Blighted Ovum (Anembryonic Pregnancy)

Article Author:
Khalid Chaudhry
Article Editor:
Marco Siccardi
Updated:
10/27/2018 12:32:09 PM
PubMed Link:
Blighted Ovum (Anembryonic Pregnancy)

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.

Epidemiology

A blighted ovum causes 1 out of 2 miscarriages in the first trimester of pregnancy.

The incidence of early pregnancy loss (before 12 weeks) is estimated to be about 15% of conceptions with significant variations according to age. The incidence ranges from 10% in women 20 to 24 years of age to 51% in women 40 to 44 years of age. Late loss, between 12 and 22 weeks, occurs less and is about 4% of pregnancies.

The prevalence of recurrent miscarriage is lower (ranges from 0.8% to 3%) compared to sporadic miscarriage (Larsen et al., BMC Medicine, 2013)

Clinical miscarriages only, prevalence is only 0.8% to 1.4%, and if biochemical losses are included, then it is slightly higher and to be about 2% to 3%.

The recent study done by Patki and Chauhan in 2015 explains that worldwide, about 10% of miscarriages are without medical termination. However, Indian women are more prone to miscarriages at a rate of 32%.

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.

Treatment / Management

Treatment/Management of Blighted Ovum

  • Expectant management: Wait to have the tissues pass away on its own if there is spotting or wait another week  (9 weeks) to see if there is any sign of the fetus in the gestational sac.
  • Medical treatment consisting of misoprostol on an outpatient basis is another option. However, it may take several days for the body to expel all tissue and may have more bleeding and side effects. The recommended dose of misoprostol is per the International Federation of Gynecology and Obstetrics (FIGO), 2017 guidelines as published in the article by Morris et al., 2017.
  • Surgical Treatment is dilation and curettage (D and C) as per the national or international guidelines. This procedure involves dilating the cervix and removal of the contents of the uterus. The pathologist can examine the tissues to confirm the reason for the miscarriage. Since the procedure immediately removes the tissue, it brings mental and physical closure sooner.

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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      Contributed by Tripthi M. Mathew, MD, MPH, MBA, PhD.