The maternal vascular transformation required for a successful pregnancy is initiated during the menstrual cycle by a coordinated series of hemodynamic adaptations that appear to be endocrinologically mediated. These events include a decrease in uterine artery vascular impedance and an increase in uterine blood flow that sets the stage for implantation and trophoblast development. The failure of this uterine vascular response is associated with specific reproductive inadequacy, including infertility, fetal growth restriction and pre-eclampsia. This project is focused on defining, in humans, the changes in the uterine and systemic circulation that occur through the menstrual cycle into early pregnancy. Specific hormonal effects within the menstrual cycle will be examined as a function of add-back estrogen and progesterone in women with drug induced ovarian suppression. These responses will be individually compared to spontaneous ovulatory cycles. We intend to demonstrate: 1) that the uterine vascular response is distinguishable from the systemic vascular response through the menstrual cycle and into pregnancy, 2) that these responses (both uterine and systemic) are the result of estrogen and progesterone action, 3) that the hemodynamic responses that begin in the menstrual cycle represent the initiation of a physiologic continuum of endocrine signaling that continues through early pregnancy, and 4) that endogenous steroid responses can be reproduced using an ovarian suppression model with hormonal add-back validating a powerful research technique.
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