Wiegel RE, Danser AHJ, Steegers-Theunissen RPM, et al. - Prorenin, renin’s inactive precursor, is secreted by the corpus luteum (CL) and may contribute to the renin-angiotensin-aldosterone-system (RAAS) activation that is needed for maternal adaptation in pregnancy. Researchers here examined maternal RAAS determinants in early pregnancy via performing two observational prospective cohort studies. They performed stratification of pregnancies (n = 277) by CL number and in vitro fertilization (IVF) protocol: 0 CL (programmed cycle frozen embryo transfer [FET], n = 28), 1 CL (natural cycle FET, n = 41 and spontaneous conceptions, n = 139), and more than 1 CL (ovarian stimulation and fresh embryo transfer, n = 69). In the absence of a CL, lower prorenin and renin were noted at all time points when compared to 1 CL, whereas higher prorenin, renin, and aldosterone were noted in the presence of more than 1 CL vs 1 CL. They noted positive correlation of Prorenin, and to a lesser degree of renin, with serum progesterone and relaxin, but not with serum estradiol. The additional determinants of circulating prorenin were total follicle diameter, BMI, polycystic ovary syndrome, and antimüllerian hormone. Finally, there was a higher likelihood to develop preeclampsia in correlation with pregnancies conceived in the absence of a CL.