From the Guidelines
The diagnostic workup for recurrent pregnancy loss should include a comprehensive evaluation of potential causes, including parental chromosomal analysis, uterine cavity assessment, endocrine evaluation, antiphospholipid syndrome testing, and testing for inherited thrombophilias, as recommended by the most recent guidelines 1. The diagnostic workup for recurrent pregnancy loss (RPL) is crucial to identify the underlying causes and provide targeted interventions to improve outcomes in subsequent pregnancies.
Key Components of Diagnostic Workup
- Parental chromosomal analysis through karyotyping of both partners to identify genetic abnormalities that may contribute to pregnancy loss
- Uterine cavity assessment via hysteroscopy, sonohysterography, or hysterosalpingogram to detect structural abnormalities such as fibroids, polyps, or a septate uterus
- Endocrine evaluation, including thyroid function tests (TSH, free T4), hemoglobin A1c for diabetes screening, and prolactin levels
- Antiphospholipid syndrome testing, including lupus anticoagulant, anticardiolipin antibodies, and anti-β2 glycoprotein-I antibodies, with positive tests repeated after 12 weeks for confirmation
- Testing for inherited thrombophilias, such as Factor V Leiden and prothrombin gene mutation, may be considered in selected cases with personal or family history of thrombosis
Additional Testing
Additional testing may include assessment of ovarian reserve with antimüllerian hormone levels and evaluation for immunologic factors in certain cases, as recommended by the American College of Radiology 1.
Importance of Comprehensive Evaluation
A comprehensive evaluation is necessary because RPL, defined as two or more pregnancy losses before 20 weeks gestation, has multiple potential etiologies, and identifying specific causes allows for targeted interventions that may improve outcomes in subsequent pregnancies 1.
From the Research
Diagnostic Workup for Recurrent Pregnancy Loss
The diagnostic workup for recurrent pregnancy loss (RPL) typically involves a comprehensive evaluation of various factors that may contribute to pregnancy loss. According to 2, good quality evidence links parental chromosomal rearrangements, uterine anomalies, and antiphospholipid syndrome (APS) to RPL.
Evaluation Components
The evaluation components for RPL may include:
- Parental chromosomal analysis to detect balanced translocations or other chromosomal abnormalities, as reported in 3
- Uterine anomaly evaluation using pelvic sonohysterography, hysterosalpingogram, or hysteroscopy, as mentioned in 4
- Endocrine imbalance assessment, including thyroid function tests, as noted in 4
- Autoimmune factor evaluation, including tests for lupus anticoagulant and anticardiolipin antibodies, as mentioned in 4
- 24-chromosome microarray analysis of miscarriage tissue to identify genetic abnormalities, as reported in 4
Timing of Evaluation
The timing of evaluation for RPL is a topic of debate, with some guidelines recommending testing after two pregnancy losses, while others advise testing after three losses, as discussed in 5. However, the results of 5 suggest that investigations after two pregnancy losses may be supported.
Benefits of Comprehensive Evaluation
A comprehensive evaluation, including 24-chromosome microarray analysis of miscarriage tissue, can identify a probable or definite cause of pregnancy loss in over 90% of patients, as reported in 4. This approach can also provide a cost-efficient solution, resulting in a 50% savings in cost to the healthcare system and to the patient, as noted in 4.
Key Findings
Key findings from the studies include:
- Parental chromosomal abnormalities, uterine anomalies, and APS are significant risk factors for RPL, as reported in 2
- 24-chromosome microarray analysis of miscarriage tissue can identify genetic abnormalities in a significant proportion of patients, as reported in 4
- A comprehensive evaluation, including genetic testing and evidence-based diagnostic tests, can identify a probable or definite cause of pregnancy loss in over 90% of patients, as reported in 4