Context: The corpus luteum (CL) secretes prorenin, renin’s inactive precursor. It may thus contribute to the renin-angiotensin-aldosterone-system (RAAS) activation that is required for maternal adaptation in pregnancy. Whether this activation is disturbed in pregnancies lacking a CL is unknown. Objective: The objective of this work is to investigate maternal RAAS determinants in early pregnancy. Design and Setting: Two observational prospective cohort studies took place at 2 tertiary referral hospitals. Patients and Intervention(s): Pregnancies (n = 277) were stratified 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). Methods: Quantification was performed for maternal prorenin, renin, and aldosterone blood levels at 5, 9, and 11 weeks of gestation. Results: Prorenin and renin were lower in the absence of a CL at all time points when compared to 1 CL, whereas prorenin, renin, and aldosterone were higher in the presence of more than 1 CL vs 1 CL (P < .05). Ovarian stimulation with menopausal gonadotropin resulted in higher prorenin, renin, and aldosterone concentrations during the late first trimester than recombinant follicle-stimulating hormone (P < .05). Prorenin, and to a lesser degree renin, correlated positively with serum progesterone and relaxin, but not serum estradiol. Total follicle diameter, body mass index (BMI), polycystic ovary syndrome (PCOS), and antimüllerian hormone (AMH) were additional determinants of circulating prorenin. Finally, pregnancies conceived in the absence of a CL were more disposed to develop preeclampsia. Conclusions: CL number, IVF protocol, BMI, PCOS, and AMH affect maternal RAAS activation in early pregnancy, and may thus contribute to pregnancy complications.

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Keywords renin-angiotensin-aldosterone-system, in vitro fertilization, corpus luteum, pregnancy, prorenin, preeclampsia
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Journal Journal of Clinical Endocrinology and Metabolism
Wiegel, R.E., Danser, A.H.J, Steegers-Theunissen, R.P.M, Laven, J.S.E, Willemsen, S.P, Baker, V.L., … von Versen-Höynck, F. (2020). Determinants of Maternal Renin-Angiotensin-Aldosterone-System Activation in Early Pregnancy: Insights From 2 Cohorts. Journal of Clinical Endocrinology and Metabolism, 105(11). doi:10.1210/clinem/dgaa582