Anembryonic Pregnancy

Etiology

The exact etiology of 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 the following:

• Morphological abnormalities of an embryo prevent implantation or prevent long-term survival of the embryo after implantation. These morphological abnormalities are thought to be related to chromosomal abnormalities.[4]                                                                                                                                               
• 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 primary fetal chromosomal abnormality in sporadic cases of miscarriage (30% of all miscarriages) and represent 60% of chromosomally abnormal miscarriages (recurrent miscarriages). 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 gave rise to rudimentary embryonic growth with an empty sac, while other trisomies often resulted in early embryonic demise.[6]                                                                                                                                                         
• Other genetic and chromosomal abnormalities include translocations, inversions, single-gene perturbations, and placental mosaicism.[7] Consanguineous marriages resulting in anembryonic pregnancies have also been noted, suggesting the role of single-gene determinants.[8] There is a probable link between DNA damage in sperm and miscarriage.[9]                                                            
• Obesity and advanced maternal age are well-established factors associated with EPL.[10]                                                                                                                                                     
• Infection is thought to play a role. Tuberculosis in the developing world, as well as reproductive tract infections worldwide, can predispose to EPL.[11] The complications of genital tract infections, including intrauterine adhesions, can impede implantation and embryo growth.                                                                                             

• Malformations of the uterus, including didelphic, bicornuate, and septate uteri, can impede or prevent the long-term 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, including thyroid autoimmunity and thyroid dysfunction, play a complex role in miscarriage. Polycystic ovarian syndrome is also associated with infertility and pregnancy loss.                                                                          

• Alcohol consumption has been established to have an associated increased risk of miscarriage.[12]                                                                              

Epidemiology

Although difficult to definitively establish, anembryonic pregnancy possibly represents half of all miscarriages in the first trimester of pregnancy.[13][14] The incidence of early pregnancy loss (before 12 weeks) is estimated to be about 15% of clinically evident conceptions, with significant variations in incidence based on patient age. The incidence ranges from 10% in women aged 20 to 24 years to 51% in women aged 40 to 44 years.[15] A prior history of early pregnancy loss also predisposes a patient to miscarriage.[16] 

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 obstetric sonogram. If an anembryonic pregnancy progresses to an early pregnancy loss, the patient can present with abdominal cramping and vaginal bleeding. Conversely, 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 of an anembryonic pregnancy. 

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

Ultrasound examination (transabdominal or transvaginal) classically demonstrates an empty gestational sac without an embryo (see Image. Anembryonic Pregnancy)

An anembryonic pregnancy is established on ultrasound imaging when no discernable embryo is 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

Treatment / Management

The 3 treatment options for early pregnancy loss include expectant management, medical management, and surgical treatment. Medical management with mifepristone and/or misoprostol and surgical management are effective treatment options for anembryonic gestations. Ultimately, the decision on which option to proceed with is based on an informed conversation between the patient and clinician.

• Expectant Management
  • This constitutes the "watchful waiting" approach.
  • The patient is closely followed without intervention for spontaneous and complete passage of tissue.
  • Repeat sonograms and trending hCG levels may be employed to confirm the complete passage of tissue.
  • A negative hCG level after the passage of tissue vaginally is recommended.

• Medical Management 
  • This employs mifepristone and/or misoprostol administered vaginally, orally, or buccally, with various doses and timing regimens that may be utilized.
  • Optimal dosage is an ongoing area of research.
  • This management option allows for a more predictable treatment course.

• Surgical Treatment 
  • Surgical management employs uterine evacuation with a manual vacuum or dilation and curettage.
  • This approach is frequently employed in patients with hemodynamic instability or who cannot tolerate the cramping and bleeding associated with medical management.
  • Uterine aspiration/evacuation is quicker to complete, especially when performed on an outpatient basis.[5]

Differential Diagnosis

The differential diagnosis for an anembryonic pregnancy includes the following:

• Pseudogestational sac, which reveals a small amount of intrauterine fluid but no pregnancy tissue             
• Early intrauterine pregnancy                                                                                                                 
• An ectopic pregnancy
• Implantation bleeding from an otherwise viable pregnancy
• Gestational trophoblastic disease
• Complications relating to a viable pregnancy 

Prognosis

The prognosis and successful management of an anembryonic pregnancy depends on various factors, including gestational age. The prognosis is generally considered good with all 3 management options.

• Expectant management: In a meta-analysis of 20 studies, expectant management and medical management were deemed acceptable treatment options for incomplete abortion.[17]                                                                                                                                                                                                                 
• Medical management: Medical management is more successful with multiple-dose regimens of misoprostol. Patients with incomplete abortions are treated more successfully with medical management than expectant management.                                                                                                                                               
• Surgical Treatment: At least 1 large randomized control trial determined a higher success rate with surgical treatment than with medical management, although it concluded the general safety of both treatment options.[18]

Complications

Serious complications of treatment are uncommon. Such complications can include the following:

• Heavy bleeding/hemorrhage
• Uterine perforation from surgical management
• Infection or septic abortion, which can be fatal
• Complications from a missed diagnosis of ectopic pregnancy [5]