembryology 387
Figure 36.2 Comparison between computer animation model of embryonal development and a series of in vivo obtained images of the human
embryo by 3D sonography, emphasizing development of the embryo in the early pregnancy
Figure 36.3 Volume calculation (VOCAL) software feature enables Figure 36.4 Three-dimensional power Doppler showing uterine
measurement of chorionic volume from the surrounding structures and perfusion during implantation, the trophoblast erodes lying near
quantitative measurement of vascular signals maternal capillaries and maternal blood enters to a direct contact with
the conceptus
maternal blood enters to a direct contact with the conceptus. uteroplacental arteries having the ability of adapting the
The intercommunicating lacunar network begins to be the increasing blood supply.
intervillous space of the placenta (Fig. 36.4).
Throughout the 4th week, the migrating trophoblast Endometrium
penetrates the uterine wall and invades venous sinusoids of With the advent of 3D ultrasonography, it became possible
increasing size and superficial arterioles. Trophoblastic cells to perform reliable sonographic endometrial volume
can be discovered inside the spiral arteries at approximately calculations and to correlate them with pregnancy rates
the 6th week following fertilization. Increasing blood flow undergoing in vitro fertilization (IVF).15,16 More recently,
produces progressive distention of these arteries into the subendometrial blood flow was quantitatively analyzed
Figure 36.5 Three-dimensional power Doppler image of the endometrium on the day of embryo
transfer. Note the color histogram at the bottom right, which shows vascularization flow index
by using the color histogram mode in 3D power Doppler asymmetrically in the uterine cavity (Fig. 36.6). Gestational
(Fig. 36.5).25 sac at this time measures approximately 5 mm and grows
By 3D ultrasound, it is possible for us to determine 1−2 mm/day.
the quantity of the endometrial volume and predict the As the fetal and the placental structures develop, their
probability of implantation because quantitative volume vascular network becomes more pronounced. Hence, it is
measurements appear to be more accurate than estimation of possible to observe three separate and yet unified units: (i)
the endometrial thickness. It is suggested that quantification the maternal, (ii) placental and (iii) fetal portions of the
of endometrial volume by 3D ultrasound in combination vascular network.
with blood flow studies may be the most useful method to
predict pregnancy rates as a sequel of the medically assisted Maternal Portion
reproduction.25 The maternal portion of the placental circulation consists
of the main uterine arteries and their branches that spread
Ovaries throughout the uterus until they reach the decidual plate
At the 8th week of gestation, luteal flow becomes less of placenta. The main uterine arteries originate from the
detectable and the visualization rate is 60−80%. There is internal iliac arteries, and they give off branches, which
no obvious connection between the 2D ultrasonographic extend inward for about a third of the myometrium
and Doppler characteristics of the corpus luteum and first thickness without significant branching. At this point, they
trimester pregnancy outcome. The role of 3D ultrasound subdivide into an arcuate wreath encircling the uterus. From
in the evaluation of the corpus luteum morphology and this network, smaller branches, called the radial arteries,
vascularity has still to be investigated. arise and are directed toward the uterine lumen. The
radial arteries branch into basal arteries and endometrial
spiral arteries as they pass the myometrial-endometrial
Events Following Implantation border. Basal arteries, that are relatively short, terminate
The earliest visible sign of pregnancy is a new formed in a capillary bed that serves the stratum basale of the
gestational sac that can be seen during 5th week of pregnancy. endometrium. The spiral arteries project further into the
Ultrasonographically, it is presented as a hypoechoic oval endometrium and terminate in a vast capillary network
structure, surrounded by a hyperechoic ring, situated that serves the functional layer of the endometrium. All of
The increment in blood flow through the uterine network
is, probably, caused by an urgent need of the placenta and
fetus for nourishment.
Uterine Artery Blood Flow in

Nonpregnant and Pregnant Patients
The main uterine artery can be visualized at the level
of the internal cervical os, as it approaches the uterus
laterally and curves upward alongside the uterine body.
Pulsed Doppler waveform profiles of the main uterine
artery are characteristic, comprising a high peak-systolic
component with a characteristic notch in the protodiastolic
part and very low end-diastolic flow. Numerous Doppler
studies have demonstrated a gradual decrement in the
Figure 36.6 Three-dimensional images of gestational sac uterine artery resistance index during the first trimester
during 5th week of pregnancy of pregnancy.27-30
Characteristic notch in the protodiastolic part of sonogram
is gradually disappearing; diastolic flow is characterized by
them can be clearly identified in the pregnant uterus by their
high velocity, and difference between systolic and diastolic
anatomical position and characteristic waveform profile.
flow velocities decreases. This kind of changes indicates
Intrauterine placental development requires adaptive
normal development of pregnancy (trophoblast invasion).
changes of the uterine vascular environment. The fact that
Obviously, this decrement continues during the second
the uterine vascular network elongates and dilates throughout
trimester of pregnancy and can be observed in all the
the pregnancy is well known from anatomical studies.26
segments of the uteroplacental circulation.
Doppler Findings
Arcuate and Radial Arteries Blood Flow in
Flow velocity waveforms from small arteries show Nonpregnant and Pregnant Patients
significantly lower pulsatility and blood velocity as
compare to the main uterine artery. The branching of the Arcuate arteries may be seen within the outer third of
uterine circulation and the increased total vascular cross- the myometrium, while the radial arteries are identified
sectional area, which results in lower impedance to blood within the two inner thirds of the myometrium. Doppler
flow, is the background of this phenomenon. Most authors sonograms of the arcuate and radial arteries are very similar,
have demonstrated that the progressive decrement in the with moderate peak-systolic and diastolic components of
impedance to blood flow observed in the main uterine artery blood flow. However, differences exist in the values of the
during early pregnancy occurs in all the segments of the resistance (RI) or pulsatility (PI) indices. These are lower
uteroplacental circulation.27-30 in the radial than in the arcuate arteries, corresponding to
Transvaginal color and pulsed Doppler allows the lower peripheral impedance to blood flow.
identification of the uterine vascular transformation.
Normal Finding of Spiral Arteries in
Furthermore, the invasion of larger maternal blood vessels
Pregnant Patients
of higher pressure results in higher velocity and larger
diastolic component of Doppler signal. During early pregnancy, the spiral arteries are progressively
Kurjak and colleagues 31 have pointed to vascular converted to nonmuscular dilated tortuous channels. The
changes in early pregnancy even before visualization of the normal musculoelastic wall is replaced with a mixture of
gestational sac. With advancing gestational age, impedance fibrinoid material and fibrous tissue. Easy to be detected
to blood flow decreases from the main uterine to spiral above the chorion (near the placental implantation site),
arteries. At the same time, an increase in blood flow by spiral arteries are characterized by lower resistance index
means of peak-systolic velocity has a decreasing trend and higher peak-systolic velocities followed by turbulent
from the uterine, through the arcuate to the radial arteries. flow (Fig. 36.7). This kind of flow is typical for wide
smooth chorion. The placenta is mostly derived from fetal

tissues, when maternal component contributes little to the
architecture of the definitive placenta.
Normal placentation requires a progressive transformation
of the spiral arteries and an infiltration of trophoblastic
cells into the placental bed. These physiological changes
normally extend into the inner third of the myometrium, and
in normal pregnancies, all the spiral arteries are transformed
into uteroplacental arteries before 20 weeks of gestation.33
In some cases of early pregnancy failure and pregnancy-
induced hypertension, there is an adequate placentation
with a defective transformation of spiral arteries.34
Three-dimensional Power Doppler Studies in

Assessment of Early Chorionic Circulation
Figure 36.7 Transvaginal 3D power Doppler image on early pregnancy
demonstrates blood flow signal derived from spiral arteries New developments on the cutting edge of the ultrasound
technology enabled us to expand investigations of early
tortuous blood vessels and has hemodynamic characteristics placental vascular supply. Three-dimensional power
of an arteriovenous shunt. The active trophoblast induces Doppler is able to depict the integral 3D image of placenta
vascular adaptation, which ensures adequate blood supply and embryo, and their vascular network.5,23 Additionally, it
to the growing embryo. is possible to quantify and express numerically data related
to vascular signals in the investigated volume.
Pulsed Doppler waveform signals obtained from
Development of the process of placentation begins after
spiral arteries show low impedance to blood flow and a
the first contact between trophoblast and decidua has been
characteristic spiky outline. The sonogram presents the blood
established. There are two waves of trophoblastic invasion.
flow from more than one spiral artery. The spiral arteries
First occurs at 8 weeks of pregnancy. It is characterized
change their wall structure with gestation and become vessels
by invasion of interstitial trophoblast invasion into the
with completely different hemodynamics in relation to other
myometrium and cytotrophoblast (endothelial trophoblast)
arteries of the uteroplacental circulation.
into complete decidua, but not myometrium. Second wave
is characterized just by invasion of endothelial trophoblast
Placenta into the myometrium and occurs between 16 and 18 weeks
Development and the Ultrasound Imaging of gestation.35
Primary chorionic villi develop between 13th and 15th Uteroplacental arteries are not responsive to the
day after the ovulation (during 4th week of gestation) and autonomous nervous system. In the second lunar month,
mark the beginning of the placental development. At the the intervillous space increases as the result of the extensive
same time, the formation of blood vessels starts in the branching of the villi. The intervillous space, combined
extraembryonic mesoderm of the yolk sac, the connecting with the villi, is the functional unit of the human placenta,
stalk and the chorion.32 By 18−21 days (during 5th week where maternal-fetal metabolic exchange occurs.36 In this
of gestation), the villi have become branched and the period, many terminal parts of the spiral arteries near the
mesenchymal cells within the villi have differentiated into intervillous space contain plugs of cytotrophoblastic cells.
blood capillaries and formed an arteriocapillary venous At the same time, centrally placed communications between
network. Chorionic villi cover the entire surface of the the decidual veins are numerous and large. After 40 days,
gestational sac until the end of the 8th week. At that time, spiral arteries show direct openings into the intervillous
the villi on the side of the chorion proliferate toward the space and the cytotrophoblastic cells appear within their
decidua basalis to form the chorion frondosum, which lumen. The maternal blood reaches the intervillous space
develops into the definitive placenta. The villi in contact through the gaps between the cells of the endovascular
with the decidua capsularis begin to degenerate and trophoblast. These events can be nicely studied by 3D color
form an avascular shell, known as the chorion laeve or and power Doppler ultrasound (Figs 36.8A to D).
A B C D
Figures 36.8A to D Three-dimensional power Doppler image of early gestation and its vascular supply: (A) 5 weeks, (B) 6 weeks, (C) 8 weeks,
and (D) 9 weeks
During pulsed Doppler analysis two types of waveform translucent image, and a maximum-intensity projection was
can be visualized: (i) pulsatile arterial-like and (ii) applied for a surface rendered vascular image. The former
continuous venous-like flow. Lumen of the spiral arteries was superior in assessment of the spatial interrelationship
is never completely obstructed by the trophoblastic plugs. of the vascular structures, and the latter was useful in
These data indicate that establishment of the intervillous the assessment of the morphology and outer surface of a
circulation is a continuous process rather than an abrupt confined vascular structure.
event at the end of the first trimester. Hafner et al.37 did cross-
sectional study in a group of patients in gestational age 5−11 The 5th Week
weeks. After acquiring the volume containing 3D power Characteristic embryological findings: The deep neural
Doppler data of the pregnant uterus, the signals belonging groove and the first somites are present. The embryo is
to the chorion were isolated. Vascular 3D measurements almost straight and somites produce conspicuous surface
were undertaken and expressed by VI and VFI. Volume of elevation. The heart prominence is distinct and the optic
the chorion increased exponentially throughout observation pits are present.
period. The VI and VFI positively correlated with the CRL The attenuated tail with its somites is also a characteristic
and chorion volume, and showed gradual increment through feature.
the investigation period (Figs 36.9A to E). Three-dimensional ultrasound findings: Gestational sac can be
visualized as a small spherical anechoic structure placed inside
Fetal Portion one of the endometrial leaves. Three-dimensional sonography
The assessment of the fetal portion of circulation includes enables precise measurement of exponentially expanding
the umbilical and fetal circulation. Hemodynamic changes gestational sac volume during the first trimester (Fig. 36.11).
Kupesic and coworkers39 found that 3D measurement of yolk
in the umbilical artery represent the placental side of the
sac volume and vascularity may be predictive of a pregnancy
uteroplacental circulation. Signals from the umbilical artery
outcome. Using this noninvasive modality, one can obtain
may be clearly visualized at the embryo’s lateral edge
multiplanar and surface images in reduced scanning time.
connected to the placenta. The fetal circulation is usually Surface images seem to be beneficial in the evaluation of the
analyzed through assessment of the fetal heart, fetal aorta, yolk sac echogenicity and detection of the hyperechoic yolk
carotid arteries and intracranial circulation (middle cerebral sac which may indicate chromosomal abnormality. Automatic
artery in particular) (Fig. 36.10). and manual volume calculation allows analysis of the precise
The appearance of blood flow in these arteries is relationship between the yolk sac and gestational sac volumes,
described separately for each gestational week and as well as assessment of the correlation between yolk sac
compared to the main histological and conventional gray- volume and CRL measurements. Planar mode tomograms are
scale ultrasound findings. Kurjak and Kupesic38 used useful for detecting the embryonic pole inside the gestational
combined B-mode and power Doppler imaging in order to sac. The embryo itself can be seen 24−48 hours after
evaluate fetal growth and development of fetal circulation. visualization of the yolk sac, at approximately 33 days after
Different rendering modalities were used in color-coded menstruation, at which it is 2−3 mm long.40 Adjacent to the yolk
data processing and presentation. A minimum-intensity sac, embryo can be seen as a small straight line measuring by
projection of the vascular network was used to create a the end of 5th gestational week.
A B C
D E
Figures 36.9A to E Correlation between vascular activities in the chorion detected by 3D power Doppler. (A) Chorionic
volume (Vch) related to the crown-rump length (CRL). (B) Chorionic vascularization index (VI) related to CRL. (C) Chorionic
vascularization flow index (VFI) related to CRL. (D) Chorionic vascularization index (VI) related to the chorionic volume.
(E) Chorionic vascularization flow index (VFI) related to the chorionic volume
sprouts of early intervillous and spiral artery blood flow. At

the end of the 5th week, when the gestational sac exceeds 8
mm, the small secondary yolk sac is visible as the earliest
sign of the developing embryo.
The 6th Week

Characteristic embryological findings: The embryo has a
C-shaped curve. The growth of the head (caused by the rapid
development of the brain) exceeds that of the other regions.
Three-dimensional ultrasound findings: Rounded bulky
head and thinner body characterize 3D image of an embryo
during the 6th week of pregnancy (Fig. 36.13). The head is
prominent due to the developing forebrain. Limb buds are
rarely visible in this stage of pregnancy. However, umbilical
Figure 36.10 Three-dimensional power Doppler demonstrated signals cord and vitelline duct are always clearly seen. At 6 weeks
from the umbilical artery, fetal heart, fetal aorta at the embryo’s lateral of gestation, ductus omphalomesentericus can be as much
edge connected to the placenta as three to four times the length of the embryo itself. The
amniotic membrane is also visible, initially at the dorsal part
Three-dimensional power Doppler findings: Three- of the embryo. A few days later, it surrounds the embryo but
dimensional power Doppler reveals intensive vascular not the yolk sac, which remains in the extracelomic cavity.
activity surrounding the chorionic shell staring from the first Three-dimensional power Doppler findings: Aortic and
sonographic evidence of the developing pregnancy during umbilical blood flow is well depicted. Initial branches of
the 5th week of gestation (Fig. 36.12). Gestational sac can the umbilical vessels are visible at the placental umbilical
be detected as a tiny ring-shaped structure at the beginning insertion (Fig. 36.10). Three-dimensional power Doppler
of gestational age of 5 weeks. Three-dimensional power detects embryonic heartbeats as early as 5 weeks and 4
Doppler reveals intense vascular activity surrounding it. A days menstrual age, at the embryo CRL of 3 ± 4 mm. At
hyperechoic chorionic ring is interrupted by color-coded this very early stage, this finding may help clinicians to
Figure 36.11 Three-dimensional ultrasound in 5 weeks of pregnancy. Figure 36.12 Three-dimensional power Doppler reveals intensive
The deep neural groove and the first somites are present. The embryo vascular activity surrounding the chorionic shell starting from the first
is almost straight and somites produce conspicuous surface elevation. sonographic evidence of the developing pregnancy during the 5th
Gestational sac can be visualized as a small spherical anechoic week of gestation
structure placed inside one of the endometrial leaves
the cardiac prominence. The trunk and the neck have begun
to straighten. Hand and foot plates are formed and digital
or finger rays started appearing.
Three-dimensional ultrasound findings: During the 7th
gestational week, spine gradually becomes visible, as well
as limb buds, lateral to the body. Amnion can be seen as a
spherical hyperechoic membrane, still close to the embryo.
Chorion frondosum can be distinguished from the chorion
laeve. Fast development of rhombencephalon (hind-brain)
occurs. This process gives even more prominence to the
head. Head becomes the dominant embryonic structure.
Using the multiplanar mode, developing vesicles of the brain
can be depicted as anechoic structures inside the head. The
biggest, and usually the only visible, is rhombencephalon
Figure 36.13 Rounded bulky head and thinner body characterize 3D placed on the top of the head (vertex). The head is strongly
image of an embryo during the 6th week of pregnancy. The head is flexed anterior being in contact with the chest (Fig. 36.14).
prominent due to the developing forebrain. Limb buds are rarely visible
in this stage of pregnancy The hypoechogenic brain cavities could be identified,
including the separated cerebral hemispheres. The lateral
ventricles are shaped like small round vesicles. The cavity
diagnose the viability of the pregnancy. Near the end of of the diencephalon (future third ventricle) runs posterior.
the 6th week, first signs of aortic and umbilical blood flow In the smallest embryos, the medial telencephalon forms a
within the embryo’s trunk are visible. The initial branches continuous cavity between the lateral ventricles. The future
of the umbilical vessels are visible at the placental-umbilical foramen of Monro is wide. In the sagittal plane, the height
insertion. of the cavity of the diencephalon (future third ventricle)
is slightly greater than that of the mesencephalon. Thus,
The 7th Week the wide border between the cavities of the diencephalon
Characteristic embryological findings: The head is now and the mesencephalon is indicated. The curved tube-
much larger in relation to the trunk and is more bent over like mesencephalic cavity (future Sylvian aqueduct) lies
Figure 36.14 Three-dimensional image during the 7th gestational Figure 36.15 Three-dimensional power Doppler findings demonstrated
week, spine gradually becomes visible, as well as limb buds, lateral to the aorta and umbilical blood flow, at the end of the 7th week. Three-
the body. Amnion can be seen as a spherical hyperechoic membrane, dimensional power Doppler depicts features of early vascular anatomy
still close to the embryo on the base of the skull. The intracranial circulation becomes visible
during this gestational age
anterior, its rostral part pointing caudal. It straightens embryos show a cranial pole flexion that makes it almost
considerably during the following weeks. impossible to see the face. Insertion of the umbilical cord is
Three-dimensional power Doppler findings: Besides the visible on the anterior abdominal wall. During the 8th week
aorta and umbilical blood flow, at the end of the 7th week, of pregnancy, there is expansion of the ventricular system
3D power Doppler depicts features of early vascular of the brain (lateral, third and midbrain ventricles). Due to
anatomy on the base of the skull. Vessels are evolving these processes, the head erects from the anterior flexion.
laterally to the mesencephalon and cephalic flexure. The vertex is now located over the position of the midbrain.
Apart from embryonic circulation, 3D power Doppler can Structures of the viscerocranium are not visible due to their
obtain blood flow signals from the intervillous space. The small size. Arms and feet are clearly visible. Insertion of
gestational sac occupies about one-third of the uterine the umbilical cord is visible on the anterior abdominal wall.
volume. The main landmark now is an echogenic fetal During the 8th and 9th weeks, the developing intestine is
pole consisting of embryo adjacent to a cystic yolk sac. being herniated into the proximal umbilical cord.
The intracranial circulation becomes visible during the Blaas and coworkers41 reported on a 7 weeks and 5
7th week of gestation. At this time, discrete pulsations of days gestational age embryo whose brain structures were
the internal carotid arteries are detectable at the base of the analyzed in detail by 3D ultrasound. They described distinct
skull (Fig. 36.15). hemispheres how the rhombencephalic cavity (future
fourth ventricle) deepens gradually with the growth of the
The 8th Week embryos, at the same time decreasing its length.41 At this
time, it has a pyramid-like shape with the central deepening
Characteristic embryological findings: By the beginning of
of the pontine flexure as the peak of the pyramid.42
the 8th week, the embryo has developed a skeleton, which
is mostly cartilaginous and gives form to its body. The Three-dimensional power Doppler findings: During the
communication between the primitive gut and the yolk sac 8th and 9th weeks, developing intestine is being herniated
has been reduced to a relatively small duct (the yolk stalk). into the proximal umbilical cord, which can be assessed
Three-dimensional ultrasound findings: The most using this technique (Fig. 36.17). By the 8th week, an
characteristic finding is a complete visualization of the embryo’s length is between 10 and 16 mm, and the CRL
limbs, which end in thicker areas that correspond to the is easily measured. The visualization rate of the fetal aorta
future hands and feet. The shape of the face begins to appear and umbilical artery is higher. Blood flow in the fetal heart
but is not clearly seen (Fig. 36.16). The great majority of and aorta as well as in the umbilical and intracranial arteries
Figure 36.16 Three-dimensional Ultrasound findings demonstrated Figure 36.17 Three-dimensional power Doppler visualized the fetal
complete visualization of the limbs, which end in thicker areas that aorta and umbilical artery. Developing intestine is being herniated into
correspond to the future hands and feet. The shape of the face begins the proximal umbilical cord, which can be assessed using this technique
to appear but is not clearly seen. The communication between the
primitive gut and the yolk sac has been reduced to a relatively small
duct (the yolk stalk) and 10th weeks of pregnancy. Visible are lateral ventricles
containing hyperechoic choroid plexuses. The head is
is clearly visualized. At this stage of pregnancy 3D power clearly divided from the body by the neck. External ear is
Doppler imaging allows visualization of the entire fetal sometimes depicted in the 3D surface image. Herniation
circulation. of the midgut is present. Dorsal column, the early spine,
can be examined in its whole length. The arms with elbow
The 9th to 10th Weeks and legs with knees are clearly visible. Feet can be seen
Characteristic embryological findings: The head is approaching the midline.
more rounded and constitutes almost half of the embryo The size of the lateral ventricles increases rapidly. While
(Figs 36.18A and B). The hands and feet approach each the third ventricle is still relatively wide at the beginning of
other. The upper limbs develop faster than the lower limbs, this week, its anteromedial part narrows due to the growth
and toward the end of the 9th week, the fingers are almost of the thalami. In the fetuses of 25 mm CRL and more,
entirely formed. The intestines are in the umbilical cord there is a clear gap between the rhombencephalic and the
(physiological midgut herniation). mesencephalic cavity due to the growing cerebellum. The
isthmus rhombencephaly is narrow and in most cases,
Three-dimensional ultrasound findings: Merz and
it is not visible in its complete length. The cavity of the
coworkers43 were able to provide striking images of the
diencephalon decreases in the larger fetuses (CRL = 25
fetal face at this gestational age. They reported cases in
mm), and becomes narrow, especially at its upper anterior
which transvaginal 3D ultrasound produced remarkably
part. The spine is still characterized by two echogenic
well-defined facial images as early as 9 weeks of gestation.
parallel lines.
Sometimes even the external ear can be depicted using 3D
surface imaging. Herniation of the midgut is still present Three-dimensional power Doppler findings: Fetal structures
as it is a consequence of the rapid growth of the bowel are now clearly discernible and they are represented by
and liver before closure of the abdominal wall. Although distinct parts of the fetal body-head, trunk and limbs. The
this is a physiologic phenomenon, it does not appear in head measures two-thirds of the entire body and becomes
each fetus. Possibly, we cannot visualize it, or else its size a distinct anatomical structure (Fig. 36.19). The common
may vary. At 10 weeks, the bowel undergoes two turns of and internal carotid arteries may be visualized at the end
180º, returning to its original position, at the same time of the 8th gestational week and the beginning of the 9th
that closure and development of the abdominal wall end. week. A cerebral circulation (circle of Willis and its major
Cerebral hemispheres continue to develop during the 9th branches) can be documented at 8 weeks in the form of
A B
Figures 36.18A and B Three-dimensional image at (A) 9 weeks and Figure 36.19 Three-dimensional power Doppler image showed the
(B) 10 weeks of pregnancy. The head is more rounded and constitutes cerebral circulation (circle of Willis and its major branches) in the form of
almost half of the embryo. The hands and feet approach each other. discrete pulsations of the intracerebral part of the internal carotid artery
The upper limbs develop faster than the lower limbs, and toward the
end of the 9th week the fingers are almost entirely formed
discrete pulsations of the intracerebral part of the internal using the transparent, X-ray-like mode (Figs 36.20A and B).
carotid artery. From the 9th gestational week, arterial With the use of the transparency X-ray system, starting at 13
pulsations can be detected on transverse section, lateral to weeks, the medullar channel, each vertebra and rib can be
the mesencephalon and cephalic flexure. visualized and even the intervertebral disks can be measured.
This opens unexpected possibilities for early diagnosis of
The 11th Week skeletal malformations.
Characteristic embryological findings: The midgut The 12th Week
herniation disappears and fetal kidneys produce urine that
Characteristic embryological findings: Fetal sex is clearly
is excreted into the amniotic fluid.
distinguishable by 12 weeks. The neck is well defined, the
Three-dimensional ultrasound findings: During the 11th week face is broad and the eyes are widely separated. By the end
of pregnancy, development of the head and neck continues. of the 12th week, erythropoiesis decreases in the liver and
Facial details, such as nose, orbits, maxilla and mandibles, begins in the spleen. The decidua capsularis adheres to the
are often visible (Figs 36.20A and B). Herniated midgut decidua parietalis.
returns into the abdominal cavity. Its persistence after 11th
Three-dimensional ultrasound findings: Visualization by
week of gestation is presumptive of an omphalocele. Planar
3D ultrasound in 12th week of gestation enables more
mode enables detailed analysis of the embryonic body with
visualization of the stomach and urinary bladder. Kidneys detailed analysis of fetal anatomy, especially limbs. It is
are often visible. Arms and legs continue with development. possible to count fingers and toes (Fig. 36.21). Growing
Hata and coworkers27 conducted a study on visualization of cerebellum is clearly visible. Lateral ventricles dominate
fetal limbs by 2D and 3D sonography. The ability to visualize the brain.44
fetal hands/fingers and feet/toes was better with 3D than with
Three-dimensional power Doppler findings at 11th and 12th
2D ultrasonography in the late first trimester (detection rates
weeks of gestation: With the use of the 3D power Doppler,
were 65% and 41% by 3D ultrasonography for hands and
feet, respectively, and 41% and 12% by 2D ultrasonography). it is possible to depict major branches of the aorta: common
Long bones can be visualized as hyperechoic elongated iliac and renal arteries. Circle of Willis and its branches
structures inside upper and lower extremities. Detailed 3D are easily visible (Fig. 36.22). From this week, a more
analysis of the fetal spine, chest and limbs is obtainable by detailed anatomical survey can be obtained, including the
A B
Figures 36.20A and B (A) Three-dimensional image during the 11th Figure 36.21 Visualization by 3D ultrasound in 12th week of gestation
week of pregnancy showing development of the head and neck. Facial enables more detailed analysis of fetal anatomy, especially limbs
details such as nose, orbits, maxilla and mandibles are often visible. (B)
Detailed 3D analysis of the fetal spine, chest and limbs is obtainable
by using the transparent, X-ray-like mode
cerebral and cardiovascular systems and the digestive and

urinary tracts. At this stage, the pulsations of the middle
cerebral artery can be easily discerned as a separate vessel.
However, until the end of the tenth gestational week, the
ultrasonically detected vascular network should be called
intracranial circulation (Fig. 36.23). Until the end of the
first trimester, the absence of end-diastolic blood flow in
fetal and placental components of the circulation is a normal
physiological finding.
Yolk Sac
Three-dimensional ultrasound imaging may give
additional data to functional Doppler studies for research
in developmental anatomy and embryology. This method Figure 36.22 By using 3D power Doppler technique, it is possible to
allows a detailed morphologic and volumetric analysis of depict major branches of the aorta: common iliac and renal arteries.
Circle of Willis and its branches are easily visible
extraembryonal static structures. Conventional methods for
measuring volumes of fluid-filled spaces include modeling
of shapes (e.g. using an ellipsoidal approximation). exponential growth of the gestational volume throughout
Using 3D planar mode, the position of the yolk sac the first trimester of pregnancy.
wall is accurately spatially assessed. Measurement of the With the formation of the extraembryonic celomic
volume, rather than estimation from a simple geometric cavity at the end of the 4th week, the primary yolk sac is
model, increases the accuracy of the measurement. Growth replaced with newly formed secondary yolk sac. During
and appearance of the yolk sac have been correlated with the organogenesis and before the placental circulation is
outcome of the pregnancy.45 Kupesic and Kurjak46 measured established, the yolk sac is the primary source of exchange
gestational sac volume (Fig. 36.24) and yolk sac volume, between the mother and the embryo. It has nutritive,
and vascularity in pregnancy between 5 and 12 weeks metabolic, endocrine, immunological, excretory and
of gestation (Fig. 36.25). Regression analysis revealed hematopoietic functions. At the beginning of the 5th week,
Figure 36.23 Three-dimensional power Doppler image demonstrated Figure 36.24 Three-dimensional embryonic structure demonstrated
the pulsations of the middle cerebral artery as a separate vessel. gestational sac and amniotic cavity. Growth and appearance of the
However, until the end of the 10th gestational week, the ultrasonically yolk sac have been correlated with the outcome of the pregnancy.
detected vascular network should be called intracranial circulation Regression analysis displayed exponential growth of the gestational
volume during the first trimester of pregnancy
it becomes visible as the first structure inside the chorionic

cavity. At this time, a circular, well-defined, echo-free area
measures 3−4 mm in diameter,47 while the gestational sac
measures about 8−10 mm. The yolk sac grows slowly until
it reaches a maximum diameter of approximately 5−6 mm
at 10 weeks. Its stalk can be followed from its origin all
the way to the embryonic abdomen. As the gestational sac
grows and the amniotic cavity expands, the yolk sac as an
extraembryonic structure is gradually separated from the
embryo. Different theories exist about the destiny of the
yolk sac. Until recently, it was assumed that it gets caught
and compressed between amnion and chorion and then
ultimately disappears by the end of the 11th week.
Recent studies emphasized that instead of getting
compressed the yolk sac degenerates first and then Figure 36.25 Vascularity in pregnancy between 5 and 12 weeks of
consequently disappears. The ultrasound appearance of the gestation. Regression analysis revealed exponential growth of the
gestational sac volume throughout the first trimester of pregnancy
yolk sac (Figs 36.26A to C) has already been proposed as a
prognostic parameter for the outcome of pregnancy. Kurjak
and coworkers48 established some criteria for distinguishing be defined and assessed prior to 10 gestational weeks.
between normal and abnormal yolk sac appearance. In Abnormal yolk sac size may be the first sonographic
their experience, yolk sac should always be visible before indicator of associated failure. Primarily, the presence of
the viable embryo; it measures 4−5 mm in diameter until an embryo without the visible yolk sac before the 10th
7−8 weeks of gestation and reaches 6.0−6.5 mm by the end gestational week is mostly an abnormal finding.
of the 9th week. It is evident that sonographic detection According to some authors, the inner diameter of the yolk
of abnormal yolk sac morphology may predict abnormal sac is always less than 5.6 mm in a normal pregnancy before
fetal outcome. Absence of yolk sac, its abnormal size, the 10th week of gestational age. Lyons49 established that for
echogenicity, shape and number are predictive indicators a mean gestational sac diameter of less than 10 mm, the yolk
of early pregnancy failure. All these parameters should sac diameter should be less than 4 mm. In 15 patients who
A B C
Figures 36.26A to C The yolk sac is the primary source of exchange between the mother and the embryo. It has nutritive, metabolic, endocrine,
immunological, excretory and hematopoietic functions: (A) at the beginning of the 5th week using 2D ultrasound, it becomes visible as the first
structure inside the chorionic cavity, (B) visualization of yolk sac vascularization with fetoscopy, (C) visualization of yolk sac using 3D technique
had abnormally large sacs, six had no embryo, five aborted was performed before the termination of pregnancy for
spontaneously and only one conceptus survived. Out of nine psychosocial reasons. The highest visualization rates for
others with embryo and large yolk sac, eight patients aborted yolk sac vessels were in the 7th and 8th weeks of gestation,
and in one patient with trisomy 21 was detected at the 24th reaching value of 90.71%. A characteristic waveform profile
gestational week. The yolk sac can be too small, and this is included low velocity (5.8 ± 1.7 cm/s), and the absence of
accepted as a marker of poor pregnancy outcome. Green and diastolic flow was found in all the examined yolk sacs.
Hobbins50 reported a group of patients distributed between The pulsatility index showed a mean value of 3.24 ±
8 and 12 weeks of gestational age, with a yolk sac diameter 0.94 without significant changes between subgroups. The
less than 2 mm associated with an adverse outcome. authors found a positive correlation between gestational age
It is unknown whether abnormalities of the yolk sac and volumes of the yolk sac until 10 weeks of gestation.
are related primarily to the yolk sac or secondary to the At the end of the first trimester, yolk sac volume remained
embryonic maldevelopment. According to the present constant, while gestational sac volume continued to grow.
data, it seems that the yolk sac plays an important role in Three-dimensional ultrasound may significantly contribute
maternofetal transportation in early pregnancy. Changes to in vivo observation of the yolk sac’s “honeycomb”
in size and shape could indicate or reflect the significant surface pattern (Fig. 36.27).
dysfunction of this system, and, therefore, could influence Increased echogenicity of the yolk sac walls were
early embryonic development. Currently, major benefits of reported as a sign of dystrophic changes that occur in a
the sonographic evaluation of the yolk sac are: nonviable cellular material indicating early pregnancy
À Differentiation of potentially viable and non-viable loss.52 Automatic volume calculation will allow us to
gestations estimate precise relationship between the yolk sac and
À Confirmation of the presence of an intrauterine gestational sac volumes, as well as to obtain the correlation
pregnancy against a decidual cast between yolk sac volume and CRL measurements. Kupesic
À Indication of a possible fetal abnormality. and coworkers53 measured gestational sac volume and
Recently, Kupesic and associates 51 performed a yolk sac volume, and vascularity in 80 women with
transvaginal color Doppler study of yolk sac vascularization uncomplicated pregnancy between 5 and 12 weeks of
and volume estimation by 3D ultrasound. They examined gestation. Regression analysis revealed an exponential
150 patients whose gestational age ranged 6−10 weeks from growth of the gestational sac volume throughout the
the last menstrual period during normal uncomplicated first trimester of pregnancy. Gestational sac volume
pregnancy. Transvaginal 3D and power Doppler examination measurements can be used for estimation of the gestational
from the surface of the yolk sac (Fig. 36.27). The same
technique can be used to study the evolution from the
embryo-vitelline toward embryoplacental circulation. Since
yolk sac and vitelline blood vessels are prerequisites for the
oxygen transfer, absorptive and transfer processes during
the first trimester, alterations in this early circulatory system
may have some prognostic value for predicting pregnancy
outcome.
Three-dimensional Ultrasound in
Multiple Pregnancy
Three-dimensional surface rendering may be greatly
facilitated in determination of chorionicity and amnionicity
Figure 36.27 Three-dimensional color Doppler study of yolk sac during the end of first trimester (Figs 36.28A and B).
vascularization demonstrated the yolk sac’s “honeycomb” surface All of the reliable criteria can be used. These comprise:
pattern. Three-dimensional ultrasound and power Doppler will allow
us to study turgescent blood vessels withstanding from the surface determining the total number of placentas, determining
of the yolk sac whether each embryo is within its own amniotic sac,
drawing the appearance of the separating membrane
and examining the presence of a triangular projection of
age in early pregnancy. Abnormal gestational sac volume placental tissue beyond the chorionic surfaces (Figs 36.29).
measurement could potentially be used as a prognostic
It is possible to establish a variety of anomalies involving
marker for pregnancy outcome. The yolk sac volume was
one of a twin pair by high-resolution 3D sonography. It
found to increase from 5 to 10 weeks of gestation. However,
enables the early and precise detection of abnormal multiple
when the yolk sac reaches its maximum volume at around
pregnancy. Most common anomaly is the early spontaneous
10 weeks, it has already started to degenerate, which can be
demise of one of the fetuses, vanishing twin (Fig. 36.30).
indirectly proved by a significant reduction in visualization
The characteristics of faulty formations affecting twins can
rates of the yolk sac vascularity.
be classified into those remarkable to twins, particularly
As suggested earlier, the disappearance of the yolk sac
monochorionic twins, like conjoined twins (Fig. 36.31), and
in normal pregnancies is, probably, the result of yolk sac
those malformations not unique to twins such as neural tube
degeneration rather than of a mechanical compression of
defects and congenital heart defects. The most common type
the expanding amniotic cavity. These events suggest that
of conjoined twins arise from a postimplantation separation
the evaluation of the biological function of the yolk sac
of the zygote between the 13th and 16th day following
by measuring the diameter and/or the volume is limited.
conception is thoraco-omphalopagus (28%).55 Recently,
Therefore, a combination of functional and volumetric
Meizner et al.56 presented on the prenatal diagnosis of
studies is necessary to identify some of the more important
thoraco-omphalopagus conjoined twins at 9 weeks of
moments during early pregnancy.
gestation. There is still challenge area in early prenatal
Kurjak et al.48 reported vascularization of the yolk sac in
diagnosis of conjoined twins, especially in choosing
normal pregnancies between 6 and 10 weeks of gestation.
accurate treatment options for both parents and the infants.
Pulsed Doppler signals characterized by low velocity and
high pulsatility were obtained in 85.71% of the yolk sacs
during 7th and 8th gestational weeks. Although the reports Three-dimensional Ultrasound as a
on yolk sac and vitelline circulation are very exciting, it Tool for Measurement of the Nuchal
should be noted that such studies are not ethically feasible
in ongoing human pregnancies since the secondary yolk sac
Translucency
is a source of primary germ cells and blood stem cells.54 The decade of the 1990s has announced in the prospect of
Three-dimensional ultrasound and power Doppler will first trimester ultrasound screening for fetal chromosomal
allow us to study turgescent blood vessels withstanding abnormalities. The technique of measuring NT, which gave
A B
Figures 36.28A and B (A) Dichorionic/diamniotic twins at 11 weeks of gestation. Dividing membrane is visualized by 3D surface-mode
reconstruction. (B) Monochorionic/monoamniotic twins at 11 weeks of gestation
Figure 36.29 Three-dimensional ultrasound determination of the Figure 36.30 The early spontaneous demise of one of the fetuses,
chorionicity in the late second trimester. “Mercedes” sign represents vanishing twin. Using 3D ultrasound, it is possible to diagnose a variety
the junction of fetal membranes of anomalies involving one of a twin pair
rise to the remarkably higher detection rate of chromosomal section of the fetus, allowing precise NT measurements.
abnormalities, still has to overcome some technical This is possible due to the ability of 3D ultrasound to
difficulties. The unsuccessful NT measurements were reorient the fetal position using multiplanar imaging.
reported in many studies.57,58 It seems that establishment Better intraobserver reproducibility was obtained for 3D
of the training regimen for NT measurement as reported by than for 2D ultrasound. Three-dimensional transvaginal
Monni et al.59 and Braithwaite et al.60 may overcome some ultrasound improves accuracy of NT measurement
of these methodological problems. Kurjak and coworkers61 allowing appropriate midsagittal section of the fetus and
demonstrated that 3D transvaginal ultrasound (Fig. clear distinction of the nuchal region from the amniotic
36.32) enables the depiction of the successful midsagittal membrane.
bones. A certain amount of brain tissue or angiomatous

stroma may develop in several circumstances. 62 It is
believed that the primary event is the lack of development
of the neurocranium.64,65 As the consequences, this follows
in subsequent degeneration and missing of the brain tissue
that is left uncovered to the amniotic fluid.
Three-dimensional sonography is a very powerful
tool for anomaly detection throughout the first trimester.
Multiplanar imaging makes possible detailed examination
of fetal shape and anatomical structure. Surface mode
Figure 36.31 Three-dimensional ultrasound scan of conjoined twins
rendering describes the morphology with sculpture-like
(thoraco-omphalopagus) appearance, leaving certainly in diagnosis. The lack of
cranial development can be discovered exactly. Surface
or maximum rendering depicts the abnormal form of the
cranium and the complete absence of the development of
calvarian bones (Fig. 36.33).
Encephalocele
The encephalocele is caused by lack of ossification of the
rostral part of the neural tube. Any part could be affected
by imperfection of the ossification and closure of the neural
tube. Mostly, the fault is situated posteriorly and in the
midline, forming herniation of the meninges and the brain
tissue. In the literature, we can find the diagnosis of an
encephalocele at the end of the first trimester.63 Diagnosis
was built on the inquiring of bulging meningeal and brain
tissue among the defect of the bone. Three-dimensional
Figure 36.32 Three-dimensional transvaginal ultrasound enables the sonography can exactly describe the anomalous contour
depiction of the midsagittal section of the fetus, allowing precise NT
measurements
of the head in the case of an encephalocele (Fig. 36.34).
Both multiplanar imaging and surface rendering can be
used for this work.
Three-dimensional Ultrasound in
Early Detection of Fetal Anomalies Intracranial Malformations
Anencephaly and Exencephaly (Acrania) Hydrocephaly
Diagnosis of anencephaly during early pregnancy by Hydrocephaly is described by an abnormal collection of the
ultrasound which is based on the demonstration of absent cerebrospinal fluid in the ventricular system of the brain. The
cranial vault and cerebral hemisphere has been possible for blockage can be located at different regions. The most common
more than 25 years with incidence about 1:1,000 births. place is the obstruction of the aqueduct of Sylvius causing
Diagnosis is established when no bones can be imaging accumulation of the cerebrospinal fluid in the lateral and the
above the orbits, regardless of the quantity of neural third ventricles. This results in enlargement of the ventricles
soft tissue.62 Due to many resemblances, it was assumed because of the growth pressure of the fluid. The enlargement
that exencephaly is a forerunner or a different form of process of the ventricles is progressing by degrees. In this
anencephaly.63-65 The existing record of anencephaly begins way, it was considered that diagnosis of hydrocephaly
with failure of closure of the cephalic end of the neural was not possible before midpregnancy.66 Diagnosis was
tube. As a consequence, it implies the absence of the established if an irregular hemisphere width to lateral ventricle
telencephalon, mesencephalon and failure growth of the width was found (Figs 36.35A and B). Development of 3D
cranial vault, comprising the frontal, parietal and occipital ultrasound devices enabled diagnosis of hydrocephaly in early
Figure 36.33 Three-dimensional images of anencephaly: the lack of cranial development can be detected precisely. Surface/maximum rendering
depicts the anomalous shape of the cranium and the complete absence of the development of calvarian bones
The most severe is alobar holoprosencephaly that

occurs after a total ceasing of prosencephalon cleavage.
This produces formation of a monoventricular cavity with
thalamus and basal ganglia fused in the midline, while
the midbrain, brainstem and cerebellum are structurally
normal. Alobar holoprosencephaly is frequently connected
with serious facial malformations, for example, cleft lip
and palate, severe hypotelorism and cyclopia, arhinia with
proboscis and also can be found in some aneuploidies,
usually trisomy 13 and trisomy 18. A frontal monoventricle
is present in the semilobar holoprosencephaly and there
is posterior partial formation of the occipital lobes. In the
lobar holoprosencephaly the hemispheres may be fused
and the lateral ventricles may extensively communicate
Figure 36.34 Three-dimensional sonography can precisely depict because of the absence of the septum pellucidum. Due
the abnormal outline of the head in the case of an encephalocele. to severe interruption of the normal intracranial anatomy
Diagnosis was made upon the finding of bulging meningeal and brain ultrasound diagnosis of holoprosencephaly can be done
tissue through the defect of the bone
at the end of the first trimester.71,72 The lack of normally
grown telencephalon including hyperechoic choroid
plexuses, frontally positioned monoventricle and facial
anomaly (severe hypotelorism) are characteristics that
pregnancy.67,68 Visualization and measurement of the choroid
should support sufficient diagnosis (Fig. 36.36). Three-
plexus is possible from the 11th week of gestation. In a normal
dimensional sonography enables careful and precise
brain, choroid plexus fills the atrium and the body of the lateral
analysis of anatomical features in very early pregnancy,
ventricle. When pressure of the cerebrospinal fluid rises, the
making the diagnostic process accurate and fast.
dilatation of the lateral ventricles gives a particular appearance
to the choroid plexus.69
Dynamic Real-time 3D Ultrasound (4D
Holoprosencephaly
Technique) as a Tool for Assessment
Holoprosencephaly arises from absent or incomplete
separation of the prosencephalon in two cerebral
of Fetal Behavior in Early Pregnancy
hemispheres and lateral ventricles. It is classified into Three-dimensional sonography has become the new standard
alobar, semilobar and lobar types.70 in prenatal diagnosis. This technique enables detailed
A B
Figures 36.35A and B (A) Three-dimensional reconstruction of the abnormality of the posterior fossa is clearly demonstrated. (B) Multiplanar
3D analysis is helpful for fast selection of the adequate section of the abnormal lateral ventricle in hydrocephaly
essential prerogative for 3D ultrasound devices. The latest

development of calculating units enables 3D reconstruction
at a frame rate of up to 20 images per second. In the human
eye this frame rate produces quite smooth dynamic realtime
3D images, also known as four dimensional (4D) image.73
The first trimester of pregnancy is a period of early
human development of incomparable intensity. Before the
‘ultrasound era’, investigation of this field was reserved for
postmortem embryological analysis. However, transvaginal
realtime B-mode, color Doppler, and, in the last few
years, different forms of 3D sonography have enabled
noninvasive and safe investigation in vivo. Due to the size
of the pregnant uterus and relatively large amount of fluid
surrounding the embryo, the first trimester is very suitable
Figure 36.36 Three-dimensional sonography image of for 4D sonography. We already investigated embryonic or
holoprosencephaly at 12 weeks of gestation (Trisomy 13): Compare fetal movements, and several movements were classified
the 3D finding of hypotelorism with the postmortem fetus. Three- as following (Fig. 36.37):
dimensional sonography enables analysis of anatomical features in
early pregnancy, making the diagnostic process accurate and fast À Gross body movements consisted of changing the
position of the head toward the body
À Limb movements consisted of changes in position of
examination of the fetal anatomy and higher quality depiction extremities toward the body without extension or flexion
of some anomalies. Until recently, the main drawback of 3D in elbow or knee
sonography was its inability to present a real-time motional À Complex limb movements consisted of changes in
image. Furthermore, motoric activity of the fetus yielded position of the limb segments toward each other, such
with significant artifacts in the image, making it inadequate as extension or flexion in elbow or knee.
for diagnostic purposes. Three-dimensional depiction is According to CRL, the pregnant women were divided into
technologically based on high velocity processing of the four groups:
data. Development of the computer processors was the À Group 1: CRL less than 9 mm (< 7 weeks of gestation)
Figure 36.37 Four-dimensional ultrasound sequence of the fetus at 12 weeks of gestation

showing general movements. The complex movements of the limb, trunk and head are clearly
visible and cause a shift in fetal position. In the first sequence, the right hand is flexed in elbow
joint. In the next sequence, the fetus dropped the hand and began to deflect in elbow joint. In
the last sequence, further elevation of hand is seen
À Group 2: CRL more than 9 mm and less than 15 mm of fetuses from the fourth group gross body movements
(between 7 and 8 weeks) and in 63% limb movements were presented. Additionally,
À Group 3: CRL more than 16 mm and less than 30 mm in 42% spontaneous complex limb movements were
(between 8 and 10 weeks) visualized.
À Group 4: CRL more than 31 mm and less than 50 mm The straightforward development of 3D ultrasound has
(between 10 and 12 weeks). led to the possibility of performing 3D imaging in a realtime
Matters of interest were the gestational age at which mode. This modality has been named 4D sonography.
each of these three kinds of movements appeared, and This improvement greatly facilitates the assessment of
their visualization with advanced technology. A total of fetal movements because they can be visualized in three
98 pregnant women were analyzed. In the first group no dimensions. Thus, it is much easier to assess fetal motoric
movements were found. In the other groups, the incidence status than with 2D. For each embryonic structure, there
of each type of embryonic or fetal movements is presented is a period between genesis and ultrasonic visualization.75
in Table 36.1. As technology advances, the period becomes shorter.
At the 7th week, 38% embryos had spontaneous gross Limbs begin to move from 7th week onward.76 Using 2D
body movements. At this gestational age, we found no transvaginal ultrasound technique body movements are
limb movements. In 42% of fetuses from the third group visualized between 8th and 9th weeks, and limb movements
spontaneous gross body movements were presented. are visualized between 9th and 10th weeks.77 The embryo
Furthermore, in 26% of fetuses only simple limb body movements, which were absent before 7 weeks of
movements were visualized at this gestational age. In 84% gestation, were observed after 8 weeks with a sensitivity
Table 36.1 The incidence of spontaneous embryonic/fetal movement according to gestational age
Gestational age CRL (mm) No Gross body Limb Complex limb

(weeks) movements movements movements movements
7−8 0−5 31 12 0 0
9 − 10 16 − 30 26 11 7 0
11 − 12 31 − 50 19 16 12 8
74
Source: Adapted from Kurjak A et al. (2002)
of 100%, specificity of 92.8%, positive predictive value Delay in motoric development has been described in
of 94.3% and negative predictive value of 100%.78 With diabetic pregnancies.79 There is a 1−2 weeks delay in the
4D, we found gross body movement at 7 weeks, and limb first appearance of all movement patterns, which normally
movements at 8−9 weeks. New technology enables the emerge during the first 12 weeks of pregnancy. This
visualization of the moving phenomenon a week earlier indicates the possible existence of a specific diabetes-related
than 2D transvaginal ultrasound. The use of 4D technology influence on the functional development of the embryonic
should thus enable the diagnosis of motoric development and fetal nervous system. Hyperglycemia, for example,
failure at the end of the first trimester. It also makes possible may be responsible, as the delay in the emergence of fetal
the evaluation of complex limb movement, the visualization general movements was most profound in women whose
of simultaneous movement of all extremities and the spatial periconceptional quality of glucose control was poor.79
evaluation of movements. Limb movements are essential to the normal development
At 7 gestational weeks, the dominant embryonic feature of joints.76 Early disturbances in motoric development result
is the head that is strongly flexioned anteriorly. Upper and in absence of limb movement, joint contracture and multiple
lower limb buds are visible on the lateral aspects of the joint contracture (arthrogryposis). Spinal muscular atrophy
embryo. However, embryonic movements are not frequent is characterized with multiple arthrogryposis.80
and consist mainly of moving the head toward the rest of Four-dimensional ultrasound technology offers a
the body, while fetal limb movements are absent.74 possibility to predict the development of arthrogryposis
At 8−9 weeks, the embryo has different body features in high risk pregnancies on the basis of the evaluation of
to be observed. The head is less flexioned and limbs are fetal movements. Etiology of the disease is the progressive
elongated. Segments of the arms and legs are distinguishable. degeneration of anterior horn cells in the spinal cord and
Embryonic movements can be divided in two main groups: motor nuclei in brainstem.74
(i) gross body movements that consist of changes of the Authors also noticed lateralization of movements. There
position of the head toward the body and (ii) movements was a highly significant preference for fetuses to move
of the extremities: arms and legs are moved vigorously. their right arm more than their left arm. This observation
However, no flexion or extension in elbow or knee can be agrees with Hepper’s findings.81 In his study 85% of fetuses
seen.74 At 10−12 weeks of gestation, complex body and limb exhibited more right arm than left arm movements.
movements can be seen. At this gestational age, there was a
great resemblance of fetal movements to those in neonates.
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CHAPTER
37 Cesarean Scar Hysterotomy: Assessment

by 3D Transvaginal Echography
Juan M Troyano Luque, MT Clavijo, I Martinez-Wallin, OY Marco,
W Mahtani, PS Casas, Jose Bajo Areans, Ulrich Honemeyer
Background Echography Survey of Hysterotomy-

Hysterotomy-made scars are a key factor for assessing Made Scars
further gestations in the same patient and so need to be
A number of requirements must be met in hysterotomy
monitored from the early puerperium through a whole year
practice in order to avoid failed cicatrization patterns in future
period following surgery. Other monitoring factors involve
gestations, e.g. post-parturition or resting uterus tearing,
placenta previa, placenta accreta, atopic cervical gestation
placenta previa or accreta, or even abruptio placentae.1-3
or uterus tearing both on parturition and at rest.
Two-dimensional (2D) transvaginal echography has The main requirement consists of the hysterotomy being
proved a successful method in the detection of scar failures of applied to the band of the uterine segment which is frontier
the myometrium early in the puerperal period and afterward, between the cervix and the uterus, the so-called transverse,
or in routine echographic exploration. Furthermore, three- segmentary hysterotomy (Figs 37.1A and B). The contours
dimensional (3D) echography facilitates the monitoring of of this uterine segment faint as the cervix grows thin and is
hysterotomy-made scars whereby total areas and depths of embodied by the corpus uteri with the progress of labor.
healed versus failing myometrium tissue can be quantified. Hysterotomy is facilitated in three ways by the uterine
The combined study of 2D and 3D echographic segment thinning out during parturition, i.e. bleeding is
records may be useful to diagnose wound dehiscence reduced, the surgical suture becomes straightforward and
from hysterotomy and to forecast the welfare of future the cicatrization process is aided. In contrast, inexperience
gestations. In that respect, irregular cicatrization patterns by the practitioner or unexpected problems in labor may
can be identified from the early puerperium over the whole result in hysterotomy incisions into the anterior myometrial
post-parturition recovery period, and may encourage the wall, some 1–2 cm above the target uterine segment
need for further cesarean in new pregnancies to come. (Figs 37.2A and B).
A B
Figures 37.1A and B Isthmic area between the cervix and corpus uteri, which is the target
of transverse segmentary hysterotomy
Chapter 37  Cesarean Scar Hysterotomy: Assessment by 3D Transvaginal Echography 411
A B
Figures 37.2A and B Hysterotomy incision into the myometrial layer located above the uterine
segment. This is the major factor bringing about wound dehiscence problems
The latter may be called transverse, corporal incisions, On the contrary, extensive hypoechogenic areas between
and compromise a relatively thick layer of myometrium that the borders of hysterotomy-made scars are already visible
may reach endometrium tissue between the two scar borders. only 4 days following cesarean surgery, and are indicative
Although frequently unnoticed by the surgeon, of failed cicatrization that can be further confirmed 4
transverse, corporal incisions are the main factor months and 1 year after surgery. This results in boomerang-
precluding labor in future gestations where they may lead shaped scars (scar stigma) permanent over the whole of the
to pathologies like uterine tearing, wound dehiscence or women’s life (Figs 37.4A to C).
uterus dysdynamogenesis. A total of 30% of pregnant To enhance the welfare of future gestations and
women presenting normal cephalopelvic dimensions deliveries, scar stigma must be characterized by quantifying
and following a former delivery subjected to transverse, both the hysterotomy-affected myometrium area (in
corporal hysterotomy could not avoid a further cesarean due a transverse direction) and the depth of the scar notch
to impoverishment of uterine dynamics.1,2,4 This may be due between the uterine surface and the endocervical channel.
to the fact that myometrium cicatrization and fibrosis above This can be fairly easily attained by means of 3D
the uterine segment prevent the transmission of electric transvaginal echography, where the estimation for ratios
signals in the inferior third of the uterus, so interfering with of healed to failed myometrium cicatrization percentages
the gradual dilation and attenuation of the cervix. is straightforward (Figs 37.5A and B).
Furthermore, hysterotomy-made wound dehiscence has
been often associated with pelvic pain, nonspecific dysuria
and anomalous uterine bleeding in women subjected to past
Material and Methods
cesarean.5 Between March 2000 and February 2004, the random
Whatever the hysterotomy strategy being applied, samples of 42 female patients were subjected to transvaginal
transvaginal echography represents a complementary and echographic exploration at three sampling times, namely:
useful tool for assessing and monitoring uterine scars from 4 days, 4 months and 1 year following hysterotomy. All of
the puerperium onward. Scar borders manifest themselves in these women recovered successfully from their cesarean and
an echogenic line going perpendicular to the axis between the were discharged from hospital only 5 days after parturition.
peritoneal border and the endocervical channel, ornated by Explorations were carried out by means of an ALOKA
the echogenic marks of the stitch material (Figs 37.3A to C). 5,000 Prosound echographer. Two-dimensional and three-
From 4 months to 1 year after hysterotomy in patients having dimensional surveys were subsequently undertaken at
a fit recovery from surgery, the uterine scar may become each of the three study times. Four days after surgery, the
completely unnoticeable by echography or at most translate 2D echography aimed at evaluating the early evolution of
into a little echogenic area in the posterior vesical wall. the uterine scar. On the other hand, 3D echographies were
A B C
Figures 37.3A to C Normal scar 4 months following cesarean surgery: (A) Bidimensional ultrasound, (B) Endometrial cavity and segmentum
uteri integrity by 3D ultrasound B and (C) Failure scar in endometrial cavity near segmentum uteri, 3D ultrasound
A B C
Figures 37.4A to C Extensive hypoechogenic areas between the borders of hysterotomy (4 days following cesarean surgery). This results in
“Boomerang-shaped” scars (scar stigma) permanent over the whole of the women’s life
implemented frame-to-frame, in a transverse direction, from run perpendicular to the complete extent of the internal
the right to left sides of the uterus. myometrium layer and bordered the anterior uterine wall
(Table 37.1).
By considering the length of the hysterotomy-derived
Results
notch over the whole study period, two types of scars could
Four days after each hysterotomy was undertaken, be differentiated through 2D echographic surveys, i.e. scar
incomplete closure over two-thirds of the scar length was notches greater than two-thirds (n = 9) or less than or equal to
observed in 14 out of the 42 women explored. This was one-third (n = 4) of the total scar length (Table 37.2). Notch
deemed to be a sign of wound dehiscence along most of the depths between scar borders can be also seen in Table 37.2.
internal myometrium layer. Three-dimensional echographic No echographic patterns could be observed in wound-
records from those dehiscent wounds displayed at this time dehiscentless women (n = 29) by neither of the echographic
a wide, irregular hypoechogenic area crossed over by linear methods employed throughout the study period, with little
structures representing the suture material (Vicryl). Such echogenic areas being rarely detected in the isthmic region.
a record was called a shark bite pattern (Figs 37.6A to C). Six of the thirteen wound-dehiscent women monitored
The latter puerperal dehiscence pattern persisted in the in this study who became pregnant within 2 years after
isthmic region for 4 months and 1 year after delivery. It their former cesarean. All were subjected to a second
consistently featured a notch between the scar borders that hysterotomy, before which an in situ examination of the
Chapter 37  Cesarean Scar Hysterotomy: Assessment by 3D Transvaginal Echography 413
A B
Figures 37.5A and B Scar stigma must be characterized by quantifying both the hysterotomy-affected myometrium area (in transverse direction).
This can be fairly easily attained by means of 3D transvaginal echography
A B C
Figures 37.6A to C Incomplete closure over two-thirds of the scar length by 3D echographic records. This is a typical image of hysterotomy
dehiscence. Irregular hypoechogenic area crossed over linear structures representing the suture material (Vicryl). Such a record was called a
“shark bite”
Table 37.1 Uterine scar patterns as surveyed by transvaginal Table 37.2 Two-dimensional echographic patterns with details of
echography exploration after hysterotomy (n = 42) dehiscence extent originating from hysterotomy (n = 13)
Post-cesarean period Scar notch

4 days 4 months 1 year 4 months 1 year
Dehiscent Yes Yes No Notch length Depth (mm Wideness Depth
scars (n = 13) relative to total (mm) (mm)
scar length
Dehiscentless No No No
wideness (mm)
scars (n = 29)
2/3 (n = 9) 9 6 7 4
previous uterine scar could be made as shown in Table 37.3. 1/3 (n = 4) 3 4 3 4
In a different study, between 2000 and 2004, a total of
317 women, going through hysterotomy within the previous in younger women and anomalous uterine bleeding in
6 years and showing ensuing pathological cicatrization postmenopausal women were most outstanding, and caused
in the isthmic region, were subjected to clinical and major stress on the patients.
echographical exploration. The whole sample of patients No control group was available for the latter study, but
displayed an array of pathologies that were not obvious authors’ data strongly suggests that an association between
before the cesarean had been carried out (Table 37.4). the application of hysterotomy and the occurrence of genital
Among these pathologies, dysmenorrhea and coitalgia pathologies was at work.
Table 37.3 Scar patterns from women subjected to a second Table 37.4 Pathological scars in the isthmic region in women
hysterotomy after the study period (n = 6) (in = 317) subjected to single hysterotomy in the previous 6 years
Second cesarean Wound Dysmenorrhea 195
(100%) state
Spotting 15
No pattern 4 Dehiscent 5* Dehiscentless 1**
Anomalous uterine bleeding 31
Fetal suffering 1
Coitalgia 61
Podalic 1
position Menorrhagia 15
*Scar narrow, retractile and rigid

**Scar narrow and fibrous
Conclusion References
Uterine scar patterns and their pathologies have been recently
studied by a number of authors elsewhere,6,7 and the adequateness of 1. van Ham MA, van Dongen PW, Mulder J. Maternal
invasive methods, such as hysterosonography, has been proposed.8 consequences of cesarean section. A retrospective study
These methods are 2D, therefore it is authors’ own view that they intra-operative and postoperative maternal complications
cannot provide with accurate estimates for scar length and depth and
of caesarean section during a 10-year period. Eur J Obstet
for wideness of the notch between the two scar borders. Moreover,
their application is unfeasible during the early puerperium, and must Gynecol Reprod Bio. 1997;74(1):1-6.
so be delayed to the late post-parturition recovery period or their use 2. Leung AS, Leung EK, Paul RH. Uterine rupture after
confined to routine echographic explorations when the detection of
previous cesarean delivery: maternal and fetal consequences.
pathologies may be casual. Early puerperal echography focusing
on hypoechogenic areas across the borders of hysterotomy-derived Am J Obstet Gynecol. 1993;169(4):945-50.
scars under suturing pressure must be undertaken by means of 2D 3. Miller DA, Chollet JA, Goodwin TM. Clinical risk factors
transvaginal echography, with the bonus that such exploration can
be extended through several months to 1 year period after surgery.
for placenta previa-placenta accreta. Am J Obstet Gynecol.
In fact, scar stigma remains so throughout the patient’s life. The 1997;177(1):210-4.
extent of dehiscent myometrium areas and the depth of the notch 4. Glazener CM, Abdalla M, Stroud P, et al. Postnatal maternal
remaining between the serose and the cervical channel of the stigma
can be used as reliable indicators for failing cicatrization processes and morbidity: extent, causes prevention and treatment. Br J
should be used as background information aiding in future gestations. Obstet Gynecol. 1995;102(4):282-7.
Three-dimensional transvaginal echography provides the
5. Chazotte C, Cohen WR. Catastrophic complications
practitioner with thorough records of myometrial failure and enhances
the morphological study of iatrogenic pathologies originating from of previous cesarean section. Am J Obstet Gynecol.
cesarean surgery. 1990;163(3):738-42.
Hysterotomy incisions above the uterine isthmus invariably lead to
6. Godin PA, Bassil S, Donnez J. An ectopic pregnancy
scar structural failures by 1 year after cesarean have been applied,
but can be detected by 4 days post-parturition. developing in a previous caesarean section scar. Fertil Steril.
The length and wideness of the areas experiencing structural 1997;67(2):398-400.
failure are proportional to the distance between the hysterotomy
incision and the uterine segment.
7. Monteagudo A, Carreno C, Timor-Tritsch IE. Saline infusion
Failing cicatrization patterns result from cicatrization involving sonohysterography in non-pregnant women with previous
only the surface layers of the myometrium tissue, with two-thirds cesarean delivery: the “niche” in the scar. J Ultrasound Med.
of the deeper myometrium layer remaining dehiscent. 2001;20(10):1105-15.
The state and extent of healed versus failing cicatrization areas
can be easily assessed by means of 3D transvaginal echography. 8. Lonky NM, Worthen N, Ross MG. Prediction of cesarean
Unlike the measurement of the depth of the scar notch, no reliable section scars with ultrasound imaging during pregnancy. J
spatial references can be used to measure the distance between Ultrasound Med. 1989;8(1):15-9.
the surface serose and the peak of the scar notch, so the latter has
been excluded from the methodological protocol presented herein.
CHAPTER
38 Assessment of Normal and Abnormal

Ovaries by Transvaginal Sonography
Asim Kurjak, Matija Prka, Ma Angela Pascual, Jose Bajo Arenas, Biserka Funduk Kurjak
Introduction Sonographic Parameters

Sonography is the diagnostic method of choice for Pelvic sonography has an important role in examining
evaluation of pelvic masses, particularly for those thought, a pelvic mass that may have been palpated or suspected on
on the basis of clinical examination, to be benign. Although pelvic examination. It is particularly useful in patients in
the sonographic features of a pelvic mass frequently do not whom an adequate pelvic examination cannot be performed,
permit a specific histopathologic diagnosis, sonography or in whom a poorly defined pelvic mass is found on
examination.
usually provides clinically important parameters for the
pelvic mass.1 Since some masses may be outside the range of the
examiner’s finger, sonography may occasionally detect
A number of studies proved superiority of the transvaginal
masses that cannot be palpated adequately. In this situation,
approach to transabdominal ultrasonography. 2-4 The
a real-time sonographic examination during pelvic
resolution as well as the specificity of information about
examination can be used to demonstrate the presence or
sonographic findings of specific diseases depend on the
absence of a mass.8 Transvaginal sonography can be used
proximity at which the transvaginal probe can be placed to
to particular advantage in the delineation of the uterus and
the pelvic contents, as well as the transducer frequencies
ovaries in obese patients. In fact, sonography has been
used (optimally >5 MHz).
found to be more reliable than palpation in the identification
Information gained by transvaginal gray scale sonography,
of normal-sized ovaries, even in the postmenopausal
taken into account with other diagnostic modalities, is
women.9
useful in guiding the gynecologic surgeon through decisions
regarding surgical intervention (Table 38.1). Generally, the
consensus is that a surgical treatment is required in cases Origin and Size
when masses that are over 10 cm in average dimension Transvaginal sonography can provide detailed delineation
contain irregular solid components, or are associated with of a pelvic mass smaller than 10 cm, and determine its
significant (over 20 ml) of intraperitoneal fluid.5 Similarly, origin.2,10,11 The uterus serves as a central landmark for
pelvic masses that are associated with acute pelvic pain may identifying the location of a mass within the pelvis. An
require immediate surgical intervention because they may be additional landmark for delineation of its borders is the
associated with adnexal torsion.6 On the other hand, masses echogenic endometrial interface within the uterus. 12
that are completely cystic and smaller than 5 cm may only Masses within the ovary can usually be identified by the
be observed over a few months with repeated sonograms, rim of compressed parenchyma (“beak”) that is present
to document any change in size. In postmenopausal women, between the mass and the remaining portion of the ovary.
only a low percentage (approximately 3%) of small (<5 cm) This feature is particularly well depicted with transvaginal
adnexal masses will represent a malignant neoplasm.7 scanning.
This chapter brings up certain differential points that are Abnormally distended tubes originate from the lateral
clinically important when evaluating a patient with a pelvic aspect of the uterine cornu and their fusiform enlargement
mass via transvaginal sonography. as they extend from the uterus into the pelvis. This
Table 38.1 Preoperative investigation and malignancy risk assessment in the diagnosis of ovarian tumors
Standard investigation Risk for malignancy Advanced investigation
Anamnesis
• Reproductive data (parity, abortions), menstrual history, oral contraceptive use, infertility treatment, hormonal replacement therapy, earlier
operations (ovary)
Age
• Premenopausal Low
• Postmenopausal High
Family history of ovarian and/or breast cancer Genetic counseling
• Negative Low
• Positive High
Symptoms (if occur) abdominal Exclude an extraovarian disease
(X-rays, CT, MRI)
• Abdominal distention, fullness or pressure in the abdomen or High
pelvis, abdominal or lower back pain, frequent urination or urgency,
constipation, lack of energy, lack of appetite, weight loss
Bimanual palpation
• Smooth, round, mobile, unilateral, <10 cm Low
• Uneven, nonmobile, bilateral, hard, with adhesions, > 10 cm High
Transvaginal gray-scale sonography Three-dimensional sonography
Volume In comparison to 2D US superior in:
• <20 cm3— premenopausal Low — Showing characteristics of internal
<10 cm3— postmenopausal cyst walls
• >20 cm3— premenopausal High — Identifying the extent of capsular
>10 cm3— postmenopausal infiltration of tumors
— Calculating ovarian volume
Morphology
• Smooth cystic wall, thin septa, no solid parts, anechoic Low
• Intracystic growth, papillary projections, thick septa, solid parts, mixed High
echogenicity
Transvaginal color/power Doppler Three-dimensional power Doppler
Blood flow parameters Qualitative analysis of tumor blood
vessels:
• PI > 1.0, RI > 0.42 Low — Position
• PI < 1.0, RI ? 0.42 High — Structure
Location of blood flow — Branching pattern
• Peripheral Low
• Central High
Tumor markers
• CA-125 < 35 U/ml Low Second generation CA-125, CA 15-3,
• CA-125 ? 35 U/ml High CA-19-9
is particularly helpful when differentiating between which are separable from the uterus. This serves as a
inflammatory disease that may involve the tube or ovary, differentiating factor between the two.
such as a tubo-ovarian abscess and simple hydrosalpinx. Occasionally, the size of a pelvic mass can help in
Applying gentle pressure between the mass and the differential diagnosis. Physiologic cysts, for example, are
uterus may further elucidate the origin of a mass. For rarely larger than between 3 and 5 cm average dimension,
example, pedunculated subserosal fibroids are attached while symptomatic ovarian tumors are generally about
to the uterus by a pedicle, in contrast to an adnexal mass, 10 cm. Exceptions to this may be encountered in acute
Chapter 38  Assessment of Normal and Abnormal Ovaries by Transvaginal Sonography 417
hemorrhage or torsion of the ovary, when it can quickly present within a mass suggest that it is more likely to be
enlarge over 24−48 hours. malignant.5,14 Papillary excrescences also usually mean the
Size alone, however, is not a specific criterion because possibility of malignancy. Irregularities and disruption in
it depends on when the patient presents for an examination the borders of the mass suggest that malignant spread or
relative to the growth pattern of the mass. rupture through the capsule has occurred.
Internal Architecture Associated Lesions

In over three-fourths of women studied, transvaginal Sonography is very accurate in detecting the amount of
sonography allows for a detailed delineation of the internal intraperitoneal fluid, sometimes associated with adnexal
consistency of a pelvic mass, adding diagnostically specific masses. Although a small amount (3−5 ml) of fluid may
information.13 The mass that has no internal echoes, has be present due to physiologic processes, it is uncommon to
smooth borders, and is enhanced through transmission, can have more than 10 ml of fluid in the cul-de-sac or peritoneal
be inferred. Occasionally, low-level echoes may be present cavity of a healthy woman. Intraperitoneal fluid associated
within a cyst arising from proteinaceous fluid, blood or with pelvic masses increases the likelihood of a lesion to
cellular debris. A truly solid mass typically contains internal be neoplastic, and the possibility of malignant spread or
echoes, whereas a complex mass contains both solid and rupture. In some cases, such as ovarian torsion, however,
cystic components. the fluid can represent a transudate related to obstructed
Generally, ovarian masses are more often cystic, venous and lymphatic return.6 Rarely, intraperitoneal fluid
whereas nonovarian masses solid. Thin and echogenic can be associated with an ovarian fibroma or other benign
internal septations suggest the diagnosis of an epithelial adnexal masses.
ovarian neoplasm, usually a cystadenoma. However,
the internal interfaces can also be found in hemorrhagic Sonographic Differential Diagnosis
cysts resulting from partial coagulation of an internal
clot. Hyperechoic material within an area can be seen in
of Pelvic Masses
some dermoid cysts that contain sebaceous material, bone This discussion of the transvaginal sonographic differential
tissue or teeth. Homogeneous echogenic internal contents, diagnoses of pelvic masses is organized according to the
such as endometriomas that contain clotted blood, may most frequently seen sonographic appearance of particular
also be encountered in a mass. Areas of hemorrhagic types of a pelvic mass (Table 38.2). If a particular pelvic
necrosis present as irregular anechoic regions within a mass has a spectrum of sonographic appearances, it is
mass. The more solid and irregular components which are mentioned in more than one category.
Table 38.2 Sonographic differential dignoses of pelvic masses

a,b
Cystic Complex Solid

Completely cystic Predominantly cystic Ovarian origin
• Physiologic ovarian cysts • Cystadenomas • Fibroma
• Cystadenomas • Tubo-ovarian abscess • Thecoma
• Hydrosalpinx • Dermoid cyst
Uterine origin
• Endometrioma
Predominantly solid • Pedunculated subserosal fibroid
• Paraovarian cyst
• Cystadenoma (carcinoma)
• Hydatid cyst of Morgagni
• Germ cell tumor
Multiple
• Endometriomas
• Multiple follicular cysts
Septated
• Cystadenoma (carcinoma):
– Serous
– Mucinous
(Source: Adapted from Fleischer AC, Manning FA, Jeanty P, et al (Eds). Sonography in Obstetrics and Gynecology, 6th edition. New York:
McGraw-Hill; 2001. pp. 883-912)
a
Based on most common appearance
b
Pelvic masses with a spectrum of sonographic appearances are mentioned in more than one category
This differentiating scheme should be used only as a usually has echogenic content (Fig. 38.2). The increased
general approach to the sonographic characterization of a echogenicity of the cyst wall is probably the result of
pelvic mass. Sonographic findings must be correlated with its higher fat content.18 The corpus luteum may appear
the clinical ones. The sonographic depiction of morphology predominantly solid after complete collapse of the cyst. This
is helpful in determining the chance that a mass is malignant. appearance may range from an echogenic slit surrounded
The presence of wall or septal irregularity, or papillary by a hypoechoic halo to a large, solid mass. These masses
excrescences correlates with the chance of malignancy. tend to be very vascular and show low-impedance flow.
Hemorrhagic ovarian cysts can present as a variety
Cystic Masses of sonographic findings, depending on the size and
Pelvic masses appearing as cystic adnexal masses on organization of internal clot. Due to the presence of
transvaginal sonography most often include physiologic
(follicular or luteal) ovarian cysts, hydrosalpinges,
endometriomas and paraovarian cysts. Even with the similar
sonographic appearance of several types of cystic adnexal
masses, the diagnostic possibilities can usually be narrowed
to one or two entities based on clinical presentation and
evaluation. In general, most cystic masses that arise within
the pelvis are of ovarian origin. Depending on the referral
population, physiologic ovarian cysts or hydrosalpinges
will be the most common cystic pelvic masses encountered
by the sonologist.
Physiologic Ovarian Cysts

Since functional cysts are usually asymptomatic, their
precise incidence is unknown. They are most common
during the reproductive years, but may occur at any age.
Several types of cystic masses can result from abnormalities Figure 38.1 Transvaginal sonogram showing follicular cyst. Note
that occur at different stages of folliculogenesis. In general, smooth, thin cystic wall. Surrounding ovarian tissue is compressed
follicular cysts occur either due to failure of a mature by cystic structure
follicle to rupture at the time of ovulation, or following the
collection of blood within the follicle after ovulation occurs
(corpus luteum cyst). In most women, a mature follicle
average size ranges 15−20 mm.7,15 Follicular cysts of the
ovary are usually larger than a mature follicle, ranging
3−8 cm in size. Luteal cysts, compared to follicular cysts,
usually have a thicker wall and tend to contain hemorrhagic
areas. Patients with hemorrhagic cysts may experience the
abrupt onset of lower abdominal or pelvic pain.16,17 Because
this history can also pertain to cases of ruptured ectopic
pregnancy, it is important to obtain an accurate pregnancy
test in these patients.
Sonography has an important role in documenting
any change in size of the cyst during and after clinical
observation or treatment. At transvaginal sonography, a
typical follicular cyst is clear, unilocular, and has a smooth,
thin wall (Fig. 38.1). A corpus luteum cyst most commonly Figure 38.2 Hemorrhagic corpus luteum cyst containing fibrin strands
has a thick hyperechoic, occasionally crenulated wall, and appearing as a web-like complex of thin, branching linear interfaces
hemorrhage, the complicated functional cyst can have to salpingitis caused by pelvic inflammatory disease
an appearance suggestive of that of a malignant tumor.18 of bacterial origin.20 It usually appears as a unilateral
Although fibrinolyzed clot is typically hypoechoic, acute inflammatory conglomerate within which the ovary and
hemorrhage frequently appears as an irregular echogenic tube are still recognizable. This may or may not progress to
area, and may mimic a solid mass. As the clot begins to a tubo-ovarian abscess, in which there is a total breakdown
hemolyze, a reticular network of low-amplitude net-like of the adnexal structures on one or both sides.21 With
strands is often demonstrated. Color Doppler can help to resolution, the only sequelae may be tubo-ovarian fibrous
support the diagnosis of hemorrhage by demonstrating adhesions, but a healed abscess occasionally becomes
absence of vascularity within solid portions consisting of a tubo-ovarian cyst, which may ultrasonographically
organized clot. resemble a cystic ovarian neoplasm.
It is important to point out that 53−89% of all functional The typical symptoms are abdominal or pelvic pain
cysts will undergo spontaneous regression; therefore, unless and, less consistently, fever, vaginal discharge or bleeding,
it is clinically unwise to delay surgical exploration (e.g. the and urinary symptoms. A history of pelvic inflammatory
presence of a very large mass),19 a follow-up scan after 4−6 disease is present in only one-third to one-half of patients,
weeks is recommended. suggesting common subclinical infections.
Sonographic markers for tubal inflammatory disease
Hydrosalpinx/Tubo-ovarian Complex or Abscess have been described by Timor-Tritsch et al.21 The following
Hydrosalpinges occur as a result of an inflammatory findings were considered helpful:
process, which produces adhesions of the fimbriated end ÀÀ Thickening of the tube wall of greater than or equal to 5
of the tube, trapping intraluminal secretions. The secreted mm (100% of acute and 3% of chronic cases)
fluid distends the tube, resulting in a fusiform anechoic ÀÀ “Cogwheel” sign,22 defined as a sonolucent cogwheel-
adnexal mass (Fig. 38.3). The tapered fusiform shape shaped structure visible in cross-section of a tube with
and lack of peristalsis of a hydrosalpinx usually allows it thick walls (86% of acute and 3% of chronic cases)
to be differentiated from fluid-filled small bowel loops. ÀÀ Incomplete septa, correlating with folds or kinks in
In addition, the typical configuration of a hydrosalpinx the dilated tube, which may be sonolucent or contain
(tapering as it enters the uterus and enlarging distally) is low-level echoes. These were seen in 92% of all cases;
helpful in its sonographic recognition. however, they were not discriminatory between acute
A tubo-ovarian complex may arise if the inflammatory and chronic cases
process involves the ovary; almost always secondary ÀÀ “Beads-on-a-string” sign, defined as hyperechoic
mural nodules, measuring about 2−3 mm and seen on
the cross-section of a fluid-filled distended structure.
This is considred to represent flattened and fibrotic
endosalpingeal folds (0% of acute, 57% of chronic cases)
ÀÀ Tubo-ovarian complex, defined in the setting of pelvic
inflammatory disease in which the ovaries and tubes are
recognized but the ovary cannot be separated from the
tube by pushing with the vaginal probe (36% of acute
and 2% of chronic cases)
ÀÀ Tubo-ovarian abscess, in which an acutely ill patient
with marked tenderness at the touch of the ultrasonic
probe demonstrates a total breakdown of the normal
architecture of one or both adnexa, with formation of a
conglomerate mass or fluid collection
ÀÀ Cul-de-sac fluid (50% of acute and 10% of chronic
cases).
Although the true sensitivity and specificity of
Figure 38.3 Transvaginal sonogram of sausage-like dilated tube
with a small intraluminal projection (at upper part) that represents an transvaginal sonography findings are not known,
endosalpingeal folds within a hydrosalpinx demonstration of sonographic markers as outlined
previously, in the appropriate clinical setting, can assist

in establishing the correct diagnosis. This will lower the
frequency of more invasive diagnostic procedures. In the
absence of a clinical history or findings in keeping with
pelvic inflammatory disease, differentiation of a tubo-
ovarian complex or tubo-ovarian abscess from a neoplastic
process may be difficult sonographically.
Endometriosis
Endometriosis is defined as the presence of endometrial
tissue outside of the endometrium and myometrium. It can
involve a wide variety of locations, most commonly ovaries,
uterine ligaments, rectovaginal septum, cul-de-sac and
pelvic peritoneum.20 The true prevalence of endometriosis is
unknown because most cases are asymptomatic. Estimates
for the prevalence of the disease in women of reproductive
Figure 38.4 “Ground glass” appearance of an endometrioma. This
age (80% of patients) range up to 15%.20 Endometriosis has well-defined mass is partly echogenic and demonstrates attenuation.
been documented in 15% of infertile women.23 Notice that the degree of echogenicity is less than that associated
with dermoids
Typical symptoms attributed to pelvic endometriosis
are acquired dysmenorrhea, lower abdominal, pelvic, and
back pain, dyspareunia, irregular bleeding and infertility.20 with a specificity of 89−97.7%.26-30 False-positive diagnoses
The recurrent cyclic menstrual, inflammatory and fibrotic were mostly hemorrhagic cysts.26,27
changes within endometriotic lesions are likely responsible Although the ultrasonographic findings are sometimes
for most of the symptoms, although there is often no direct nonspecific, generally, differentiation from functional
relationship between the extent of the disease and severity hemorrhage cysts or other echogenic cysts is possible by
of symptoms. demonstrating multiple thick walls, homogeneity of the
Endometriotic foci may appear as punctate spots or echogenic content, and multiplicity of the lesions.18 In
patches of variable color, with a slightly raised or puckered addition, unlike endometriomas, hemorrhagic cysts will
surface, forming nodules, cysts, or both. In one-third to usually demonstrate regression over subsequent cycles.
one-half of cases, ovarian endometriotic cysts are bilateral. Also, the presence of punctate or linear bright echogenic
They can partially or almost completely replace the foci in the wall of the cyst favors the diagnosis of an
normal tissue. The cysts rarely exceed 15 cm in diameter. endometrioma.
They are commonly covered by dense fibrous adhesions, The uses of color velocity imaging, pulsed Doppler26 or
which may result in fixation to adjacent structures. The tumor markers (CA-125, CA-19-9)29 do not improve the
cyst walls are usually thick and fibrotic, with a smooth or diagnostic accuracy of transvaginal sonography.
shaggy, brown- to yellow-colored lining. The cyst content
is typically altered, semifluid, or inspissated, chocolate- Paraovarian Cysts
colored material.20 Adnexal cystic masses that do not arise directly from the
Transvaginal sonography does not detect endometriotic ovaries include paraovarian cyst, peritoneal inclusion cyst
implants.24,25 Endometriomas have a variety of appearances, and cyst of Morgagni, which arises from the fimbriated
ranging from an anechoic cyst to a cyst containing end of the tube.
diffuse low-level echoes (Fig. 38.4) with or without solid The most common type is the paraovarian cyst which
components to a solid-appearing mass. Kupfer et al.25 arises from Wolffian duct remnants in the mesovarium.
described a typical sonographic pattern of a “cystic It usually measures 3−5 cm, but can be as large as a
pelvic mass with homogeneous hypoechoic low-level pelvoabdominal cystadenoma. Occasionally, these
echoes” in 82% of 38 surgically proven endometriomas. cysts contain hemorrhage, and rarely contain internal
Further studies confirmed these findings and showed that septations.31,32 Paraovarian cysts and tumors can usually be
transvaginal sonography had a sensitivity of 82.4−88.9%, distinguished from the ovarian ones by their location. As in
ovarian tumors, paraovarian ones that contain solid areas or
septation should be considered as potentially malignant.33
Complex Masses
Complex masses contain both fluid and solid areas. They
can be predominantly cystic, or predominantly solid.
Ovarian tumors that contain solid components or irregular
septations, e.g. dermoid cysts, and most common surface
epithelial-stromal ovarian tumors of a serous, mucinous
and endometrioid subtype, are usually classified into this
complex mass category.
Ovarian Dermoid Cysts

Mature cystic teratomas of the ovary, or dermoid cysts, are
the most common benign germ cell tumors, and the most
common ovarian neoplasms,34 constituting 5−25% of all Figure 38.5 Complex dominantly cystic adnexal mass of ovarian
ovarian neoplasms. They occur most commonly during dermoid. Regional diffuse bright echoes are evident. Multiple
hyperechoic lines and dots on the right side of the picture are
the reproductive years. Unlike other germ cell tumors of characteristic of a dermoid cyst
the ovary, however, they have a wider age distribution and
may be encountered from infancy to old age.20
A dermoid cyst is composed of well-differentiated Sonographic features ascribed to dermoid masses
derivatives of the three germ layers: (i) ectoderm, (ii) include the presence of regional diffuse bright echoes
mesoderm and (iii) endoderm, with ectodermal elements with or without posterior acoustic shadowing (Fig. 38.5),
predominating. In its pure form it is benign, but a hyperechoic lines and dots, shadowing echodensity and a
malignant transformation in one of its elements can occur fluid-fluid level.18,35
in approximately 2% of the cases. The feature that most commonly defines an ovarian
In 8−15% of the cases, the ovarian dermoid cysts are mass as a cystic teratoma is regional diffuse hyperechoic
bilateral, with the possibility of several tumors being solid components that attenuate the acoustic beam. Two
presented in the same ovary. Grossly, the tumors vary types of tissue can produce this finding: clumps of hair
in size from 0.5 cm to more than 40 cm. Approximately in a cystic cavity or fat in a Rokitansky’s protuberance.36
60% measure 5−10 cm in diameter, and more than 90% Hyperechoic lines and dots in a dermoid mass are attributed
measure less than 15 cm in diameter. The cut surface of the to the presence of hair.37,38 Regional diffuse bright echoes
tumor reveals a cavity filled with fatty material, similar to and hyperechoic lines and dots are highly specific features
normal sebum, and hair surrounded by a firm capsule of of ovarian dermoids. Calcified structures, such as bone or
varying thickness. It is usually unilocular, but may also be teeth, result in shadowing echodensity, which is nonspecific.
multilocular.20 Fluid-fluid levels are presumably a result of sebum layered
Usually a single, but possibly a multiple protuberance on serous fluid.39
(Rokitansky’s protuberance) arises from the cyst wall In an evaluation of 252 adnexal masses, 74 of which
and projects into the lumen. The protuberance is most were cystic teratomas, the positive predictive value for
commonly solid (although it can be partly cystic) and individual sonographic features associated with dermoid
consists of a variety of different tissues. The hair present in masses was 80% for shadowing echodensity, 75% for
the tumor arises from this protuberance, and bone or teeth, regionally bright echoes, 50% for hyperechoic lines and
when present, tend to be located within this area. dots, and 20% for a fluid-fluid level. Fifty-five (74%) of
Dermoid cysts are often discovered as an incidental the dermoids had two or more dermoid features, whereas
finding. When symptomatic, they usually present with none of the nondermoid masses had more than one feature,
abdominal pain, abdominal mass or swelling and abnormal giving a positive predictive value for two or more ultrasonic
uterine bleeding. dermoid features of 100%.35
Kurjak et al.40 using a morphologic scoring system for the three growth patterns: (1) cystic, (2) papillary, and (3)
dermoid cysts achieved a sensitivity and specificity of adenofibromatous. Most cystic tumors are unilocular, but
93.1% and 99.4% respectively, in a study of 887 adnexal multilocular forms occur and vary in size up to 30 cm
masses. When the presence of vascularity was assessed diameter. The cysts are usually filled with serous fluid. The
using color Doppler, 72% of cystic teratomas were mostly linings of the cysts are either entirely flat or have focal,
avascular, which, when combined with the scoring system, grossly visible, coarse papillary projections. Such papillary
produced a sensitivity and specificity of 99% and 99.8% excrescences rarely cover the entire inner surface of the
respectively. benign serous cysts. The third (adenofibromatous) variant
is a solid neoplasm.20
Ovarian Tumors Originating from Atypically proliferating serous tumors have gross
the Surface Epithelium features similar to those of benign serous tumors, but
Surface epithelial-stromal ovarian tumors account for about tend to have finer, more friable and exuberant papillary
60% of all ovarian neoplasms, and 80−90% of primary projections.20
ovarian malignancies. Three broad epithelial categories, on Well-differentiated carcinomas are mostly cystic,
the basis of epithelial differentiation, predominantly occur multilocular tumors with soft, friable papillae, partly or
in this group: serous, mucinous and endometrioid, with mostly filling the cavities, and containing usually turbid
frequencies of 46%, 36.5% and 7.5% respectively. or bloody fluid. External surfaces may be smooth or
The spectrum of proliferative change these tumors bosselated, and sometimes include surface papillae. Tumor
exhibit is divided arbitrarily into three categories: benign, adhesions to surrounding organs are common.20
atypically proliferating (“of low malignant potential”, Psammomatous calcifications are present in 15% of
“borderline”) and malignant. The intermediate group of benign tumors and 60% of malignant tumors, and may
atypically proliferating tumors is defined as exhibiting occasionally be very prominent, producing macroscopic
greater cellular proliferation than that encountered in the calcification.20
benign form of the same type of tumor but showing no Sonographically, benign serous cystadenomas appear
destructive invasion of the stromal component.20 as sharply marginated, anechoic masses that may be large
The mean age of patients with benign epithelial tumors is and are usually unilocular. Internal thin walled septations
45 years, and 50 years for those with atypically proliferating (Fig. 38.6) and, occasionally, papillary projections may be
neoplasms. Invasive epithelial tumors are uncommon before seen, the later often more florid in borderline tumors.20
40 years of age. These tumors do not produce specific
symptoms (Table 38.1).
Serous tumors: Benign serous tumors are common,
accounting for about one-quarter of all benign ovarian
neoplasms, and 50−70% of all ovarian serous tumors.
Although reported at all ages, they show a peak incidence
in the fourth and fifth decade of life.20
Between 10 and 15% of ovarian serous tumors are
categorized as atypically proliferating serous tumors. Their
peak incidence is between 45 and 50 years of age.20
Malignant serous tumors account for approximately
40−50% of malignant ovarian neoplasms. They occur most
frequently between 45 and 65 years of age, and in 80−85%
of the cases they are widely disseminated at diagnosis.20
Between 12 and 20% of the benign serous tumors are
bilateral (more often in the elderly women), while about
66% of malignant serous tumors are bilateral.20
Figure 38.6 Transvaginal sonogram of “borderline” serous
Variations in gross appearances of benign serous tumors cystadenoma. Note many internal thin-walled septations within the
are due to the relative prominence in a given lesion between complex ovarian tumor
Serous cystadenocarcinomas are usually multilocular,
containing multiple papillary projections and septations;
echogenic material is occasionally present within loculi.
Cystadenofibroma tends to have a solid component and
is the most likely to mimic a malignant lesion. Ascites
is common in serous cystadenocarcinomas but quite
uncommon in cystadenomas.41
Mucinous tumors: Benign mucinous cysts and cystadenomas
comprise 20−25% of all benign ovarian neoplasms, and
75−85% of all ovarian mucinous tumors. They occur most
often during the third to fifth decade of life, and are bilateral
in only about 2−3% of the cases.20
Atypically proliferating mucinous tumors comprise
14% of all mucinous tumors. They have peak prevalence
in women in the 30s, and are bilateral in 6−8% of tumors
with intestinal-type epithelium, and 40% of tumors with Figure 38.7 Multiloculated appearance of an ovarian mucinous
cystadenocarcinoma. Solid parts and thick, irregular septa are clearly
endocervical-like epithelium.20
visible. Note fine, homogeneous echo of a thick, mucinous contents
Malignant mucinous tumors comprise 5−10% of malignant
primary ovarian neoplasms and a similar percentage of all malignant ovarian epithelial tumor, accounting for
ovarian mucinous tumors. They occur most commonly 20−25% of all ovarian carcinomas. They are bilateral in
between the fourth and the seventh decade of life. Although 28% of cases, and occur most frequently in the fifth and
in 15−20% of the cases they are bilateral, only 5% show sixth decade of life. About 20−25% of these carcinomas
extension beyond the ovaries at the time of laparotomy.20 are associated with a histologically similar lesion of the
Grossly, benign mucinous tumors and atypical endometrium. Endometrioid carcinoma accounts for 70%
proliferating mucinous tumors are typically multiloculated, of the tumors arising from endometriosis. Direct origin of
cystic tumors measuring up to 50 cm in diameter. endometrioid carcinoma from endometriotic tissue has been
The serosal surface of the usually thick outer wall is reported in up to 24% of the cases in some series.20
smooth and opaque. The cysts contain a thick, tenacious Grossly, endometrioid carcinomas are primarily cystic,
mucinous material, occasionally somewhat more watery most measuring 12−20 cm in diameter. On section,
in consistency. Loculi are usually small and multiple, but cysts contain friable, soft masses or papillae, as well as
tumors may be parviocular or even a large simple cyst. The bloodstained fluid. Less commonly, neoplasms are solid,
frank mucinous carcinomas tend to be cystic, multiloculated with widespread necrosis and hemorrhage.20
neoplasms, usually measuring 15−30 cm in diameter. Ovarian endometrioid tumors are defined by “the presence
Sonographically, mucinous cystadenomas have thicker of epithelial elements, stromal elements, or a combination
and more numerous septations and frequently contain of the two, that resemble closely the components of typical
fine, gravity-dependent echoes produced by the thick tumors of the endometrium”. 20 Endometrioid ovarian
contents (Fig. 38.7).42 The presence of debris may cause carcinomas generally are regarded as having an overall better
them to mimic solid components; however, gentle tapping prognosis than either serous or mucinous carcinomas.20
on the cyst wall with the probe may result in movement, Sonographically, endometrioid tumors usually present
confirming the diagnosis of a pseudomass. as a cystic mass containing papillary projections, although
Mucinous cystadenocarcinomas usually appear as large in some cases they are a predominantly solid mass.43
multiloculated cystic lesions containing echogenic material
and papillary excrescences. They have papillary projections Solid Masses
less frequently than the serous type.41 Sex cord-stromal ovarian tumors (i.e. fibromas, thecomas,
Endometrioid tumors: Approximately 80% of ovarian granulosa cell and Sertoli-Leydig cell tumors) account for
endometrioid tumors are malignant. Endometrioid approximately 8% of all ovarian tumors. They are mostly
carcinomas are the second most frequently encountered solid; fibromas account for approximately one-half of cases,
thus representing the most common ovarian lesion to appear Morphologic Assessment
on transvaginal sonography as a solid mass. Transvaginal grayscale sonography plays an important
role in the assessment of adnexal masses; however, the
Fibromas
significant number of false-positive results produced limits
Fibromas account for 4% of all ovarian tumors. They occur the accuracy of the technique. Ultrasonic signs of malignant
at all ages but are most frequent in middle-aged women ovarian tumors include multilocular or multiple cysts, thick
(mean age, 48 years).20 Ovarian fibromas may also be part or irregular septa or walls, poorly defined borders, papillary
of basal cell nevus syndrome, a hereditary disease, when projections, solid components and echogenic elements.46,47
they are typically bilateral, multinodular and calcified. In an attempt to improve specificity, different morphologic
Meigs’ syndrome (ascites and pleural effusion criteria, many of which are given a numeric value to produce
accompanying a fibrous ovarian tumor, usually a fibroma, a summated score, have been examined.48-50 Depending on
and disappearing after the removal of the tumor) complicates the value of the score, investigators hope to distinguish
about 1% of ovarian fibromas. Ascites alone is present in between benign and malignant masses using a cut-off value.
10−15% of ovarian fibromas larger than 10 cm in diameter.20 In a prospective comparison of four previously published
Fibromas range in size from microscopic to very large. morphologic scoring systems and a new “multicenter
Sectioning typically reveals hard, flat, chalky-white score”, Ferrazzi et al. 51 demonstrated a significant
surfaces that have a whorled appearance. Focal or diffuse improvement in diagnostic accuracy with the multicenter
calcification and bilaterality are each observed in fewer system. This was accounted for mainly by the introduction
than 10% of the cases. Microscopy reveals intersecting of two criteria that allowed correction for typical dermoids
bundles of spindle cells producing collagen. The absence of and endohemorrhagic corpora lutea. Even so, although the
fat differentiates a fibroma from a thecoma. Differentiation scores were sensitive, they were not specific, with the best
from a fibrosed thecoma, however, is not always possible.20 diagnostic accuracy of 72%, obtained with a sensitivity of
Sonographically, two typical appearances have been 87% and specificity of 67%. By lowering the cut-off score
described. The first has features similar to that of a by 1 point from 9 to 8, a sensitivity of 93% was achieved;
uterine fibroid, with variable attenuation and multiple- the specificity fell to 56%.
edge shadows, occurring because of the whorl gross
Several investigators examined adnexal masses with
appearance of these tumors. This type of fibroma may be
three-dimensional ultrasound (3D US) and found the
difficult to differentiate from a pedunculated fibroid if it
simultaneous, multiplanar display of perpendicular planes
completely replaces normal ovarian tissue and reaches large
advantageous for examining the structure of masses or
dimensions.18 The second appearance is that of a hypoechoic
cystic collections and for assessing papillary projections or
mass with substantial attenuation.18,44 Atypically, fibromas
irregularities in the walls (Fig. 38.8) of otherwise benign
may be hyperechoic or may demonstrate a mixed
appearing cysts. Bonilla-Musoles et al.52 reported on 76
heterogeneous pattern. Calcification may be identified.45
women with ovarian masses studied with both 2D US and
3D US and found that 3D US was superior in: (i) evaluating
Evaluation of an Ovarian Mass for papillary projections, (ii) showing characteristics
During preoperative evaluation of an ovarian mass, of cystic walls, (iii) identifying the extent of capsular
transvaginal gray scale sonography is a “golden standard” infiltration of tumors, and (iv) calculating ovarian volume.
for sonographic orientation in a female pelvis, localization In one patient, papillary projections were identified on 3D
of suspected ovarian lesion, and collecting of basic US that were not seen on 2D US. In a series of 45 patients
morphologic findings (Table 38.3). Further blood flow with ovarian tumors, Weber et al.53 found that it was the
analysis obtained by transvaginal color Doppler provides multiplanar capability that was the most advantageous
clinically useful information about ovarian tumor nature. in examining these tumors. It was particularly helpful in
Recent technological advances, such as 3D volume grading the tumors that were cystic.
acquisition and 3D power Doppler imaging, have an
important role in accurate diagnosis of ovarian cancer, and Doppler Parameters
especially in the early identification of abnormal ovarian Transvaginal color Doppler sonography has been shown to
vascularity and architecture (Table 38.3). be a clinically useful adjunct to grayscale sonography for the
Table 38.3 Two-dimensional and three-dimensional sonographic and Doppler criteria for diagnosis of the ovarian malignancy
2D 3D
Volume
3
Premenopausal <20 cm 0 0
3
>20 cm 2 2
3
Postmenopausal <10 cm 0 0
3
>10 cm 2 2
Cyst wall Smooth <3 mm 0 0
thickness/structure Smooth >3 mm 1 1
Papillarities <3 mm 1 1
Papillarities >3 mm 2 2
Shadowing Present 0 0
Absent 1 1
Septa No septa 0 0
Thin septa <3 mm 1 1
Thick septa >3 mm 2 2
Solid parts Solid area <1 cm 1 1
Solid area >1 cm 2 2
Echogenicity Sonolucency/low level echo 0 0
Mixed/high level echo 2 2
Relationship with Normal – 0
surrounding structures (3D) Disturbed – 1
Tumoral blood flow (2D) RI >0.42 0 –
RI <0.42 2 –
Vessels’ architecture (3D) Linear – 0
Chaotic – 2
Branching pattern (3D) Simple – 0
Complex – 2
Total score (2D) = sum of individual scores. Cutoff score ≥4 for morphology index and ≥6 for combined (2D morphology and color Doppler
score) index was associated with high-risk of ovarian malignancy.
Total score (3D) = sum of individual scores. Cutoff score ≥5 for morphology index and ≥7 for combined (3D morphology and power Doppler
score) index was associated with high-risk of ovarian malignancy.
evaluation of patients with pelvic masses.54,55 Color Doppler to blood flow than to those in benign adnexal masses (Figs
evaluation of the presence or absence of flow, the distribution 38.9 and 38.10).
of flow and the flow velocity waveforms seems to be helpful Tumor blood vessels have a paucity or lack of muscular
in distinguishing benign from malignant ovarian lesions. media of normal vessels and are more distensible. This
The advantages of color Doppler in evaluation of the combined with arteriovenous shunts seen in the tumor
adnexal masses were demonstrated and used for the first vascular network results in low-impedance flow. However,
time in the late 1990s by groups in Zagreb and London.56,57 because of focal areas of narrowing and dilatation within
The Zagreb group has studied pelvic masses, and observed tumor vessels, focal areas of high systolic velocity can also
low-impedance intratumoral blood flow (RI < 0.41) in be found. Another factor that confounds this is the fact that
malignant ovarian lesions. Both groups agreed that color most tumors have areas of variable perfusion. Our study
Doppler can detect ovarian cancer as early as FIGO stage reported on pre-existing vessels with normal wall structure
IA, and can be used as a screening technique for the disease. in 60% of malignant ovarian tumors.66 This contributes
From those days on, nothing has essentially changed. A lot to uneven tumor blood flow that makes it difficult to
of research has been done to prove or dispute the use of generalize a “characteristic” flow of ovarian tumors.67
color Doppler, but the final verdict was never reached.58-65 Diagnostic accuracy of values of flow indices in
It is a fact that a difference in vascularity exists, and blood differentiating benign from malignant ovarian lesions has
vessels in malignant adnexal lesions show lower resistance varied considerably, from over 96% to less than 40%.68
Figure 38.8 Three-dimensional US examination of a small papillary Figure 38.10 A malignant ovarian tumor with its characteristic image
projection located on the internal cystic wall by simultaneous, created by a solid counterpart. Color Doppler waveform analysis shows
multiplanar display of perpendicular planes low resistance to blood flow, suggestive of ovarian malignancy
important to provide information involving the vascular

network rather than particular vessels.
A solution to this problem has been offered by the
introduction of three-dimensional power Doppler imaging.71
While 2D color Doppler is useful in detecting vascularized
structures, 3D power Doppler is superior in the study of
vascular morphology. Microscopically, ovarian tumor
vasculature is highly heterogeneous and does not conform to
normal vascular organization.72 In a recently published work,
authors presented results of 3D power Doppler imaging in the
interactive analysis of ovarian tumor microcirculation anatomy
(Fig. 38.11); irregular and randomly dispersed vessels with
complex branching were suggestive of ovarian malignancy.73
One year after, Cohen et al. reported that 3D power
Doppler ultrasound improves the diagnostic accuracy
Figure 38.9 A transvaginal sonogram of an ovarian tumor with small for ovarian cancer prediction.74 In their study, 71 women
papillary formation protruding into the lumen. Color Doppler imaging with a known complex pelvic mass were referred for a
demonstrates high resistance to blood flow, indicative for benign
ovarian tumor preoperative ultrasound evaluation with both 2D gray-scale
and 3D sonography with power Doppler facilities. They
More than 15 years of experience in multiple centers correctly identified all 14 ovarian malignancies (2 FIGO
has shown that overlap in the specific impedance values stage I, 2 FIGO stage II, 7 FIGO stage III, and 3 metastatic
obtained from vessels surrounding the ovary by color colon) by both 2D grayscale and 3D power Doppler imaging
Doppler imaging precludes differentiation of benign versus (sensitivity of 100%), and moreover, 3D power Doppler
malignant ovarian masses on the basis of impedance values significantly improved the specificity, from 54% to 75%,
alone.69 Other limiting factors for this type of imaging as compared with 2D gray-scale sonography.
represent slow flow and vessels of small diameter which Very recently, retrospective analysis on preoperative
are barely detectable.70 Also, part of the problem with this sonographic assessment of 43 referred patients with
technique is that only those vessels that are depicted can suspected stage I ovarian cancer was published by
be adequately studied. More specifically, it seems more our group.75 Despite initial studies reported improved
Figure 38.11 Malignant tumor neovascularization is characterized Figure 38.12 Three-dimensional power Doppler scan of malignant
by more than three generations of the vessels, areas of stenosis, tumor vessels located in a papillary projection, characterized by
microaneurysms and blind-ending lakes. All these features can be irregular course and complicated branching. Histopathology revealed
assessed using 3D power Doppler imaging stage IA endometrioid adenocarcinoma of the ovary
morphological evaluation of ovarian tumors by using 3D 125 has only a limited role because of its poor sensitivity and
sonography alone,52,76 in our analysis 3D sonography reached specificity. Signs indicating the possibility of malignancy are
unsatisfactory detection rate of 74.4%, while combined enlargement, development of irregular solid areas and ascites.
3D sonography and power Doppler imaging achieved the
highest detection rate of 97.7% in preoperative sonographic Conclusion
assessment of suspected ovarian lesions (p < 0.002). Evaluation of adnexal masses is of particular importance in
gynecological practice. Two main problems need answers:
As a result, authors proved that 3D sonography with
discrimination of benign and malignant ovarian tumors and choice
power Doppler facilities allows accurate detection of the of the appropriate surgical treatment, if necessary. Because
earliest appearance of ovarian malignancy, i.e. FIGO stage ultrasound depicts the mass, characterization of the mass is
typically performed during the same examination. Thus, de facto,
I ovarian cancer (Fig. 38.12). ultrasound becomes the main triage method prior to treatment.
In most institutions, the type of surgery performed (laparotomy
vs laparoscopy) depends on the probability of malignancy. The
Persistent versus Regressing Masses optimal ultrasound technique and diagnostic criteria to use when
In the premenopausal or perimenopausal women, a follow- characterizing a suspected ovarian neoplasm remain controversial.
It is now well established that transvaginal grayscale sonography
up examination may be indicated 6−8 weeks after the initial is accepted as the “golden standard” in the preoperative evaluation
sonographic finding, in those masses thought to be benign, of ovarian masses.
even though some may persist up to 2−3 months. About Papillary formations on the inside of the cyst wall and
nonhyperechoic solid components protruding into the cystic cavity
70% of cysts in premenopausal women will demonstrate are the most important morphologic predictors of a malignant
regression in 2−3 months.77 If regression does not take place, ovarian tumor. Transvaginal color Doppler demonstrates the
one should consider other etiologies. Acute enlargement can vascularity of an ovarian mass, revealing the tumor histology and
metabolism. Therefore, blood flow data should be considered to
result from intraluminal hemorrhage and/or torsion. indicate the angiogenic intensity of a tumor, rather than indicating
In postmenopausal women there is an increased risk of malignancy itself. It is a fact that sonographic estimation of ovarian
a pelvic mass malignancy. However, one study showed that masses should include color Doppler analysis, but there is still no
concensus which Dopler parameter and what cutoff value are the
up to 15% of asymptomatic postmenopausal women had most predictive of malignancy. Three-dimensional power Doppler
cystic masses up to 3 cm in size.78 If followed for 6 months, provides a new tool for measuring the quality of tumor vascularity,
over half regress and approximately one-fourth enlarge, and and its clinical value is being evaluated. Improved detection and
classification of ovarian tumor angiogenesis contributes to better
one-fourth stay the same in size.79 Clinical judgment in these diagnostic accuracy and consequently reduction of false-positive
cases is needed to determine which patients may benefit from findings and invasive procedures, which might lead to a significant
reduction of morbidity and mortality from ovarian cancer.
surgery, aspiration and cytology, or observation. Serum CA-
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CHAPTER
39 Screening for Ovarian

Cancer by Different Modes of
Transvaginal Sonography
Asim Kurjak, Matija Prka, Jose Bajo Arenas
Introduction limit the number of unnecessary surgical procedures to 10

for each case of cancer detected.5 A specificity lower than
In developed countries more women die annually from this is likely to be unacceptable in this population, although
ovarian cancer than from all other gynecologic malignancies may be acceptable to those with a positive family history
combined. For example, in the United States, approximately of breast or ovarian cancer.
25,580 new cases are diagnosed each year, and 16,090 of
these women will die of the disease.1 Symptoms usually do
not become apparent until the tumor compresses or invades
Attempts to Screen—
adjacent structures, ascites develops, or metastasis becomes Some Lessons Learned
clinically evident. As a result, around 65% of women During the last decade, large prospective studies of
with ovarian cancer have advanced disease (stage III/IV) screening for ovarian cancer have been performed.6 Two
at diagnosis with 5-year survival rate of only 20–30%, distinct strategies have emerged: (i) based on ultrasound
compared with the 5-year survival of over 90% in patients as the primary test and (ii) involving the serum tumor
with stage IA ovarian cancer, when disease is confined to marker CA-125 for primary screening with ultrasound as
the ovary.2 Given the burden of suffering associated with the secondary test (multimodal screening). Tables 39.1
the development of ovarian cancer and the clear survival and 2 summarize the prospective ovarian cancer screening
gradient related to the stage of disease at diagnosis,3 there is studies in the general population.7–22 If we exclude those
much enthusiasm for the development of effective screening which used transabdominal ultrasound, an abandoned
methods/assays for the early detection of epithelial ovarian screening strategy due to unacceptably high rate of false-
cancer. positive results, several important lessons can be learned
for forthcoming trials.
Difficulties in Ovarian Cancer Screening As seen in Tables 39.1 and 39.2, the data suggest that
The ability to detect early-stage epithelial ovarian cancer sequential multimodal screening has greater specificity
by a simple test has long been desired yet never achieved. and PPV compared to strategies based on transvaginal
Several aspects of ovarian cancer have led to the frustrations ultrasound (TVUS) alone. For each case of ovarian cancer
that have been encountered in attempts to screen for the detected, 5 women underwent surgery in the multimodal
disease.4 First, the anatomic location of the ovaries is not studies compared to 24 women in the studies using
amenable to any direct inspection. Additionally, in contrast ultrasound alone. However, TVUS as a first line test may
to cervical neoplasia, epithelial ovarian cancers (EOC) lack offer higher sensitivity for early stage disease given that 23
any defined precursor lesion and have a poorly defined out of 37 (62.2%) cancers detected using ultrasound alone
natural history. The time required for localized disease to were stage I, compared to 8 out of 19 (42.1%) cancers
progress to disseminated disease is unclear; therefore, the detected by the multimodal strategy. An ultrasound-based
appropriate interval at which to pursue screening is at this strategy may have a greater impact on ovarian cancer
point chosen arbitrarily. Other impediments to screening mortality, albeit at a higher price in terms of surgical
relate to the low prevalence of ovarian cancer in the general intervention for false-positive results.
population. Therefore, a specificity of 99.6% is required to This chapter updates the status of ovarian cancer
achieve a positive predictive value (PPV) of 10%, i.e. to screening and addresses most relevant studies published
Table 39.1 Prospective ovarian cancer screening studies using ultrasound as the primary test in the general population
Study Inclusion criteria Screening No. of screened No. of invasive No. of positives No. of positive
strategy epithelial screens/cancers
ovarian detectedb
detecteda
Ultrasound (US) Approach
Grayscale US (Level 1 screen), than repeat grayscale US (Level 2 screen)
7
van Nagell et al. Age >50 years TVS 14,469 11 (6) 180 16.4
and post- Annual 5 stage
menopausal screens
or >30 Mean 4
with positive screens/
family history women
Hayashi et al.
8
Age >50 years TVS 23,451 3 (3) 258 c
9
Tabor et al. Aged 46–65 TVS 435 0 9 –
years
10
Campbell et al. Age >45 years TAS 5,479 2 (3) 326 163
or with positive 3 screens at 18 2 stage I
family history monthly intervals
(4%)
11
Goswamy et al. Age 39–78 TAS 1,084 1 not –
Postmenopausal 1 stage I precised
Grayscale US and CDI (Level 1 screen)
12
Vuento et al. Aged 56–61 TVS and CDI 1,364 (1) 5 –
years
13
Kurjak et al. Aged 40–71 TVS and CDI 5,013 4 38 9.5
years 4 stage I
14
Schulman et al. Age >40 years TVS and CDI 2,117 1 18 18
or > 30 with
positive
family history
Gray-scale US (Level 1 screen) and other tests (Level 2 screen)
15
Sato et al. Age >30 years TVS then tumor 51,550 16 (6) 324 20.3
markers if TVS +, 12 stage I
CT and MRI
if all previous +
16
Parkes et al. Aged 50–64 TVS then CDI 2,953 1 15 15
if TVS + 1 stage I
17 d
Holbert et al. Postmenopausal TVS then CA-125 478 1 33 –
Aged 30–89 if TVS + 1 stage I
years
e
TOTAL 37 (16) 880 23.8
23 stage I
a
The borderline/granulosa tumors detected are shown in parenthesis.
b
Only invasive epithelial ovarian cancers included.
c
Only 95 women consented to surgery and there are no follow-up details on the remaining.
d
Only 11 of these women underwent surgery.
e
Studies used TAS are excluded
(Abbreviations: TAS, transabdominal ultrasound; TVS, transvaginal ultrasound; CDI, color Doppler imaging; MRI, magnetic resonance
imaging; CT, computed tomography)
during the last 5 years. The developments that followed the technology, especially 3D power Doppler imaging, in early
review are best summarized in reference to the screening and accurate detection of ovarian malignancy is discussed.
tests, target populations and newly published trials. Finally, authors describe their new ovarian cancer screening
The possible role of three-dimensional (3D) ultrasound trial, which started in January 2001.
Chapter 39  Screening for Ovarian Cancer by Different Modes of Transvaginal Sonography 433
Table 39.2 Prospective ovarian cancer screening studies using serum CA-125 as the primary test in the general population
Study Inclusion criteria Screening No. of screened No. of invasive No. of positives No. of positive
strategy epithelial screens screens/cancer
ovarian cancers detectedb
detecteda
CA-125 only
18
Einhorn et al. Age >40 years Serum CA-125 5,550 6 175 29.2
2 stage I
Multimodal Approach
CA-125 (Level 1 screen), then Gray-scale US (Level 2 screen)
19
Jacobs et al. Age >45 years RCT 10,958 6 29 4.8
Postmenopausal Serum CA-125 3 stage I
TAS/TVS, if CA-
125↑
3 annual screens
20
Jacobs et al. Age >45 years Serum CA-125 22,000 11 41 3.7
Postmenopausal TAS, if CA-125↑ 4 stage I
21
Adonakis et al. Age >45 years Serum CA-125 2,000 1 (1) 15 15
TVS, if CA-125↑ 1 stage I
22
Grover et al. Age >40 years Serum CA-125 2,550 1 16 16
or with positive TAS/TVS, if CA-
family history 125↑
(3%) 3 screens
a
TOTAL 19 (1) 101 5.3
8 stage I
a
Only multimodal approach studies included
(Abbreviations: RCT, randomized controlled trial; TAS, transabdominal ultrasound; TVS, transvaginal ultrasound)
Screening Tests identified as being at increased risk. This approach is an

integral part of the multimodal screening strategy adopted
Screening for ovarian cancer has been based on strategies in the St Bartholomew’s Hospital newest randomized
using serum tumor markers or TVUS images of the ovaries. control trial.26
Another limitation of serum CA-125 represents that
Serum Tumor Markers it is not specific for ovarian carcinoma because it can be
In epithelial ovarian cancer, a number of tumor markers elevated in many benign conditions such as endometriosis,
have been identified. Serum CA-125 continues to be the uterine fibroids, pelvic inflammatory disease, ascites or
tumor marker most extensively used in ovarian cancer pleural effusion.27 It is now known that the CA-125 antigen
screening.23 Although CA-125 is elevated (>35 U/ml) in carries two major antigenic domains classified: (i) A (the
more than 80% of patients with epithelial ovarian cancer, domain-binding monoclonal antibody OC-125) and (ii)
it is only 25% sensitive for early stage disease.24 Indeed, its B (the domain-binding monoclonal antibody M11). New
value as an initial screening tool is limited since picking up generation assays, combining monoclonal antibodies to the
stage III disease at an earlier time may not alter outcome. To two distinct regions of the molecule, have been shown to
improve further the performance of CA-125 as a screening have improved specificity for the detection of early ovarian
tool, an algorithm incorporating age, rate of change of CA- cancer.28
125 and absolute levels to calculate an individual’s risk Lysophosphatidic acid (LPA), a bioactive phospholipid
of ovarian cancer has been described.25 This increases the with mitogenic and growth factor-like activities,29 is a
sensitivity of CA-125 in comparison with a single cutoff novel tumor marker that holds promise in ovarian cancer
value, because women with normal but rising levels are screening. In a small pilot series plasma LPA levels were
elevated in 9 out of 10 patients with stage I ovarian cancer, population of 22,000 women.35 In contrast, those with
10 out of 24 patients with stages II, III and IV ovarian an elevated serum CA-125 level and abnormal ovarian
cancer, and all 14 patients with recurrent ovarian cancer.30 In morphology on ultrasound had a significantly increased
comparison, among a subset of patients with ovarian cancer, cumulative risk of 24%. The use of ovarian morphology
only 28 out of 47 had elevated CA-125 levels, including 2 to interpret pelvic ultrasound may increase sensitivity, and
out of 9 patients with stage I disease. Larger studies on the use of complex ovarian morphology may increase the PPV
use of LPA in primary screening—perhaps in combination of a multimodal screening strategy.36
with other procedures, such as TVUS—are essential for
earlier detection and improved outcome for patients with Target Populations
ovarian cancer.31
Participants for ovarian cancer screening trials are recruited
Transvaginal Ultrasound from general and high-risk populations on the basis of risk
factors for the disease.
Transvaginal ultrasound is used in most screening strategies
either as the sole screening modality or as a secondary test
General Population
after primary screening with serum CA-125 (multimodal
screening). As data regarding outcome accumulate with Age and Menopausal Status
long-term follow-up of the participants of the early The bulk of ovarian cancers occur in the general population,
screening trials, it has been possible to define further risk of and age more than 50 years and postmenopausal status have
ovarian cancer associated with various ultrasound findings. been used to define those eligible for screening. According
Particular results of the largest ultrasound-based ovarian to the recent International Federation of Gynecology and
cancer screening project from University of Kentucky might Obstetrics (FIGO) report,2 appearance of ovarian cancer is
have a definitive impact on design of future ovarian cancer most common among women in early postmenopause, at an
screening trials in the general population.32 van Nagell et al. average age of 54 years. Law et al.37 used national statistics
established that unilocular ovarian cysts less than 10 cm in to determine the number of years of life lost through deaths
diameter, found in 256 out of 7,705 (3.3%) asymptomatic from a particular cancer at each age. They concluded that
women aged more than 50 years, are associated with a screening would be most effective (i.e. associated with the
minimal risk for ovarian cancer because there were no largest number of years of life saved per person screened) if
cases of ovarian carcinoma during a 5-year follow-up done 5 years before loss of life peaked. The peak occurred
period.33 In contrast, 7 out of the 250 women in the same in ovarian cancer during the age range 55–59 years, and the
study with complex cystic ovarian tumors, including authors’ argument provides further justification for using
wall abnormalities or solid areas, had ovarian carcinoma 50 years as the cut-off to commence population screening.
suggesting that this morphologic appearances are associated
with a significant risk for malignancy. High-risk Population
In many screening algorithms, volume cut-offs are Family History and/or Genetic Predisposition
used in addition to morphology characteristics to identify Approximately 5–10% of ovarian cancers are inherited.
women for intensive surveillance. Recently, based on the Mutations in BRCA1 and BRCA2 genes account for
data on 58,673 observations of ovarian volume, authors about 75% of families with a highly penetrant dominantly
from Kentucky concluded that the upper limit of normal for inherited breast or ovarian cancer family history. Recent
ovarian volume is 20 cm3 in premenopausal women and 10 estimates of the life-time risk for ovarian cancer in women
cm3 in postmenopausal women.34 Such data are invaluable harboring a BRCA1 mutation are 40–60%. 38 Various
in determining optimal strategies for operative intervention studies have put forward schemes for stratifying women
in screening trials. into different risk categories of risk for breast and ovarian
Postmenopausal women from the general population cancer by virtue of a family history, genetic predisposition
with an elevated serum CA-125 level but normal ovarian or both. Pharoah et al.39 reviewed the relevance of family
morphology on ultrasound were found to have a cumulative history in defining the target population for familial ovarian
risk of ovarian cancer during a median follow-up of 6–8 cancer screening, and propose the adoption of a unified
years of 0.15%, which was similar to 0.22% of the entire management strategy based on eligibility criteria from the
Table 39.3 Eligibility criteria for the United Kingdom National Familial Ovarian Cancer Screening Study
39
An eligible woman must be over 25 years of age and a first degree relative of an affected member of an “at risk” family. At-risk families are
defined by the following criteria:
a
1. Two or more first degree relatives with ovarian cancer.
2. One first degree relative with ovarian cancer and one first degree relative with breast cancer diagnosed under 50 years of age.
b
3. One first degree relative with ovarian cancer and two first or second degree relatives with breast cancer diagnosed less than 60 years of
age.
4. An affected individual with one of the known ovarian cancer predisposing genes.
5. Three first degree relatives with colorectal cancer with at least one diagnosed before the age of 50 years and at least one first degree
relative with ovarian cancer.
a
A first degree female relative is mother, sister or daughter.
b
A second degree female relative is grandmother, grand-daughter, aunt or niece.
UK National Familial Ovarian Cancer Screening Study is encouraging about these results is that annual TVUS
(Table 39.3). screening appeared to achieve the primary goal of earlier
A survey by Vasen et al.40 of the European Familial Breast detection of disease, which translates into a reduction in
Cancer Collaborative Group found that the following high-risk mortality associated with ovarian carcinoma. On the other
populations were offered ovarian cancer screening: BRCA1 hand, data from this study suggested that in certain cases,
and BRCA2 mutation carriers; members of breast/ovarian length of time required for ovarian cancer to progress from
cancer families; and, in some centers, members of “breast a localized sonographically detectable tumor to widespread
cancer only” families with an early onset of breast cancer. regional disease is quite short. In 4 patients in the false-
negative group disease progression from sonographically
Ovarian Cancer Screening Trials normal ovaries to stage II or III ovarian cancer occurred in
less than 12 months. Authors stated that in future screening
Clinical trials of ovarian cancer screening have involved algorithms, consideration should be given to a screening
strategies using ultrasound alone, and a multimodal interval of 6 months.
approach with CA-125 as a primary test and ultrasound as
In the recently published Japanese ovarian cancer
a secondary test. Prospective studies have involved both
the general and high-risk populations. screening trial, 51,550 women aged 30 years or more
attending for annual cervical screening underwent TVUS
General Population screening for ovarian cancer.15 Three hundred and twenty-
Ultrasound Screening four women with masses of more than 60 mm in diameter
In the most recent update from the University of Kentucky or with a mixed echo pattern or persistently raised tumor
trial, the results of annual TVUS screening performed on markers underwent laparotomy. Twenty-two primary
14,469 asymptomatic women aged 50 years or more and ovarian tumors and two metastatic tumors were detected.
women aged 25 years or more with a family history of Of the 22 primary tumors, 16 were EOCs, 4 were borderline
ovarian cancer were reported.7 One hundred and eighty malignancies, and 2 were germ cell tumors. Eleven (68.7%)
patients with persisting transvaginal abnormalities were of the EOCs were stage I, with tumor markers positive in 5
subjected to a surgical intervention. Seventeen primary (37.4%) of the 11 cases. The PPV of the screening strategy
ovarian cancers were detected of which 11 were EOC, 3 was 4.9%; in other words, 20 operations were undertaken
were granulosa cell tumors, and 3 were borderline tumors. for each detected case of ovarian cancer. As no follow-
Of the EOC, 5 were stage I, 3 were stage II and 3 were
up data was reported on any of the trial participants, it
stage III. In this study TVUS as a screening modality was
is difficult to assess sensitivity of the screening strategy.
associated with sensitivity of 81%, specificity of 98.9%,
PPV of 9.4%, and negative predictive value (NPV) of Prior to the onset of the screening, the authors note that
99.97% for detection of all primary ovarian cancers. The only 29.7% of 35 cancers diagnosed in the department
survival of patients with EOC in the annually screened were stage I, while after the trial was initiated 58.8% of 85
population was 92.9% at 2 years and 83.6% at 5 years. What ovarian cancers treated were stage I.
Multimodal Screening may be a phenotypic variant of familial ovarian cancer,

One of the most active groups in screening for ovarian and screening strategies for these women cannot rely on
malignancy is led by Jacobs. It recently reported the ultrasound and CA-125 testing to detect early disease.
results of the first completed randomized trial of ovarian
cancer screening.19 This study randomized asymptomatic Ovarian Cancer: The Role of 3D
postmenopausal women aged 45 years or older to no Ultrasound and 3D Power Doppler
screening (n = 10,977) or to annual multimodal screening
for 3 years (n = 10,958). In the screening group 29 women
Imaging
with raised CA-125 values and abnormal ultrasound findings Improvements in ultrasound technology such as 3D
were referred for surgical investigation. All 6 ovarian cancers volume acquisition and 3D power Doppler imaging
detected were EOCs; 3 were stage I and 3 were stage III. The may have clinical utility in a more reliable identification
authors found a high PPV of 20.7% with this scheme and of an abnormal ovarian vascularity and architecture.
were encouraged by a longer median survival (72.9 months) Three-dimensional volume acquisition allows for careful
in women with ovarian cancer in the screened group when evaluation of the internal surfaces of cyst walls for
compared to the control group (41.8 months). The mortality excrescences otherwise not appreciated by two-dimensional
rates, however, were not significantly different between the (2D) ultrasound. 42,43 While the addition of 3D power
groups. The authors concluded that the results do not justify Doppler provides a new tool for measuring the quality of
ovarian cancer screening in the general population but do ovarian tumor angiogenesis,44 improving accurate diagnosis
support the need for a larger randomized trial that is powered of ovarian malignancies,45 its clinical value for the early
to assess the impact of screening on mortality. detection of ovarian carcinoma has yet to be determined.
High-risk Population What Does 3D Ultrasound Add?

For women with a known germline mutations or with a In the pioneer work, Bonilla-Musoles et al. 42 tried to
family history suggesting a significant possibility of a determine whether 3D ultrasound may offer advantages
genetic predisposition to ovarian cancer, the appropriate over 2D ultrasound as a screening tool for the evaluation of
screening strategy remains undefined. In recent studies, ovarian lesions. Seventy-six women with ovarian masses
most authors advocate multimodality screening using first detected with 2D ultrasound were then evaluated
TVUS and serum CA-125 in patients who elect to delay with 3D ultrasound. The 3D sonographic criteria used
or decline prophylactic oophorectomy. However, there is for diagnosing ovarian malignancy were based on the
no consensus as to the appropriate interval for screening. morphologic scoring system for 2D TVUS examinations
Karlan et al. reported the results of an ovarian cancer proposed by different authors.46–49 A score greater than
screening program launched in 1991, involving 1,261 4 caused suspicion of a malignant ovarian mass.49 The
women aged over 35 years with a family history of ovarian, images were dissected in the three perpendicular planes,
breast, colon or endometrial carcinoma, or a personal history and the areas indicative of malignancy, as suggested by
of breast cancer.41 Screening with TVUS, color Doppler 2D ultrasonography, were determined to be either negative
imaging and CA-125 was initially performed biannually or positive and confirmatory. Five lesions observed on
until 1995, and annually thereafter. Two tumors of low 2D ultrasound were suspected to be malignant. Three-
malignant potential, stage I EOC and 7 cases of primary dimensional sonography identified four of these lesions as
peritoneal serous papillary carcinoma were diagnosed. malignant. The remaining one suspected to be malignant
Ultrasound abnormalities triggered surgical exploration in on 2D ultrasound was diagnosed as endometriosis with
all 3 cases of ovarian disease. In 2 out of 7 cases, elevated 3D sonography. One additional ovarian carcinoma was
levels of CA-125 were the harbinger of peritoneal serous diagnosed by 3D scanning. Two of the malignant lesions
papillary carcinoma, in 2 abnormal ultrasound findings were FIGO stage IA. The other tumors were FIGO stages IC,
prompted diagnosis, and 3 developed interval cancers 5, 6 IIC and IIIB, respectively. Authors stated that observation
and 16 months after screening. At least 3 of the patients with of papillary projections (especially those < 3 mm),
primary peritoneal cancer carried mutations of the BRCA1 characteristics of cystic walls, and the extent of capsular
gene. Multifocal peritoneal serous papillary carcinoma infiltration was superior with 3D ultrasound in comparison
to conventional 2D sonographic measurements, as was the may promote improved patient care by separating complex
calculation of ovarian tumor volume. They also pointed out benign masses from ovarian cancer, therefore, facilitating
that eventually 3D ultrasound imaging will allow diagnosis appropriate physician referral.
of ovarian malignancy at an earlier stage than is possible Kupesic and Kurjak very recently reported on the use
with currently established diagnostic techniques. of contrast-enhanced, 3D power Doppler ultrasound in the
differentiation of benign and malignant adnexal lesions.52
Advantages of 3D Power Doppler Imaging A total of 45 patients with complex adnexal lesions of
There are two potential advantages of this new imaging uncertain malignancy at transvaginal B-mode and/or color
modality: (i) more accurate diagnosis of ovarian cancer and Doppler ultrasound were prospectively evaluated with 3D
(ii) possible detection of stage I disease. power Doppler before and after injection of contrast agent.
There were 12 cases of ovarian malignancy and 33 benign
More Accurate Diagnosis of Ovarian Cancer adnexal lesions. Of the 12 ovarian cancers, 7 (58.3%)
showed vascular distribution suggestive of malignancy at
To determine whether 3D power Doppler can improve
non-enhanced 3D power Doppler imaging. After injection
the ability to differentiate benign from malignant ovarian
of contrast agent, a penetrating vascular pattern and/or a
masses, Kurjak et al. 50 performed transvaginal color mixed penetrating and peripheral pattern were detected
Doppler (TVCD) and 3D power Doppler analysis on 120 in all cases of ovarian malignancy. One cystadenofibroma
patients with ovarian lesions. As a result, in each of 11 demonstrated penetrating vessels at initial scan, whereas
ovarian malignancies preoperative diagnosis by 3D power 2 benign lesions (fibroma and cystadenofibroma) were
Doppler was confirmed by histopathology. Transvaginal misdiagnosed as malignant at contrast-enhanced 3D power
color Doppler missed 1 case of serous cystadenocarcinoma, Doppler. The use of a contrast agent with 3D power Doppler
while 3 cases of benign lesions (dermoid cyst, ovarian showed diagnostic efficiency (95.6%) that was superior
fibroma and ovarian cystadenofibroma) where considered to that of non-enhanced 3D power Doppler ultrasound.
false-positive. In 1 case of cystadenofibroma, 3D power The authors concluded that contrast-enhanced 3D power
Doppler imaging might more precisely discriminate benign
Doppler finding was falsely positive. Authors emphasized
from malignant complex adnexal masses.
that irregular and randomly dispersed vessels with complex
branching, depicted by 3D power Doppler imaging, were Detection of Stage I Disease
indicative for ovarian malignancy. Such qualitative analysis Preliminary results of authors’ team showed that 3D power
of the tumor vascularity architecture had a sensitivity, Doppler ultrasound can enhance and facilitate morphologic
specificity, and PPV of 100%, 99.1% and 91.7% in and functional evaluation of an early stage ovarian cancer.53
detection of ovarian malignancy, respectively. Five-year retrospective analysis was performed on the data
In the recently published study by Cohen et al.51 71 from 43 referred patients with suspected stage I ovarian
women with a known complex pelvic mass were referred cancer subsequently confirmed by histopathologist. All the
for a preoperative ultrasound evaluation with both 2D patients were preoperatively evaluated by 4 complementary
gray-scale and 3D power Doppler ultrasound. All the sonographic methods: (i) two-dimensoinal transvaginal
women underwent surgical exploration, and 14 had gray-scale and (ii) two dimensional TVCD, (iii) three-
ovarian cancer. Two-dimensional gray-scale ultrasound dimensional ultrasound, and (iv) three-dimensional power
identified 40 masses as suspicious for cancer including Doppler, during the week prior to surgery. Authors’ results
all 14 malignancies, yielding in a sensitivity, specificity clearly demonstrated the significant impact of 3D power
and PPV of 100%, 54% and 35%, respectively. However, Doppler imaging on the accurate detection of stage I ovarian
evaluation with 3D power Doppler identified only 28 cancer. By using combined 3D morphology and vascular
cases as suspicious (including all cancers), resulting in a score indexing, authors reached diagnostic accuracy of
sensitivity, specificity and PPV of 100%, 75% and 50%, 97.7% in preoperative sonographic assessment of the
respectively. Despite all malignancies were correctly suspected lesions (Table 39.4). These findings justify
identified by both 2D and 3D imaging, the specificity implementation of 3D ultrasound with power Doppler
was significantly improved with the addition of 3D power facilities in ovarian cancer screening programs, especially
Doppler. This improved diagnostic accuracy, authors stated, as a secondary screening tool.
Table 39.4 Diagnostic accuracy of four different techniques [two- Flow chart 39.1 Screening algorithm of the Zagreb ovarian cancer
dimensional (2D) transvaginal ultrasound (TVUS), 2D transvaginal screening trial
color Doppler (TVCD), three-dimensional (3D) ultrasound and 3D
power Doppler (3D PD)] in preoperative sonographic assessment of
53
43 patients with suspected stage I ovarian cancer
Technique No. of detected No. of missed
cancers (%) cancers (%)
2D US 30 (69.8) 13 (30.2)
a
2D US/TVCD 37 (86.0) 6 (14.0)
3D US 32 (74.4) 11 (25.6)
3D PD 41 (95.3) 2 (4.7)
b
3D US/3D PD 42 (97.7) 1 (2.3)
a
Combined 2D morphology and color Doppler score
b
Combined 3D morphology and power Doppler score
Zagreb Ovarian Cancer Screening Trial

Following authors’ first attempt to screen for ovarian
cancer,13 in January 2001 they initiated the new ovarian
cancer screening trial at their Department, based on new
diagnostic tools now used routinely by them.
asymptomatic, 57-year-old postmenopausal patient
included in their new screening trial. She was well educated
Subjects and Methods and concerned about family history of cancer, because
During a 5-year period, approximately 10,000 asymptomatic her mother and mother’s sister had breast cancer. Besides
postmenopausal women greater than or equal to 50 years regular mammography and gynecological check-ups, the
and women greater than or equal to 25 years of age with a patient decided to perform gynecological ultrasound in an
positive family history of ovarian and/or breast cancer in outpatient clinic, for the first time in her life.
at least one primary or secondary relative will be offered to Transvaginal gray-scale sonography, performed by her
participate in the trial. The screening algorithm is illustrated primary care gynecologist, revealed a complex cystic-solid
in Flow chart 39.1. tumor of the right ovary, measuring 8 cm in diameter, with
Primary screening includes annual TVUS and TVCD noticeable solid component and thick, irregular septum
examination/scoring according to the sonographic and color (Fig. 39.1). Regarding ovarian morphology indicative
Doppler criteria established previously from authors’ team.54 for malignancy, she was immediately directed to our
Women with an abnormal first level screen undergo a repeat department for further ultrasound evaluation.
TVUS sonogram, with addition of TVCD, depending on Authors’ confirmed previous TVUS finding, and 2D
tumor morphologic appearance: in the case of simple ovarian power Doppler imaging showed highly vascularized zone
cyst, for 4–6 weeks; if complex ovarian cyst persists, within within the septum (Fig. 39.2). Another step represented
2 weeks. In patients with a persistently abnormal screen, TVCD analysis of tumoral blood flow which revealed
secondary screening will be considered necessary, including resistive index (RI) of 0.40 as the lowest value (Fig. 39.3).
3D ultrasound and 3D power Doppler imaging, with a According to authors’ color Doppler criteria, this finding
serum CA-125 determination. For an examination/scoring, was indicative for a malignant ovarian lesion.
3D sonographic and power Doppler criteria established in The vascular pattern obtained by further analysis with
authors’ previous study are used.54 In the case of an abnormal 3D power Doppler imaging clearly depicted disorganized,
second level screen, surgical removal of the ovarian tumor randomly dispersed vessels with irregular branching in
and pathological examination is recommended. solid part of the tumor (Fig. 39.4), strongly associated with
ovarian malignancy.
Illustrative Case As a result, 3D power Doppler data on tumor vessels
Here authors have presented an illustrative case of architecture enabled them to make more accurately
successfully detected stage IA ovarian cancer in an preoperative sonographic diagnosis of an early stage
Figure 39.1 Complex ovarian tumor in a 57-year-old postmenopausal Figure 39.2 Thick septa, solid component, and gross papillary
patient. The B-mode showed noticeable solid component protruding projection on the basis of the lesion were obtained more clearly by
into the cystic cavity of the tumor, measuring 8 cm in larger diameter. B-mode in different section. Also, 2D power Doppler was switched on,
Note thick, irregular septum on the basis of the lesion showing highly vascularized septum
Figure 39.3 Transvaginal color Doppler analysis of tumoral blood Figure 39.4 Three-dimensional power Doppler imaging revealed
flow within the vascularized septum revealed RI of 0.40 as the lowest malignant neovascularization within the solid part of the tumor,
value. According to authors’ 2D color Doppler criteria, this finding was characterized by irregular course of the tumoral vessels and
indicative for ovarian malignancy complicated branching. Histopathologic finding was stage IA ovarian
endometrioid adenocarcinoma
ovarian cancer. On the other hand, CA-125 serum level 1. Three-dimensional power Doppler qualitative analysis
of 16.3 U/ml was in normal ranges, giving them a false- of tumor angiogenesis allows accurate detection of the
negative impression of a benign ovarian tumor. earliest appearance of ovarian malignancy, i.e. stage IA
Standard oncological surgical procedure was performed, ovarian cancer.
and histopathology reported stage IA endometrioid 2. At the present time, higher equipment costs and more
adenocarcinoma of the ovary. sophisticated operator skills make 3D ultrasound
What is important to stress from the previously described technology ideally available in clinical and university
case for ovarian cancer screening studies to come? hospital settings as a secondary screening tool.
3. As published by Holbert,55 and noted in the case above, References

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CHAPTER
40 Four-dimensional
Technical Aspects
Gino Varga, Asim Kurjak, Ulrich Honemeyer
Introduction If one performs 2D sonography, true 3D structures

can be represented in the form of single 2D sectional
Three-dimensional (3D) sonography enables 3D imaging planes. This disadvantage was compensated by fast image
of 3D structures. Since human body and organs are 3D generation and analysis of organ of interest from multiple
structures, this type of imaging is the most appropriate for sections. Since 2D imaging does not require high processing
its confidential visualization. Organ structure and spatial capacity for fast image generation, real time sonography
relationships are simultaneously visualized, facilitating was possible by low capacity processor.
recognition of spatial anomalies. Using this type of The efforts were concentrated to increase the speed
imaging, fetal spatial anomalies, such as clubfoot and of data processing in order to create 3D imaging in real
spine deformations (scoliosis, kyphosis), were for the first time. This goal was nearly achieved after the advent and
time depicted on single image. For the same result with introduction of very fast microprocessors with high capacity
two-dimensional (2D) sonography, it was necessary to of data processing. Fast generation of 3D images was
visualize several sections and reconstruct spatial images precondition for introduction of 3D sonography in everyday
in the examiner’s mind. Stated in other words, delicate practice and four-dimensional sonography (4D US).
functions that the examiner had to perform in his own mind Four-dimensional ultrasound has recently been
are performed by machine. Recognition of spatial anomalies introduced in clinical practice, overcoming the limitations
with 2D sonography was the question of examiner mental of three-dimensional sonography (3D US). The most
capacity and art, whereas with 3D sonography is simple prominent limitation of 3D technology is related to the
routine task. static reconstruction of fetal anatomy. Three-dimensional
Moreover, in polymalformed fetuses, two anomalies image freezes the object and, therefore, does not provide
such as omphalocele with foot amelia or omphalocele information on movements or any information about
with kyphosis can be visualized on single image. In those dynamic changes of the object of interest. Moreover, fetal
situations, 3D imaging offers plastic reconstruction of movements were significant source of image artifacts. There
fetal external anatomy (surface rendering) that enables to were requirements to produce technique which will enable
the parents to see and understand fetal condition quickly, possibility of performing 3D imaging in a real time mode.
totaly and easily. This facilitates parental decision on fetal This technique can also be called live 3D ultrasound or
future and necessity for pregnancy termination. On the other 4D ultrasound, as coined by a manufacturer, because time
hand, in parents who faced with polymalformed fetus in becomes a parameter within the 3D imaging sequence.
previous pregnancy, confirmation of normal fetal anatomy Four-dimensional sonography is characterized by spatial
in subsequent pregnancy with plastic comprehensive image visualization in almost real time. From technical point of
as direct proof results in parents’ tension relief. view, this visualization is based on the continuous data
Despite 3D images are more informative than 2D, acquisition by volume scanning with generating of surface
its application is still limited due to its disadvantages. spatial image. Modern machines are capable of the 20
Disadvantages include: long processing period needed for volume scans in second associated with surface rendering
image generation and necessity of movement absence during and image display at frame rate of 12 images in second.
scanning period. Because of that 3D technology was very Such presented images create movie. In contrast to the 3D
time-consuming and not suitable for everyday routine work. sonography, 4D sonography is characterized by continuous
volume scanning with creation of surface rendered image, fetal movements. The only limiting factor for 4D sonography
whereas 3D US is characterized by single volume scanning. is quantity of adjacent amniotic fluid.
Implementation of this new technology is still challenging The acquisition of volume datasets is performed by 2D
for perintologist. At present, it has been recognized scans with special transducers (linear, convex, transvaginal)
that benefits of new technology can be achieved in the designed for 2D scans, 3D and real time 4D volumes (Fig.
evaluation of fetal heart, fetal behavior and in invasive 40.2).2 Realtime 4D mode is obtained from simultaneous
procedures. volume acquisition and computing of 3D images. At this
Understanding of technical aspects of 4D US is important time, it is possible to speak of multidimensional ultrasound
for proper using of 4D and for obtaining its full potential. (Fig. 40.3).3 The movement of the ultrasound beam over
In this chapter authors systematically present the most the region of interest (ROI) is automatic. Such design
important technical details needed for performing 4D enables simplified 3D and 4D acquisitions. Ultrasound
sonography. probes include scanning mechanism moved by built-in
electromotor. Processing speed allows continuous acquisition
and processing of 4D volumes. Special endocavitary and
Technicalities transvaginal probes supports also working in Doppler
Four-dimensional Imaging modes and harmonic imaging. Supported applications are
Rapid development of digital ultrasound systems allows 3D in Gynecology, Obstetrics, Fetal Cardio and Urology.
image reconstructions and lately 4D real time inspection
of anatomical regions and pathological changes. Three- Starting a Four-dimensional Mode
dimensional images are static and do not provide information The volume acquisition begins with a 2D image and
of movements and dynamic changes of the object of superimposed volume box. The start 2D image is the central
interest1 (Fig. 40.1). Moreover, fetal movements are the 2D image of the volume. According to dimensions of the
source of significant artifacts, and volume scanning should volume box, volume scan sweeps between the margins
be performed during fetal inactive phase. Stated in other of the volume box. The volume box is set to frame ROI.
words, whenever fetus is active, qualitative 3D image is During the 3D and 4D acquisition, sweep time depends
unobtainable. This fact limits usage of classic 3D ultrasound. on the volume box size, scan quality and adjusted scan
Four-dimensional overcomes above-mentioned disadvantage, parameters such as depth, number of focuses and other
making possible to obtain qualitative 3D image regardless of parameters which affect B-mode image frame rate.
Figure 40.1 Difference between 2D and 4D real-time sonography. Fetal 4D image of pregnancy 14 weeks old. The advantages of surface rendered
over 2D image include higher informativity concerning fetal surface anatomy and spatial relationships between parts of fetal bodies. Information about
facial details, ear, hands, leg and positional relations between these extremities, body and umbilical cord can be obtained from single surface rendered
image. Furthermore, generation of real-time surface rendered reconstruction (4D real-time sonography) is capable of visualization of fetal movements
in three-dimensions. Observation of movements visualized on such way is much more informative than 2D real-time sonography
Chapter 40  Four-dimensional Technical Aspects 445
and Doppler gain are important. All 2D image artifacts will
be also present on 3D and 4D image reconstruction.
Good 4D image acquisition depends on the following
important points: ROI size and volume box size, ROI
position or direction of view and accessibility to the
object. The render box determines the contents that will be
rendered. Structures that are not selected by volume box
will be cut from 3D reconstruction.
Region of interest can be sized, moved and rotated in
all directions arbitrary by operator. Volume data can be
acquired from different 2D modes: grayscale imaging,
CFI and power Doppler imaging. There are different
rendering modes available: surface, transparent (maximum,
minimum, X-ray) and light, some of them can be active
Figure 40.2 Surface rendered image of intertwin contact provides an simultaneously in real time.
examiner with information about intertwin contacts. Unfortunately, due
to static nature of this mode, intertwin dynamics cannot be observed. Volume rendering is a process of visualizing 3D
For this purpose, 4D sonography is the method of choice structures on animated 2D screen. Render modes determine
how 3D image will be presented on screen.
ÀÀ Orientation in real-time 2D mode
ÀÀ Selection of region of interest Surface Rendering or Grayscale Rendering
ÀÀ Starting the volume scan. Volume data are shown in a In the surface rendering mode, only signals from the
multiplan display on the monitor (transverse, sagittal surface of ROI are extracted and displayed in the plastic
and coronal). appearance. Surface rendering examination of fetus focuses
sonographer’s attention exclusively on fetal external
Three-dimensional and Four-dimensional anatomy. This mode is capable of clear visualization of
Rendering fetal normal surface anatomy or surface anomalies such as
Pixel is the smallest element of 2D images while voxel encephalocele, spina bifida, cleft lip/palate and abdominal
is the smallest information unit in 3D and 4D imaging. wall and limb defects. Furthermore, visualizing spatial
Volume rendering provides visualization of animated voxel- relationship between surface structures enables accurate
based images on 2D screen. Thanks to instant computer diagnosis of subtle malformations and anomalies such
technology development and fast data transmission, volume as micrognathia, overlapping fingers, hexadactilia and
acquisition and data processing are accelerated to enable 3D auricular malposition or malformation.
rendering in real time (4D). Fast volume data processing Surface rendering gives best result when ROI structures
enables calculation of 5−30 volumes per second depending are surrounded by fluid or hypoechoic tissue. Selecting
on the system hardware and size of the render box. As 4D the threshold level, voxels with gray values below the
imaging is not really a real time, there is always some delay threshold value selected are not shown on reconstructed
as a result of time needed to reconstruct 3D image from 2D image. Selecting threshold parameter influences quality of
scans. It is always desirable to achieve as many volumes surface rendered image.
per second (volume rate) as possible. Number of volumes Surface image can be displayed in “textural” mode. The
per second is some kind of trade between image quality gray values can be colored by different color maps, but
and frame rate. Three-dimensional and four-dimensional most successful map for 3D/4D image is “body heat” map.
image quality mostly depends on 2D image quality. Prior to Texture mode can also be “smoothed”, showing smooth
volume acquisition, it is important to achieve best 2D image surfaces on 3D/4D reconstructions. Texture and smooth
quality, adjusting: depth, focus position and number of surface display are suitable for use in applications like: fetal
focuses, frequency and gain. Using CFI and power Doppler face, abdominal wall, genitals, umbilical cord, surfaces of
imaging adjusting velocity (PRF), wall filter, persistence urinary bladder (Figs 40.4 to 40.6).4-6
Figure 40.3 Four-dimensional image showing

all three planes and reconstructed 3D image of
fetal 26 weeks old pregnancy. Figure illustrates
limitation of modern sonography. Visualization
of total fetal body on single image is impossible
in advanced pregnancy (after 17 weeks of
pregnancy). Four-dimensional sonography
enables real-time observation of mulitplanar view
and surface rendered image fetal body parts
(face). Real time surface rendered imaging of
fetal face is superior than multiplanar, because it
allows assessment of integrity of neuromuscular
functions by observation of fetal mimics eyelid
movements
reconstruction of internal structure of ROI. According to

echogenicity of extracted signals there are two submodalities:
(i) maximum and (ii) minimum modes. In maximum mode only
the signals of highest echogenicity, whereas in minimum mode
only the signals of lowest echogenicity are extracted from the
entire volume. In transparent mode only maximum gray values
are displayed. This mode is suitable for visualization of fetal
bones, endometrium and breast.
Minimum Mode
Minimum gray values are displayed for visualization of
vessels, cystic structures and parenchyma of different
organs in Figure 40.8.8
Maximum Mode
Figure 40.4 Surface rendering in texture mode (32 weeks of pregnancy).
Texture surface display is suitable for recognition of small elevations or
Maximum gray values are displayed. Maximum mode
depressions on fetal skin. This type of surface display is recommended is suitable for visualization of fetal bone structures
for observation of facial expressions and subtle mimic activities (Fig. 40.9).9 It is the method of choice for imaging of
the spatial relationships between bones. Moreover, this
Surface can be displayed in “light” mode. modality offers an option of complete visualization of
Closer structures are brighter while distant structures are curved bones such as ribs or clavicle on single image.
displayed darker. Evaluation of complete skeleton, particularly thoracic
Variation of the light mode is “gradient light mode” showing skeleton in the developing fetuses often is difficult with
virtual illumination from spot light source (Fig. 40.7).7 2D US because of curvature of the bones. Ribs can be
completely observed using the 3D US transparency mode.
Transparent Mode This modality reduces the echogenicity of soft tissues,
In transparent mode, contrary to surface mode, only the signals leaving behind echogenic structures, namely the bones. The
from the inner layers of ROI are extracted providing spatial curvature and relationship of the rib ends to the vertebral
Figure 40.5 Multiplanar and surface rendered

reconstruction of head-to-head intertwin contact
in monochorionic-monoamniotic twin pregnancy.
Surface rendered image is capable of providing
information about the exact topography of the body
parts that were in contact (cheek to parietal contact)
and facial expression. If one compares these
visualization modalities regarding the informativity
of surface rendered reconstruction surpasses all
our expectations
Figure 40.6 Enlarged surface rendered image of head-to-head contact Figure 40.7 The surface rendered image can be presented on several
in monochorionic-monoamniotic twin pregnancy. This option allows to ways. This mode is called light gradient mode and used very often
concentrate examiner attention on facial expressions and intertwin area.
Therefore, it is suitable for behavioral studies in multiple pregnancy
bodies and the anterior chest wall can be demonstrated as malformations of fetal spine can be identified easier
well as the entire length. using 3D surface and transparent mode reconstruction
The vertebral column is originally curved anter together. Specific vertebral body level may be accurately
oposteriorly. If it is pathologically curved laterally, it is identified by simultaneous evaluating of axial planes of
impossible to display the whole vertebral column in single the spine within the volume rendered image. It is difficult
sectional image by 2D US. The advantage of 3D ultrasound to acquire the entire spine in a single volume and thus
is the ability to visualize both curvatures at the same time. multiple volumes are often necessary to evaluate the spine
Anomalies such as scoliosis, kyphosis, lordosis and spina completely.
bifida may be overlooked by 2D ultrasound, but are easy Extremities consist of three parts: (i) proximal, (ii)
to recognize by using 3D maximum mode. Congenital medial and (iii) distal. With this mode, all three segments
Figure 40.8 Minimum mode provides spatial visualization of soft Figure 40.9 Tree-dimensional transparent reconstruction of fetal
tissues such as liver. On this image, liver veins can be recognized skeletal system in monochorionic-monoamniotic twin pregnancy
and spatial relationships between them could be analyzed Complex anatomy of bone elements is confirmed on
in three dimensions. Therefore, the deviation of normal transparent mode image.
anatomical axis, such as pathological angulations of hands
and foots, can be excluded by 3D US examination.9 Volume Contrast Imaging (VCI)
Three-dimensional analysis of fetal extremities can be Using 4D it is possible to make high contrast 2D images.
performed in two modes. If one interests spatial relationship The render algorithm is a combination of surface texture
between segments of fetal extremity, then surface rendering mode and minimum transparency 4D mode. It is possible
mode should be used (Fig. 40.10A). However, if in the to display couple of millimeters thin volume slice showing
focus of interests is relationship between bone elements very good contrast between different tissues. User can
of fetal extremity, then transparent mode should be used define thickness of slice that is scanned using 4D image
(Fig. 40.10B). By combination of these two modalities, rendering. Reconstructed image is showing improved
more detailed analysis of fetal anatomy can be performed. tissue contrast. The VCI is used for better visualization of
This illustrates that fetal skin, subcutaneous tissue and nodular or diffuse lesions in parenchyma of organs such as
bone structures can be evaluated. As fingers are clearly liver and spleen.
visible in the surface mode, this technique is very useful in
demonstrating the normal morphology of these structures Spatiotemporal Image Correlation (STIC), Fetal
(Fig. 40.11). Cardio Mode
Spatial relations between medial and distal segment of
The STIC is a new method in fetal heart investigation.
fetal leg can be assessed on surface rendering mode. Normal
Reconstructed volume scan can be presented on screen in
anatomical axis and her deviations can be confirmed. The
slow motion. Four-dimensional data of one heart cycle can
number and position of toes are clearly demonstrated on
be analyzed in all three planes and rotated. The STIC is not
surface mode (Fig. 40.11). On such image toes can be
a real time 4D technique, but it is using the same technical
counted and also pathological angulations can be conformed
possibilities (Fig. 40.14).10
or excluded with higher confidence.
Using two modalities of the 3D ultrasound step by
step we can evaluate fetal foot from external appearance
Removing Overlaying Structures
to complex bone inner and intratopographic relations This option is called Magic-cut or the electronic scalpel.
(Fig. 40.12). Surface of the skin and the external spatial During 3D and 4D scanning, in most cases there are
relations are shown on surface rendering image (Fig. 40.13). structures that are interfering or are superimposed to the
A B
Figures 40.10A and B (A) Normal fetal hand reconstructed in surface rendered mode; (B) Transparent mode reconstruction of the same hand
with clearly visible skeletal structures and soft tissue
Figure 40.11 Surface rendered mode reconstruction of fetal lower Figure 40.12 Surface rendered fetal foot in plantar projection
legs. Normal anatomy and topographic relationships of lower legs are
clearly depicted
reconstructed image. Magic-cut tool enables successful Reduced study time, faster examination procedure, and
removal of overlaying structures using 3D imaging. increased perspective from volume data provide better
Unwanted structures can be cut off from the image in all qualitative and quantitative information about selected area.
three directions along x, y, z axes. Lately, there is also a
possibility of using this tool to remove some structures Applications and Advantages of 4D Ultrasound
from real time 4D volumes. The cutting tool enables the Obstetrics:
operator to have improved visibility to the object from all ÀÀ Fetal morphology, malformation, agenesis
directions (Fig. 40.15).11 ÀÀ Bone shape abnormalities: Spina bifida, dwarfism, cleft
palate, cleft lip
Advantages and Possibilities of 4D and ÀÀ Skeletal dysplasia
3D Imaging ÀÀ Fetal heart: Better correlation between valves, chambers
Three-dimensional and four-dimensional ultrasound as and vessels; volume calculation of heart cavities; atrial
new methods in ultrasound diagnostic have numerous and ventricular communication; assessment of valvular
advantages in comparison to classical grayscale imaging.12 function
ÀÀ Diagnose fetal heart defects in utero and prepare

conditions for later treatment.
Gynecology:
ÀÀ Exact volume measurement of endometrial hyperplasia
(3D/4D)
ÀÀ Virtual hysteroscopy (3D/4D), using slicing technique
ÀÀ Exact volume measurement of cysts (postmenopausal),
polyps, myoma or fibroma
ÀÀ Exact localization and measurement of ovarian and
endometrial tumors
ÀÀ Gynecological tumor monitoring after treatment
(chemotherapy)
ÀÀ Contrast media use to check tumor vascularization and
blood supply
Figure 40.13 Changing to transparent mode normal skeletal structure ÀÀ Gynecological contrast media for tumor follow-up (4D)
and soft tissue are visualized ÀÀ Placental abnormalities (placenta previa).
Breast and small parts:

ÀÀ Variety of fetal volume evaluation: Urinary bladder, ÀÀ Four-dimensional biopsy in all three planes, exact
stomach, cyst placement of the needle
ÀÀ Fetal biopsy: Umbilical blood sampling punctures with ÀÀ Breast tumor volume evaluation
precision, amniocentesis, kidney dilatation, uropathy ÀÀ Breast tumor treatment monitoring (chemotherapy)
ÀÀ Fetal movement and mimic: Normal and abnormal fetal ÀÀ Skin tumor infiltration evaluation
gestures; evaluation of fetal sleep and awakening, hand ÀÀ Contrast media use on breast tumors (4D)
and feet motion, eyelid, limbs and mouth motion ÀÀ Sectual planes to define margins of different tumors.
ÀÀ Fetal neuromyopathy genetic diseases: Fetal reactivity/
Urology:
tonicity
ÀÀ Four-dimensional biopsy
ÀÀ Cord insertion using power-Doppler and 3D
ÀÀ Needle visualization in all three planes
ÀÀ Frontal bones. ÀÀ Evaluation of the prostate parenchyma due to addition
STIC and fetal cardio: of coronal plane
ÀÀ Fast, efficient assessment ÀÀ Prostate and urinary bladder volume measurement and
ÀÀ Information acquired can be stored allowing processing

prostatic or bladder tumors
ÀÀ Correct positioning of urinary catheter
of reproducible views
ÀÀ Exact assessment of the post-micturitional residue.
ÀÀ Simultaneous visualization of 2−3 planes: Easier for
obstetrician to learn spatial orientation of fetal heart Internal medicine:
ÀÀ Better correlation between valves, chambers and vessels ÀÀ Precise evaluation of acute abdominal syndrome
ÀÀ Four-dimensional biopsy (liver, kidney)
ÀÀ Volume calculation of heart cavities
ÀÀ Excellent evaluation of parenchyma/tumor volumes
ÀÀ Better access to heart pathology: Left ventricular and
ÀÀ Lithiasis localization in the urethra during renal colic
right ventricular outflow tracts; opening and closing of (3D, C-plane)
the foramen ovale ÀÀ Contrast media use in abdominal tumor (kidney, liver)
ÀÀ Atrial and ventricular communication: Ventricular wall ÀÀ Evaluation of cholecystitis
can be seen in relation to the chambers or cutaway the top ÀÀ Abdominal tumor volume follow-up and monitoring
of the atria and look into the ventricles using Magic-cut in 3D
tool or analyze septum alone ÀÀ Tumor location and vascularization during chemotherapy
ÀÀ VSD and relation to pulmonary artery ÀÀ Obstruction determination in icterus mechanism.
Figure 40.14 Fetal heart using fetal cardio mode
it is possible to review the saved examinations without

any loss of image quality. Stored data can be interactively
processed with additional 3D reconstruction possibility. The
3D and 4D provides additional aspects to conventional 2D
sonography. The main advantage of ultrasound in general
is dynamic imaging of human body. The 4D imaging is
following this tradition pointing dynamic changes inside
body and organs. Using 4D ultrasound in obstetrics, it is
possible for the first time to monitor quality and quantity
of fetal movements on 3D real-time reconstructed images.
Conclusion
Understanding technical aspects of 4D US is important either for
proper using of 4D or for obtaining its full potential. Furthermore,
image post processing should be considered as a part of
examination. Sometimes, additional information about ROI can be
Figure 40.15 Omphalocele 3D, 13 weeks’ old fetus. Magic cut tools provided with post processing.
used for better visualization of fetal malformation Undoubtedly, 4D US is the technology of future whose potential
still needs to be discovered and evaluated. For proper evaluation of
Pediatrics: benefits of 4D sonography, full range of its options should be used.
ÀÀ Neonatal brain, 3-plane view of chamber symmetry; The knowledge of basics and principles 3D US is precondition for
successful application of 4D US, because 4D US is based on 3D
volume measurements imaging. In contrast to the classic 2D imaging, after 3D image is
ÀÀ Color or power-angio vessel correlation obtained it can be processed in order to improve image quality and
ÀÀ Hip measurement. to obtain additional information. Postprocessing includes rotation of
surface rendered image and magic cut.
Data Review and Networking

Volume data sequences can be stored on hard disk of
References
ultrasound unit or at different media (CD-R, MO) in various 1. Kurjak A, Azumendi G, Vecek N, et al. Fetal hand
formats: 2D image, 2D cine (selected sequence of 2D movements and facial expression in normal pregnancy
images), 3D volume (sequence of 3D rotating images) and studied by four-dimensional sonography. J Perinat Med.
4D volume. Since the complete volume data set is saved, 2003;31(6):496-508.
2. Hu W, Wu MT, Liu CP, et al. Left ventricular 4D 8. Mangione R, Lacombe D, Carles D, et al. Craniofacial
echocardiogram motion and shape analysis. Ultrasonics dysmorphology and three-dimensional ultrasound: a
2002;40(1-8):949-54. prospective study on practicability for prenatal diagnosis.
3. Kossoff G. Basic physics and imaging characteristics of Prenat Diagn. 2003;23(10):810-8.
ultrasound. World J Surg. 2000;24(2):134-42. 9. Kurjak A, Hafner T, Kos M, et al. Three-dimensional
sonography in prenatal diagnosis: a luxury or a necessity?
4. Timor-Tritsch IE, Platt LD. Three-dimensional ultrasound
J Pernatal Med. 2000;28(1):194-209.
experience in obstetrics. Curr Opin Obstet Gynecol. 10. De Vore GR, Falkensammer P, Sklansky MS, et al. Spatio-
2002;14(6):569-75. temporal image correlation (STIC): new technology for
5. Lee W. 3D fetal ultrasonography. Clin Obstet Gynecol. evaluation of the fetal heart. Ultrasound Obstet Gynecol.
2003;46(4):850-67. 2003;22(4):380-7.
6. Arzt W, Tulzer G, Aigner M. Realtime 3D sonography of 11. Vinals F, Poblete P, Giuliano A. Spatio-temporal image
correlation (STIC): a new tool for the prenatal screening
the normal fetal heart—clinical evaluation. Ultraschall Med.
of congenital heart defects. Ultrasound Obstet Gynecol.
2002;23(6):388-91.
2003;22(4):388-94.
7. Yanagihara T, Hata T. Three-dimensional sonographic 12. Kurjak A, Vecek N, Hafner T, et al. Prenatal diagnosis:
visualization of fetal skeleton in the second trimester of what does four-dimensional ultrasound add? J Perinat Med.
pregnancy. Gynecol Obstet Invest. 2000;49(1):12-6. 2002;30(1):57-62.
CHAPTER
41 Fetal Upper Limb Movement in the

First Half of Pregnancy Detected by
Transvaginal 4D Ultrasound
Ritsuko K Pooh, Tomoko Ogura
Introduction repeated, resulting in a “somersault” that enabled the fetus

to change position within the uterine cavity and that in
After introduction of high frequency transvaginal contrast, during later gestational periods, the fetuses hands
transducer, morphological natural history of normal and were directed to and manipulated body parts and features
abnormal structure has been comprehensively clarified, of the environment, such as the umbilical cord. Thus, later
and “sonoembryology, embryology in vivo” have been in pregnancy, the hands exhibited manipulative capability
established. There still exist, however, unknown facts in and suggested “intentionality”.4 In 1999, the same author
a field of fetal behavior. Fetal movements may deeply observed longitudinally fetuses from 14 weeks till neonatal
relate to embryological and fetal development in utero of stage.5 This resulted that fetal and neonatal movements did
skeletal, muscular and nervous system. Recent advance of not appear to be random and appeared to be directed or
three-dimensional (3D)/four-dimensional (4D) ultrasound aimed at specific targets and that fetal movements to or at
has clearly demonstrated details of fetal movement. In this the head and face and the observations scored at 32 weeks
article, detailed fetal hand/finger positioning and movement of gestation were the best predictors of neonatal movement.
before 16 weeks are described. The 3D ultrasound study of normal and abnormal fetal
hand was reported by Budorick et al. 6 in 1998. They
Ultrasound Approach to described 3D provided additional information to two-
dimensional (2D) data, including the provision of three
Fetal Movement orthogonal planes with one volume acquisition, allowing
Approaches to fetal movement by real-time ultrasound rotation of the volume so that hands could be evaluated in
studies have been reported so far. de Vries et al.1 focused planes, assessment of a hand with loosely curled fingers
on fetal movement in the first half of pregnancy. They as normal, the ability to evaluate thumb and fingers
described the rate of occurrence of all fetal movement simultaneously, and improved assessment of abnormal
patterns emerging. Roodenburg et al.2 investigated the hands. After introduction of real-time 4D ultrasound, it
second half of pregnancy. Sparling et al. 3 described has been expected that this amazing technology would
spontaneous movements in fetuses from 12 to 35 weeks contribute much to an evaluation and assessment of fetal
of gestation and recorded the characteristics of hand behavior. In 2002, Kurjak et al.7 described the developing
movement. Many movements appeared to be directed to pattern of hand movement by 4D ultrasound technology
a body part or the uterine wall. The hands of the fetuses and concluded that 4D ultrasound enables visualization of
moved with a variety of frequencies and apparent force. more details of the dynamics of small anatomical structures
Joint ranges of motion changed throughout the movements and that body and limb movements can be visualized a
rather than remaining the same, as in floating. These week earlier than with 2D. Kurjak et al. also examined
movements suggested primary and secondary circular normal fetal hand movements and facial expression by
reactions in which a movement is repeated, presumably 4D ultrasound8 and described that 4D ultrasound made it
because it has functional importance to the organism. possible to determine exactly the direction of the fetal hand,
Sparling3 also described that early in fetal development, but the exact number of each type of hand movements
quick, progressively larger head flexion movements were could still not be determined.
Normal Fetal Hand and Finger 15 weeks (Fig. 41.5). After 13 weeks, number of clenching
and unclenching fists increased and this movement seemed
Positioning and Movement in Early to be often observed. Independent movement of each finger
Pregnancy by 3D/4D Technology is occasionally seen from 13 or 14 weeks of gestation
(Figs 41.6 and 41.7). From 13 weeks, hand/finger movements
Authors have examined 65 normal fetuses by 3D/4D
appeared to increase activity and strength.
ultrasound to investigate natural course of fetal hand and
finger position. Authors used Voluson 730 Expert (GE
Medical systems, Milwaukee, USA) with transvaginal Abnormal Positioning and
3D/4D transducer. All of saved 4D image datasets were Contracture of Fetal Hand/Fingers
reviewed and detailed movements of fetal hand and fingers
Limb deformity and abnormal hand/finger positioning
were evaluated by volume cine data. Furthermore, each
are known to be associated with chromosomal aberration
appearance of fingers, thumb and wrist was confirmed by
viewing on three orthogonal planes. From authors’ data, at
9 weeks and the beginning of 10 weeks, fetal hands were
located in front of the chest and no movements of wrists
and fingers are visualized (Fig. 41.1). Fetal digits including
thumbs are located on the same layer at this stage. From
the middle of 10 weeks of gestation, active arm movements
associated with active body and lower limb movement
(Fig. 41.2). Despite active movements of glenohumeral and
elbow joints at this stage, wrist and finger movements were
not visualized in most cases. In 11 weeks, change of finger
positioning was seen. At this stage, all cases still open their
palms, but five digits are no more on the same layer. Mild
adduction of the thumb and atonic fingers were observed
and the palm appearance was clearly different from that in 9
and 10 weeks (Fig. 41.3). At 12 weeks of gestation, fetuses
start to clench and unclench their fists (Fig. 41.4), but fist at Figure 41.1 Fetus at 9 weeks: fetal hands are located in front of the
12 weeks seem to be mild compared with that observed at chest and no movements of wrists and fingers are visualized
Figure 41.2 Fetal movement at 10 weeks and 6 days: active arm movements associated with active body and lower limb movement. Despite
active movements of glenohumeral and elbow joints at this stage, wrist and finger movements were not visualized in most cases
Chapter 41  Fetal Upper Limb Movement in the First Half of Pregnancy Detected by Transvaginal 4D Ultrasound 455
Figure 41.3 Fetus at 11 weeks: fetus at 11 weeks still opens the palms Figure 41.4 Fetus at 12 weeks: at this stage, fetuses start to clench
but five digits are no more on the same layer. Mild adduction of the and unclench their fists
thumb and atonic fingers were observed and the palm appearance
was clearly different from that in 9 and 10 weeks
Figure 41.5 Comparison of clenched fist between 12 (upper) and 15 weeks (lower). Fist at
12 weeks seem to be mild compared with that observed at 15 weeks
and/or syndromic diseases. Paluda et al.9 evaluated the of the tendons of extensor digitorum and digiti minimi, with
relationship of the fetal hand to the forearm in second- overlapping of the fourth and fifth fingers radially and
and third-trimester by 2D ultrasound and described that index finger in an ulnar direction. However, it has not been
an abnormal fetal wrist position is associated with a high clarified when and how fetal fingers are flexed, overlapped
incidence of karyotype and movement abnormalities. Kos et and contracted. Quintero et al.11 performed transabdominal
al.10 reported 3D detection of limb deformity. Overlapping thin-gauge fetoscopy at 12 and 14 gestational weeks in
finger is well-known hand deformity often observed in a case of trisomy 18. They described finger malposition
cases of trisomy 18. Overlapping finger is formed due to was not apparent at 12 weeks, but evident at 14 weeks and
muscle variations along the radial margin of forearm and concluded that malpositioning of the fingers in trisomy 18
hand, absence of the thenar muscles, anomalous tendons occurs sometime between 12 and 14 weeks of gestation.
and attachments and fusions among the arm/forearm flexor Figure 41.8 shows 2D image at 11 weeks, 3D images at
group. These variations result in radial or ulnar displacement 12 and 17 weeks in authors’ case of trisomy 18. Normal
extended fingers were demonstrated at 11 weeks. Clenched
fist without overlapping fingers were depicted at 12 weeks
and overlapping fingers were clearly detected at 17 weeks
of gestation. From both Quintero’s case and authors’ case,
it is suggested that overlapping of fingers may not occur
before 13 weeks of gestation. However, authors had another
interesting case of trisomy 18 with left wrist malposition. In
this case, on referral due to nuchal translucency at 11 weeks,
abnormal left hand appearance was demonstrated and wrist
malposition already formed was strongly suspected. Serial
3D/4D ultrasound examination confirmed wrist malposition
before amniocentesis at 16 weeks (Fig. 41.9). This case had
an abnormal palmar flexion instead of overlapping fingers.
From this case, it is indicated that there may be different
mechanism associated with other muscular and tendon
variation to cause abnormal palmar/wrist flexion in earlier
Figure 41.6 Independent finger positioning at 14 weeks: from 13 or 14
weeks, in addition to clenching and unclenching, independent finger
stage from abnormal digital flexion such as overlapping
movement and positioning can be seen fingers.
Figure 41.7 Independent finger movement at 14 weeks: independent movement of each finger is occasionally seen from 13 or 14 weeks of gestation
Chapter 41  Fetal Upper Limb Movement in the First Half of Pregnancy Detected by Transvaginal 4D Ultrasound 457
Figure 41.8 Intrauterine course of overlapping fingers in a case of trisomy 18: two-dimensional image at 11 weeks (left), 3D images at 12 (middle)
and 17 weeks (right). Normal extended fingers were demonstrated at 11 weeks. Clenched fist without overlapping fingers were depicted at 12
weeks and overlapping fingers were clearly detected at 17 weeks of gestation
Acknowledgments
Authors would like to express their great appreciation
to GE Medical Systems (Milwaukee, USA) and
Kretztechnik (Zipf, Austria) for their technical support in
3D/4D ultrasound technology and clinical collaborative
cooperation.
References
1. de Vries JI, Visser GHA, Prechtl HF. The emergence of
fetal behaviour, II: Quantitative aspects. Early Hum Dev.
1985;12(2):99-120.
Figure 41.9 Wrist malpositioning from 11 weeks in another case 2. Roodenburg PJ, Wladimiroff JW, van Es A, et al.
of trisomy 18: at 11 weeks (left), abnormal left hand appearance is
Classification and quantitative aspects of fetal movements
demonstrated and wrist malposition already formed was strongly
suspected. Right figure shows left wrist malpositioning at 16 weeks during the second half of normal pregnancy. Early Hum
Dev. 1991;25(1):19-35.
Conclusion
3. Sparling JW, Wilhelm IJ. Quantitative measurement of
Fetal sensorimotor development may detect behavioral patterns fetal movement: fetal-posture and movement assessment
characteristic of impairment. As described in this article, noninvasive (F-PAM). Physical and Occupational Therapy in Pediatrics.
technology of 3D/4D ultrasound provides an objective and precise
information of detailed fetal hand/finger positioning and movement 1993;12(2/3):97-114.
in utero from early pregnancy. It is expected to elucidate unknown 4. Butterworth G, Hopkins B. Hand-mouth coordination
natural history of normal and abnormal intrauterine behavior of
in the new-born baby. British Journal of Developmental
unborn infants. Further studies with qualitative and quantitative
approaches by 4D ultrasound will be necessary investigating the Psychology. 1988;6:303-14.
relationship between nervous system impairment and fetal behavior 5. Sparling JW, Van Tol J, Chescheir NC. Fetal and neonatal
such as postural positioning and detailed movement.
hand movement. Phys Ther. 1999;79(1):24-39.
6. Budorick NE, Pretorius DH, Johnson DD, et al. Three- 9. Paluda SM, Comstock CH, Kirk JS, et al. The significance
dimensional ultrasound examination of the fetal hands: normal of ultrasonographically diagnosed fetal wrist position
and abnormal. Ultrasound Obstet Gynecol. 1998;12(4):227-34. anomalies. Am J Obstet Gynecol. 1996;174(6):1834-7.
7. Kurjak A, Vecek N, Hafner T, et al. Prenatal diagnosis: 10. Kos M, Hafner T, Funduk-Kurjak B, et al. Limb deformities and
what does four-dimensional ultrasound add? J Perinat Med. three-dimensional ultrasound. J Perinat Med. 2002;30(1):40-7.
2002;30(1):57-62. 11. Quintero RA, Johnson MP, Mendoza G, et al. Ontogeny of
8. Kurjak A, Azumendi G, Vecek N, et al. Fetal hand movements clenched-hand development in trisomy 18 fetuses: a serial
and facial expression in normal pregnancy studied by four- transabdominal fetoscopic observation. Fetal Diagn Ther.
dimensional sonography. J Perinat Med. 2003;31(6):496-508. 1999;14(2):68-70.
CHAPTER
42 Advanced Sonographic Assessment of

Benign Endometrial Disease
Mladen Predanic
Introduction detection of hyperplasia is more common. During the

menopause, the morphological endometrial changes
Within the last three decades, a diagnostic ultrasound vary according to the number of years since menopause,
encountered rapid and extensive change. It came a long and usually endometrium atrophies unless woman is on
way from the static “dinosaurs” type of ultrasound scanners hormone replacement therapy. Numerous studies addressed
to amazing real-time three-dimensional (3D) sonographic the “appropriate” endometrial thickness in premenopause
machine. In addition, a color and pulsed Doppler modalities and menopause women. The most common endometrial
became almost a standard package of any ultrasound unit. thickness of less than 14–15 mm in premenopause and less
Therefore, the assessment of uterine cavity and endometrial than 5–8 mm in menopause (in the absence of hormone
characteristics evolved from solely measuring of endometrial substitution) has been quoted. Any endometrial thickness
thickness by two-dimensional (2D) sonography, to improved above these numbers requires further investigation.
visualization of the lesion, faster and more accurate
Endometrial hyperplasia is usually described as
volume quantification via 3D and four-dimensional (4D)
uniform, homogeneous and hyperechoic thickening of the
ultrasound. Even more, an application of color and pulsed
endometrium with the absence of uterine intracavitary line
Doppler modalities describe the tissue/lesion’s state of
(trilaminar appearance) by 2D conventional sonography.
“activity”, whereas 3D/4D power Doppler imaging render
Sometimes, non-homogeneous endometrial ultrasonic
“angiographic” images of the lesion’s vascularity.
appearance with subtle cystic changes can be noted. If that
The purpose of this chapter is to re-evaluate the role
the case, distinguishing between hyperplastic process from
of the ultrasound at present stage of technology in benign
large endometrial polyp, or possible malignant disease is
endometrial disease assessment. Our knowledge about
almost not possible. In addition, endometrial carcinoma
benign endometrial changes limited to endometrial
can develop as a localized and focal disease, in otherwise
hyperplasia, polyps and endometrial tamoxifen changes
normal endometrium, or as a diffuse process making
will be described through the conventional 2D or B-mode
detection and differentiation of endometrial disease even
endovaginal ultrasound, color/power and pulsed Doppler, as
more difficult (Figs 42.1 and 42.2).
well as 3D sonographic findings. Myometrial and cervical
lesions including submucosal fibroids, as well as malignant In comparison to 2D sonography, 3D ultrasound
endometrial lesions, and endometrial changes observed is capable of accurate and successful evaluation of
infertile and patients with pelvic inflammatory disease are endometrial volume.1 Endometrial volume was successfully
described elsewhere in this book. measured in 94% of patients and was determined as superior
to endometrial thickness alone due to lesser overlap in
results when compared between benign versus malignant
Endometrial Hyperplasia endometrial change. If endometrial cavity is distended
Endometrial hyperplasia is referred to abnormal thickening with isotonic solution via sonohysterography, a further
of the endometrium due to unopposed estrogen stimulation. endometrial morphologic evaluation is enabled due to clear
It is unusual to encounter this condition in premenopausal delimitation of endometrial surface. Three-dimensional
patients with regular menstrual cycles. In those patients rendering and volumetric studies permitted observation
with oligo- and amenorrhea, or, for example, obese patient of focal endometrial hyperplasia (polypoid endometria) in
with pattern of irregular and unovulatory uterine bleeding, comparison to normal proliferative endometria or a polyp.2
Figure 42.1 A sagittal scan through the uterus shows a thick Figure 42.2 Same patient as on Figure 42.1. A sonohysterography
endometrium (1.3 cm), presumed endometrial hyperplasia performed and installed intracavitary fluid separated by two equally
thick endometrial layers and no evidence of endometrial polyp(s)
An addition of color Doppler is of some benefit when pattern and moderate to high resistance to blood flow, that
thick endometrium is encountered. In 71 postmenopausal is highly suggestive to benign endometrial hyperplasia, at
women with thick endometeria no statistical difference the present time of ultrasound knowledge about endometrial
between endometrial benign hyperplasia and carcinoma disease a final diagnosis has to be done by histological
(16.2 ± 15.9 mm vs 18.7 ± 17.1 mm, respectively) examination of the endometrial tissue.
was observed.3 However, intratumoral blood flow was
detected by color Doppler in more than 70% of cases with Endometrial Polyps
endometrial cancer, whereas only in 5.6% of cases (1 out
of 18) with endometrial hyperplasia. These findings were in Endometrial polyps are solitary or multiple pedunculated
agreement with depicted endometrial vascularity by power tumors of the uterine cavity originating from the hyperplastic
Doppler showing poorly developed vascular network in endometrium. They are usually round or oval in shape
hyperplastic endometria when compared with malignant connected with the long, thin stalk or broad base to the
endometrial change (12.2% vs 81.2%, respectively). 4 uterine wall. Clinical significance of the endometrial
Vascularity pattern in hyperplastic endometria is usually polyps is in common cause of the intermenstrual or
demonstrated as sparse peripheral vessel distribution mainly excessive bleeding in premenopausal women as well as
localized to the basal endometrial layer5 (Fig. 42.3). An in postmenopausal patients. Although the golden standard
assessment of impedance to blood flow in endometrial in evaluation of irregular and excessive uterine bleeding
vessels showed moderate vascular resistance in patients is endometrial biopsy or curettage, tissue sampling does
with endometrial hyperplasia with the mean resistance not commonly provide diagnosis because they are easily
index (RI) value of 0.66 ± 0.18.4 When vascular resistance missed if sampling is done blindly with Pipelle or curette.
in endometrial hyperplasia patients was compared to The only possibility to accurately diagnose these lesions
malignant endometrial disease, a statistically significant is via noninvasive (ultrasound) or invasive (hysteroscopy)
lower impedance to blood flow was observed in endometrial imaging techniques.
carcinoma.4,6 Other studies yielded opposite results claiming Two-dimensional gray-scale sonography describes
useless of pulsed Doppler evaluation of endometrial blood endometrial polyp as an oval structure; mainly
vessels in differentiation between benign versus malignant hyperechogenic when compared with surrounding
disease.7,8 Therefore, due to large overlap in blood flow proliferative endometrium; well delineated and usually
indices between endometrial lesions, a clinical significance homogenic in texture if smaller, or nonhomogenic with
of pulsed Doppler is dubious. Regardless of the ultrasonic cystic changes if larger in size (Fig. 42.4). Size of the
findings of a thick endometrium with subtle vascularity polyps ranges from minute ones to easily diagnosed
Chapter 42  Advanced Sonographic Assessment of Benign Endometrial Disease 461
Figure 42.3 A color Doppler superimposed over thick endometrium Figure 42.4 An endometrial polyp—oval structure with non-
demonstrates poor peripheral vascularity, typical for endometrial homogeneous echogenic structure filled with small cysts—a “Swiss
hyperplasia cheese” appearance
large intraluminal masses. However, neither the size intermingling between each other, but each one of them
of the polyps nor its ultrasound depicted morphologic would reach central part of the endometrium. This was
features (e.g. cystic changes) correlates with the polyp initially described as a “pedicle artery sign” that may
histologic type. Majority of the non-functional endometrial suggest the presence of solitary or multiple endometrial
polyps are present in postmenopausal patients, whereas polyps.9 In the study of 182 patients with histologically
proliferative and secretory polyps are mainly found in proved endometrial polyps, the presence of pedicle artery
premenopausal women. 7 There is significant overlap test achieved sensitivity for detection of polyps of 76.4%,
between non-functioning and functioning polyps, and in specificity of 95.3%, positive and negative predictive
addition, polyps with malignant changes are found at any values of 81.3% and 93.8%, respectively.9 Authors also
age and any polyp’s size. Therefore, once endometrial concluded that due to an overlap in results between other
polyp is diagnosed, a dilemma is created: to surgically endometrial pathology including submucosal fibroids and
remove or monitor polyp(s) via ultrasound every few endometrial polyps, a presence of “pedicle artery sign” is
months. To answer this dilemma, diagnosis of endometrial highly suggestive of any “focal” endometrial abnormality
polyps has to be differentiated with certainty from benign and requires further invasive investigation. In authors’ own
or malignant endometrial hyperplasia. If the endometrial sample of women with endometrial polyps subsequently
mass suggestive of polyp is poorly delineated from the confirmed with sonohysterography and histology, 41 out of
remaining endometrium (due to similar echogenicity 46 patients had positive “pedicle artery sign”. One-third of
or technical difficulties, e.g. myometrial shadowing), patients were premenopausal and two-thirds of patients were
2D sonography is unable to differentiate polyp(s) from postmenopausal. In the group of 41 polyps with observed
endometrial hyperplastic changes. Therefore, an additional pedicle artery, polyps were diagnosed as proliferative or
study is required to elucidate the origin of the lesion. Two secretory ones, whereas 5 polyps without pedicle artery
techniques that improve diagnostication of the endometrial sign were described as non-functional ones by histologic
polyp(s) are described—an addition of color/power examination and were found in postmenopausal patients.10 An
Doppler to conventional endovaginal sonography and arterial blood flow pattern of the endometrial polyp showed
sonohysterography. moderate resistance to blood flow: the mean RI value was
An application of color or power Doppler demonstrates 0.58 ± 0.2, range 0.34 – 0.78. Other studies also observed a
polyp’s “pedicle” or “stalk” vessels. These vessels are large range in RI values between different histologic types
easily visible at the base of the polyp, penetrating from of endometrial polyps. No statistical correlation between
the myometrium into the center of the polyp (Fig. 42.5). resistance to blood flow and the endometrial histopathology
Occasionally, more than one feeding vessels can be seen determined as functional (proliferative or secretory) or
Figure 42.5 A power Doppler demonstrates two clearly separated Figure 42.6 Same patient as on Figure 42.5. A sonohysterography
pedicle arteries piercing from the underlying myometrium into the performed and two large endometrial polyps noted. These findings
endometrial tissue. These findings suggest two separate endometrial correlated with the presence of two separated pedicle artery vessels
polyps noted previously by power Doppler
non-functional polyps, hyperplasia and endometrial cancer, into the uterine cavity, a benefit supersedes any risk
were reported.7 In contrast to this study, an evaluation of and complication that this procedure may cause. 12,13 A
806 patients with endometrial polyps showed lower RI in presence of intracavitary fluid makes sonohysterogram
38 polyps with atypia when compared to benign polyps.11 a perfect media for 3D/4D sonogram. There is some
The mean RI between both endometrial polyps with atypia benefit in volume calculation that is much easier to
and benign ones revealed no statistical significance; 0.46 perform with 3D sonogram. However, when compared
versus 0.48, respectively. However, in 35 out of 38 polyps to 2D sonography, a small difference but statistically not
with atypia versus 16 out of 768 benign polyps lower RI than significant one (p = 0.325) between 2D and 3D calculated
0.5 was noted. Although these findings were promising, at polyps’ volumes is noted; the mean 669.3 + 219.1 mm3
the present time, pulsed Doppler evaluation of the vascular (range 50–4,330 mm3) versus 626.8 + 226.3 mm3 (range
resistance in the endometrial polyps’ vascular network in 40–4,320 mm3), respectively.10 Nevertheless, it appears
relation to histologic type has a little of clinical significance that 3D sonohysterography has allowed the visualization of
due to large overlap in results. the entire uterine cavity, endometrial thickness and lesions
By contrast to pulsed Doppler, authors observed that more accurately than any other ultrasound technique such
color/power Doppler is very useful by demonstrating as transvaginal 2D conventional and sonohysterography,
a “pedicle artery sign” as previously described. On the color Doppler and hysteroscopy.2 When 3D rendering is
other hand, an absence of this sign is more confusing than applied to the evaluation of uterine cavity and endometrial
helpful because it causes an overlap in results between lesions during the sonohysterography in 36 patients with
endometrial non-functional polyps and endometrial postmenopausal bleeding, obtained ultrasound images
hyperplasia where vascularity is more diffused and mildly corresponded to those observed with hysteroscopy.2
pronounced at the endometrial basal layer. In those patients In summary, it appears that ultrasound at present time can
where ultrasonographic findings are still suspicious for accurately and noninvasively diagnose endometrial polyps
endometrial polyps, a sonohysterogram is a method of at the level that is comparable to diagnostic hysteroscopy.
choice to accurately diagnose these sessile lesions. A presence of “pedicle artery sing” and sonohysterography
An injection of isotonic solution through the are major tools to differentiate endometrial polyp from
intracervically placed catheter separates uterine cavity and hyperplasia. Albeit, there are conflicting results in terms
creates a “window” around the pedunculated endometrial of categorizing the endometrial polyps as non-functional to
lesion if present. Any sessile endometrial mass becomes functional ones, as well as a predictive tool in detection of
clearly visible and easily measurable (Fig. 42.6). Although atypia within the polyp tissue by means of color and pulsed
sonohysterogram is invasive in terms of fluid injection Doppler evaluation.
Endometrial Changes in appearance of the endometrium in tamoxifen-treated patients
actually represents small, subendometrial sonolucencies in
Tamoxifen Patients the proximal myometrium, rather than intracavitary lesions.19
A hormonal treatment of the breast cancer is usually These findings were named “subendometrial cysts” or “cystic
directed to 5 years long use of a tamoxifen, a nonsteroidal stroma edema”. Therefore, sonohysterography became
selective estrogen receptor modulator with agonistic and an important adjunctive tool to differentiate honeycomb
antagonistic estrogen qualities. Although an antiestrogenic endometrial appearance as polyps versus abnormal
effect is obvious on a breast tissue, paradoxically, cystic endometrial-myometrial junction that is usually
tamoxifen acts as a weak estrogen on the endometrial atrophic lining.15 More revealing study about presence of
cells. It is administered in standard dosage of 20 mg/dL, “subendometrial cysts” and findings of atrophic endometria
and it was found to be associated with increased risk of evaluated hysterectomy specimens in 11 women undergoing
endometrial polyps, hyperplasia, and most important of tamoxifen treatment.20 The evaluation of specimens showed
all—endometrial carcinoma up to 2 – 3 folds.14 Endometrial that these cystic changes are not related to subendometrial
changes noted with tamoxifen use are usually related to region or myometrium, but rather represent atrophic basal
abnormal endometrial thickening with non-homogeneous endometrial layer with cystic changes named “endometrial
echogenicity and small cystic structures. This characteristic cystic atrophy”. An important notion was that endometrial
honeycomb appearance was found in 44% of patients on cystic atrophy could be diagnosed only on hysterectomy
tamoxifen, and was associated with high incidence of specimens (9 out of 11), whereas on hysteroscopy with
endometrial polyps, more than 40% of cases.15 Additional targeted biopsy would be diagnosed in 1 out of 24 patients.20
studies confirmed high prevalence of endometrial polyps It appears that tamoxifen produces endometrial changes
in tamoxifen patients.16,17 Although a large portion of these that are related to polyp(s) or endometrial cystic atrophy
cystic structures appear to represent endometrial polyps, in majority of the patients. Based on these findings,
some reports demonstrated much lower incidence of someone could speculate that vascularity patterns of such
polyps (18%) in tamoxifen patients.18 Regardless of the endometria will correspond to initial findings established by
incidence of the endometrial polyps, remaining 60–80% of 2D conventional and sonohysterography ultrasounds. For
thickened and cystic endometria are related to other type example, if endometrial polyp is encountered, presence of
of endometrial changes induced by tamoxifen (Fig. 42.7). “pedicle artery sign” will be found, or if cystic atrophy is
Use of sonohysterography established findings that observed, scanty or no vascularity by color/power Doppler
described this bizarre, heterogeneous ultrasonographic will be revealed. Indeed, initial reports revealed minimal
or no vascularity in tamoxifen patients that had cystic
changes but no polyps.18,21 Not only that vascularity was
almost absent in patient with endometrial cystic atrophy,
but also resistance to blood flow in those endometria where
it could be observed was higher than in placebo group.18
In 19 out of 61 patients with detectable endometrial blood
flow, the mean RI was 0.69 ± 0.16 versus 0.59 ± 0.04
in placebo group. These findings were contradicted by
another study that showed increased endometrial blood
perfusion with significant reduction of the RI compared
to untreated control menopausal women. 22 However,
reported endometrial RI in tamoxifen patients was 0.79
± 0.11, which is in agreement with previous studies,18,21
although statistically lower when compared to untreated
menopausal women (RI, 0.82 ± 0.02). Nevertheless, color/
Figure 42.7 A sonohysterogram of a tamoxifen patient. A large
intraluminar polyp is observed after installation of fluid. An absence
power and pulsed Doppler findings on vascularity of
of vascularity amiable to color Doppler correlates with non-functional cystically changed endometria in tamoxifen patients could
status of the polyp be summarized in Table 42.1.
Table 42.1 A summary of main ultrasonographic 2D conventional, color/power and pulsed Doppler features in relation to endometrial pathology
Endometrium 2D ultrasound Vascularity as per color Vascularity pattern Resistance to blood
or power Doppler flow
Atrophy Thin Absent None –
Hyperplasia Thick Minimal Scanty, peripheral High
Polyp(s) Thick, polyp “Pedicle artery sign” Mainly only stalk Moderate
confirmed by if functional or none vessels visualized
sonohysterogram if non-functional
Cancer Thick, irregular Abundant, intratumoral Diffuse Low to moderate
Tamoxifen Atrophy Absent None –
treatment Polyp “Pedicle artery sign” Polyp stalk Low to moderate
Cystic atrophy Absent None –
Finally, 3D/4D ultrasonography can better visualize endometrium using a “power” angio-Doppler technique.
uterine cavity and endometrial changes in tamoxifen Eur J Gynaecol Oncol. 2000;21(4):405-7.
patients too. Using the multiplanar views and 3D rendering, 5. Kurjak A, Shalan H, Sosic A, et al. Endometrial carcinoma
polypoid structures were clearly demonstrated.2 However, in postmenopausal women: evaluation by transvaginal
color Doppler ultrasonography. Am J Obstet Gynecol.
3D rendering is significantly improved if performed in 1993;169(6):1597-603.
association with sonohysterography that clearly delineates
6. Allem F, Predanic M, Calame R, et al. Transvaginal color
intracavitary mass, therefore, enhancing visualization of and pulsed Doppler sonography of the endometrium: a
any sessile polypoid structure in comparison to endometrial possible role in reducing the number of dilatation and
cystic atrophy changes. curettage procedures. J Ultrasound Med. 1995;14(2):139-45.
7. Goldstein SR, Monteagudo A, Popiolek D, et al. Evaluation of
Conclusion endometrial polyps. Am J Obstet Gynecol. 2002;186(4):669-74.
In conclusion, 2D conventional endovaginal sonography, in 8. Arslan M, Erdem A, Erdem M, et al. Transvaginal color
association with color/power and pulsed Doppler assessment
Doppler ultrasonography for prediction of pre-cancerous
and 3D/4D utilities when used with sonohysterography, establish
noninvasive diagnostic tool that will not replace a golden standard— endometrial lesions. Int J Gynaecol Obstet. 2003;80(3):299-
tissue evaluation via biopsy or curettage, but guide clinician when 306.
to perform an invasive diagnostic test. Therefore, its role becomes
9. Timmerman D, Verguts J, Konstantinovic ML, et al. The
clear as an enormous help to clinician to accurately diagnose,
prognosticate and counsel patient in relation to endometrial pedicle artery sign based on sonography with color Doppler
pathology. imaging can replace second-stage tests in women with
abnormal vaginal bleeding. Ultrasound Obstet Gynecol.
2003;22(2):166-71.
References
10. Predanic M. The accuracy of color Doppler ultrasound
1. Gruboeck K, Jurkovic D, Lawton F, et al. The diagnostic in detection of “pedicle artery sign”: as a novel modality
value of endometrial thickness and volume measurements
in detection of endometrial polyps: a comparison with
by three-dimensional ultrasound in patients with
sonohysterogram results. J Ultrasound Med (submitted for
postmenopausal bleeding. Ultrasound Obstet Gynecol.
1996;8(4):272-6. publication).
2. Bonilla-Musoles F, Raga F, Osborne NG, et al. Three- 11. Perez-Medina T, Bajo J, Huertas MA, et al. Predicting
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tumors: comparison with conventional transvaginal 2002;21(2):125-8.
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Gynecol Onscol. 1997;65(2):245-52. for evaluation of the endometrium in women treated with
3. Emoto M, Tamura R, Shirota K, et al. Clinical usefulness tamoxifen. Am J Roentgenol. 2001;177(2):337-42.
of color Doppler ultrasound in patients with endometrial 13. Turner RT, Berman AM, Topel HC. Improved demonstration
hyperplasia and carcinoma. Cancer. 2002;94(3):700-6. of endometrial polyps and submucous myomas using saline-
4. Szpurek D, Sajdak S, Moszyński R, et al. Estimation enhanced vaginal sonohysterography. J Am Assoc Gynecol
of neovascularisation in hyperplasia and carcinoma of Laparosc. 1995;2(4):421-5.
14. Bissett D, Davis JA, George WD. Gynaecological monitoring in a randomised breast cancer prevention trial. Lancet.
during tamoxifen therapy. Lancet. 1994;344(8932):1244. 1994;343(8909):1318-21.
15. Achiron R, Lipitz S, Sivan E, et al. Changes mimicking 19. Goldstein SR. Unusual ultrasonographic appearance of the
endometrial neoplasia in postmenopausal, tamoxifen-treated uterus in patients receiving tamoxifen. Am J Obstet Gynecol.
women with breast cancer: a transvaginal Doppler study. 1994;170(2):447-51.
Ultrasound Obstet Gynecol. 1995;6(2):116-20. 20. McGonigle KF, Shaw SL, Vasilev SA, et al. Abnormalities
16. Lahti E, Blanco G, Kauppila A, et al. Endometrial changes in detected on transvaginal ultrasonography in tamoxifen-
postmenopausal breast cancer patients receiving tamoxifen. treated postmenopausal breast cancer patients may
Obstet Gynecol. 1993;81(5 Pt 1):660-4. represent endometrial cyst atrophy. Am J Obstet Gynecol.
17. Exacoustos C, Zupi E, Cangi B, et al. Endometrial 1998;178(6):1145-50.
evaluation in postmenopausal breast cancer patients 21. Aleem FA, Predanic M. Endometrial changes in patients on
receiving tamoxifen: an ultrasound, color flow Doppler, tamoxifen. Lancet. 1995;346(8985):1292-3.
hysteroscopic and histological study. Ultrasound Obstet 22. Achiron R, Lipitz S, Frenkel Y, et al. Endometrial blood flow
Gynecol. 1995;6(6):435-42. response to estrogen replacement therapy and tamoxifen in
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Index
Page numbers followed by f refer to figure and t refer to table, respectively.
A Aliasing 336f Anteverted uterus 250f

Alpha angle 321 Anteverted uterus by transvaginal
Abdomen 34 Alterations of heart frequency 106 approach 8f
Abdominal Amniotic Anti-Müllerian hormone 232, 238
aorta 73 band syndrome 92f Antral follicle count 234, 238
circumference 131 cavity and stuck to uterine wall 41f in PCO and hormonal implications 238
wall defects 39 vesicle usually of yolk sac 104f Antral follicles on sono AVC 234f
Abnormal Anal Aortic
collagen biosynthesis 31 fistula 278 atresia 77, 78
course of pregnancy 109 incontinence 324 of gestation 82f
karyotypes of trisomy 61 levator muscle 274, 277f misalignment 80f
positioning and contracture of fetal papillae 277f reverse flow in three-vessels view 82f
hand 454 Analysis of fetal anatomy 397f stenosis 77, 78
uterine bleeding 250, 300 Anatomical data 367 Appearance of hemorrhoid plexuses 279f
venoatrial connections 77, 78 Anatomy of Aqueduct of sylvius 32
yolk sac 61 pelvic floor 272 Arachnoid cyst 97
Abnormalities of yolk sac development 49 pelvis minor 272 Arcuate
Absence or presence of nasal bone 55 Anencephaly 36, 37 and radial arteries blood flow 389
Abundant map color in tubal wall 296f and exencephaly 402 vessels 128
Accessories of transvaginal probe 5 Angio-Doppler survey of mictional flow Arnold-Chiari malformation 38
Accumulation of liquid in cavity 296f transurethral 284f Arrangement of follicles 238
Achondrogenesis 41 Angiogenesis in Arterial
Acquired brain benign ovarian tumors 378 and venous flow Doppler spectra 335f
abnormalities in utero 97 borderline tumors 380 organization in anal and rectal channels
damage in utero 86 malignant ovarian masses 380 278f
Acrania 37, 402 Angiomode of perifollicular vascularity Artifacts 340
Active follicle 232 207f Asherman’s syndrome 361
Acute Annual pelvic examination 312 Assessment by 3D transvaginal
appendicitis 296f Anomalies of echography 410
phase 289 gestational sac 106, 107 Assessment of
salpingitis 289, 291f heart frequency interpreted in function Fetal
Adenomyosis 182, 247, 360 of electrocardiogram 107 central nervous system 85
Advantages and limitations of yolk sac 106, 108 lung maturity 18
hystero-contast-salpingography 362t Anterior normal and abnormal ovaries by
magnetic resonance imaging in fontanelle 86 transvaginal sonography 415
urogynecology 325t fontanelle 87 placental vascularization by three-
Advantages of pelvic dimensional power Doppler
3D power Doppler imaging 437 area 272 ultrasound 125
multiplanar imaging in management of region 281 stromal abundance 239
multiple pregnancy 163t wall 316 Asymptomatic simple ovarian cyst in
ultrasound imaging in urogynecology vaginal fornix and cervix 10f postmenopausal women 218
325t Anterolateral fontanelle 87 Atrial septal defects 77, 78
Age and menopausal status 434 Anteroposterior bladder neck displacement Atrioventricular septal defect 77, 78, 79f
Agenesis of corpus callosum 92 285 Atrophic endometrium 308
468 Donald School Textbook of Transvaginal Sonography
B C Chaotic vessels architecture 185

Characteristic embryological findings
B mode features of Calculating 391-93, 395, 396
endometrium with good receptivity endometrial volume by vocal 209f Chiari type II malformation 94f
210 follicular volume by vocal 205f Chorionic
mature follicle 202 shell volume of follicle for perifollicular plate 47
Balloon placed in cervical canal 302f 3D PD assessment 207f thickness and volume 371
Banana sign 38, 91 Cancer 304 volume
in 13-week fetus 39f Cardiac and intervillous blood flow in
Barcelona experience 223 defects 39 normal first trimester
Basic anatomical knowledge of deviation 80f pregnancies 367
Cardiovascular system 252 during first trimester normal
coronal cutting section of brain 85f
Case of pregnancies 369
sagittal cutting section of brain 85f
curved cervix 145f in abnormal early pregnancies
ventricular system of brain 85f
dichorionic-triamniotic triplets 169 372
Basic
living embryo 113f Chorionicity and amnionicity
limitations of Doppler examinations
threatened abortion 113 determination second trimester
339 162
Caudal regression syndrome 40
probe movements 21 Causes of infertility 354t Choroid plexus 92
techniques in transvaginal scanning 8 Cavity of rhombencephalon 31f cysts 58, 97
Beads-on-a-string 291 Center for disease control and prevention size (lower) pregnancy 89f
sign 419 289 Chronic inflammatory disease 278
Bending-type convex probe 4f Central Circle of Willis and branches 397f
Benign hypoechoic 257 Circulation of yolk sac 49, 49f
breast disease 251 nervous system defects 37 Cogwheel 291
endometrial disease 459 Cerebellar Color and
Best predictor of preterm delivery 136 asymmetry 36 power Doppler ultrasound 179
Bicornuate uterus 165 dysplasia 97f pulsed Doppler of ovarian blood flow
hypoplasia 97 220f
Bilateral
Cerebrovascular system 251 Color
internal carotid arteries 89f
Cervical comet sign. 368
pleural effusion 69f
length 155 Doppler
Biparietal diameter 131 enables visualization of ureteric jets
Bladder 34 measurement first trimester of
318f
neck 274 pregnancy 154
facility 258
neck-symphysis distance 321 pregnancy 262
features of placenta accreta include
Cervicoisthmic length 155
proper 274 interruption of myometrial vessels
Cervicometry in first
Blighted ovum 46 121f
and second trimesters 157
in 7-week pregnancy 47f of ovarian blood flow in luteal part
trimester 156
Blood flow velocity 337 of menstrual cycle 377f
Cervix 10 poor peripheral flow 229f
Body stalk anomaly 36, 41, 41f Cesarean
Bones of ultrasound 248
delivery 48 Comparing cervical length, first and
female pelvis 316f scar hysterotomy 410 second trimester 157t
pelvis 315 Changes in Complete placenta previa 116f
Bradycardia 107 detrusor dyssynergia observed by with Swiss-cheese morphology 121f
Brain transvaginal ultrasound Complex
anatomy in sagittal and coronal sections echography 287t dominantly cystic adnexal mass of
for neuroimaging diagnosis 85 three parameters indicator for urinary ovarian dermoid 421f
vesicles 32 stress incontinence masses 421
Breast pathologies 285t Conceived cases 204
and small parts 450 uterine artery blood flow in ovulatory Confidence interval 195, 197
disease 251 and anovulatory cycles 351f and intraobserver differences 128f
Index 469
Conflicting data on intervillous circulation Deciding stimulation protocol 242 parameters 425
368 Decidual cells 46 of follicle 209
Congenital heart Defects of urinary tract 40 of uterine 51
defects 71 Delayed nasal bone at trisomy 21 fetus 56f ultrasound studies 368
disease 68 Demonstrated endometrial hyperplasia Dose calculation 243t
Congenital 183f Ductus venosus velocimetry 56
malformations in low-risk population Dense hyperechoic stroma of PCO 240f
77t E
Dermoid cyst 10f
uterine anomalies 359
Descriptive anatomy and clinical
Continuous wave and pulse wave Doppler Early fetal echocardiography 73f, 74f
exploration by transvaginal
336f by 2D and power Doppler 79f
Contrast media 340 ultrasound echography 269
by 2D in structurally normal heart 75f
Contribution of transvaginal scanning in Detection
Early
visualizing fetal anatomy to crown- of stage I disease 437
pregnancy 71
rump-length 36t rate of cardiac defects 77t secretory transformation of
Convex probe 3, 4f Development of yolk sac 48 endometrium 347f
for obliquely 4f Diabetes 39 stage of Dandy-Walker malformation
housed in head 5f Diagnosis of 96f
Coronal suture 87 congenital heart defects 74 Eccentric nodule in ovarian cyst 313f
Corpus luteum 224f, 232, 344 endometrial carcinoma increased 311f Echogenic endometrial fluid collection
blooms 343 PCOS 232 with mass in posterior aspect 310f
with diffuse echoes and peripheral polycystic ovarian disease 240 Echographic records of
vascularization 224f vaginal abnormalities 23 anal levator muscle 274f
without color Doppler 224f Diaphragmatic hernia 39 pubococcygeal muscle 274f
Correlation of vascularization index 131f Dichorionic/diamniotic twins 401f
Corresponding to missed abortion 105f Ecoanatomy of rectal channel 275
Diencephalon 32 Ectopia cordis 39
Counting of placental disks 164f
Difference between gestational and Ectopic pregnancy 255
Craniocaudal
pseudogestational sac 46t Effect of hormone replacement therapy on
bladder neck displacement 285
displacement of bladder neck in Different Doppler instruments 342t endometrial thickness 249
response to Valsalva’s Difficulties in ovarian cancer screening morphology of uterus and ovaries 249
maneuver 286f 431 vascular reactivity of other vessels 252
Cranium bifidum 91 Disappearance of venous pulsation in Effect of
and spina bifida 91 cases with hydrocephalus 92f route of hormone replacement therapy
Crohn’s disease 283f Disorders of prosencephalic development 246
Crown-rump length 13, 52, 102, 103, 91 various hormone replacement therapy
107, 386 Distribution of rectoperineal fistula 282f regimens 246
first trimester 54f Dominance of aorta 80f Efficacy of TRS in pelvic abscess 26
Cumulus 205 Doppler Electronic beam 3
oophorus in preovulatory follicle 206f and three-dimensional ultrasound 179 Elimination of undercounting phenomenon
Cyclic angiography or power Doppler 338f 164
combined 247 effect 333 Embryo
sequential 247 evaluation 462 lacking heartbeat 105f
Cystic
of ovary 376 with normal heartbeat 61
hygroma 54, 68, 68f, 69f
features of Embryonic pregnancy 46
masses 418
endometrium with good receptivity Emphasizing development of embryo in
Cystocele 318
211 early pregnancy 387f
good pre-hCG follicle 203 Empty uterus 257
D
flow Empty-bladder preferable for transvaginal
Dandy-Walker alterations 112 sonography 7f
complex 94 velocity 15 Encephalocele 402
malformation 36, 40, 96 indices 335 Endoanal 325
variant 96 of endometrium 192 Endocardial fibroelastosis 82f
Endocervical length 155, 156 Failure scar in endometrial cavity near nuchal cystic hygroma 54
Endometrial segmentum uteri 412f portion 391
amplitude mapping 194f Fallopian profile 33f, 55f
cancer 462 tube 289 structural anomaly 61
carcinoma 184 with liquid in abdominal cavity upper limb movement in first half of
changes in tamoxifen patients 463 290f pregnancy detected by
evaluation 209 False-negative cases 78 transvaginal 4D ultrasound
fiow index 197 early fetal echocardiography 78f 453
fluid collections 310 Features of good endometrial receptivity Fetus 10
hyperplasia 183, 459 213 chromosomal aberration 65f
and malignancy 19 Feces and recto-sigma boundary 277f depicted obscurely 11f
myometrial junction 210f Female in fetu 166
pattern 192 pelvic floor 269 with cystic hygroma 57f
polyps 27, 180, 302, 360, 460 pelvis in cross-section 317f with myelomeningocele 65f
ring sign 346 Femur length 131 Fibroid 251
thickness 191 Fertilization and pregnancy rates 355 with degeneration 311f
and vascularity 352 Fetal Fibromas 424
vascularity zones 212f Field of infertility 343
abdominal abnormalities 61
vascularization Fire-ring 224f
abnormality 61
flow index 197 First trimester of pregnancy 56, 112
anatomic structures taccording to
index 197 Five-chamber view 74f
crown-rump-length 36
volume 194, 195 Flow
anatomy 33
Endometrioid tumors 423 index 199
on first trimester of pregnancy 31
Endometriosis 251, 296f, 379, 420 versus velocity 337
anemia and congenital infections 31
Endometritis 294 Focal increased echogenicity 309f
back
Endometrium 387 Follicle
and vertebral structure 87f
in postmenopausal patient with number per ovary 238, 243
surface 87f
retroverted uterus 250f on inversion mode rendering 234f
brain to neonatal periventricular stimulating hormone 343, 344
polyp 28f
leukomalacia 19f stimulation hormone 232
polypectomy under transrectal
cardio mode 448 Follicular
sonography guidance 25f
central assessment 202
Enlarged cervix draw attention to possible
nervous system 85 monitoring 202
cervical carcinoma 23f
structure in early gestation 87f or preovulatory phase 344
Enterocele 322
distress 48 volume by vocal 206f
Epilepsy 39
growth Follicular/proliferative phase 344
Epithelial ovarian cancers 431
disorders 54 Foramen ovale 73
Estrogen alone 247
restriction 48 Four-dimensional
Evaluation of ovarian mass 424
hand 35f imaging 444
Exfoliated endometrium and clots 180
heart 449 sonography 172
Existence of interabdominal liquid permits
anomalies 78f in multiple pregnancy 172
visual of fallopian tube 290f
anomalies diagnosed early technical aspects 443
Exomphalos 39
echocardiography 77t Fractional moving blood flow volume 125
Exstrophy of bladder in first trimester 66f
rate 57, 107 Free androgen index 238
External
using fetal cardio mode 451f Frequency of spontaneous abortion 102
anal sphincter 318
heartbeat 68f Frontal
sphincter 271f, 274, 277f
iliac angle measurement on transverse bone 87
section of fetal pelvis 58f of skull 38
F
kidneys 35f view of transvaginal approach 86f
Face 33, 33f liver 19f Function of yolk sac 49
of aborted fetus 64f movement to gestational age 406t Functional
Facial anomaly 64f movements 106 cyst 226f
Index 471
with extensive hemorrhage 226f Hemorrhoid plexuses 275 Improved
with septal structures and diffuse Heterogeneous pattern in functional detection rate of anomalies 165
echoes 225f ovarian cyst 226f, 227f determination of placentation 169
ovarian cyst 226f High prediction of spontaneous abortion
with clot 228f blood flow velocity 350f 164
with echogenic pattern 229f frequency vaginal transducer 61 In vitro fertilization 192, 261
with hemorrhagic phenomenon pulse rate frequency 336 embryo transfer 170
resistance blood flow in uterine artery Incidence of spontaneous embryonic 406t
226f
249f
with peripheral flow 229f Incomplete septa 291
Highly vascular ovary visualized by color
Fundal uterine fibroid 25f Indications of
Doppler 220f
Future early fetal echocardiography 81
High-order multiple pregnancies 164
aspects 99 transrectal sonography 22, 23t
High-risk pregnancies 33
challenges 382 Histogram for perifollicular flow 208f Inferior
Holoprosencephaly 36, 38, 91, 403 anal nerve 317
G Hormone replacement therapy 245, 249, border of pubic symphysis 274f
250f, 307 ramus 315
Gastroschisis 40 Infertility 301, 379
assessment 249
General cystic pattern 356 Infusion of saline into uterine cavity 12f
Hormones in hormone replacement
Genetic predisposition 434
therapy protocols 246 Initial acute salpingitis 291f
Gestational
Huge yolk sac 61, 62f Inner cell mass 46
age 155
Human chorionic gonadotrophin 46, 192, Instrumentation for Doppler measurements
sac 46 193, 196, 202, 232, 349 336
undercounting in quadruplet Hydrocephalus and ventriculomegaly 87 Internal
pregnancy 163f Hydronephrosis 36 anal sphincter 318
Giant yolk sac 108f Hydropic fetus 68f architecture 417
Glass body mode of endometrial 3D Hydrops 69f carotid artery 251
power Doppler vascularity 214f Hydrosalpinx 296, 297f, 419 cerebral vein 91
GLHW Hymen injury 23 medicine 450
ratio multiplied by gestational weeks Hyperechogenic sphincter 271f, 274, 277f
19f ovarian stroma 356 Interstitial
values 20 skull 91 pregnancies 262
Gonadotropin-releasing hormone 245 yolk sac 61
Gray pregnancy 261
Hyperechoic Interventions for cervical incompetence
index 128 endometrium 309f
level histogram 20 139
yolk sac 63f Intervillous blood flow 369, 372
width levels 19f Hyperemia of myometrial vessels 121f
width of endometria 20f identified continuous venous type 369f
Hyperplasia 304, 462 Intestine adenocarcinoma 283f
Gynecology 450 Hypertension 48
with GLHW 20 Intra-abdominal pregnancy 263
Hypoechoic and homogeneous appearance Intra-arterial invasion 368
302f Intraclass correlation coefficient 127, 128,
H Hypophosphatasia 42
194, 195, 197
Head circumference 131 Hypoplastic left heart 77, 78
Intracranial
Heart 34 at 14 weeks of gestation 81f
hemorrhage 97
defects 39 Hysterosalpingosonography 297
malformations 402
four-chamber view 34f Hysterotomy incision into myometrial
pressure 91f, 92
three-vessel view 34f layer 411f
Intrauterine
Heating effect of ultrasound 13 bleeding, hematomas 109
Hematocolpometrium 27 I device 255
evident by transrectal sonography 24f Iliococcygues 316 removal guided by transrectal
Hematomas located in uterine corpus or Implications of flow parameters on ovum sonography 25f
fundus 111f quality 203 fetal growth restriction 132f
insemination 203 Low sector probe 3, 4f

synechiae, adhesions 181 abortion probability 105 housed in head 5f
Invasive adenocarcinoma 247 flow in PCO 242 Meckel-Gruber syndrome 40
Ipsilateral corpus luteum 259f placenta with round lower edge 118f Medical illustration of
Irregular placental volume technique 127f reserve ovaries 232, 235, 237f cystocele 321f
Isoechoic homogenous grade C vascular resistance 350f enterocele 323f
endometrium 211f Lower extremity 35f Mega cisterna magna 96
Isthmic length 156 Low-frequency ultrasound 10f Megacystis 40, 56
Low-lying placenta with invasion through Meigs’ syndrome 424
J entire myometrium 120f Menopause 245
Lowset ear and micrognathia 64f and postmenopausal symptoms 245
Japan industrial standard 13 Menstruation 344
Luteal
Junction of interfetal membranes 163 phase 344
conversion 358
cyst in pregnancy 225f Metopic suture 87
K phase defect 343, 358 Mictional flow caused by detrusor
Kidneys 34 secretory phase 346 dyssynergia 286f
Klinefelter’s syndrome 54 Luteinized unruptured follicle 223, 225f Middle cerebral arteries 89f
Kyphoscoliosis in 14-week fetus 41f syndrome 357 Migration disorder 94
with peripheral vascularization 225f Miller-Dieker syndrome 94
L Luteinizing hormone 238, 344 Mitral
Lymphatic stasis 54 regurgitation 82f
Lambdoid suture 87 Lysophosphatidic acid 433 stenosis 77
Laparoscopic classification of PID 295f Moderate resistance in uterine arteries
Large M 242
hematoma causing some distortion Monochorionic-monoamniotic twins 171f
effect in gestational sac 112f Magnetic resonance neurography 269 Morphologic assessment 424
yolk sac 50f Main portal vein 242 Most common pitfalls in two-dimensional
Last menstrual period 102 Malformations diagnosis 161
Late appearing twin or undercounting 161 in multiple pregnancy 166t Most receptive endometrium grade A,
Lateral pelvic wall 316 unique for twins 166 multilayered 210f
Left Malignant mucinous tumors 423 Mucinous tumors 423
atrium 73 Marginal placenta previa 117f Mucosa 271f
extraovarian adnexal tubular mass with thin beak-like lower edge 117f Multicystic dysplastic kidneys 36
312f Maternal Multilayered endometrium grade B,
ventricle 73 blood 47 intermediate 211f
ventricular septal defect 80f portion 388 Multiloculated appearance of ovarian
Legs of aborted fetus 65f Maximum implantation point 215f mucinous cystadenocarcinoma
Leiomyoma 186 Mean 423f
Leiomyosarcoma 187 gray value 195, 199 Multimodal screening 436
Lemon sign 38, 91 Multiple
venous velocity 131
in 13-week fetus 38f anechoic spaces often evident in
Measurement of
Lethal skeletal dysplasia 42 invasive placenta 120f
assessment, and pitfalls 144
Lissencephaly 94 interstitial and subserous fibroids 311f
cervical length 146f
Local anesthesia or enema 27 myomas or submucosa 113
endometrial thickness and echogenicity
Long cycle sequential 247 pregnancy 160
Longitudinal patterns 192f Muscles of
and transverse sections of ovary 233f fetal bladder in 12-week fetus 56f pelvic floor 316f
transabdominal sonogram of urinary gray level histogram width 18f pelvis 316
bladder 318f Measuring ovarian stromal flows 233f Myomata 247
view 297f Mechanical Myometrium in menopause 310
of uterus of premenopausal woman effect of ultrasound 14 Mystery of human reproduction lies in
303f index 13 cyclic changes 343
Index 473
N O floor 316
inflammatory disease 255, 379
Nasal bone 54 Occipital bone 87 organ prolapse 315
Natural history of postmenopausal ovary Omphalocele 39, 57 quantification system 315
218 Orientation problem of transcavitary organs 7
Needle guide and sonography 22f Pencil-line echogenicity 307f
long needle for aspiration 6f Osteogenesis imperfecta type II 42 Pentalogy of cantrell 39
transvaginal probe 6f Ovarian Perineal abscess 278
Negative predictive value 149, 223 and endometrial changes during Periovulatory phase 345
Neonatal menstrual cycle 344t Peripheral
mortality and morbidity with artery color and pulsed doppler 377f cystic pattern 238, 356
gestational age 154 cancer 436 venous spectrum 334
periventricular leukomalacia 19 screening trials 435 Peritoneum 289
Neurosonography 86 causes of infertility 353 Peritumoral vessels demonstrate low
Neurulation disorders 91 circulation 347 resistance index 184f
Nitabuch’s layer of decidua 118 cyst 27, 37f, 223 Periventricular echodensity 17
Nomograms of ventricular size f 89 dermoid cysts 421 of fetal brain 19
Nonconceived cases 204 Doppler 376 Persistent versus regressing masses 427
Nonmedical use of diagnostic ultrasound hyperstimulation syndrome 243 Physiologic ovarian cysts 418
15 pregnancy 263 Placenta 390
Nonrespiratory distress syndrome 18, 19f tumors originating from surface accreta 118, 118f
Nonsepta cystic hygroma 54f epithelium 422 and transvaginal sonography 116
Normal volume increta 119f
and abnormal yolk sac characteristics calculated by vocal 235f previa 116
50t calculation 3D US 240t Placental
appearance of amniotic membrane 92f Ovaries during menstrual cycle 343 abruption 48
atrophic Ovary 289, 388 biopsy in
ovaries in postmenopausal patient and ovarian cancer screening 310 fetal growth 131
312f in cul-de-sac 10f normal pregnancies 125
ovary 310 with follicle 9f separation abnormalities 48
cerebral venous circulation 91f vascular
cervical length 135f P biopsy technique by 3D power
development in first trimester of Doppler angiography 126f
pregnancy 103 Parallel to abdominal wall 8
Parameters to evaluate endometrium 308 tree depicts by 3D power Doppler
endometrium in menopause 307 angiography 128f
fetal hand reconstructed in surface Parametritis 289
Paraovarian cysts 420 tree throughout normal pregnancy
rendered mode 449f 129f
finding of spiral arteries in pregnant Paraurethral vascularization and Retzius’
space 276f volume 128
patients 389 Planes of sonographic examination 22f
first trimester fetus 31 Parietal bone 87
Plasma
ovaries 232, 234, 237f Park’s ligament 277f
follicle-stimulating hormone 245
ranges and standard deviations to Partial placenta previa 117f
protein-A 31
gestational age in twin Pathology of simple cysts 219
Polycystic
pregnancies 147t Pattern of
ovarian
tricuspid wave flow by power Doppler fetal movements 111
morphology 238
79f reconstructive neovascularization 284f
syndrome 356
uterus 179 PD for follicular assessment 206 ovaries 27, 27f, 232, 237, 238
Nuchal translucency 13, 31, 52 PD indices and follicular quality 208 pattern and peripheral polycystic
in 12-week fetus 53f Peak systolic velocity 49, 183, 233, 243 pattern 239f
thickness in 12-week fetus 52f Pelvic Poor prognosis of pregnancy 107
Nulliparous women 151 abscess 291 Poor responding ovary 232, 235, 238f
Number of gestational sacs 162f anatomy 315 Porencephaly 97
Positive predictive value 145, 149, 223, Presence of funnel 146f R

431 Presumed endometrial hyperplasia 460f
Radial
Postembryonic period 32 Preterm
transrectal sonography 24f
Posterior delivery 48, 154
vessels 128
fontanelle 86, 87 labor 134
Rate of nuchal translucency 385
fossa anomalies 94 Prevalence of simple ovarian cysts in Real-time Doppler spectrum 335f
pelvic asymptomatic postmenopausal Rectal
area 272 women 218t channel 272f
region 275 Primary yolk sac 48 longitudinal muscle 277f
wall 316 P rinciples of D oppler effect and Rectocele 322
urethrovesical angle 285 application in medicine 333 Rectosigma border 273f
vaginal fornix 10f Probability of spontaneous abortion in Rectovaginal wall 273f
Postmenopausal function of sonographic findings Rectum 318
bleeding 308 103t Recurrent pregnancy loss 301
women 307 Probe insertion and rotation 7 Region of interest 17
Post-parturition clinico-functional state of Procedure of nuchal translucency 53 Regression equations for placental volume
pelvic floor 284 Progesterone challenge test 248 130t
Potential role of transvaginal 71 and ultrasonography 248 Relation
Pouch of douglas 8 Progressive stages of hydrocephalus 92 between ultrasound beam and flow
Power Doppler Proliferation in functional ovarian cyst 334f
of transrectal sonography probe to
assessment of spiral artery perfusion 228f
pelvic anatomy 21f
351f Proliferative phase 344
Relationship within pelvic cavity 317f
ultrasound 338 Provides spatial visualization of soft
Relative bradycardia 107
Prediction of preterm delivery by tissues such liver 448f Repeatability coefficient 195
transvaginal measurement of cervix Prune-Belly syndrome 65f Result sheet of sono AVC 235f
146 Pseudogestational sac 260 Results of color Doppler 229t
Pre-eclampsia 48 and dilated tube in ectopic pregnancy Retroplacental
Pregnancy rate 46f pulsatility index 131
to endometrial Pubic branches and pubourethral ligament resistance index 131
blood flow type 193t 274f systolic velocity 131
thickness 192t Pubococcygeus 316 Retzius’ space 274, 274f
volume 196f Puborectalis 316 Reverse flow in aortic arch 81f
Pre-hCG Pulmonary artery 74 Reversed flow during a-wave 57f
endometrial volume and 3D PD values three-vessel view 80f Ribs 32
214f Pulsatility index of Rich vascularization in Retzius’ space
perifollicular 3D PD values 210f umbilical artery 57 276f
Premature sonolucent ventricular system uterine 48 Right
87f Pulsating arterial type 369f atrium 73
to left sides of uterus 412
Prenatal Pulse
ventricle 73
classification of uterine anomalies 165 Doppler of endometrial vascularity
Robert’s syndrome 42
US image of myelomeningocele 93f 212f
Rokitansky-Küster syndrome 27
Preovulatory follicle repetition frequency 233 Rokitansky-Küster-Hauser syndrome 27
on B mode 203f Pulsed Doppler 15 Role of
with pulse Doppler low resistance flow waveform analysis of luteal blood flow biochemical markers in ectopic
205f 378f pregnancy 255
with vascular ring surrounding follicle waveform analysis of uterine artery CA-125 221
204f 351f ultrasound in
Preovulatory uterine artery waveform Pushed excessively with probe head 11f diagnosis of ectopic pregnancy 256
213f Pyosalpinx 293f, 294f special conditions 250
Index 475
S Simple cyst obtained with Sonohysterogram of tamoxifen 463f
convex probe 4f Sonohysterography 249, 300
Safety mechanical sector probe 5f Sonolucent contents 297f
and accuracy of trasvaginal ultrasound Simple ovarian cyst 11f Spatial reconstruction of membrane 170f
116 Single Spatiotemporal image correlation 448
of 3D transvaginal ultrasound 15 amniotic cavity 171f Spina bifida 38, 91
of Doppler ultrasound 15 erythrocytes reflect 333 in 13-week fetus 38f
Sagittal ventricle 77 Spine 32, 33, 33f, 73
image of color Doppler 91f Singleton pregnancy in didelphic uterus Spiral vessels 128
plane 54f 166f Spontaneous
section of Sion test 303 abortion 61
retroverted uterus 9f Site of
interruptions of development of
uterus 12f umbilical cord 48
conceptus 102
suture 86, 87 implantation 261
Stages of PID 289t
view of cervix with echogenic Skeletal
Standard deviation 128, 195, 197
endocervical mucosa 145f defects 40
dysplasias 41 Starting four-dimensional mode 444
Saline infusion
Skull 32 Sternal cleft 39
sonography 360
and brain 33, 33f Stomach 34, 73
sonohysterography 310f
Small crown-rump length for gestational Straight sinus 91
Salpingitis 289
age 111 Straight-type
with pelviperitonitis 291, 292f
Santorini plexus 274f referred to gestational sac 112f convex probe 4f
Sarcoma 247 Small hyperechoic yolk sac 50f mechanical sector probe 4f
Scanning of mechanical sector probe 5f Small simple cyst in postmenopausal Streak ovaries 27
Scars in isthmic region in women 414f ovary 220f Stress urinary incontinence 319
Scattering of ultrasound yields multiple Solid Stromal
back-scattered wavelets 334f looking PCO 239f abundance 239
Scheme of transvaginal sonography 86f mass seems pedunculated myoma 11f in PCO and hormonal implications
masses 423 240
Screening for structural defects by first
ovarian neoplasm 379 vascularity 241
trimester ultrasound 36
Sonographic in PCO and hormonal implications
Secretory transformed endometrium
criteria to maximize quality of nuchal 241
visualized by transvaginal
translucency sonography 53 volume calculated using threshold
ultrasound 348f
differential diagnosis of pelvic masses volume after vocal of ovary 236f
Section of uterus 7
417, 417t Structure of
Sensitive drainage guide to pelvic abscess
marker for abortion 109f fetal CNS 86
perforation 298
time control 17 yolk sac 48
findings of pelvic inflammatory disease
Separate endometrial polyps 462f Subarachnoid space 92
295t
Septa inside fallopian tube 293f Subchorionic hemorrhage 47
findings suggesting malignancy 220
Serous tumors 422 findings to diagnose an interrupted in 6-week pregnancy 47f
Serum tumor markers 433 pregnancy 105 Subendometrial flow index 197
Severe parameters 415 Submucosal leiomyoma 303, 360
hemorrhoid syndrome 277, 280f sign of beads-on-a-string 292f Summary of Doppler artifacts 340t
megacystis end of first trimester 56f Sonography 431 Superimposed color Doppler 187f
Shadow of metal speculum 26f of cervix in Superior
Short-rib polydactyly syndrome 42 high-risk asymptomatic women ramus 315
Sign of cogwheel 293f 136 sagittal sinus 91, 92
Signal processing 337 low-risk population 137 vena cava 74
Signs corresponding to interrupted multiple pregnancies 138 Surface rendered
pregnancy, summary of 106t preterm premature rupture of fetal foot in plantar projection 449f
Signs of poor prognosis for fetal viability, membranes 139 mode reconstruction of fetal lower legs
summary of 106t of pelvic infection 289 449f
Surface rendering of image of early gestation and echography 269, 269f

or grayscale rendering 445 vascular supply 391f sonography 21, 27f, 28f
preovulatory follicle 347f indices of endometrium obtained by requires full-bladder 7f
Survey of hysterotomy-made scars 410 vocal software 195f ultrasound 247, 256, 307
Swiss cheese 182 of functional ovarian cyst with of urinary bladder 318f
appearance 461f diffuse echoes 225f Translabial 325
Switching active transducer 5f of placenta 122f Transparent mode 446
Symphysis 274 placental vascular biopsy 125 Transperineal echography 270, 270f
Syndrome by stein-leventhal 239 reconstruction of umbilical cord Transrectal
Syndrome of visible ovary 218 172f echography 270
reveals intensive vascular activity sonography 21, 28f
T 393f advantage of detecting distant
studies in assessment of early ovarian pathologies 24f
Tachycardia and general edema 68 probes 22f
Tamoxifen therapy 20f chorionic circulation 390
volume of ovary 233f Transvaginal 325
Tamoxifen-exposed patients 300 approach to fetal brain 85
Ta rg e t o f t r a n s v e r s e s e g m e n t a r y sonoembryology 385
sonographic and assessment of
hysterotomy 410f cervix 144
Technique of Doppler study 376 Doppler criteria for diagnosis of
ovarian malignancy 425t congenital central nervous system
Techniques for anomalies 91
baseline scan of ovaries 232 power Doppler criteria for diagnosis
of endometrial malignancy 185t cervical length measurement in
evaluation of fetal behavior 173f predicting successful labor
Tetralogy of Fallot 78, 80f sonography 229f
in diagnosing multiple pregnancy induction 151
Therapeutic cervical cerclage for color Doppler
prevention of preterm delivery 150 163
assessment of ovarian and uterine
Thermal spatial reconstruction 169
blood flow 347
effect of ultrasound 13 transvaginal
of polycystic ovary 357f
index 13 probes 4, 5f
color Doppler scan of
issues 14 sonography 86
cervical pregnancy 263f
Thick hyperechoic endometrium 12f ultrasound 381
endometrial carcinoma vessels 184f
Thin-walled clear and power Doppler of endometrium
interstitial pregnancy 262f
paraovarian cyst 312f 193
small endometrial polyp 180f
simple cyst seen in left ovary 312f findings 391, 392, 393, 394, 395,
small gestational sac 258f
Three-dimensional 396
uterine tumor 188f
and 3d power Doppler ultrasound f i n d i n g s f r o m o v u l a t i o n t o
uterus 187f
markers of implantation 352 implantation 386
echography 270, 272f
and four-dimensional rendering 445 in assessment of tubal ectopic
a p p l i c a t i o n s i n p e l v i c f l o o r
angio mode 171 pregnancy 260 exploration 272t
Doppler indices in early detection of fetal anomalies median image 97f
during normal gestation 128 402 power Doppler of hyperstimulated
normal pregnancy 130f in multiple pregnancy 400 ovary after gonadotropin
of endometrial perfusion 196 of normal uterine cavity 359f induction 355f
image of of polycystic ovaries 356f probe
preovulatory follicle 346f of septate uterus 360f prepared with condom 6f
gestational sac 389f of urethra 320f technical aspect 3
lambda sign and intertwin membrane scan of conjoined twins 402f scan 13
170f tool for measurement of nuchal scanning in women 308
multiplanar translucency 400 sonogram of
image analysis 88f Tomographic ultrasound imaging of borderline serous cystadenoma
imaging 163 urethra 320f 422f
power Doppler 229f Tranrectal sonography 27f infertile patient with intrauterine
findings 392, 394, 395 Transabdominal 325 synechiae 182f
Index 477
sonography 3, 134 flow measurement 338 transvaginal color Doppler not helpful
in women with symptoms of sonography in diagnosing multiple for predicting pregnancy 113f
preterm labor 135 pregnancy 160 Uterine
of uterus 343 transvaginal sonography 169f Artery
ultrasound 154, 248, 256, 307, 434 ultrasound 179 blood flow in nonpregnant and
a s s e s s m e n t o f p o s t e r i o r and Doppler of endometrium 191 pregnant patients 389
urethrovesical angle 319f Types of Doppler 211
echography 271f motor activity 172 body and endometrium 9f
of triple line endometrium 347f spontaneous interruptions of pregnancy causes of infertility 359
Transversal volumetric section of anal 105 cavity 255
sphincter 288f Typical with fluid collection and debris
Transverse banana sign 94f 308f
section 54f for endometrial hyperplasia 461f circulation 350
section of abdomen 34f lemon sign 94f fibroids 27
view of typical endometrial polyp 303f fundus 11f
Tree-dimensional transparent rec U leiomyoma 301
onstruction of fetal skeletal system lesions 179
Ultrasonic bioeffect 13
in monochorionic-monoamniotic malformations 113
Ultrasonographic signs of poor pregnancy
twin pregnancy 448f perfusion in infertile patients 351
outcome 102
Trichorionic-triamniotic triplets 161 synechia 301
Ultrasound
Tricuspid atresia or dysplasia 77, 78 vessels 251
anatomy of normal heart 72
Trimester of pregnancy 154 Uterus 289, 386
approach to fetal movement 453
Trophoblastic thickness at embryonic didelphys 165
imaging of early extraembryonic
implantation site 109
structures 46
True-positive cases at early fetal V
markers of aneuploidy in first trimester
echocardiography 77t
52 Vaginal
Tubal
role 245 bleeding 111
causes of infertility 361
in pretreatment assessment 247 delivery 117
contents 291
safety in b-mode 14 transducers 248
fimbrias 290f
scanner with transvaginal probe by Validation of placental vascular biopsy
patency 303
gynecological examination table 3f method 127
tract 290f
techniques 325 Variants of Y junction 164f
Tubo-ovarian
Umbilical Vascular villous branches of
abscess 291, 295f
artery pulsatility index 57 1st order 128
complex 291, 419
cord 57 2nd order 128
or abscess 419
cord insertion 34f 3rd order 128
Tumor lakes 380
pulsatility index 131 Vascularity indicates normal uterine
Tumor marker levels and gray-scale
ultrasonography 312 resistance index 131 receptivity 353f
Turbulent flow in lacunae 121f systolic velocity 131 Vascularization flow index 126, 128, 195,
Turner’s syndrome 54, 68 vessels 128 199, 386
Tw o - a n d t h r e e - d i m e n s i o n a l Unicornuate uterus 165 Vein of galen 91
sonoembryology 167f Unique to twinning 166 Venosus pulsatility index of veins 57
Two lambda signs on single placental disk Upper mediastinum 80f Venous organization in hemorrhoid
confirm trichorionic-triamniotic Urethra 274 plexuses 279f
triplets 164f Urinary bladder 317 Ventricular septal defect 77, 78
Two-dimensional or rectum 120 or valvular stenosis 75
color Doppler display 338 Urogynecology 315 Ventricular system 85
echographic patterns with details of Urology 450 Vertex presenting fetus and transvaginal
dehiscence extent originating Use in pelvic diagnosis 269 transducer 86f
from hysterotomy 413t Use of Viability of each triplet 161f
flow mapping 336f tamoxifen 251 Viable heterotopic 262
Villous vascular tree 370 for follicular assessment 204 with bleeding without hematoma 110
Virtual organ computer aided analysis parameters of good pre-hCG follicle with multiple gestations 134
193, 195, 197, 370 204 Wumb safety statement on Doppler
Visualization Volumetric calculations 170 ultrasound in pregnancy 15
of fetal nose in midsagittal view of fetal Vulva and anus 26
profile 55f
rates of W Y
4-chamber view according to
Wall Yolk sac 48, 397
gestational age 37t
o u t f l o w t r a c t s a c c o r d i n g t o of urinary bladder 120f of multiple pregnancy 109f
gestational age 37t thickness 291 Y-shaped telencephalon 32
Volume Wipe head of probe 7
contrast imaging 448 Women
Z
ultrasound subjected to second hysterotomy after
assessment of endometrium 212 study period 414t Zagreb ovarian cancer screening trial 438

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Donald School

Jose Bajo Arenas MD PhD

Jaypee Brothers Medical Publishers (P) Ltd

Jaypee Brothers Medical Publishers (P) Ltd

Marina, Marinita and Juan

Alenka Aksamija Santiago Bau

Biserka Funduk Kurjak L Martínez-Cortés

Cihat Sen Nobuhiro Yamamoto

Section 1: General Aspects

2. Basis of Transvaginal Scanning 7

3. Ultrasound Safety in Transvaginal Scan 13

4. Ultrasonic Tissue Characterization with Gray Level Histogram Width 17

7. Ultrasound Imaging of Early Extraembryonic Structures 46

8. Ultrasound Markers of Aneuploidy in the First Trimester 52

9. Early Detection of Fetal Abnormality 61

10. Echocardiography in Early Pregnancy 71

11. Assessment of Fetal Central Nervous System 85

12. Ultrasonographic Signs of Poor Pregnancy Outcome 102

13. Placenta and Transvaginal Sonography 116

14. Assessment of Placental Vascularization by Three-dimensional Power Doppler Ultrasound:

15. Cervical Measurements and Preterm Labor 134

17. Cervix in the First Trimester of Pregnancy 154

18. Transvaginal Sonography in Multiple Pregnancy 160

Section 3: Gynecology and Infertility

21. Follicular Monitoring 202

22. Asymptomatic Simple Ovarian Cyst in Postmenopausal Women:

24. Baseline Scan and Ultrasound Diagnosis of PCOS 232

26. Ectopic Pregnancy 255

27. Female Pelvic Floor: Descriptive Anatomy and Clinical Exploration by

29. Sonohysterography 300

30. Transvaginal Sonography in Postmenopausal Women 307

31. Use of Different Ultrasound Techniques in the Field of Urogynecology 315

Section 4: Doppler Sonography

33. Use of Ultrasound in the Field of Infertility 343

Section 5: 3D and 4D Transvaginal Sonography

37. Cesarean Scar Hysterotomy: Assessment by 3D Transvaginal Echography 410

38. Assessment of Normal and Abnormal Ovaries by Transvaginal Sonography 415

40. Four-dimensional Technical Aspects 443

42. Advanced Sonographic Assessment of Benign Endometrial Disease 459

Convex Probes Figure 1.1 An ultrasound scanner with a transvaginal probe by a

Figure 1.6 Principle of the scanning of a mechanical sector probe.3 The

Figure 2.2 A display of a sagittal section of an anteverted uterus by

the probe as near as possible. And then observe it with

fornix. If it does not work satisfactorily or the object is too Reference

4 Ultrasonic Tissue Characterization

Abstract characterizations were reported.3-5 The results are excellent,

In clinical application, contrast is recommended to be

Introduction Both TRS and TVS probes are designed as elongated

Figure 5.2 Transrectal sonography probes

Table 5.1 Indications of transrectal sonography

Postmenopausal vulvovaginal atrophy, atrophy following

masses situated within 12 cm of the anus. They also

Technique and Preparation

Table 5.2 Results of the study References

Introduction of the neck, abnormal collagen biosynthesis, fetal anemia

Figure 6. 2 Skull and brain Figure 6.3 Face

Figure 6.4 Fetal profile Figure 6.5 Spine

Figure 6.10 Fetal kidneys Figure 6.11 Fetal bladder

Figure 6.12 Lower extremity Figure 6.13 Fetal hand

Abbreviations: NE, not examined; NS, not specified

Abbreviation: NE, not examined

the appearance of the brain varies from echogenic and are

Holoprosencephaly (Birth Prevalence 1 in 5,000)