Project 1. Kirk P. Conrad PI. The overarching hypothesis of the proposed Program Project is that pregnancies conceived by ART begin in a state, which is not physiological for the mother, secondary to the abnormal status of the corpus luteum, its production of relaxin or other hormones. The corpus luteum and maternal circulating relaxin may be absent altogether, or there may be multiple corpora lutea and supraphysiological concentrations of relaxin depending on the ART protocol. Kirk P. Conrad PI and colleagues in Project I propose that these abnormalities of the corpus luteum in ART, which are often iatrogenically imposed, compromise optimal maternal cardiovascular adaptations during pregnancy (also see Project 11). This novel hypothesis is founded upon tantalizing and provocative, yet compelling preliminary evidence from both animal and human studies. Dr. Conrad and coworkers propose a comprehensive exploration of maternal cardiovascular adaptations in women conceiving by ART in the University of Florida CTSI.
Aim 1 will focus on maternal systemic hemodynamics and arterial mechanical properties, renal function and volume status.
Aim 2 will investigate maternal baroreflex function. Thus, we will be able to ascertain whether relaxin or other corpus luteal product(s) supports optimal maternal cardiovascular adaptations during early and late pregnancy. If maternal cardiovascular adaptations during pregnancy are abnormal in ART patients as we hypothesize, then this could contribute to the increased incidence of adverse pregnancy outcomes observed in these patients such as compromised fetal growth and pregnancy induced hypertension (see Project 111). When ovarian function is absent or suppressed, and circulating relaxin is absent, relaxin supplementation might be warrented. Alternatively, in the case of ovarian stimulation, less stimulation might be recommended, in order to reduce the number of corpora lutea, and thus, circulating relaxin. Finally, if maternal cardiovascular adaptations to pregnancy are normal in ART patients, then this outcome should be reassuring to both REI physicians and their patients.

Public Health Relevance

Emerging evidence suggests that ART is associated with increased risk for adverse pregnancy outcomes. In Project 1, we propose to test a new concept that may contribute to this increased risk. That is, we hypothesize that pregnancies conceived by ART begin in a state, which is not physiological for the mother secondary to the abnormal status of the ovary and its hormones. This, in turn, compromises maternal cardiovascular adaptations to pregnancy, thereby predisposing to adverse pregnancy outcomes.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Program Projects (P01)
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Special Emphasis Panel (ZHD1-DSR-Z)
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University of Florida
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Conrad, Kirk P; Davison, John M (2014) The renal circulation in normal pregnancy and preeclampsia: is there a place for relaxin? Am J Physiol Renal Physiol 306:F1121-35
Andridge, Rebecca R; Shoben, Abigail B; Muller, Keith E et al. (2014) Analytic methods for individually randomized group treatment trials and group-randomized trials when subjects belong to multiple groups. Stat Med 33:2178-90
Simpson, Sean L; Edwards, Lloyd J; Styner, Martin A et al. (2014) Separability tests for high-dimensional, low sample size multivariate repeated measures data. J Appl Stat 41:2450-2461
Chi, Yueh-Yun; Gribbin, Matthew J; Johnson, Jacqueline L et al. (2013) Power calculation for overall hypothesis testing with high-dimensional commensurate outcomes. Stat Med :
Conrad, Kirk P; Baker, Valerie L (2013) Corpus luteal contribution to maternal pregnancy physiology and outcomes in assisted reproductive technologies. Am J Physiol Regul Integr Comp Physiol 304:R69-72