We aimed to conduct a comprehensive meta-analysis of the association between methionine synthase reductase (MTRR) c.66A>G variant and Recurrent pregnancy loss (RPL) susceptibility.

We conducted a comprehensive systematic search of literature published before February 25, 2023 using PubMed, Embase, Web of Science, and Cochrane Library. Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included studies. The odds ratio (OR) was used to estimate the association between MTRR c.66A>G variant and RPL susceptibility. The I squared (I²) statistic and Q statistic were used to assess the heterogeneity among the included studies. And Begg's test and Egger's regression were then used to test the existence of publication bias.

In this meta-analysis, we included 10 studies comprising 1842 RPL cases and 2173 healthy pregnant women to investigate the relationship between MTRR c.66A>G variants and the susceptibility of RPL. In the overall population analysis, MTRR c.66A>G variant was not significantly associated with the risk of RPL in different comparison models. Since 9 of the included studies were conducted in Asia, we performed analyses separately for Asian populations, including a total of 1855 cases and 2127 controls. Results showed, in Asian populations, there is no significant correlation between c.66A>G variant and the risk of RPL. Subgroup analyses according to ethnicity and country yielded similar results.

Our findings suggested that the MTRR c.66A>G variant was not significantly associated with the risk of RPL.