Polymorphisms of plasminogen activator iInhibitor-1 4G/5G, coagulation factor XIII Val34 Leu and angiotensin converting enzyme I/D impact on recurrent implantation failure

Abstract

Repeated implantation failure (RIF) is recognized when transferred embryos fail to implant following repeated in vitro fertilization (IVF) cycles. A functional balance of fibrinolysis and coagulation may secure adequate trophoblast invasion, which is crucial for a regular implantation. During cytotrophoblast invasion, plasminogen activator inhibitor 1 (PAI-1) appears to be involved in controlling proteolysis and remodeling of maternal tissue. Coagulation factor XIII (FXIII) may have an impact on the ability of the trophoblast to invade into the endometrium and to stabilize attachment with fibrin cross-linking. Angiotensin converting enzyme (ACE) participates in the regulation of vascular tone and changes in vascular metabolites affect the functions of the fetoplacental complex and may induce abnormalities of blood circulation in the placenta. The aim of this study was to assess the predictive value of PAI-1 4G/5G, FXIII Val34Leu and ACE I/D polymorphisms on the IVF outcome in Egyptian women with repeated IVF failure. The present study was conducted on 60 women with repeated IVF failure, three or more previous IVF-embryo transfer cycles and 60 healthy age-matched women eligible for IVF. PCR-RFLP for the PAI-1 4G/5G, FXIII Val34Leu and ACE I/D polymorphisms was done for cases and control groups. Cases with RIF showed higher prevalence of the 4G allele of the PAI-1 -675 4G/5G polymorphism (P = 0.029). Higher frequencies of the heterozygous and homozygous FXIII polymorphism were noted in cases (P = 0.016, 0.020, respectively) together with higher risk to carry the Leu allele (P = 0.001). The heterozygous ACE I/D polymorphism was predominant in the studied cases (P = 0.011). The data point to the importance of the PAI-1 4G/5G and the FXIII Val34Leu and to a lesser extent the ACE I/D, polymorphisms as possible biomarkers to select populations at risk of implantation failure prior to attempting pregnancy. Nevertheless, larger scale studies are recommended to support the results.