Potential Role of the Corpus Luteum in Maternal Cardiovascular Adaptation to Pregnancy, and Preeclampsia Risk

Abstract Studies in the gravid rat model revealed a key role for the corpus luteal hormone, relaxin, in the maternal circulatory changes of early pregnancy epitomized by profound systemic vasodilation and increased arterial compliance. To determine whether the corpus luteum may play a similar role in human pregnancy, women who conceived by in vitro fertilization were studied. Implementation of artificial (programmed) cycles for embryo transfers, which precluded formation of a corpus luteum, was associated with significant attenuation of the gestational rise in cardiac output and fall in carotid-femoral pulse wave velocity (reflecting impairment of both arterial dilation and increased compliance, respectively), as well as deficiencies in other cardiovascular changes normally observed during the first trimester. Cardiac output and carotid-femoral pulse wave velocity were restored after the first trimester consistent with rescue by placental vasodilators such as placental growth factor. In addition, a potential role of corpus luteal factor(s) in reducing the risk of developing preeclampsia was also hypothesized. In the majority of single and multiple center, prospective and retrospective cohort (and registry) studies, the risk for developing preeclampsia and preeclampsia with severe features was significantly enhanced in women undergoing autologous frozen embryo transfer in artificial cycles without the formation of a corpus luteum relative to natural, modified natural, stimulated or controlled ovarian stimulation cycles, and spontaneous pregnancies—all associated with the formation of at least one corpus luteum. Taken together, these observational studies are sufficiently compelling to warrant randomized clinical trials comparing preeclampsia risk in autologous frozen embryo transfer in natural versus artificial cycles. Impaired endometrial function due to suboptimal hormonal administration is an alternative, but not mutually exclusive explanation for increased preeclampsia risk in autologous frozen embryo transfer-artificial cycles. Potential mechanisms by which the corpus luteum may reduce the risk of developing preeclampsia, and whether autologous frozen embryo transfer-artificial cycles are associated with increased risk for preterm preeclampsia, term preeclampsia or both are discussed. Last, suggestions for future investigations are noted.