Polymorphisms of Plasminogen Activator Inhibitor-1 4G/5G, Coagulation Factor XIII Val34Leu and Angiotensin Converting Enzyme I/D Impact on Recurrent Implantation Failure

Abstract

Recurrent implantation failure (RIF) is recognized when failure of transferred embryos to implant occurs following repeated in vitro fertilization (IVF) cycles. During cytotrophoblast invasion, plasminogen activator inhibitor 1 (PAI-1) appears to be involved in controlling proteolysis and maternal tissue remodeling. 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 crosslinking. 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 the present work was to compare the predictive value of PAI-1 4G/5G, FXIII Val34Leu and ACE I/D polymorphisms on the IVF outcome in women with RIF. The present study was conducted on 60 women with RIF (RIF group) and 60 healthy, age-matched women eligible for IVF with positive β-human chorionic gonadotropin (β-HCG) two weeks after embryo transfer (control group). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the PAI-1 4G/5G, FXIII Val34Leu and ACE I/D polymorphisms was performed for all participants. The RIF group showed higher predominance of the 4G allele of the PAI-1 polymorphism -675 4G/5G (P= 0.029). Higher frequencies of the heterozygous and homozygous FXIII polymorphism were noted in the RIF group (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 RIF group (P= 0.011). It could be concluded that certain studied polymorphisms (PAI-1 4G/5G and the FXIII Val34Leu, and to a lesser extent the ACE I/D) could be associated with repeated implantation failure.