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Anembryonic pregnancy, a form of early pregnancy loss, occurs when a gestational sac develops without the formation of a viable embryo. Although historically termed a blighted ovum, current practice favors the more descriptive terminology. Anembryonic pregnancy represents a substantial proportion of first-trimester miscarriages, with early pregnancy loss defined as spontaneous loss before 13 weeks’ gestation. This course outlines the multifactoral etiologies of anembryonic pregnancy, which commonly include chromosomal abnormalities such as trisomies, monosomy X, and triploidy, along with uterine malformations, infection, immunologic disorders, endocrine dysfunction, obesity, and advanced maternal age and its diagnostic evaluation relying on clinical presentation, positive pregnancy testing, and ultrasound criteria demonstrating an empty gestational sac at defined mean sac diameter thresholds or absent embryonic development on interval imaging. This activity reviews the differentiation of anembryonic pregnancy from other causes of early pregnancy failure, including ectopic pregnancy, essential for accurate diagnosis. Participants will also gain an understanding of standardized ultrasound criteria, underlying genetic and systemic risk factors, and management options, including expectant management, medical management with mifepristone and misoprostol, and surgical evacuation. This activity for healthcare professionals is designed to enhance the learner's competence in identifying anembryonic pregnancy, performing the recommended evaluation, engaging in shared decision-making, providing patient counseling, recognizing complications, developing individualized care plans, and implementing an appropriate interprofessional approach when managing this condition to optimize patient safety and outcomes. Objectives: Screen pregnant patients effectively to identify those at risk for anembryonic pregnancy. Select appropriate diagnostic tools to accurately confirm the diagnosis of anembryonic pregnancy. Implement evidence-based protocols for managing anembryonic pregnancy. Collaborate with interprofessional healthcare team members to provide comprehensive care to patients with an anembryonic pregnancy. Access free multiple choice questions on this topic.

An anembryonic pregnancy is characterized by a gestational sac that forms and grows while an embryo fails to develop. People with anembryonic pregnancies usually present with symptoms of early pregnancy failure. Although the terms anembryonic pregnancy and blighted ovum are synonymous, the latter is falling out of favor with 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 births occurring in only 30% of all pregnancies.[1][2][3] Many patients with early pregnancy loss (including anembryonic pregnancies) are unaware of their miscarriage, particularly when the loss occurs in the early stages of pregnancy. Early Pregnancy Loss 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.[4][5] Early pregnancy loss is the preferred terminology for these pregnancies, including the anembryonic pregnancy.[6] 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 in the United States may vary by state law.[4][7] Biochemical Miscarriage 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 Clinical miscarriage is diagnosed 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 to 20 weeks of pregnancy).

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 of anembryonic pregnancies include the following: Morphological abnormalities: 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.[5] Chromosomal abnormalities Autosomal trisomy, polyploidy, sex chromosomal polysomy, and monosomy X are likely the most common etiologies of EPL. However, half of all anembryonic pregnancies have been found to have normal chromosomes.[8] 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, the most common chromosomal abnormality found in 15% of anembryonic pregnancies, gave rise to rudimentary embryonic growth with an empty sac, while other trisomies often resulted in early embryonic demise.[9] The incidence of other trisomies in anembryonic pregnancies is as follows: trisomy 22 (9.6%), trisomy 15 (3.8%), and trisomy 19 (3.8%).[8] Other genetic and chromosomal abnormalities: Translocations, inversions, single-gene perturbations, and placental mosaicism are some of the other genetic abnormalities that can cause anembryonic pregnancies.[10] Consanguineous marriages resulting in anembryonic pregnancies have also been noted, suggesting the role of single-gene determinants.[11] A probable link between DNA damage in sperm and miscarriage has been noted.[12] Obesity and advanced maternal age: These factors are well-established contributors to EPL.[13] Aneuploidies are more commonly seen in anembryonic pregnancies in women of advanced maternal age than in younger women.[8]

Other genetic and chromosomal abnormalities: Translocations, inversions, single-gene perturbations, and placental mosaicism are some of the other genetic abnormalities that can cause anembryonic pregnancies.[10] Consanguineous marriages resulting in anembryonic pregnancies have also been noted, suggesting the role of single-gene determinants.[11] A probable link between DNA damage in sperm and miscarriage has been noted.[12] Obesity and advanced maternal age: These factors are well-established contributors to EPL.[13] Aneuploidies are more commonly seen in anembryonic pregnancies in women of advanced maternal age than in younger women.[8] Infection: Infectious etiologies are thought to play a role in anembryonic pregnancies. Tuberculosis in the developing world, as well as reproductive tract infections worldwide, can predispose to EPL.[14] The complications of genital tract infections, including intrauterine adhesions, can impede implantation and embryo growth. Uterine abnormalities: Malformations of the uterus, including didelphic, bicornuate, and septate uteri, can impede or prevent the long-term implantation of an embryo. Immunologic disorders: Maternal immunologic conditions, eg, 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:  Low levels of progesterone and endocrinological disorders, including thyroid autoimmunity and thyroid dysfunction, are a few of the hormonal factors that may play a complex role in miscarriage. Polycystic ovarian syndrome is also associated with infertility and pregnancy loss. Alcohol consumption: Maternal alcohol use has been established to have an associated increased risk of miscarriage.[15]

Although difficult to definitively establish, anembryonic pregnancy possibly represents half of all miscarriages in the first trimester of pregnancy.[16][17] 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.[18] A prior history of early pregnancy loss also predisposes a patient to miscarriage.[19]

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 asymptomatic. A previous anembryonic pregnancy is a risk for another similarly abnormal pregnancy.

Clinical signs and symptoms, along with pregnancy testing and ultrasound evaluation, confirm the diagnosis of an anembryonic pregnancy. Pregnancy testing may be performed using urine or serum hCG levels to support clinical suspicion and guide further assessment. Transabdominal or transvaginal ultrasound classically demonstrates an empty gestational sac without visualization of an embryo (see Image. Anembryonic Pregnancy). Diagnostic confirmation occurs when ultrasound imaging shows no discernible embryo within a gestational sac measuring 25 mm or more in mean sac diameter. Diagnosis may also be established on follow-up endovaginal imaging when no embryo is visualized by 11 days or more after a prior scan that demonstrated a gestational sac with a yolk sac but no embryo, or 14 days or longer after a scan that demonstrated a gestational sac without an embryo or a yolk sac.

The 3 treatment options for early pregnancy loss include expectant management, medical management, and surgical treatment. Medical therapy with mifepristone and/or misoprostol, as well as surgical intervention, represents effective treatment for anembryonic gestations. Selection of a management strategy depends on an informed discussion between the patient and clinician, unless a clear indication for surgical intervention exists. If the success rate for medical management were higher than 65%, then most patients would prefer to manage their anembryonic pregnancy in this manner. Expectant Management Expectant management is a watchful-waiting approach in which the patient undergoes close follow-up without immediate intervention to allow for spontaneous and complete passage of tissue. Repeat sonograms and serial hCG measurements help confirm complete tissue expulsion. Confirmation of a negative hCG level after vaginal passage of tissue is recommended. Medical Management Medical management involves administration of mifepristone and/or misoprostol through vaginal, oral, or buccal routes, using varying doses and timing regimens. Ongoing research continues to evaluate optimal dosing strategies. This option offers a more predictable clinical course. Surgical Treatment Surgical treatment involves uterine evacuation using manual vacuum aspiration or dilation and curettage. Clinicians frequently select this approach for patients with hemodynamic instability or for those unable to tolerate the cramping and bleeding associated with medical therapy. Uterine aspiration or evacuation provides a faster completion time, particularly in the outpatient setting.[7]

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 (Please see StatPearls' companion resource, "Gestational Trophoblastic Disease," for further information) Complications relating to a viable pregnancy

Maternal amino acids are crucial for early embryonic growth because the developing embryo relies entirely on the mother’s supply, delivered through uterine secretions and later the placenta. Proper placental development and a healthy maternal–fetal interface depend on adequate amino acid levels and transport. In a normal early pregnancy, maternal amino acid concentrations typically decline as the embryo begins to use them. However, despite evidence that abnormal placentation contributes to anembryonic pregnancy, changes in maternal serum amino acid patterns in these pregnancies have not previously been studied. The viability of many early pregnancies is difficult to determine by ultrasound alone. Maternal serum amino acids are higher in individuals with anembryonic pregnancy. Using 17 amino acid levels, especially as a combined profile, has been shown to improve the diagnostic accuracy. This approach may offer a useful tool for early risk screening of anembryonic pregnancy in the future.[20]

Prognosis and successful management of an anembryonic pregnancy depend on multiple factors, including gestational age. Outcomes are generally favorable with all 3 management approaches. Expectant management has demonstrated acceptable outcomes. A meta-analysis of 20 studies concluded that both expectant and medical management represent appropriate treatment options for incomplete abortion.[21] Medical management shows improved success with multiple-dose misoprostol regimens. Patients with incomplete abortion experience higher success rates with medical therapy compared with expectant management. Surgical treatment demonstrates high efficacy. At least 1 large randomized controlled trial reported a higher success rate with surgical intervention than with medical management, while also concluding that both approaches maintain an overall favorable safety profile.[22]

Serious complications of anembryonic pregnancy treatment are uncommon, but can include: Heavy bleeding and hemorrhage Uterine perforation from surgical management Infection or septic abortion, which can be fatal Complications from a missed diagnosis of ectopic pregnancy [7]

Necessary consultations in the management of an anembryonic pregnancy involve the following: Obstetrician Primary care clinician Psychologist/psychiatrist Emergency department physician Radiologist/sonographer (especially when clinical features of an ectopic pregnancy are noted)

The following represent critical points in patient education: Pregnant patients in the first trimester should be advised to present to their emergency department if they experience severe pain or heavy vaginal bleeding (2 pads per hour for approximately 2 consecutive hours). Signs and symptoms of infection should be discussed with patients, especially following surgical management and with those choosing expectant management. Treatment with mifepristone and misoprostol can cause a febrile reaction that may be misinterpreted as a sign of infection. Prophylactic antibiotics are not routinely administered except with surgical management. Patients should adhere to follow-up sonograms and outpatient appointments, particularly when additional doses of misoprostol are considered clinically necessary. A miscarriage can be a traumatic experience for a patient. Reassurance and empathy are vital in helping patients navigate the grieving process.

Pertinent factors that should be kept in mind when managing an anembryonic pregnancy include: Pregnancy loss is a common complication in the first trimester of pregnancy. Most pregnancy losses occur in the first trimester. Early pregnancy loss without embryo development is likely due to chromosomal and genetic abnormalities. Specific sonographic criteria have been established for diagnosing an anembryonic pregnancy. A pseudogestational sac, an ectopic pregnancy, and an early viable pregnancy are important differential diagnoses to consider when evaluating an anembryonic pregnancy. Expectant management, medical treatment, and surgical treatment are the 3 primary management options.

Interprofessional teams are more effective when they work collaboratively and efficiently. Developing a well-defined strategy for managing anembryonic pregnancies is vital. Healthcare teams should establish standardized protocols for diagnosis, treatment options, and patient counseling. An evidence-based approach should guide decision-making, ensuring strategies align with the latest research and guidelines. Each healthcare team member, from physicians to advanced care practitioners, nurses, and pharmacists, has distinct responsibilities. Physicians are responsible for diagnosing and developing treatment plans for anembryonic pregnancies. Nurses provide patient care, emotional support, and education. Pharmacists may be involved in prescribing or dispensing medications. All team members must respect patients' autonomy by providing clear information about their condition and available choices, including expectant management, medication, and surgery. Mental health professionals play a critical role in following up with patients and ensuring the appropriate mental health management of a possibly traumatic experience for patients. Physicians, advanced care practitioners, nurses, and pharmacists should communicate and collaborate seamlessly to provide consistent patient-centered care. Confirming the diagnosis of an anembryonic pregnancy can be difficult by ultrasound at times. Communication with the radiologist, relaying hCG lab values and patient presentation, can help avoid a missed diagnosis of an ectopic pregnancy. The sonographer is also essential in accurately evaluating a patient to exclude an ectopic pregnancy appropriately. Patients presenting with complications on initial presentation or from treatment often present to the emergency department. Close communication between an emergency department clinician and an obstetric specialist includes providing a detailed, thorough patient history and physical exam. This particularly includes signs of sepsis and hemodynamic instability.

Physicians, advanced care practitioners, nurses, and pharmacists should communicate and collaborate seamlessly to provide consistent patient-centered care. Confirming the diagnosis of an anembryonic pregnancy can be difficult by ultrasound at times. Communication with the radiologist, relaying hCG lab values and patient presentation, can help avoid a missed diagnosis of an ectopic pregnancy. The sonographer is also essential in accurately evaluating a patient to exclude an ectopic pregnancy appropriately. Patients presenting with complications on initial presentation or from treatment often present to the emergency department. Close communication between an emergency department clinician and an obstetric specialist includes providing a detailed, thorough patient history and physical exam. This particularly includes signs of sepsis and hemodynamic instability. Regular team meetings, continuing education, and shared decision-making processes enhance team performance. Reducing the physical complications and emotional impact of these losses through a coordinated, patient-centered approach is essential for providing high-quality care. Recognizing the unique contributions of each team member and fostering a culture of mutual respect and trust further strengthens the team's ability to provide optimal care for patients with anembryonic pregnancies.