Anembryonic Pregnancy – Causes, Symptoms, Treatment

An Anembryonic Pregnancy is characterized by a gestational sac that forms and grows while an embryo fails to develop. Although the terms anembryonic pregnancy and blighted ovum are synonymous, the latter is falling out of favor for the more descriptive former term. Anembryonic pregnancy constitutes a significant but unknown proportion of miscarriages with the American Pregnancy Association estimating anembryonic pregnancy to constitute half of all first trimester miscarriages. Approximately 15% of all clinically recognized pregnancies end in first-trimester loss with live birth occurring in only 30% of all pregnancies. [rx][rx]

A blighted ovum is a pregnancy in which the embryo never develops or develops and is reabsorbed. In a normal pregnancy, an embryo would be visible on ultrasound? by six weeks after the woman’s last menstrual period. Anembryonic gestation is one of the causes of a miscarriage of pregnancy. A blighted ovum or anembryonic gestation is characterized by a normal-appearing gestational sac, but the absence of an embryo. It likely occurs as a result of early embryonic death with continued development of the trophoblast. When small, the sac cannot be distinguished from the early normal pregnancy, as there may be a yolk sac, though a fetal pole is not seen.

In the first trimester, the terms early pregnancy loss, miscarriage, or spontaneous abortion are often used interchangeably. Early pregnancy loss is defined as the spontaneous loss of a pregnancy before 13 weeks of gestation.[rx][rx]

What is a Miscarriage?

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.[rx]

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 and confirmation.

Clinical miscarriage – is when ultrasound? examination or histologic evidence has confirmed the existence of an intrauterine pregnancy. Clinical miscarriage is classified as early (before 12 weeks of pregnancy) and late (12 weeks to 20 weeks).

Causes of Anembryonic Pregnancy

The exact etiology for anembryonic pregnancies is difficult to ascertain. The etiological factors for anembryonic pregnancies are generally understood and studied in the broader context of early pregnancy loss (EPL) which includes both embryonic and anembryonic pregnancies. Etiologies include:

• Morphological abnormalities of an embryo that prevents implantation or prevents long term survival of the embryo after implantation. These morphological abnormalities are thought to be related to chromosomal abnormalities. [rx]
• Chromosomal abnormalities that collectively include autosomal trisomy, polyploidy, sex chromosomal polysomy, and monosomy X likely represent the most common etiologies for EPL. 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. According to a study by Edmonds in 1992, trisomy 16 was found to give rise to rudimentary embryonic growth with an empty sac, while other trisomies often resulted in early embryonic demise.
• Other genetic and chromosomal abnormalities include translocations, inversions, single-gene perturbations, and placental mosaicism. [rx] Consanguineous marriages resulting in anembryonic pregnancies have also been noted, suggesting a role of single gene determinants. [rx] There is a probable link between DNA damage in sperm and miscarriage. [rx]
• Obesity and advanced maternal age are well-established factors associated with early pregnancy loss. [rx]
• Tuberculosis in the developing world as well as reproductive tract infections worldwide can predispose to EPL. [rx] The complications of genital tract infections that include intrauterine adhesions can impede implantation and embryo growth.
• Malformation of the uterus that includes didelphic, bicornuate, and septate uteri can impede in or prevent the longterm implantation of an embryo.
• 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 factors (such as low levels of progesterone) and endocrinological disorders(thyroid? autoimmunity and thyroid dysfunction) play a complex role in miscarriage. The polycystic ovarian syndrome is also associated with infertility and pregnancy loss.
• The role of alcohol consumption and it’s associated increased risk in miscarriage has been well established. [rx]

Diagnosis? of Anembryonic Pregnancy

History and Physical

The signs and symptoms of an anembryonic pregnancy can potentially mirror those of an ectopic pregnancy. Anembryonic pregnancy is often incidentally noted on an initial first-trimester pregnancy sonogram. If an anembryonic pregnancy progresses to an early pregnancy loss, the patient can present with abdominal cramping and vaginal bleeding. Early pregnancy loss in the setting of an anembryonic pregnancy can be clinically silent.

Evaluation

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

A pregnancy test – can be obtained using urine or serum hCG levels.

Ultrasound? exam – (transabdominal or transvaginal) classically demonstrates an empty gestational sac without an embryo.

An anembryonic pregnancy is established on the endovaginal ultrasound? technique when there is no discernable embryo seen in a gestational sac with a mean sac diameter of ≥25 mm.

Alternatively, an anembryonic pregnancy can be established when there is no embryo on a follow-up endovaginal scan:

• ≥11 days after a scan demonstrating a gestational sac with a yolk sac, but an absent embryo
• ≥ 2 weeks (14 days) after a scan demonstrating a gestational sac without an embryo or a yolk sac

An anembryonic pregnancy may be diagnosed:

• when there is no embryo seen on endovaginal scanning in a gestational sac with mean sac diameter (MSD) ≥25 mm ⁴

Or

• there is no embryo on follow-up endovaginal scan¹⁰
  • ≥11 days after scan showing gestational sac with yolk sac, but no embryo, or
  • ≥ 2 weeks after a scan showing gestational sac without yolk sac or embryo

Assessment of interval mean sac diameter (MSD) growth has been shown to be insufficiently accurate in the diagnosis? of anembryonic pregnancy, due to an overlap of gestational sac growth rates of viable and non-viable pregnancies.

Other ancillary features have been described, and may be considered poor prognostic factors, but do not contribute to the formal diagnosis? of a failed pregnancy. These include:

• absent yolk sac when MSD >8 mm on transvaginal ultrasound? (TVUS)
• poor decidual reaction: often <2 mm
• irregular gestational sac shape
• abnormally low sac position

Treatment of Anembryonic Pregnancy

The three treatment options for early pregnancy loss include expectant management, medical management, and surgical treatment. Medical management with misoprostol and surgical treatment is considered more effective in the management of anembryonic pregnancy. Ultimately the decision on considering one of these options is based on an informed conversation between a patient and the provider.

Expectant management

Prognosis? and successful management of early pregnancy loss depends on a variety of factors including gestation age. Prognosis is generally considered good with all three management options.

• Expectant management – in a meta-analysis of 20 studies, expectant management and medical management were both determined to be acceptable treatment options for incomplete abortion. [rx]
• Medical management – medical management is more successful with multiple-dose regimens of misoprostol. Patients with incomplete abortion are treated more successfully with medical management than with expectant management.
• Surgical Treatment – at least one large randomized control trial determined a higher success rate in surgical treatment than with medical management, with a general conclusion of the general safety of both treatment options.  [rx]

Complications

Serious complications of treatment are uncommon. Complications can include:

• Heavy bleeding/hemorrhage
• Uterine perforation(from surgical management)
• Infection? to include fatal sepsis
• Complications from a missed ectopic pregnancy

Deterrence and Patient Education

The following represent key points in patient education:

• Patients should be advised to present to their emergency department if they experience heavy vaginal bleeding(two pads per hour for approximately two consecutive hours).
• Signs and symptoms of infection? should be discussed with patients especially following surgical management.
• Treatment with misoprostol can cause a febrile reaction which can be misinterpreted as a sign of infection?.
• Prophylactic antibiotics are not routinely administered but can be considered in select patients.
• Patients should adhere to follow-up sonogram and outpatient appointments especially when additional doses of misoprostol are considered to be clinically necessary.
• A miscarriage can be a traumatic experience for a patient. Reassurance and empathy play a key role in helping patients through the grieving process.

References