Corpus Luteal Contribution to Maternal Pregnancy Physiology and Outcomes in ART

描述(由申请人提供)：本计划项目的突出假设是，许多由ART(辅助生殖技术)怀孕的孕妇开始于一种对母亲来说不是生理状态的状态，继而是黄体的异常状态及其松弛素或其他激素的产生。因此，黄体、母体循环松弛素和其他黄体激素可能完全缺失，或者可能存在多个黄体、松弛素和其他黄体激素的超生理浓度，这取决于ART方案。无论是自然发生的，还是医学上强加的，我们认为，黄体状态异常损害了母亲对怀孕的最佳生理适应，因此，容易发生产科并发症和不良的围产儿结局。这一假设是建立在我们临床前和临床研究中诱人和挑衅性的、但令人信服的初步证据的基础上的。在项目I中，我们将首次全面调查佛罗里达大学CTSI的孕妇心血管对ART妊娠的适应情况。在项目II中，将在ART受试者中探索一种新的、令人兴奋的母体对怀孕的适应，涉及骨髓来源的祖细胞，以及与母体血管扩张、动脉顺应性增加、内皮依赖性松弛和母体血管生成有关的问题。在项目III中，我们将使用辅助生殖技术协会(SART)的数据库和对斯坦福ART患者群体的前瞻性分析，询问黄体状态是否与产科并发症、围产期发病率和死亡率的增加相关。这3个项目将由3个核心加入：行政核心A、数据管理和生物统计核心B和分析核心C。在组成项目和核心之间有许多智力和后勤互动以及强大的协同作用。

DESCRIPTION (provided by applicant): 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.