PAI-1 4G/4G Genotype Is Associated with Recurrent Implantation Failure: a Systematic Review and Meta-analysis

To detect the association between PAI-1 -675 4G/5G polymorphism and recurrent implantation failure (RIF). We performed this meta-analysis by searching databases of PubMed, EMBASE, OVID, and CNKI (China National Knowledge Infrastructure) for case-control studies that evaluated the association between PAI 4G/5G polymorphism and RIF. Meta-analysis was performed using the random-effects model. The odds ratios (ORs) with 95% confidence intervals (CIs) were reported to evaluate the association. Meta-regression and subgroup analysis were performed to explore the source of heterogeneity. Sensitivity analysis and trim-and-fill analysis were performed to explore the robustness of the meta-analysis. Eight case-control studies consisted of 1273 women were included in this meta-analysis (including 697 RIF patients and 576 control participants). The combined results showed that the homozygous genotype of PAI-1 -675 4G/4G was significantly associated with RIF (OR 2.79, 95%CI 1.53-5.08, P-value = 0.0008). Meta-regression and subgroup analysis showed that sample origin is the primary source of heterogeneity (P-value for meta-regression: 0.005). Study quality also explains some heterogeneity (P-value for meta-regression: 0.03). Sensitivity analysis showed that the result was not significantly changed after excluding one study each time. Trim-and-fill analysis showed that the result was not significantly changed after filled with three studies. PAI -675 4G/4G genotype may serve as one of the predisposing factors of RIF. Women with PAI-1 4G/4G genotype were at higher risk of RIF. However, more high-quality studies are needed to confirm the conclusion.