Association of sex hormone receptor gene polymorphisms with recurrent pregnancy loss: a systematic review and meta-analysis

Objective: To investigate the genetic association between estrogen and progesterone receptor polymorphisms (ER, PR) and skewed X chromosome inactivation (XCI) and idiopathic recurrent pregnancy loss (RPL). Design: Asystematic reviewand meta-analysis using electronic database (MEDLINE and EMBASE) up to April 2011. Setting: 24 eligible studies from 14 countries. Patient(s): 2,750 RPL patients and 3,123 controls were included. Intervention(s): Meta-analyses by means of random-effects models. Main Outcome Measurement(s): Common polymorphisms of ER and PR and skewed XCI. Result(s): Of 221 potentially relevant studies, 24 case-control studies were included: 6 reports of PR polymorphisms (PROGINS), 6 reports of ER-a (3 each of rs2234693 [PvuII], rs9340799 [XbaI], and B domain) and 12 reports of skewed XCI. The integrated result showed that women with skewed XCI (>90%) had a higher risk for RPL (the summary OR [95% CI]: 2.43 [1.34-4.43]), and the subgroup analysis of those studies that included more than three consecutive miscarriages (5 studies), also showed a significant association with RPL (2.52 [1.16-5.44]). Among studies of PR (PROGINS) and ER (PuvII, XbaI, B domain) polymorphisms in RPL, the summary ORs were 1.46 (0.56-3.79), 0.90 (0.47-1.75), 0.83 (0.53-1.29), and 1.07 (0.43-2.63), respectively. Conclusion(s): Meta-analyses of the available data showed a significant association between skewed XCI and idiopathic RPL. More data on the associations between ER and PR polymorphisms and RPL would be helpful to elucidate their roles in RPL. (Fertil Steril (R) 2011; 96: 1435-44. (C) 2011 by American Society for Reproductive Medicine.)