thromboplastin and Infertility--Female

Tissue factor (TF), is a cellular receptor that binds the ligand factor VII/VIIa to initiate the blood coagulation cascade. In addition to its role as the initiator of the hemostatic cascade, TF is known to be involved in angiogenesis via an interaction with factor VIIa and protease-activated receptor-2 (PAR-2). In this article we review previous studies from our laboratory demonstrating that the pattern and level of TF expression is altered in multiple cell types derived from eutopic and ectopic endometrium from women with endometriosis compared with normal endometrium. We posit that the inflammatory environment that occurs in ectopic and eutopic endometrium from patients with disease results in high TF expression that in turn, signals via PAR-2 to further produce inflammatory cytokine or chemokine production and macrophage recruitment. Thus, our studies suggest that TF might be an ideal target for therapeutic intervention in endometriosis.

Topics: Animals; Cell Proliferation; Cytokines; Endometriosis; Endometrium; Female; Gene Expression Regulation; Humans; Immunohistochemistry; Infertility, Female; Inflammation; Mice; Models, Biological; Neovascularization, Pathologic; Thromboplastin

The aim of this study was to investigate tissue factor (TF) and its inhibitors TFPI and TFPI2 in secretory endometrium of fertile women and in women with unexplained infertility in relation to endometrial receptivity. In addition, common variation in the regulatory area of TF and TFPI genes was studied. Immunostaining of TF and TFPI, together with the appearance of pinopodes, revealed similar expression pattern in fertile endometrium throughout the secretory phase, being highest at the time of implantation. When compared protein expression levels at the time of implantation, infertile women demonstrated significantly higher TFPI expression in luminal epithelium. Furthermore, polymorphism TF -603 A/G was associated with the endometrial protein level in infertile women, being highest in women with GG genotype, and variation TFPI -287 T/C was associated with unexplained infertility, where infertile women presented more frequently T allele than fertile women. Contrary to TF and TFPI, TFPI2 showed different mRNA and protein expression patterns in fertile endometrium, and no differences between fertile and infertile women were detected. We conclude that the TF pathway is involved in normal endometrial maturation, where TF and TFPI seem to have important roles at the time of embryo implantation. Higher TFPI expression level during the time of embryo implantation and TFPI -287 T allele could be risk factors for unexplained infertility. No distinct involvement of TFPI2 in the regulation of endometrial receptivity and unexplained infertility was found.

Topics: DNA; Endometrium; Female; Glycoproteins; Humans; Immunohistochemistry; Infertility, Female; Lipoproteins; Polymerase Chain Reaction; Polymorphism, Genetic; Thromboplastin

Coagulation and fibrinolytic profiles have been studied in two groups of sterility patients receiving low dosage regimens of human gonadotropins for ovarian stimulation. This investigation was prompted by a report of two patients with severe episodes of intravascular coagulation associated with periods of "hyperstimulation" from these drugs. No statistically significant changes were found as a result of administration of one ampoule of human menopausal (HMG) or pituitary gonadotropins (HPG) for 8 days followed by 9000 units of human chorionic gonadotrophin (HCG). A course of 2-3 ampoules HMG on alternate days for longer periods of time prior to administration of HCG also failed to produce significant alterations of the coagulation or fibrinolytic mechanisms. In two patients with severe hyperstimulation there were elevated levels of factor V, platelets, fibrinogen, profibrinolysin, and fibrinolytic inhibitors. Generation of thromboplastin was also increased when plasma was diluted one to fifty in the thromboplastin generation test. These results suggest a possibly increased coagulation potential in patients with "hyperstimulation syndrome" but not in those receiving the low dosage regimens of human gonadotropins more commonly used for ovarian stimulation at the present time.

Topics: Blood Coagulation; Blood Coagulation Factors; Blood Coagulation Tests; Chorionic Gonadotropin; Estrogens; Factor V; Female; Fibrinogen; Fibrinolysis; Gonadotropins; Gonadotropins, Pituitary; Humans; Infertility, Female; Meigs Syndrome; Menotropins; Progestins; Thromboplastin; Thrombosis; Time Factors