Polymorphisms of vascular endothelial growth factor and recurrent implantation failure: a systematic review and meta-analysis

Purpose: To investigate the associations between polymorphisms of vascular endothelial growth factor (VEGF) with recurrent implantation failure (RIF).

Methods: We performed the systematic review and meta-analysis by searching databases of PubMed, EMBASE, OVID, and CNKI (China National Knowledge Infrastructure) for studies that evaluated the associations between VEGF polymorphisms with RIF. Meta-analysis was performed if the polymorphism was studied by more than two case-control studies. Data were analyzed using R software. Odds ratios (ORs) with 95% confidence intervals (CIs) were reported to assess the associations.

Results: Nine VEGF polymorphisms (-1154G > A, -460T > C, +405G > C, -7C > T, -634C > G, -2578C > A, +936C > T, 5C > T, -583C > T) were systematically reviewed. Meta-analysis was performed on VEGF -1154 G > A polymorphism. Three case-control studies consisted of 683 women were included in the quantitative meta-analysis (305 RIF patients and 378 controls). Results showed that VEGF -1154A allele was significantly associated with RIF (OR 1.39, 95% CI 1.08-1.78, P-value = 0.01). The dominant genetic model showed that VEGF 1154AA plus VEGF 1154AG genotypes were more frequent in RIF patients than VEGF 1154GG genotype (OR 1.56, 95% CI 1.10-2.20, P-value = 0.01). However, the result under the recessive genetic model showed no significant difference (OR 1.67, 95% CI 0.92-3.03, P-value = 0.09).

Conclusion: VEGF -1154A allele may serve as one of the predisposing factors of RIF. Women with VEGF 1154 AA/GA genotypes were at higher risk of RIF. However, we should consider the haplotype effect of VEGF polymorphisms in future studies.