Prothrombin G20210A mutation is associated with recurrent pregnancy loss: A systematic review and meta-analysis update

Background: Thrombophilia is reported to be a candidate etiology of recurrent pregnancy loss (RPL). No conclusive results on the association between prothrombin G20210A mutation and RPL have been reported. Methods: We undertook a systematic review and meta-analysis of 37 case-control studies using a comprehensive electronic search on papers published by May 2014. We studied 5400 cases and 4640 controls to investigate the potential association between G20210A and RPL. In this review, we define RPL as more than 2 miscarriages. Results: A significant association was found between G20210A and RPL, with a combined odds ratio (OR) of 1.81 (95% confidence interval [CI]: 1.26-2.60). However, the risks differed in the subgroup analyses, categorized by study sites, maternal age, and type of miscarriages. The pooled OR remained significant in European studies (OR: 1.80, 95% CI: 1.35-2.41), whereas in the Middle-Eastern studies, it was not significant (OR: 2.39, 95% CI: 0.96-5.92). The risk of RPL was significantly higher in women older than 29 years (OR: 1.91, 95% CI: 1.61-6.11), and a positive relationship was only observed between prothrombin G20210A mutation and fetal loss, but not embryonic loss. There was no evidence of publication bias in any of the analyses. The sensitivity analyses showed that the findings were quite stable. Conclusion: This meta-analysis suggests that the G20210A prothrombin mutation increases the risk of RPL (fetal loss, primary RPL, or secondary RPL), particularly in Europeans and women older than 29 years. We recommend further screening in more specific groups among women. (C) 2014 Elsevier Ltd. All rights reserved.