What laboratory evaluations are indicated for a pregnant woman with a history of three prior miscarriages?

Laboratory Evaluation for Pregnant Woman with Three Prior Miscarriages

A pregnant woman with three prior miscarriages requires comprehensive laboratory testing focused on treatable causes, prioritizing antiphospholipid antibodies, parental karyotyping, thyroid function, and uterine cavity assessment, while avoiding unnecessary thrombophilia panels that lack treatment benefit.

Essential Laboratory Tests

Antiphospholipid Antibody Testing (Highest Priority)

• Screen for lupus anticoagulant and anticardiolipin antibodies - this is the single most treatable cause of recurrent pregnancy loss with proven benefit for maternal-fetal outcomes 1, 2
• Antiphospholipid syndrome is present in 15% of women with recurrent first and second trimester miscarriage 3
• Women meeting laboratory criteria for antiphospholipid syndrome should receive unfractionated heparin or LMWH plus low-dose aspirin throughout pregnancy 1, 2

Genetic/Chromosomal Testing

• Perform parental karyotyping on both partners to identify chromosomal rearrangements (balanced translocations, inversions) that account for 5-7% of recurrent pregnancy losses 1
• Test products of conception when available - chromosomal errors account for 50-60% of early losses 1
• Cytogenetic analysis should be offered on pregnancy tissue of the third and subsequent miscarriage(s) 2
• For recurrent complete hydatidiform moles specifically, test for NLRP7 and KHDC3L gene mutations 4, 1, 5

Thyroid Function Assessment

• Measure TSH, free T4, and thyroid peroxidase (TPO) antibodies - thyroid dysfunction contributes to pregnancy loss and requires optimization before conception 1, 2
• Thyroxine supplementation is not routinely recommended for euthyroid women with TPO antibodies 2

Uterine Cavity Evaluation

• Begin with transvaginal ultrasound (TVUS) as initial screening for uterine cavity abnormalities 1, 5
• Proceed to sonohysterography (SIS) for superior assessment - three-dimensional SIS shows 100% accuracy in classification of uterine anomalies compared with hysteroscopy 5
• Women with recurrent miscarriage should be offered assessment for congenital uterine anomalies, ideally with 3D ultrasound 2

Additional Metabolic Screening

• Assess for polycystic ovary syndrome (PCOS) - associated with higher rates of pregnancy loss 1
• Screen for gestational diabetes in current pregnancy - glucose intolerance may contribute to pregnancy loss 1
• Measure ovarian reserve (AMH levels) - severely diminished ovarian reserve (AMH < 0.7 ng/mL) may be associated with increased miscarriage risk, especially in women < 35 years 1

Male Partner Evaluation

• Evaluate the male partner in all couples with ≥2 pregnancy losses 1, 5
• Perform karyotype testing to identify chromosomal abnormalities 1
• Consider sperm DNA fragmentation testing - increasing evidence links elevated sperm DNA fragmentation with recurrent pregnancy loss 1

Tests NOT Recommended (Critical to Avoid)

Inherited Thrombophilia Screening

• Do NOT routinely screen for protein C, antithrombin deficiency, or MTHFR mutation - these have weak association with recurrent miscarriage and no proven treatment benefit 2, 6
• Testing for Factor V Leiden and prothrombin gene mutation should only be offered for second trimester miscarriage, ideally within a research context 2
• Viscoelastic testing (TEG/ROTEM) shows no correlation with thrombophilic defects and provides no evidence of prothrombotic state in unexplained recurrent loss 4, 5

Immunological Testing

• Do NOT routinely offer immunological screening (HLA, cytokine, natural killer cell tests) outside a research context 2

Infection Screening

• Routine infection screening is not recommended outside a research context 2

Important Clinical Caveats

• Anembryonic pregnancies (blighted ovum) should be counted when calculating recurrent pregnancy losses - they represent confirmed early pregnancy losses meeting diagnostic criteria 5
• The prevalence of abnormal test results for uterine abnormalities and antiphospholipid syndrome shows no difference between women with two versus three pregnancy losses 6
• LMWH has NO evidence for prevention of recurrent pregnancy loss outside of confirmed antiphospholipid syndrome 1
• Aspirin and/or heparin should NOT be given to women with unexplained recurrent miscarriage 2

Management of Current Pregnancy

• Confirm viable intrauterine pregnancy with early ultrasound as soon as pregnancy is detected 1
• Provide regular prenatal visits with serial ultrasound monitoring throughout pregnancy 1
• Monitor for and promptly treat any endocrine conditions (thyroid dysfunction, gestational diabetes) 1, 5
• For women with antiphospholipid syndrome, aspirin and heparin should be offered from positive test until at least 34 weeks of gestation 2