Hypercoagulability, high tissue factor and low tissue factor pathway inhibitor levels in severe ovarian hyperstimulation syndrome: possible association with clinical outcome.

During ovarian gonadotrophin stimulation for ovulation induction or in vitro fertilization, a clinical severe ovarian hyperstimulation syndrome (OHSS) may occur. Only few studies have investigated the mechanism responsible for the alterations of the haemostatic system in women affected by severe OHSS. The aim of the present study was to investigate the correlation between the magnitude of ovarian stimulation and the increase in fibrin formation and degradation in severe OHSS. Twenty-five patients (age range 23-43 years) who were hospitalized for severe OHSS, 25 women undergoing in vitro fertilization who did not develop OHSS (case-control group) and 25 healthy age-matched women (healthy control group) were investigated. On the day of admission a number of haemostatic markers, including D-dimer, thrombin-antithrombin complexes (TAT), prothrombin fragment 1 + 2 (F1 + 2), plasmin-antiplasmin complexes (PAP), tissue factor (TF), tissue factor pathway inhibitor (TFPI) and von Willebrand factor antigen (vWF), were examined. In patients with severe OHSS, TF, D-dimer, TAT, F1 + 2, PAP and vWF antigen plasma levels were significantly higher than those observed both in the case-control group and in healthy controls, whereas TFPI levels were significantly lower (P < 0.005) with respect to both case-controls and healthy controls. D-Dimer levels were related with serum oestradiol levels and oocyte number recovered (r = 0.45, P < 0.001 and r = 0.47, P < 0.001, respectively). D-Dimer and TAT levels were significantly (P < 0.05 and P < 0.005, respectively) higher in OHSS patients with unsuccessful pregnancy outcome (D-dimer, 226.5, 56-1449 ng/ml; TAT, 19.8, 3.1-82.6 microg/l) with respect to those with successful outcome of pregnancy (D-dimer, 145, 29-330 ng/ml; TAT, 5.0, 1.0-19.6 microg/l). Our data indicate that a marked hypercoagulability with alterations of TF and TFPI levels is detectable in patients with severe OHSS and that it is related to the clinical outcome.