Can Factor V Leiden and prothrombin G20210A testing in women with recurrent pregnancy loss result in improved pregnancy outcomes?: Results from a targeted evidence-based review

• Published in: Genetics in medicine Vol. 14; no. 1; pp. 39 - 50
• Main Authors: Bradley, Linda A., Palomaki, Glenn E., Bienstock, Jessica, Varga, Elizabeth, Scott, Joan A.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 2012; Elsevier Limited
• Subjects: Abortion; Abortion, Habitual - diagnosis; Abortion, Habitual - genetics; antiphospholipid antibodies; Biomedical and Life Sciences; Biomedicine; Coagulation factors; Evidence-Based Medicine - statistics & numerical data; Factor V; Factor V - genetics; Female; Genetic Testing; Human Genetics; Humans; Laboratory Medicine; Literature reviews; Mutation, Missense; Pregnancy; Pregnancy Outcome; prothrombin; Prothrombin - genetics; review; Validity; thrombophilia; Factor V Leiden; habitual; abortion; recurrent pregnancy loss; systematic review; G20210A; G1691A; prothrombin
• ISSN: 1098-3600; 1530-0366
• DOI: 10.1038/gim.0b013e31822e575b

Women with recurrent pregnancy loss are offered Factor V Leiden ( F5 ) and/or prothrombin G20210A ( F2 ) testing to identify candidates for anticoagulation to improve outcomes. A systematic literature review was performed to estimate test performance, effect sizes, and treatment effectiveness. Electronic searches were performed through April 2011, with review of references from included articles. English-language studies addressed analytic validity, clinical validity, and/or clinical utility and satisfied predefined inclusion criteria. Adequate evidence showed high analytic sensitivity and specificity for F5 and F2 testing. Evidence for clinical validity was adequate . The summary odds ratio for association of recurrent pregnancy loss with F5 in case-controlled studies was 2.02 (95% confidence interval, 1.60–2.55), with moderate heterogeneity and suggestion of publication bias. Longitudinal studies in women with recurrent pregnancy loss or unselected cohorts showed F5 carriers were more likely to have a subsequent loss than noncarriers (odds ratios: 1.93 and 2.03, respectively). Results for F2 testing were similar. For clinical utility, evidence was adequate that anticoagulation treatments were ineffective (except in antiphospholipid antibody syndrome) and had treatment-associated harms. The certainty of evidence is moderate (high, moderate, and low) that anticoagulation of women with recurrent pregnancy loss and F5/F2 variants would currently lead to net harms. Genet Med 2012:14(1):39–50