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 producfion 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 concentrafions 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 provocafive, yet compelling preliminary evidence from both animal and human studies. Dr. Conrad and coworkers propose a comprehensive explorafion 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 funcfion and volume status.
Aim 2 will invesfigate maternal baroreflex funcfion. Thus, we will be able to ascertain whether relaxin or other corpus luteal product(s) supports optimal maternal cardiovascular adaptations during eariy and late pregnancy. If maternal cardiovascular adaptations during pregnancy are abnormal in ART pafients as we hypothesize, then this could contribute to the increased incidence of adverse pregnancy outcomes observed in these pafients such as compromised fetal growth and pregnancy induced hypertension (see Project 111). When ovarian funcfion is absent or suppressed, and circulafing relaxin is absent, relaxin supplementation might be warrented. Alternatively, in the case of ovarian stimulation, less sfimulafion 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 pafients, 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 adapatafions 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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University of Florida
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Conrad, Kirk P; Rabaglino, Maria Belen; Post Uiterweer, Emiel D (2017) Emerging role for dysregulated decidualization in the genesis of preeclampsia. Placenta 60:119-129
Floyd, Erin G; von Versen-Höynck, Frauke; Liu, Jing et al. (2016) Collection of pregnancy outcome records following infertility-challenges and possible solutions. J Assist Reprod Genet 33:993-9
Lathi, Ruth B; Chi, Yueh-Yun; Liu, Jing et al. (2015) Frozen blastocyst embryo transfer using a supplemented natural cycle protocol has a similar live birth rate compared to a programmed cycle protocol. J Assist Reprod Genet 32:1057-62
Baker, Valerie L; Brown, Morton B; Luke, Barbara et al. (2015) Gonadotropin dose is negatively correlated with live birth rate: analysis of more than 650,000 assisted reproductive technology cycles. Fertil Steril 104:1145-52.e1-5
Baker, Valerie L; Brown, Morton B; Luke, Barbara et al. (2015) Association of number of retrieved oocytes with live birth rate and birth weight: an analysis of 231,815 cycles of in vitro fertilization. Fertil Steril 103:931-938.e2
Rabaglino, Maria B; Post Uiterweer, Emiel D; Jeyabalan, Arun et al. (2015) Bioinformatics approach reveals evidence for impaired endometrial maturation before and during early pregnancy in women who developed preeclampsia. Hypertension 65:421-9
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
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
Chi, Yueh-Yun; Gribbin, Matthew J; Johnson, Jacqueline L et al. (2014) Power calculation for overall hypothesis testing with high-dimensional commensurate outcomes. Stat Med 33:812-27
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

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