Is tissue factor pathway inhibitor a marker of procoagulable status in healthy infertile women undergoing ovarian stimulation for assisted reproduction?

Abstract

Increased serum estradiol levels occurred during ovarian stimulation for assisted reproduction. Tissue factor pathway inhibitor (TFPI) plays a relevant role in regulating haemostatic equilibrium, and its decrease has been documented in conditions in which blood coagulation occurs. We investigated TFPI concentrations and coagulative pathway in healthy infertile women undergoing ovarian stimulation. We investigated 27 healthy infertile women, median age 37 (25-41) years, undergoing ovarian stimulation, observed during the mid-luteal phase of cycle (T0) and on day 5 (T1), and between day 7 and 9 (T2) of ovarian stimulation. Coagulative pathway was assessed by a global test [endogenous thrombin potential, (ETP)] and TFPI concentrations. TFPI values progressively and significantly decreased throughout the ovarian stimulation procedure (P = 0.03), contemporarily estradiol levels progressively and significantly increased from baseline to T2 (P < 0.0001). A significant negative correlation between changes in estradiol and TFPI levels was observed (P = 0.03). As concerns ETP parameters a significant increase of ETP (mA) and Cmax (mA/min) throughout the ovarian stimulation cycle was found (P = 0.003 and P = 0.002, respectively). TFPI values progressively and significantly decreased throughout the ovarian stimulation, and negatively correlated with estradiol, thus suggesting that TFPI may represent one of the main 'actors' involved in the hypercoagulable status, occurring during assisted reproduction. The relationship between TFPI and estradiol levels might contribute to the knowledge of mechanisms able to modify a quite milieu into a prothrombotic status. Nevertheless, the small number of individuals investigated might influence the relevance of our results.