Acquired resistance to the
anticoagulant action of activated
protein C (APC) has been proposed to explain the increased risk of
venous thrombosis associated with pregnancy,
hormone replacement therapy and the use of
oral contraceptives. In this study, we have investigated whether the hormonal changes induced during in vitro fertilization (IVF) treatment are also associated with acquired
APC resistance. Twenty-nine women, who were planned for an IVF cycle, donated blood at four time points during treatment, i.e. at baseline, down-regulation, hyperstimulation and luteal support. In the plasma samples, APC sensitivity ratios (APCsr) and the levels of
progesterone and
estradiol were measured. The changes in plasma concentrations of
hormones were in accordance with literature. The APCsr increased significantly during hyperstimulation and remained high during luteal support. The extent of
APC resistance occurring during IVF treatment was comparable to that observed during the use of second generation OC and was less pronounced than that occurring during pregnancy. The change in
estradiol between baseline and hyperstimulation correlated with the change in APCsr. Although this suggests that plasma
estrogen levels are an important determinant for acquired
APC resistance, it remains to be established which
plasma proteins are responsible for
estrogen-induced
APC resistance.