The overarcliing hypothesis of this Program Project is that many pregnancies conceived by ART (Assisted Reproductive Technology) begin in a state which is not physiological for the mother, secondary to the abnormal status of the corpus luteum and its production of relaxin or other hormones. Thus, the corpus luteum, maternal circulating relaxin and other corpus luteal hormones may be absent altogether, or there may be multiple corpora lutea, supraphysiological concentrations of relaxin and other corpus luteal hormones depending on the ART protocol. Whether naturally occuring or iatrogenically imposed, we propose that abnormal corpus luteal status compromises optimal maternal physiological adaptations to pregnancy, and consequently, predisposes to obstetrical complications and adverse perinatal outcomes. This hypothesis is founded upon tantalizing and provocative, yet compelling preliminary evidence from our preclinical and clinical studies. In Project I, we will comprehensively investigate for the first time, the maternal cardiovascular adaptations to ART pregnancies in the University of Florida CTSI. In Project II, a new and exciting maternal adaptation to pregnancy dealing with bone marrow derived progenitor cells will be explored in ART subjects, and in relation to maternal vasodilation, increases in arterial compliance, endothelial dependent relaxation and maternal angiogenesis. In Project III, we will interrogate whether the state of the corpus luteum correlates with increased obstetrical complications, and perinatal morbidity and mortality using the Society of Assisted Reproductive Technology (SART) database, and prospective analysis of the Stanford ART patient populations. These 3 Projects will be joined by 3 Cores: Administrative Core A, Data Management and Biostatistics Core B, and Analytical Core C. There are numerous intellectual and logistical interactions and potent synergisms among the component Projects and Cores.
The proposed Program Project will investigate the corpus luteal contribution to maternal pregnancy physiology and outcomes in ART using fundamental, clinical, and epidemiological approaches. Its successful completion will provide novel and groundbreaking insights into the maternal physiology of ART and spontaneously conceived pregnancies, as well as the adverse pregnancy outcomes of ART. We expect that it will also facilitate the translation of this newly gained knowledge to improving clinical practice.
|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|