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

<b>Background:</b> 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-<i>936C/T</i>, VEGF-<i>634C/G</i>, and VEGF-<i>2578C/A</i> gene polymorphisms are associated with the susceptibility for recurrent implantation failure (RIF) in Romanian females at reproductive age. <b>Materials and Methods:</b> In total, 41 infertile women experiencing recurrent implantation failure and 44 women with minor infertility were genotyped for VEGF polymorphisms using PCR-RFLP analysis. <b>Results:</b> The VEGF-<i>936C/T</i> 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-<i>2578C/A</i> 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-<i>T936</i> allele or VEGF-<i>C2578</i> allele had 2.25-fold and 2.36-fold increased odds of implantation failure (95% CI: [1.05, 4.81], <i>p</i> = 0.034) and 95% CI: [1.27, 4.39], <i>p</i> = 0.006), respectively. The results of the haplotype-based regression analysis reveal that patient carriers of the VEGF-<i>936/-634/-2578 T-C-A</i> haplotype had 12.39 increased odds of RIF. Also, carriers of the VEGF-<i>936/-2578 T-A</i> haplotype had 9.56-fold (<i>p</i> = 0.0113) increased odds of RIF after adjusting for age. <b>Conclusions:</b> We found a significant association between VEGF-<i>936C/T</i> and VEGF-<i>2578C/A</i> polymorphisms and the odds of RIF in this cohort of Romanian infertile women. Haplotype analysis suggested the role of VEGF-<i>936/-634/-2578 T-C-A</i> and VEGF-<i>936/-2578 T-A</i> haplotypes as a risk factors for RIF.