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Evaluation of the Association Between Hereditary Thrombophilias and Recurrent Pregnancy Loss
A Meta-analysis
George Kovalevsky, MD;
Clarisa R. Gracia, MD;
Jesse A. Berlin, ScD;
Mary D. Sammel, ScD;
Kurt T. Barnhart, MD, MSCE
Arch Intern Med. 2004;164:558-563.
Background Recurrent pregnancy loss (RPL) is a significant clinical problem. Recently, thrombophilias have been implicated as a possible cause. Factor V Leiden (FVL) and prothrombin gene (G20210A) mutations are the most common types of hereditary thrombophilias, but are usually undiagnosed because most carriers are asymptomatic. The relationship between FVL, G20210A, and RPL has been investigated with conflicting results. This study analyzed existing data to determine whether an association exists.
Methods A systematic review of the literature was performed. Only case-control studies that defined RPL as 2 or more pregnancy losses in the first or second trimester and that confirmed mutations by DNA analysis were included. Sixteen studies were selected for the FVL meta-analysis and 7 for the G20210A analysis. Stratified and multivariate logistic regression analyses were performed with the use of aggregate data. Results were confirmed by means of fixed- and random-effects meta-analyses models.
Results The combined odds ratios for the association between RPL and FVL and between RPL and G20210A were 2.0 (95% confidence interval, 1.5-2.7; P<.001) and 2.0 (95% confidence interval, 1.0-4.0; P = .03), respectively. Similar results were produced by the logistic regression and both fixed- and random-effects meta-analysis models.
Conclusions Carriers of FVL or prothrombin gene mutations have double the risk of experiencing 2 or more miscarriages compared with women without thrombophilias. Hereditary thrombophilias may be an unrecognized cause of RPL. We recommend testing for these mutations in women with RPL.
From the Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology (Drs Kovalevsky, Gracia, and Barnhart), and Center for Clinical Epidemiology and Biostatistics (Drs Kovalevsky, Berlin, Sammel, and Barnhart), University of Pennsylvania Medical Center, Philadelphia. Dr Kovalevsky is now with CONRAD, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk. The authors have no relevant financial interest in this article.
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