Fertility Diagnosis &

Treatment Options

Arlene J. Morales, MD, FACOG

Fertility Specialists Medical Group

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 Diagnosis of Infertility

 “unprotected coitus of 1 year

duration”
 “active” versus no contraception
exposure
 Age:
 < 35 years 1 year
 35-39 years 6 months
 > 40 years 3 months
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 Time Required for Conception:
An Inefficient Process
100
Time of Exposure % Pregnant 93
85
80 75
1 month 22%
60
3 months 57% 50
6 months 72% 40 36
1 year 85%
20 20
2 years 93%
9 13
5
0
1 2 3 6 12 24

Cumulative Pregnancy Rates (<35 yrs) 40 yrs

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Fertility Decreases with Age
100
90
80
70
60
50
40
30
20
10
0
25

35

45
Age (Years)

25 30 35 40 45
% Pregnant at 1 85 85
year
Monthly 22 22 15 5 1
pregnancy rate

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 Etiologies of Infertility

Tubal Factors:30-40% Male Factors: 30-40% Anovulation: 10-15%

Uterine Factors: 20% Cervical Factor:5-10%

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 Uterine Diagnostic
Studies

Sonohysterogram (SHG or SIS) Hysterosalpingogram (HSG)

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The forgotten uterus

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Examples of Pelvic Disease

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 Uterine Cavity
Abnormalities

Normal Polyp

Myoma Scarring Congenital

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Uterine Fibroids: Submucosal

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Severe Tubal Factor

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Other Conditions

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 Hormones
 Aging
 Cycle Day 3 FSH, Estradiol x 2 cycles
 AMH – Anti-Mullerian Hormone
 Hormonal Mileu
 TSH, Prolactin
 PCOS (FSH, LH, Fasting
Insulin/Glucose)
• Androgens (testosterone, 17OHP, DHEAS)

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 Reproductive Aging
AGE=Quality ; AMH,AF,D3=Quantity

600

500 Hutterites
400 Burgeoisie 17th
Burgeoisie 16th
300 French Village
Iranian Village
200 USA 1955
100 USA 1981

0
20-24 25-29 30-34 35-39 40-44 45-49
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 Etiologies of Male
Infertility
 Leading cause is varicocele

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 A.R.T. Laboratory
Andrology
 Basic Semen Parameters (W.H.O.
Standards)
 Days Abstinence 2-5 days
 Sperm Count  20 M/ml
 Sperm Motility  50%
 Sperm Morphology  30% (W.H.O.)
 14 % (Strict: Krueger’s)
 Sperm Volume 2-5 ml

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Indications for Genetic
Diagnosis
 ICSI
 Severe Oligospermia
 Sperm concentration < 5 mil/cc
 Chromosomal testing
 Cystic fibrosis testing

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 MESA

Electroejaculation

TESA

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 Sterilization
 Tubal Ligation Reversal
 Pro’s & Con’s

 Vasectomy Reversal
 Pro’s & Con’s

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Recurrent Pregnancy Loss
 Definition

 1st & 2nd Trimester

 Prognosis

 Workup

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 Traditional Algorithm

Detailed History and Physical Exam

Ovulation Cavity and Tubal Status Semen Analysis

Ovulation Induction
Timing of Intercourse

Ovulation Induction
Intrauterine Insemination
IVF
IVF Directly

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 Traditional Therapy
 Ovulation Induction (OI)

 Clomiphene Citrate (1-3-5 eggs)

• 2 to 3 visits over 2 weeks
 Gonadotropins (5-8-10 eggs)
• 5 to 7 visits over 2 weeks

 Intrauterine Insemination (IUI)

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 Intrauterine Inseminations
10 to 14 days

http://www.fertilityplus.org/faq/tomcat.jpg

http://www.universityfertilityassociates.com/images/art_08.jpg http://www.follistim.com/Authfiles/Images/349_91850.gif
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 Efficacy of Clomid/IUI
CLOMID - 3 trials cross-over placebo trials

 UK: 118 patients with Unexplained (100 mg)

 Cumulative preg rate was 22.3% vs 14.6% (3 cycles)
 USA: 67 patients with Unexplained (50 mg)
 Monthly fecundity of 9.5% (148 cycles) vs 3.3% (150
cycles)
 Canada: 148 couples with Unexplained (100 mg)
 Cumulative preg rates was 13.2% vs 5.6%

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 Efficacy of Gonadotropin and IUI for
Infertility

 Guzick and National Cooperative

Reproductive Medicine Network N Engl J Med 1999;340:177-83

 Couples: no identifiable etiology & motile

sperm
 4 cycles of treatment
COH & IUI IUI alone COH & ICI ICI alone
n=231/618 n=234/717 n=234/637 n=233/706

Cummulative 33 % 18 % 19 %
Per Cycle 10 %
15 % 5% 4% 2%
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 IVF
Completed Check-list
Including Sonohysterogram and Mock-Transfer

Medication Protocol
Prep “stuff” 2-4 weeks

Medication Class

Your Stimulation Cycle

Retrieval (2 to 4 weeks)
Treatment 4 to 5 weeks

Embryo Transfer (3 to 6 days later)

Pregnancy Test (7 to 10 days later)

Prenatal care Follow-up

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Egg Collection Area

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Transvaginal Aspiration Oocytes

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Oocyte Aspiration

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Embryo Culture Area

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Embryologist at Work

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Oocytes

MATURE

IMMATURE

STRIPPED

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 Insemination Methods

 Conventional Insemination
 10-30,000 motile sperm
 1-4 eggs in a 50 l drop of media
 Incubate overnight
 Check for fertilization

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Fertilized Egg From IVF

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ART Lab Techniques: ICSI

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ICSI (cont)

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Embryo Development (D2-D4)

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Blastocyst Development

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Holding pipette AJM 4/2011
Hatching pipette
Assisted Hatching

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 Preimplantation Genetic
Diagnosis (PGD)
 Consists of taking a single cell (biopsy) from
each embryo, followed by genetic analysis to
determine the normalcy of the embryo.
 Subsequent replacement to the patient of those
embryos classified by genetic diagnosis as
normal.
 Three PGD methods of analysis
 FISH (Fluorescent In Situ Hybridization)
 PCR (Polymerase Chain Recation)
 Whole Genomic

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Preimplantation Genetic Diagnosis
 Fluorescent In Situ Hybridization (FISH)
 Detects chromosomal abnormalities
• Chromosomal Aneuploidy (Missing Chromosomes)
 13, 16,18, 21, 22, X, Y

• Chromosome Translocation

 . Polymerase Chain Reaction

 Detects single gene defects
 Tay-Sachs Disease, Sickle-Cell Anemia

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Preimplantation Genetic
Diagnosis

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Preimplantation Genetic Diagnosis

 Advanced
maternal aged
• Increasing maternal
age is associated
with increased
aneuploid embryos
 Family history of
translocations
 Recurrent
Pregnancy Loss
(RPL)
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Extra chromosome 13 in an embryo
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 Inefficient Process
 High incidence of failed conception in-vivo and in-vitro
 A lot attributed to differential embryo viability

15% of embryos < 50% reach

arrest by day-3 the blast stage
? Aneuploidy

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Catheter Placement

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 We’ve come along way
 In 1978, Louise Brown born through IVF
 Since then, techniques have improved to
break the barriers of infertility

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Single Intrauterine Pregnancy

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 Embryo Transfer and Multiple
Gestation
 Multifetal pregnancies constitute an
iatrogenic complication of assisted
reproduction
80
70
60 singletons
50 twins
40 triplets
30 quadruplets
20
10
0
World ASRM
Collaborative
Report AJM 4/2011
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 Multiple Gestation; How do we
avoid?
 Judicious use of ovulation induction

 Limiting the number of embryos transferred

 How many is too many ?
 Improving cryopreservation & thawing
techniques
 Improving the quality selection criteria of the
embryos
 Improving the culture systems
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Multiple Gestation; How do
we avoid?

Day 3 embryo Day 5 or 6 embryo “ hatching blastocyst”

•Allow for screening of potential aneuploidy

•May improve the implantation rate
•Reduce the number of transferred embryos
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Inefficient Process

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ASRM Guidelines

VS <35 years old

35-37 yrs old

38-40 years old

Over 40 years

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 Other Methods of Reproduction

 Donor Oocytes
 Gestational Carriers
 Gestational Surrogate
 Donor Gametes (both oocytes and sperm)
 Frozen Embryo Transfer of donated embryos

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 Reproductive Aging
60
50
40 Donor Eggs

30
20 Own Eggs

10
0
27 31 35 39 43 47

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 What is a good ART program?
High Quality Laboratory High Quality Clinical Care
Comprehensive Services Patient Choice
Excellent Documentation Research
Professional management Cost-effective care
Psychological Support Ethical Care

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 Preconception Readiness
 Genetic Risk
 Cystic Fibrosis (ACOG Recommendation)
 African-American
• Sickle Cell Anemia
 Ashkanazi Jewish
• 9 disease screen
 Mediterrean/Asian
• Thalassemia
 Immunity
 Varicella
 Rubella
 Blood Type
 Prenatal Vitamins (Folic Acid)
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 Advances in Assisted
Reproduction

ICSI IUI

Ovulation Induction

IVF

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Luteal Phase Support
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Pronuclei

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 Day 2 (post retrieval)

Cells or
blastomeres

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Day 3 (post retrieval)

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 Day 4 (post retrieval)

Morula

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Day 5-6 (post retrieval)

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Blastocysts

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Day 5-6 (post retrieval)

Hatched blastocyst

Zona pellucida
Inner cell mass (fetus)
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