Association between Plasminogen Activator Inhibitor‐1 Gene Polymorphisms and Recurrent Pregnancy Loss: A Systematic Review and Meta‐Analysis

Human plasminogen activator inhibitor-1 (PAI-1) is closely related to embryonic development and pregnancy success. The association between PAI-1 gene polymorphisms (PAI-1-844G/A and PAI-1-675G/A) and the risk of recurrent pregnancy loss (RPL) is controversial. Therefore, we perform this review to clarify the association between PAI-1 gene polymorphisms and RPL risk. We performed a systematic search for studies that described the effect of PAI-1 polymorphisms on RPL risk. The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were considered under recessive genetic models. Furthermore, we conducted a subgroup analysis based on the studies' geographic regions of origin. Data were analyzed using Stata 11.2 software. Eighteen studies were included, and a high degree of statistical heterogeneity existed among the studies. In this study, we found a significant association between the PAI-1-675G/A polymorphism and the risk of RPL under the recessive model (OR = 1.70, 95% CI = 1.21-2.38). However, no significant association between the PAI-1-844G/A polymorphism and RPL was noted. PAI-1-675G/A (4G/5G) polymorphisms play a potential role in RPL. The screening of PAI-1 (4G/5G) gene mutations should be included during an RPL diagnostic workup, and patients should be treated using anticoagulant therapy during pregnancy if necessary.