Management of Recurrent Pregnancy Loss

Evaluation and Management Strategies

• The American College of Radiology recommends transvaginal ultrasound (TVUS) as an initial screening tool for uterine cavity abnormalities, and sonohysterography (SIS) for better assessment of the uterine cavity 1, 2
• Three-dimensional SIS has shown 100% accuracy in classification of uterine anomalies when compared with hysteroscopy 1
• Some patients with recurrent complete hydatidiform moles may have mutations in NLRP7 and KHDC3L genes, according to Praxis Medical Insights 2, 3
• Evaluation of thyroid function, polycystic ovary syndrome (PCOS), and ovarian reserve is recommended, as these factors can contribute to pregnancy loss 2, 3
• Screening for gestational diabetes in current pregnancies is also recommended 2
• The American College of Obstetricians and Gynecologists suggests that male partners should be evaluated in couples with two or more pregnancy losses, with consideration of karyotype and sperm DNA fragmentation testing 2
• Calcium and vitamin D supplementation is recommended for women with 22q11.2 deletion syndrome, according to Genetics in Medicine 4
• Optimization of thyroid function and regular monitoring for gestational diabetes are also recommended 2, 4
• Women with homozygous factor V Leiden or prothrombin 20210A mutation with positive family history for venous thromboembolism should receive antepartum prophylaxis with prophylactic or intermediate-dose low molecular weight heparin 2, 3
• Early and regular ultrasound monitoring in subsequent pregnancies is recommended for unexplained recurrent pregnancy loss 2
• Regular physical activity within guidelines is unlikely to increase the risk of pregnancy loss and may benefit factors that increase miscarriage risk, such as insulin resistance and obesity, according to Praxis Medical Insights 5
• Avoiding smoking, alcohol, and recreational drugs, as well as maintaining good nutrition and physical activity, is recommended 4
• Confirming viable intrauterine pregnancy with early ultrasound and regular prenatal visits with serial ultrasound monitoring are essential for managing current pregnancy with history of RPL 2
• Monitoring for and promptly treating any endocrine conditions, such as thyroid dysfunction and gestational diabetes, is crucial 4, 2

Evaluation of Recurrent Pregnancy Loss

Thrombophilia Screening

• Note that TEG parameters show no correlation with thrombophilic defects (protein C, protein S, factor V Leiden, prothrombin G20210A, MTHFR C677T, or lupus anticoagulant) and no evidence of prothrombotic state in unexplained recurrent pregnancy loss 6

Recurrent Pregnancy Loss Diagnosis and Anembryonic Pregnancy

Definition and Classification

• The American College of Radiology recommends that anembryonic pregnancy, previously termed blighted ovum, be counted when calculating recurrent pregnancy losses for workup purposes, as it represents a confirmed early pregnancy loss that meets diagnostic criteria for failed pregnancy 7
• An anembryonic pregnancy is specifically defined as a gestational sac measuring ≥25 mm without an embryo, or absence of an embryo on serial examinations obtained at appropriate discriminatory time intervals, according to current radiological guidelines 7

Inclusion in Recurrent Pregnancy Loss Definition

• The current definition of recurrent pregnancy loss (RPL) includes all types of confirmed early pregnancy losses, including anembryonic pregnancies, which are counted toward the diagnosis of RPL, with a key requirement that the pregnancy must be clinically recognized (confirmed by ultrasound or hCG) 7
• An anembryonic pregnancy meets this criterion because it demonstrates an intrauterine gestational sac on ultrasound and represents a confirmed conception that failed to develop properly 7, 8

Genetic and Clinical Implications

• Genetic factors, such as mutations in NLRP7 and KHDC3L genes, may be associated with recurrent anembryonic pregnancies, representing a specific autosomal recessive condition, and patients may require genetic counseling and may benefit from ovum donation rather than conventional IVF 8
• Anembryonic pregnancies frequently result from chromosomal errors (50-60% of early losses), the same underlying mechanism as other forms of early pregnancy loss, and uterine cavity abnormalities, endocrine dysfunction, and other treatable causes can manifest as anembryonic pregnancies 8