Vascular Endothelial Growth Factor Variants (936C/T, 634C/G, 2578A/C) and Their Genotype–Haplotype Association with Recurrent Implantation Failure in Infertile Women: A Single-Center Analytical Study

Background: Vascular Endothelial Growth Factor (VEGF) is a key regulator in angiogenesis and contributes to a successful implantation. The current study has the following objective: to perform genotyping and haplotyping analysis to confirm whether the VEGF-936C/T, VEGF-634C/G, and VEGF-2578C/A gene polymorphisms are associated with the susceptibility for recurrent implantation failure (RIF) in Romanian females at reproductive age. Materials and Methods: In total, 41 infertile women experiencing recurrent implantation failure and 44 women with minor infertility were genotyped for VEGF polymorphisms using PCR-RFLP analysis. Results: The VEGF-936C/T polymorphism in the dominant model, (C/T+T/T), represents an increased risk factor for recurrent implantation failure, the odds being 2.70 (95% CI: [1.04, 7.00]). Also, VEGF-2578C/A gene polymorphism represents the risk factor of RIF under the codominant (adjusted-OR = 5.28, 95% CI: [1.42, 19.65]) and recessive models (adjusted-OR = 5.15, 95% CI: [1.55, 17.09]). Patients carrying the VEGF-T936 allele or VEGF-C2578 allele had 2.25-fold and 2.36-fold increased odds of implantation failure (95% CI: [1.05, 4.81], p = 0.034) and 95% CI: [1.27, 4.39], p = 0.006), respectively. The results of the haplotype-based regression analysis reveal that patient carriers of the VEGF-936/-634/-2578 T-C-A haplotype had 12.39 increased odds of RIF. Also, carriers of the VEGF-936/-2578 T-A haplotype had 9.56-fold (p = 0.0113) increased odds of RIF after adjusting for age. Conclusions: We found a significant association between VEGF-936C/T and VEGF-2578C/A polymorphisms and the odds of RIF in this cohort of Romanian infertile women. Haplotype analysis suggested the role of VEGF-936/-634/-2578 T-C-A and VEGF-936/-2578 T-A haplotypes as a risk factors for RIF.