The Association Between Annexin A5 c.-302G > T Variant and the Risk of Recurrent Pregnancy Loss: Systematic Review and Meta-analysis

This study aimed to conduct a comprehensive meta-analysis of the relationship between Annexin A5 (ANXA5) c.-302G > T variant and susceptibility to recurrent pregnancy loss (RPL). We conducted a comprehensive systematic search of the literature published before June 17, 2023 using PubMed, Embase, Web of Science, and Cochrane Library. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included studies. The odds ratio was used to estimate the correlation of the ANXA5 c.-302 T > G genetic alteration with RPL susceptibility. The I squared (I-2) statistic and Q statistic were used to assess the heterogeneity among the included studies. And Begg's test and Egger's regression were then conducted to evaluate publication bias. In this meta-analysis, we included seven studies comprising 1535 RPL cases and 1328 healthy pregnant women to investigate the relationship between ANXA5 c.-302G > T variants and the susceptibility of RPL. No significant publication bias was detected across different comparison models. In the overall population analysis, the ANXA5 c.-302G > T variant was positively associated with the risk of RPL under the dominant, allelic, heterozygote and homozygous models. Meta-regression analysis was performed to identify the potential source of heterogeneity, revealing that neither publication year nor country contributed to heterogeneity. Our findings provided robust evidence that the ANXA5 c.-302G > T variant was significantly associated with an increased risk of RPL, highlighting its potential as a genetic marker for identifying women at high risk of developing RPL. These results emphasized the importance of genetic screening in improving the understanding and clinical management of RPL.