Cycles of ART with multiple corpora lutea (fresh IVF cycles using autologous oocytes) and absent corpora lutea (donor oocyte recipients) are both associated with increased risk of low birth weight and hypertensive disorders of pregnancy. Despite the widespread use of ART, no one to date has carefully investigated the possibility that adverse outcomes in ART-conceived pregnancies may be at least in part attributable to excessive numbers of corpora lutea or absence of the corpus luteum, both states common with ART which are clearly not physiologic for the mother. The general goal of Project III is to determine the effect of excessive numbers of corpora lutea or the absence of a corpus luteum on birth weight gestational age at delivery, and incidence of hypertensive disorders of pregnancy in ART conceptions. This project, which examines these critical clinical endpoints in large numbers of patients, complements the clinical physiology of ART patients investigated in Projects 1 and II of this P01applicafion which cannot be powered to examine perinatal outcomes. In order to determine whether the predicted effects of excessive or absent corpora lutea influence fetal outcome in large numbers of patients, this project will utilize the Society for Assisted Reproductive Technology Clinical Outcome Reporting System (SART CORS) with data from over 140,000 annual ART cycles. Because SART CORS does not contain detailed information regarding the incidence of maternal outcomes such as hypertensive disorders of pregnancy or details regarding types of fetal growth retardation or causes of pre-term labor, this project will also include analysis of outcomes from pregnancies achieved at Stanford Fertility and Reproductive Medicine Center, one of the largest academic ART programs in the country. Prospective data collection at Stanford will be performed to allow detailed and systematic recording of baseline patient characteristics, fertility treatment, and clinical endpoints. Complete review of prenatal and obstetric records will be performed and hypertensive disorders of pregnancy will be carefully juried to examine a potential association between number of corpora lutea and risk of gestational hypertension or preeclampsia. Data will be entered into an analysis-ready, secure database developed by the Data Management and Biostatistics Core B. Controls will be chosen to allow distinction between the effects of corpus luteum function from effects attributable to underlying infertility issues, unique to donor gametes. Blood samples from these carefully phenotyped patients will be collected and sent to the Analytical Core C.
If the suspected association of absent or excessive number of corpora lutea with adverse outcomes in ART cycles is confirmed, practical changes in clinical practice such as less aggressive ovarian stimulation, frozen embryo transfer in the context of a natural ovulatory cycle, or replacement of a missing product of the corpus luteum have a high potential for improving both perinatal and maternal outcomes.
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