Biomarkers of Infertility

描述（由申请人提供）：在当今时代，女性往往推迟尝试怀孕到30多岁和40多岁，由于生殖衰老，不孕率较高。尽管不孕症的发病年龄存在差异，但没有有效的标记物来监测个体妇女的生育能力。该项目的目的是研究卵巢衰老标志物预测生殖衰老导致的不孕症的能力，长期目标是建立一个预测个体生殖潜力丧失的模型。我们假设卵巢老化的标志物与自然生育能力（每个月经周期受孕的概率）、不孕症的预测以及活产的概率有关。该研究将从社区招募750名渴望怀孕的女性，并获得卵巢衰老的基线测量：卵泡期早期血清促卵泡激素（FSH）和抗卵泡激素（AMH）。在接下来的12个月里，参与者在尝试怀孕的过程中将被积极跟踪。在此期间，妇女将进行标准化的妊娠检测，并完成每日和每月日记，以收集详细的暴露数据。妊娠随访将包括超声生存能力评估和妊娠结局报告。这些方法将使我们能够实现我们的主要研究目标：1)建立最能预测不孕症的卵巢老化标志物。为了实现这一目标，我们将确定a)在6个月和12个月时测定FSH（尿液和血清中）和AMH之间的关联以及b)每个标记物的测试特征（例如敏感性和特异性）；2)建立年龄相关性不孕症的预测模型，纳入人口统计学、生殖史和卵巢衰老标志物；3)对卵巢老化标志物与流产之间的关系进行初步估计。我们的研究是创新的，它使用了未经证实的生殖潜力，以前获得避孕和生殖衰老的风险人群。这项研究的结果与其他研究相结合，将使妇女能够预测她们目前和未来的生殖潜力，最终使她们能够更好地控制生育。

DESCRIPTION (provided by applicant): In the current era women often delay attempts to conceive to their thirties and forties, ages associated with higher rates of infertility due to reproductive aging. Despite variability in the age of onset of infertility, no validated markers exist to monitor an individual woman's fertility. The objective of this project is to examine the ability of markers of ovarian aging to predict infertility due to reproductive aging, with the long term goal to develop a model that projects individual loss of reproductive potential. We hypothesize that markers of ovarian aging are associated with natural fecundability (probability of conception per menstrual cycle), predictive of infertility, and associated with the probability of live birth. The proposed study will enroll 750 women from the community, who desire to conceive, and obtain baseline measures of ovarian aging: early follicular phase serum follicle stimulating hormone (FSH) and anti-m|llerian hormone (AMH). Participants will be actively followed throughout their attempts to conceive over the following twelve months. During that time, women will conduct standardized pregnancy testing and complete a daily and monthly diary for collection of detailed exposure data. Pregnancy follow-up will include ultrasound assessment for viability and a pregnancy outcome report. These methods will allow us to address our primary research aims: 1) Establish the marker of ovarian aging that best predicts infertility. To address this aim we will determine a) measures of association between FSH (in urine and serum) and AMH and lack of conception at 6 and 12 months and b) test characteristics (e.g. sensitivity & specificity) of each marker; 2) Develop a predictive model for age-related infertility, incorporating demographics, reproductive history, and markers of ovarian aging; and 3) Generate preliminary estimates of the association between markers of ovarian aging and miscarriage. Our study is innovative in its use of a population of unproven reproductive potential with previous access to contraception and at risk for reproductive aging. Results from this research, combined with research by others, will allow women to predict their current and future reproductive potential, ultimately allowing them more reproductive control. PUBLIC HEALTH RELEVANCE: In the current era women often delay attempts to conceive to their thirties and forties, ages associated with higher rates of infertility due to reproductive aging. A simple, validated measure of reproductive potential would be of major benefit to women, who are considering initiating or delaying childbearing. Given that unproven home urinary kits are already being marketed, a prospective study to determine their ability to predict infertility in the general population is imperative.