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

Recurrent implantation failure (RIF) is recognized when transferred embryos fail to implant following repeated in vitro fertilization (IVF) cycles [1]. RIF is commonly defined as the failure of implantation after three or more consecutive IVF attempts, with which 1-2 high-grade embryos were transferred in each cycle [2]. Cytotrophoblast invasion to the proper depth of the uterus secures proper anchorage for the conceptus which is needed for successful implantation [3]. A functional balance of fibrinolysis and coagulation may secure adequate trophoblast invasion, which is crucial for a regular implantation [4]. During cytotrophoblast invasion, plasminogen activator inhibitor 1 (PAI-1) appears to be involved in controlling proteolysis and remodeling of maternal tissue [5]. PAI-1 inhibits tissueand urokinase-type plasminogen activators, thus decreasing plasmin production and the dissolution of fibrin clots. The PAI-1 gene is located on the long arm of chromosome 7 (7q21.3-q22). Plasma PAI-1 levels are linked with a common guanosine insertion/ deletion gene polymorphism, 4G/5G, 675 bp upstream from the start site of translation and higher levels have been associated with homozygosity for the deletion genotype (4G/4G) than those associated with the insertion genotype (5G/5G), and in turn with impaired fibrinolytic activity [6]. PAI-1 on one hand, inhibits urokinase plasminogen activator (uPA)-urokinase plasminogen activator receptor (uPAR) leading to inhibition of trophoblast invasion [7], and on the other, it may trigger or augment the trophoblast invasion process [8]. However, an association has been found between PAI-1 -675 4G/5G polymorphism and recurrent pregnancy loss (RPL) [9] and to a lesser extent RIF [10]. Coagulation factor XIII (FXIII) covalently cross-links fibrin and affects fibrinolysis, thus it may have an impact on the ability of the trophoblast to invade into the endometrium and to stabilize attachment with fibrin cross-linking. FXIII Val34Leu Volume 6 Issue 1 2018