Biomarkers of Infertility

描述(由申请人提供)：在当今时代，女性往往推迟到三四十岁才怀孕，这一年龄与生殖年龄导致的不孕不育率较高有关。尽管不孕不育的发病年龄存在差异，但目前还没有有效的标记来监测单个妇女的生育能力。该项目的目的是检验卵巢老化标志物预测生殖老化导致的不孕不育的能力，长期目标是开发一种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受孕能力(每个月经周期受孕的概率)、不孕症的预测以及活产的概率相关。这项拟议的研究将从社区招募750名女性，她们希望怀孕，并获得卵巢老化的基线测量：卵泡早期血清卵泡刺激素(FSH)和抗卵泡成熟激素(AMH)。在接下来的12个月中，参与者将在他们尝试受孕的整个过程中被积极跟踪。在此期间，妇女将进行标准化的怀孕测试，并完成每日和每月的日记，以收集详细的暴露数据。妊娠随访将包括超声评估生存能力和妊娠结局报告。这些方法将使我们能够达到我们的主要研究目标：1)建立最好地预测不孕不育的卵巢老化标记。为了达到这一目标，我们将确定a)测量FSH(尿液和血清中的)与AMH和6个月和12个月未受孕之间的关联，以及b)测试每个标记物的特征(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、生殖史和卵巢老化的标记物；以及3)对卵巢老化标记物和流产之间的关联性进行初步估计。我们的研究在使用未经证实的生殖潜力、既往获得避孕措施并面临生殖老龄化风险的人群方面具有创新性。这项研究的结果与其他人的研究相结合，将使女性能够预测她们当前和未来的生育潜力，最终使她们能够更好地控制生育。 与公共卫生相关：在当今时代，妇女往往推迟到三四十岁才怀孕，这一年龄与生殖老龄化导致的不孕不育率较高有关。对于正在考虑开始或推迟生育的女性来说，一种简单、有效的生殖潜力衡量标准将会给她们带来重大好处。鉴于未经证实的家用尿液试剂盒已经在市场上销售，一项前瞻性研究以确定它们预测普通人群不孕不育的能力是势在必行的。

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.