(instructions): Project II. Mark S. Segal PI. In 2007, over 138,000 assisted reproductive technology (ART) procedures were performed in the U.S. resulting in -54,700 infants. Many ART pregnancies have a nonphysiologic hormonal milieu and have been associated with an increased risk for obstetric complications, including preterm delivery and preeclampsia, as well as adverse perinatal outcomes, including low birth weight infants. Women who suffer these obstetric complications and infants who have adverse perinatal outcomes may both be at risk for future cardiovascular events. This proposal addresses one potential mechanism, corpus luteal factors, for the increased morbidity associated with ART. The corpus luteal factor relaxin plays a critical role in the hemodynamic changes that occur during pregnancy. Our preliminary data demonstrates that in mice, relaxin can increase bone marrow derived progenitor cells (BMPC), cells that may directly or indirectly play a role in endothelial function and angiogenesis. Relaxin can also induce BMPC migration in vivo and alter BMPC nitric oxide (NO) levels, thus improving BMPC function in vitro. Interestingly, BMPC have been shown to be increased in pregnancy. It is our overarching hypothesis that the hemodynamic effects of relaxin are partly due to its actions on BMPC and optimal levels of relaxin, not achieved in all ART pregnancies, are necessary to establish the proper hemodynamic alterations of gestation important to the successful outcome of a pregnancy for mother and fetus. To test this hypothesis we will perform a longitudinal clinical study of women spontaneously conceiving (control cohort) and of women undergoing ART, both egg donor recipients (no relaxin) and women undergoing ovarian stimulation (elevated relaxin). All women, in conjunction with Project I, will be studied prior to pregnancy (baseline), at gestational weeks 5-6, 7-9, 10-12, 14-16, 23-25 and 33-35, and 3-6 months post-partum. At each visit we will determine maternal BMPC number and function, arterial properties (Project I) and systemic hemodynamics, endothelial function, and capillary density. This project utilizes the Analytical Core C for measurement of relaxin, other hormones, and circulating markers of inflammation, and the Data Management and Biostatistics Core B for data storage and statistical analysis.
Women who use ART to become pregnant have an increased risk of preterm delivery, low birth weight infants, and preeclampsia. It is our hypothesis that an excess or deficiency of corpus luteal hormones such as relaxin in ART pregnancies leads to maladaptations in the vascular system accounting for these risks. This work may lead to potential therapies to decrease the risk for women who use ART.
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