Fibrinolysis alterations in infertile women during controlled ovarian stimulation: Influence of BMI and genetic components

摘要

Introduction: Ovarian stimulation protocols have been described to induce prothrombotic phenotype through alterations of both coagulation and fibrinolysis pathways. We investigated fibrinolytic changes during ovarian stimulation through a global test (CLT) and PAI-1 and TAFI concentrations at different times of ovarian stimulation procedure, and the influence of polymorphisms in genes encoding for fibrinogen chains (FGA, FGB, FGG), t-PA (PLAT), TAFI (CBP2), FXIII (FXIIA1, FXIIIB), plasminogen (PLG) and PAI-1 (PAI1) on their intermediate phenotype. Materials and methods: We evaluated fibrinolytic and genetic parameters in 110 infertile women undergoing ovarian stimulation procedure (in vitro fertilization, IVF or intracytoplasmic sperm injection, ICSI). All women were observed during the mid-luteal phase of cycle (T0) and on day 5 (T1), 7 (T2) and 9 (T3) of the ovarian stimulation. Results: Significant changes in fibrinolytic parameters from T 0 to T3 of ovarian stimulation were found (CLT p = 0.003; TAFI p = 0.009 and PAI-1 p = 0.003). CLT values, TAFI and PAI-1 concentrations significantly increased from baseline to T1 (p 0.0001, p = 0.01, p = 0.005, respectively), and decreased at T2, but remained higher than those at T0. Moreover, at baseline overweight women showed longer CLT, higher TAFI and PAI-1 concentrations than normal weight women, as well as at T1 two-fold longer CLT and higher PAI-1 concentrations were observed (p = 0.001 and p = 0.05, respectively). Significant differences of TAFI and PAI-1 concentrations during ovarian stimulation according to TAFI and PAI1 polymorphisms were observed. Conclusions: This study shows alterations of fibrinolysis and suggests the contribution of TAFI and PAI1 genes in modulating fibrinolysis changes during the ovarian stimulation cycle.