Corpus Luteal Contribution to Maternal Pregnancy Physiology and Outcomes in ART

描述（由申请人提供）：本计划项目的主要假设是，许多通过辅助生殖技术（ART）受孕的孕妇开始时，母亲处于非生理状态，继发于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不存在，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。无论是自然发生的或医源性强加的，我们建议，异常黄体状态妥协最佳的产妇生理适应怀孕，因此，易患产科并发症和不良围产期结局。这一假设建立在我们临床前和临床研究中令人着迷、挑衅性但令人信服的初步证据之上。在项目I中，我们将首次全面调查佛罗里达大学CTSI中ART妊娠的母体心血管适应性。在项目II中，将在ART受试者中探索一种新的和令人兴奋的母体对妊娠的适应，即骨髓来源的祖细胞，以及与母体血管舒张、动脉顺应性增加、内皮依赖性舒张和母体血管生成的关系。在项目III中，我们将使用辅助生殖技术协会（SART）数据库和对斯坦福大学ART患者人群的前瞻性分析，询问黄体状态是否与产科并发症增加、围产期发病率和死亡率相关。这3个项目将由3个核心组成：管理核心A、数据管理和生物统计核心B以及分析核心C。在项目和核心的组成部分之间有许多智力和后勤方面的相互作用和强大的协同作用。

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.