Purpose Methylenetetrahydrofolate reductase is one of the key enzymes in folate metabolism. But the association between polymorphism and the risk of male infertility is still controversial. Therefore, this study used a meta-analysis on the collection of data to analyze MTHFR gene C677T polymorphism (known as c.665 C > T, rs1801133, p.Ala222Val). Methods PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Wan fang. Data were searched to identify eligible studies. We sifted the data collection by Hardy-Weinberg equilibrium calculator and used odds ratios (ORs) and 95% confidence intervals (95% CIs) to conduct data through RevMan5.0 and StataSE12.0 software. Results A total of 15 studies have 3853 patients with infertility and 3613 healthy controls in this meta-analysis. Our results showed that T variant of MTHFR C677T gene polymorphism was significantly associated with an increased risk of male infertility (for T vs. C: OR = 1.38, 95% CI = 1.18–1.63; for TT vs. CC: OR = 1.86, 95% CI = 1.36–2.54; for CT vs. CC: OR = 1.34, 95% CI = 1.03–1.74; for TT vs. CT: OR = 1.52, 95% CI = 1.26–1.84; for TT vs. CT + CC: OR = 1.42, 95% CI = 1.19–1.70; for TT + CT versus CC: OR = 1.46, 95%CI = 1.05–2.04). In addition, the results indicated that T allele had the positive association which was driven by East-asian populations (random: OR = 1.44, 95% CI = 1.2–1.74; fixed: OR = 1.39, 95% CI = 1.20–1.61), Middle-eastern populations (random: OR = 1.30, 95% CI = 1.05–1.63; fixed: OR = 1.30, 95% CI = 1.05–1.63) and Mixed-race (random: OR = 1.96, 95% CI = 1.35–2.85; fixed: OR = 1.31, 95% CI = 1.20–1.43). Conclusion This meta-analysis suggests that MTHFR C677T polymorphism is associated with male infertility.
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