Submit Manuscript | http://medcraveonline.com Abbreviations: IVF, in vitro fertilization; sEPCR, soluble endothelial protein C receptor; PCR-RFLP, polymerase chain reaction restriction fragment length polymorphism; ELISA, enzyme linked immunosorbent assay Introduction In vitro fertilization (IVF) is a well-documented risk factor for thromboembolic complications. 1 Hypercoagulability could be either intrinsic or may be induced by the hormonal treatment preceding the IVF procedure. 2 Possible plasma factor compositional reasons for the link between IVF and thrombotic events include activated protein C resistance. 3 Protein C regulates blood coagulation by inhibiting the activities of factors Va and VIIIa, and hence thrombin generation. 4 Activated protein C (APC) activity is regulated by several factors, including endothelial cell activated protein C receptor (EPCR). EPCR is a 46-kDa type I transmembrane glycoprotein spanning approximately 8kbp of genomic DNA, localized to 20q11.2, and consists of four exons interrupted by three introns. 5 EPCR can increase the activity of PC/APC via the thrombin-thrombomodulin complex by fve to 20-fold, leading to markedly elevated anticoagulation activity. 6 EPCR is expressed by both the vascular endothelium of large vessels 7 and the trophoblast giant cells at the feto-maternal boundary. 8 When APC binds EPCR, it activates protease-activated receptor 1 (PAR-1), thus triggering both anti-infammatory and cytoprotective signaling events in endothelial cells. 9 Soluble EPCR (sEPCR) is a soluble form of EPCR that is constituted by metalloprotease cleavage and present in normal human plasma. 10 Soluble EPCR plays a role in maintenance of pregnancy. That is confrmed by the fndings that EPCR expression is critical for embryo development. 11 In addition, blocking of EPCR activity by anti-EPCR autoantibodies was associated with adverse pregnancy outcomes. 12 Several mutants of EPCR have been identifed with differential expression levels and function. Four haplotypes involved in alteration of soluble EPCR levels were demonstrated, among which, the haplotype 3 (H3) is linked with increased soluble EPCR levels. This haplotype is identifed by the G/C/A/G combination at positions 1651, 3610, 4216, and 6936, respectively. 13 Moreover, 4678G/C (rs 9574) is a single-nucleotide polymorphisms (SNP) representative of one of the four different haplotypes in the EPCR gene, haplotype 1 (H1). 13 Poor pregnancy outcome was associated with specifc gene variants and altered soluble EPCR levels in some 14 but not all 15 studies. The aim of this study was to assess the predictive value of EPCR gene polymorphisms (6936A/G, 1651C/G, 4678C/G) Hematol Transfus Int J. 2018;6(1):11‒15. 11 © 2018 Abbassy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and build upon your work non-commercially. Endothelial cell protein c receptor gene 6936a/G, 1651c/G, 4678g/C polymorphisms and soluble endothelial protein c receptor levels impact on in vitro fertilization outcomes Volume 6 Issue 1 - 2018 Hadeer A Abbassy, 1 Ahmed F Galal, 2 Ashraf H Abdelrahman 2 1 Department of Clinical pathology, Alexandria University, Egypt 2 Department of Obstetrics & Gynecology, Alexandria University, Egypt Correspondence: Hadeer A Abbassy, Clinical pathology department, Faculty of Medicine, Alexandria University, Ahmed Yehia street, Zezenia, Alexandria, Egypt, Fax +2035850210, Tel +201066751862, Email hadeerabbassy@gmail.com Received: November 22, 2017 | Published: January 19, 2018 Abstract Hypercoagulability could be intrinsic or may be induced by the hormonal treatment preceding in vitro fertilization (IVF) procedure. Endothelial cell protein C receptor (EPCR) enhances the generation of activated protein C by the thrombin– thrombomodulin complex. EPCR expression is critical for embryo development hence soluble EPCR plays a role in maintenance of pregnancy. Poor pregnancy outcome was associated with specific gene variants and altered soluble EPCR levels. The aim of this work was to evaluate the predictive value of EPCR gene polymorphisms (6936A/G, 1651C/G, 4678C/G) and sEPCR level on the IVF outcome. The study was conducted on 45 women with repeated IVF failure, three or more previous IVF-embryo transfer cycles, compared to 45 healthy age-matched women eligible for IVF with positive β-HCG were selected two weeks after embryo transfer as a control group. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) for the EPCR polymorphisms (6936A/G, 1651C/G, 4678G/C) was done for both cases and controls. Soluble EPCR levels were measured with ELISA. As regards the mutant EPCR (6936A/G) genotypes (AG, GG) were higher than the wild type (AA). The homozygous mutant genotype (GG) was higher in comparison to the wild type (AA). The mutant allele (G) was higher than the wild allele (A). Higher frequencies of the (1651C/G) genotype and lower soluble EPCR levels were noted, both in (C/C) and (C/G) genotype carriers. Regarding, EPCR polymorphism (4678G/C), the homozygous mutant genotype (CC) was significantly lower than the homozygous wild type (GG). The present data suggest that the 6936A/G and 1651C/G EPCR gene variants coupled with procoagulant diminished levels of sEPCR could be associated with a higher tendency for repeated implantation failure. Keywords: endothelial protein C receptor, gene, polymorphisms, repeated implantation failure, in vitro fertilization Hematology & Transfusion International Journal Research Article Open Access