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.

Bradley LA, Palomaki GE, Bienstock J, Varga E, Scott JA.

Source

From the 1Division of Medical Screening and Special Testing, Department of Pathology and Laboratory Medicine, Women & Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, Rhode Island; 2Division of Maternal Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland; 3Division of Hematology/Oncology/Blood & Marrow Transplant, Nationwide Children's Hospital; 4Division of Pediatrics, Department of Medicine, The Ohio State University, Columbus, Ohio; 5Genetics and Public Policy Center, Johns Hopkins University, Washington, DC; and 6National Coalition for Health Professional Education in Genetics, Lutherville, Maryland.

Abstract

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. 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-control 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.