Cardiovascular problems associated with IVF therapy.

We are now in the beginning of the fifth decade of in vitro fertilization (IVF) with more than ten million children born and an annual growth rate of half a million. It was recently found that there is a sevenfold increase in the incidence of pulmonary embolism (PE) during the first trimester of an IVF pregnancy as compared to spontaneous pregnancy. PE is a major cause of maternal mortality, and it is thus of outmost importance to understand the pathophysiological mechanism. The oestrogen surge during the ovarian stimulation has been hypothesized to be the initiating pathophysiological event. A support of this is a current report showing that embryo transfer performed directly after ovarian stimulation increased the risk of PE more than eightfold, whereas no such increase was noted after delayed embryo transfer. This increased risk coincides with a persisting increased oestrogen level. Further reported cardiovascular problems are arterial thromboses, pre-eclampsia and gestational hypertension. Global haemostasis tests change in the direction of increased coagulability, but mostly within normal limits. Cell-bound haemostasis and in particular platelet activation are less studied. However, a major increase in the number of microvesicles (MVs) and markers indicating platelet activation was reported during ovarian stimulation. We now need longitudinal data concerning haemostatic variables that extends into the first trimester. A major research focus should be to identify biomarkers that could be used already before instigation of IVF. Another way to avoid risk could be to delay embryo transfer by adapting a freeze-all strategy.