Response to activated protein C during normal menstrual cycle and ovarian stimulation

Oestrogen has been pointed out as a pre-thrombotic factor. Protein C is a key enzyme in the down-regulation of blood coagulation. Recent data suggest that activated protein C (APC) resistance which is not due to the factor V:Q 506 Leiden mutation and appears to be acquired, is also a risk factor for thrombosis. In this study, we evaluated the endogenous oestradiol production and its possible influence on APC. Eighteen normally menstruating women were studied during one ovulatory cycle. Furthermore, 20 women undergoing controlled ovarian stimulation, and achieving extremely high oestradiol concentrations, were investigated. Normalized APC (nAPC) ratio (clotting time of tested sample/clotting time of pooled control plasma) was measured. Samples collected on menstrual cycle days 1-3, 6-8, 13-14, 20-24 corresponded to nAPC ratios 1.02 +/- 0.19 (mean +/- SD), 1.05 +/- 0. 15, 1.02 +/- 0.16 and 1.03 +/- 0.21 respectively. During ovarian stimulation, the nAPC ratios were 0.99 +/- 0.12, 1.03 +/- 0.18, 1.01 +/- 0.16 and 0.97 +/- 0.13 at oestradiol minimum, days 5-8 pre-oocyte retrieval, oestradiol maximum and at oocyte retrieval respectively. In spite of the great difference in the concentrations of oestradiol between women in normal menstrual cycle and women undergoing ovarian stimulation, no difference in nAPC ratios was observed.