Blighted Ovum (Anembryonic Pregnancy)

Khalid Chaudhry; Marco a. Siccardi1.

1
Santa Corona Hospital Pietra Ligure

Last Update: May 21, 2018.

Introduction

A blighted ovum is a fertilized egg that implants but does not develop. In a blighted ovum, a
gestational (embryo) sac forms and grows; however, the embryo does not develop. A blighted
ovum is also known as anembryonic pregnancy. A blighted ovum is the leading cause of
miscarriage (50%).

In the first trimester, the names early pregnancy loss, miscarriage, or spontaneous abortion
are all interchangeably used as there is no consensus in the literature.

Early pregnancy loss is the spontaneous loss of a pregnancy before 13 weeks of gestation.

What is a Miscarriage?

In the United Kingdom, miscarriage is the loss of an intrauterine pregnancy before 24

complete weeks of gestation. The World Health Organization (WHO) and the Centers for
Disease Control and Prevention (CDC) define miscarriage as the loss of a pregnancy before
20 weeks of gestation or the ejection or removal of an embryo or fetus that weighs 500 g or
less. This definition is used in the United States; however, it may vary based on State laws.

Biochemical miscarriage is a loss that occurs after a positive urine pregnancy test (hCG) or a
raised serum beta-hCG before ultrasound or histological verification.
Clinical miscarriage is when ultrasound examination or histologic evidence has confirmed the
existence of an intrauterine pregnancy.

In general, clinical miscarriage is classified as early (before 12 weeks of pregnancy) and late
(12 weeks to 20 weeks). In Europe, the late loss is defined as one that occurs between 12 and
22 weeks.

Miscarriage classified as sporadic and recurrent. Sporadic miscarriage is the more common
than recurrent. Sporadic miscarriage is when 2 or 3 consecutive pregnancy losses occur.

According to the European Society of Human Reproduction and Embryology (ESHRE)

guidelines, recurrent miscarriage (RM) is defined as 3 or more consecutive pregnancy losses
before 22 weeks of gestation.
Etiology

The most common cause of blighted ovum is genetic. This is often due to chromosomal
defects from a poor quality sperm or egg (too many or too few chromosomes in them).
However, in India, in addition to a genetic cause, causes include infections (tuberculosis
[TB]) or structural defects of the uterus.

Genetics

According to Buckett, WM, and Regan (Sporadic and Recurrent Miscarriage, Clinical Gate),
L trisomies are the major fetal chromosomal abnormality in sporadic cases of miscarriage
(30% of all miscarriages) and 60% of chromosomally abnormal miscarriages (recurrent
miscarriage). Trisomies with Monosomy X (15% to 25%) and triploidy (12% to 20%)
account for over 90% of all chromosomal abnormalities found in sporadic cases of
miscarriage.

Trisomies of all chromosomes have been found except for Chromosome 1 and Y. However,
the frequency of these trisomies varies (Chromosome 16 and to a lesser extent 2, 13, 15, 18,
21, 22, accounts for the majority of trisomic abnormalities). According to a study by
Edmonds in 1992, trisomy 16 was found to give rise to the most rudimentary embryonic
growth with an empty sac, while other trisomies often resulted in early embryonic demise.

A 1992 study by Alberman implicated trisomies and monosomies for miscarriage at the
modal peak of 9 weeks; whereas, triploidy pregnancy losses spanned 5 to 16 weeks of
gestation.

Recurrent Miscarriage due to Blighted Ovum

Recurrent miscarriage due to blighted ovum was significantly higher (68.5% versus 31.5%)
in consanguineous marriages according to the study Chromosomal Study of Couples with the
History of Recurrent Spontaneous Abortions with Diagnosed Blighted Ovum)by Shekoohi et
al. (2013) done in Iran.

Sperm DNA Fragmentation

There is a link between DNA damage in sperm and miscarriage. According to the research
article by Larsen et al. in 2013, "a meta-analysis of 16 studies found a highly significant
increase in miscarriage rate in couples where the male partner had elevated levels of sperm
DNA damage compared to those where the male partner had low levels of sperm DNA
damage (risk ratio = 2.16 (1.54, 3.03, P <0.00001)."

Nutrition/Body Mass Index (BMI) Status

According to the study done by Popovic et al. (2016) in Serbia, published in the European
Review for Medical and Pharmacological Sciences, low levels of copper (Cu), prostaglandin
E2, and anti-oxidative enzymes (except for superoxide dismutase) and significantly high
levels of lipid peroxidation products in the plasma have been attributed to the etiology of
blighted ovum miscarriages.
According to Larsen et al., there are many pregnancy-related complications associated with
obesity, including miscarriage. “A meta-analysis from 2008 including primary studies on
infertile populations showed significantly increased miscarriage rates in women with a body
mass index (BMI) greater than or equal to 25 kg/m2 were compared to women with a BMI
less than 25 kg/m2.”

“This tendency has also been demonstrated in women with recurrent marriage although it
must be emphasized that a significantly increased risk of another miscarriage was
demonstrated only in obese women; that is, BMI ≥30 kg/m2.”

Infections

According to the WHO (1998) 1 in 5 women who have an unsafe abortion, suffer from
reproductive tract infections (RTI’s) and as a result, lead to infertility. According to the study
done by Maharana in 2011, the occurrence of spontaneous abortion (defined as pregnancy
loss without the application of any deliberate method to terminate it during early weeks of
pregnancy) is 10% and induced abortion (often done using several dangerous procedures and
under substandard clinical and sanitary conditions) is 3%.

In India, which includes 11 major states, the occurrence of induced abortion among women
with RTIs is 2 times higher than those not affected by RTIs. (Maharana, 2011, International
Institute for Population Sciences, Mumbai, India).

According to Patki and Chauhan (2015), the most common cause of blighted
ovum/miscarriage in addition to genetics is infections (TB) and structural defects of the
uterus.

Anomalies of the Uterus

According to the study (New Insights into Mechanisms Behind Miscarriage) by Larsen et al.,
BMC Medicine (2013) uterine malformations which can be congenital or acquired are the
cause of recurrent miscarriage. Congenital includes arcuate, didelphic, bicornuate, and septate
uteri.

Drugs and Vaccines

According to the SAGE Working Group On Dengue Vaccines and WHO Secretariat (March
17, 2016), an additional SAE (serious adverse event) found by the investigator in the 28 days
to 6 months post-CYD (dengue) injection was blighted ovum.

Other Causes

Immunologic

Immunologic disorders in the mother such as NK Cell Dysfunction, autoantibodies,

hereditary and acquired thrombophilia, among others) can lead to the maternal
immunological rejection of the implanting embryo in the uterus resulting in miscarriage.
Hormonal

Low levels of progesterone can lead to miscarriage.

Endocrine Disorders

Thyroid disorders (thyroid autoimmunity and thyroid dysfunction) and ovarian disorders
(e.g., polycystic ovarian syndrome [PCOS]) are associated with infertility and pregnancy
loss. According to Larsen et al. (2013), “the prevalence of PCOS among women with
Recurrent Miscarriage is estimated to be 8.3% to 10%."

Alcohol Consumption

Even modest amounts of alcohol increase miscarriage risk significantly. Moreover, study
results suggested that the risk increased in a dose-related manner.

History and Physical

Signs and symptoms of a miscarriage are common and include vaginal bleeding and spotting.
Menstrual periods may be heavier than normal. The patient may experience abdominal
cramps.

Evaluation

Clinical signs and symptoms, a pregnancy test, and by ultrasound exam confirm the
diagnosis.

A pregnancy test can be done using urine or serum. There is an increase in serum and urine
hCG. The indicator of the pregnancy test kit shows a weak positive (usually a pink color
instead of red).

Ultrasound exam (transabdominal or transvaginal) showing an empty sac with no embryo

confirms the diagnosis of a blighted ovum. The criteria of the ultrasound for diagnosis is as
follows:

According to Campion et al. (2013), “A pregnancy is anembryonic if a transvaginal

ultrasound reveals a sac with a mean gestational sac diameter (MGD) greater than 25 mm and
no yolk sac, or an MGD >25 mm with no embryo. Transabdominal imaging without
transvaginal scanning may be sufficient for diagnosing early pregnancy failure when an
embryo whose crown-rump length is 15 mm or more has no visible cardiac activity.”

There are other diagnostic criteria for confirming with an ultrasound. “According to the
Encyclopedia of Medical Imaging, the criteria for a diagnosis of blighted ovum are:

Failure to identify an embryo in a gestational sac measuring at least 20 mm via

transabdominal ultrasound.

Failure to identify an embryo in a gestational sac measuring approximately 18 mm or more

via transvaginal ultrasound.

Failure to identify a yolk sac in a gestational sac measuring 13 mm or more.”

In the United Kingdom, the Royal College of Obstetricians and Gynecologists recommends
doctors to use the new guidelines to diagnose a blighted ovum, which is to monitor a growing
gestational sac until it reaches at least 25 mm.

Genetic Testing/Histopathology (Karyotyping of the conceptus) will show trisomies,

monosomy or triploidy as discussed earlier in the etiology section.

Prognosis

Prognosis is positive with correct diagnosis and therapy.

Complications

A dangerous clinical situation could happen when the diagnosis is missed. Heavy vaginal
bleeding can lead to anemia. In an unpublished case report of a patient at 15 weeks from her
last menstrual period, without any bleeding nor menstruation, the sonographic examination
showed a thick and dense endometrium. The surgical procedure led to a massive
intraoperative bleed. It required intrauterine long gauze bandage positioning to stop the
bleeding and a transfusion procedure to improve her hematocrit level.

Deterrence and Patient Education

Although there is no prevention for blighted ovum cases (most often it is a one-time
occurrence), steps can be taken to increase the chance of successful pregnancy based on its
multifactorial etiology.

Fertility Diets

Since blighted ovum has multifactorial etiology, the overall health, and well-being of the
patient should be considered. To conceive one of the things emphasized by an obstetrician
and gynecologist is having a well-balanced diet (consume food for both mother and baby)
with all the necessary and recommended daily intake of nutrients and maintaining a healthy
weight, is necessary. The diet must be rich in all recommended elements (example copper,
folic acid, iron) required for the development of the fetus. In countries like India, where the
Hindu population is usually vegetarian, diets lack sufficient iron. Iron is found in meats, eggs,
among other foods. Serbian or Hungarian goulash is a meat and vegetable soup or stew.
Goulash is considered an aphrodisiac and a dish that might enhance fertility. In women with a
low BMI, such diets rich in iron and other elements might increase the chance of conception.

In the case study, the patient had a normal BMI, so food rich in iron is not needed. However,
having a protein, iron, and trace elements rich diet such as this could enhance the immune
system to fight or prevent infections (UTI) which she had.

Medicines

There are herbal medicines (alternatives to sildenafil and tadalafil) used by different cultures
for conceiving and enhancing fertility. In India, some Ayurvedic medicines include Speman
for men, Evecare and Shatavari for women. A Himalayan drug company manufactures these.
Speman enhances sperm motility and increases the chance of conception in women.

At present, there is a pharmaceutical company located in Hawaii that manufactures products

from the Mandrake roots exported from Morocco and marketed as tinctures for general well-
being and ailments including male fertility problems. However, there are no mandrake
products for female infertility problems, only other plants as an aphrodisiac.

Genetic Testing and Counseling

Genetic testing (karyotype) and counseling are recommended if a recurrent miscarriage is

there in the couple’s history. As mentioned earlier in the Etiology section, recurrent
miscarriage due to blighted ovum was significantly higher (68.5% versus 31.5%) in
consanguineous marriages according to the study (Chromosomal Study of Couples with the
History of Recurrent Spontaneous Abortions with Diagnosed Blighted Ovum) by Shekoohi et
al. (2013) done in Iran. Therefore, couples need to be aware of this at the time of marriage
and consult a genetic counselor when planning to start a family.

Religious Belief

Some couples are hesitant to do a D and C as per the gynecologist or obstetrician's

recommendation. There are several cases when the couple is told that they are going to
miscarry. However, they wait it out through prayer and meditation, and when an ultrasound is
done again after some time, they find the embryo in the sac. One such example was
mentioned earlier in this presentation as examples of errors in diagnosis.

Guidelines

As per the Royal College of Obstetrics and Gynecologist new guidelines, monitor until
gestation sac is at least 25 mm on ultrasound and wait 1 week more if no complications or
symptoms of a miscarriage so that viable pregnancies are not misdiagnosed as miscarriages.

Recommendation

Doctors most often recommend couples wait for 1 to 3 regular menstrual cycles before trying
to conceive again after any miscarriage (americanpregnancy.org).

According to Chauhan et al. (2010), recommendations of the common obstetric guidelines by

ACOG and RCOG on different topics were not comparable the majority of the time. In the
United Kingdom, the Royal College of Obstetricians and Gynecologists (RCOG) as per the
new guidelines, recommends that physicians monitor a growing gestational sac until it
reaches at least 25 mm (this would be about 9 weeks into pregnancy) before diagnosing a
blighted ovum. One can be misdiagnosed as having a blighted ovum if diagnosed at 8 weeks
or sooner.

Many women who have a tilted uterus look 1 to 2 weeks behind and can be misdiagnosed as
having a blighted ovum, so they should wait until at least 9 weeks (if no complications) when
most women see the baby.
The expertise of different ultrasound technicians (positioning of the woman especially with a
tilted uterus) on the same day can affect the ultrasound measurements. These measurements
can be off 4 mm or 5 mm which can result in misdiagnosis.
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