Association of ESR1 Xba1 (rs9340799) With Male Infertility: A Systematic Review and Meta-Analysis

Variations in the estrogen receptor genes, particularly the Xba1 (rs9340799) SNP in the ESR1 gene, may influence the effects of estrogen on male fertility. Results from previous studies on this SNP for male infertility have been inconclusive. This review aimed to determine the association of ESR1 Xba1 (rs9340799) with male infertility. Relevant case-control studies published in English were searched from Google Scholar, Embase, Scopus, Web of Science, Cochrane Library, and PubMed using keywords of ESR, polymorphism, and male infertility. Studies on animals, reviews, and abstracts were excluded. Pooled odds ratios (ORs) were calculated for four genetic models, with heterogeneity assessed by I². A fixed or random effect model was applied based on I², and trial sequential analysis (TSA) was conducted with 5% significance for type I error and 95% power. ESR1 expression levels were examined in testes, hypothalamus, prostate, and pituitary using GTEx Analysis. Nine studies (four Asian, four Caucasian, one African) met the criteria. The G allele was protective against infertility overall (OR: 0.80; 95% confidence interval [CI] = [0.70, 0.92]) and in Caucasian men (OR: 0.71; 95% CI = [0.54, 0.92]). Lower infertility risk was observed in Asian (AA vs. GG OR: 0.65; 95% CI = [0.43, 0.98]) and Caucasian men (OR: 0.49; 95% CI = [0.28, 0.83]). TSA indicated no further studies are likely to change these results. No significant change in expression of ESR1 was observed due to this SNP. The present meta-analysis suggests that the SNP Xba1 (rs9340799) in ESR1 is protective against male infertility, with current data sufficient to confirm these findings.