Evaluation of Recurrent Pregnancy Loss
Begin with parental karyotyping, anatomical uterine evaluation via sonohysterography, antiphospholipid antibody testing, and thyroid/endocrine screening—this four-pronged approach identifies the majority of treatable causes. 1, 2, 3
Initial Diagnostic Workup
Genetic Evaluation
- Obtain karyotype analysis for both partners in couples with two or more pregnancy losses to identify chromosomal abnormalities that may be contributing to recurrent loss 2, 3
- Consider testing for NLRP7 and KHDC3L gene mutations in patients with recurrent complete hydatidiform moles 1, 2
- Male partner evaluation should include karyotype and sperm DNA fragmentation testing, as abnormal male karyotype and elevated sperm DNA fragmentation are increasingly linked to recurrent pregnancy loss 1, 2
Anatomical Assessment
- Transvaginal ultrasound (TVUS) serves as the initial screening tool for uterine cavity abnormalities including Müllerian anomalies, intrauterine synechiae, and cervical incompetence 1, 2
- Sonohysterography (SIS) provides superior assessment of the uterine cavity with 100% sensitivity and specificity when compared to hysteroscopy, and accurately diagnoses 100% of defects confirmed surgically 1, 4
- Three-dimensional SIS achieves 100% accuracy in classifying uterine anomalies compared to hysteroscopy 1
- Hysterosalpingography is less reliable, with only 90% sensitivity, 20% specificity, and 45.5% accuracy in diagnosing defects compared to surgical findings 4
Endocrine Evaluation
- Measure thyroid-stimulating hormone (TSH), prolactin, and glucose levels as part of the hormonal profile 1, 3
- Evaluate for polycystic ovary syndrome (PCOS), which is associated with higher rates of pregnancy loss 1, 2
- Assess ovarian reserve, particularly anti-Müllerian hormone (AMH) levels, as severely reduced AMH may be associated with increased miscarriage risk 2
- Screen for gestational diabetes in current pregnancies 1
Thrombophilia Screening
- Perform antiphospholipid antibody (APLA) testing as part of the basic examination 3
- Test for inherited thrombophilias including factor V Leiden and prothrombin 20210A mutations 2
- 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 5
Important Clinical Considerations
Prognosis
- Women with recurrent pregnancy loss have approximately 75% live birth rate in the next pregnancy when managed in a specialized RPL clinic, even with idiopathic cases 3
- The likelihood of successful pregnancy depends on maternal age and number of previous losses 6
Common Pitfalls
- Approximately 50% of recurrent pregnancy loss evaluations remain negative despite thorough workup 3, 6
- Avoid overreliance on hysterosalpingography for uterine cavity assessment given its poor specificity (20%) and accuracy (45.5%) compared to sonohysterography 4
- Do not use low-molecular-weight heparin solely for prevention of recurrent fetal growth restriction, as there is no supporting evidence 2
Management of Subsequent Pregnancy
- Confirm viable intrauterine pregnancy with early ultrasound 1, 2
- Provide regular prenatal visits with serial ultrasound monitoring 1, 2
- Monitor and promptly treat endocrine conditions including thyroid dysfunction and gestational diabetes 1
- For women with homozygous factor V Leiden or prothrombin 20210A mutation with positive family history for venous thromboembolism, provide antepartum prophylaxis with prophylactic or intermediate-dose low molecular weight heparin 1, 2
Lifestyle Modifications
- Counsel patients to avoid smoking, alcohol, and recreational drugs 1
- Encourage regular physical activity within guidelines, which is unlikely to increase pregnancy loss risk and may benefit insulin resistance and obesity 1, 2
- Recommend calcium and vitamin D supplementation for women with 22q11.2 deletion syndrome 1