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

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.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 (T(0)) and on day 5 (T(1)), 7 (T(2)) and 9 (T(3)) of the ovarian stimulation.Significant changes in fibrinolytic parameters from T(0) to T(3) 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 T(1) (p<0.0001, p=0.01, p=0.005, respectively)(,) and decreased at T(2,) but remained higher than those at T(0). Moreover, at baseline overweight women showed longer CLT, higher TAFI and PAI-1 concentrations than normal weight women, as well as at T(1) 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.This study shows alterations of fibrinolysis and suggests the contribution of TAFI and PAI1 genes in modulating fibrinolysis changes during the ovarian stimulation cycle.