Effect of in vitro fertilization treatment and subsequent pregnancy on theprotein C pathway

Thirty-three women who were planned for an in vitro fertilization (IVF) cyc le donated blood at four time points during treatment: at baseline, after d ownregulation. hyperstimulation and luteal support. Levels of progesterone, 17 beta -oestradiol and indicators of the protein C pathway, i.e. activate d protein C sensitivity ratios (APCsr), protein C. protein C inhibitor and protein S were measured. Compared with baseline, oestradiol decreased twofo ld at downregulation and increased 40-fold at hyperstimulation. Progesteron e was elevated 2.5-fold at hyperstimulation and 40-fold at luteal support. The APCsr increased slightly at downregulation, significantly increased dur ing hyperstimulation and remained high during luteal support. The plasma le vels of the anticoagulant proteins did not change or changed moderately dur ing treatment. During downregulation. progesterone correlated negatively wi th APCsr (r = -0.398, P = 0.024). At hyperstimulation oestradiol correlated with the APCsr (r =0.615, P < 0.0005). Moreover, there was a significant c orrelation (r = 0.599, P < 0.0005) between the difference in baseline and h yperstimulation values of oestradiol (Delta E2 = 6.6 nmol/l) and the APCsr (Delta APCsr = 0.30). Six women who participated in this study became pregn ant. Compared with baseline, the APCsr was increased 1.9-fold (Delta APCsr = 1.48) and free protein S free level decreased 30% at 7 weeks of pregnancy . This study demonstrates that despite the considerable changes in endogeno us oestradiol and progesterone during an IVF cycle, changes in plasma level s of anticoagulant proteins are moderate. The significant increase in the A PCsr during hyperstimulation indicates that acquired APC resistance observe d during sex steroid hormone changes in women is at least partially caused by high oestrogen levels. Our findings demonstrate that IVF treatment is ac companied by the development of a mild prothrombotic condition.