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).


METHODS
A systematic review and meta-analysis using electronic database (MEDLINE and EMBASE) up to April 2011.


METHODS
24 eligible studies from 14 countries.


METHODS
2,750 RPL patients and 3,123 controls were included.


METHODS
Meta-analyses by means of random-effects models.


METHODS
Common polymorphisms of ER and PR and skewed XCI.


RESULTS
Of 221 potentially relevant studies, 24 case-control studies were included: 6 reports of PR polymorphisms (PROGINS), 6 reports of ER-α (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.


CONCLUSIONS
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.
Department of Obstetrics and Gynecology, National Cheng Kung University College of Medicine, Tainan, Taiwan. sumeitsz@mail.ncku.edu.tw
Mei-Tsz
MT
Su
Sheng-Hsiang
SH
Lin
Yi-Chi
YC
Chen
D000026:Abortion, Habitual / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D020964:Embryo Loss / Q000235:genetics / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies / Q000706:statistics & numerical data; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006801:Humans; D011110:Polymorphism, Genetic / Q000502:physiology; D011247:Pregnancy; D011987:Receptors, Steroid / Q000235:genetics* / Q000378:metabolism
D012739:Gonadal Steroid Hormones; D011987:Receptors, Steroid