The aim of the study was to investigate the combined impact of the genetic heterogeneity of the glycoproteins Ia (GpIa) and IIIa (GpIIIa) and the platelet-endothelial cell adhesion molecule-1 (PECAM-1) and P-Selectin genes on IVF embryo transfer implantation failures (IVF-ET failures). Sixty nulligravida women with previous IVF-ET failures and 60 fertile controls were genotyped for the GpIa-C807T, GpIIIa-PlA1/PA2, PECAM-1-C373G (Leu125Val) and P-Selectin-A37674C (Thr715Pro) polymorphisms by pyrosequencing. Compared with wild-type combined homozygotes, carriers of combinations of risk alleles in two gene loci were at significantly increased risk for IVF-ET failure, whereas carriers of the combination of GpIa-807T, GpIIIa-PlA2 and PECAM-1-373G alleles had OR = 52.50 (95%CI: 4.05-680.95, p < .001). The area under the receiver-operating characteristic curve (AUC) based on the number of polymorphisms and the number of risk alleles per subject was 75.4% (95%CI: 66.7%-82.8%, p < .001) and 72.5% (95%CI: 63.6%-80.3%, p < .001), respectively. The OR per polymorphism and risk allele increase was 4.26 (95%CI: 2.15-8.41, p < .001) and 2.85 (95%CI: 1.71-4.76, p < .001), respectively. The above associations were more robust among younger women. The combined analysis of these polymorphisms revealed strong association of combined carriers with IVF-ET failures especially for younger women and provided a genetic risk score with good diagnostic accuracy in the prediction of IVF-ET failures.
The GpIa-C807T and GpIIIa-PlA1/PlA2 polymorphisms and more pronouncedly their combination are associated with increased risk of spontaneous abortions. The correlations were stronger for younger patients. Our results indicate that GpIa-807T and GpIIIa-PlA2 are susceptibility alleles for fetal loss in the Greek population.
Thrombophilic genetic factors have been shown to play an important role in implantation outcome after in vitro fertilisation (IVF). In this pilot study we investigated the frequencies of glycoprotein Ia (GpIa)-C807T and GpIIIa-PlA1/PlA2 polymorphisms in 60 nulligravidae women with a history of unexplained IVF implantation failures and compared them with 60 healthy fertile women. We found statistically significant associations between the GpIa-C807T and GpIIIa-PlA1/PlA2 polymorphisms and IVF implantation failure (odds ratio [OR] = 3.45, 95% confidence interval [CI]: 1.63-7.30, p = 0.001; and OR = 2.86, 95% CI: 1.27-6.45, p = 0.010, respectively) with the risk being higher for combined carriers of GpIa-807T and GpIIIa-PlA2 alleles (OR = 10.13, 95% CI: 2.85-35.99, p < 0.001), suggesting a synergistic effect of the two polymorphisms. The above associations were strongest for the youngest age group. Our results indicate that GpIa-807T and GpIIIa-PlA2 may be susceptibility alleles for IVF implantation failure.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.