Infertility History and Chronic Disease Profile

项目总结/摘要 不孕症是一种常见病，在美国每年影响150万妇女。是 不同的病因和严重程度，不同的生物学机制导致不同类型的 不孕虽然患有不孕症的妇女已知有许多不良妊娠的风险较高， 结果，研究表明，这些妇女在以后的生活中患慢性病的风险也会增加， 和NIH优先需要了解不孕症作为一个潜在的标志，为妇女的整体健康（PA- 17-091，“生育状况作为整体健康的标志”）。先前对患有乳腺癌的妇女的长期健康的研究 不孕症的研究受到随访时间短、统计学效力低和无法采取有效措施的限制。 不孕症诊断、生育治疗和慢性疾病的异质性。我们的建议 结合了前瞻性收集的116，430名参与者的广泛表型数据， 超过30年的随访、生物样本和遗传数据，以解决现有文献中的这些空白。 我们的长期目标是了解经历过不孕症的妇女是否有不良的长期 与从未经历过不孕症的妇女相比，健康状况以及造成这些差异的因素。我们 具体目标将解决：目标1：慢性病发病率：评估不孕症之间的关系 （总体和亚型）和心血管疾病（心肌梗死和中风）的风险，2型 糖尿病和乳腺癌。目的2：慢性疾病的生物标志物：调查 与不孕症患者相比，不孕症患者的炎症、心脏代谢和激素生物标志物特征发生了改变。 没有经历过不孕症的女性。目标3：共享遗传学：评估女性是否经历 不孕症有不同的遗传概况相比，妇女从未经历过不孕症使用双向 孟德尔随机化没有研究利用这些组合的表型，生物学和遗传学数据， 解决与妇女长期健康有关的基本公共卫生问题所需的规模， 不孕症-我们在本提案中解决的一个科学空白。大约六分之一的女性 不孕症，了解不孕症与长期的潜在公共卫生影响的关系 健康需要在这一领域进行研究。这些目标是一个严格和有效的机会， 调查不孕症与女性整体长期健康轨迹的关系。

Project Summary/Abstract Infertility is a common disease, which affects 1.5 million women each year in the United States. It is heterogeneous in both etiology and severity, with different biologic mechanisms causing different types of infertility. While women suffering from infertility are known to have a higher risk of many adverse pregnancy outcomes, research suggests that these women may also be at increased risk of chronic diseases later in life, and NIH has prioritized the need to understand infertility as a potential marker for a woman’s overall health (PA- 17-091, “Fertility Status as a Marker for Overall Health”). Prior research on the long-term health of women with infertility has been limited by studies with short duration of follow-up, low statistical power, and inability to take heterogeneity of infertility diagnoses, fertility treatment, and chronic diseases into account. Our proposal combines extensive phenotypic data from 116,430 participants Nurses’ Health Study II collected prospectively over 30 years of follow-up, biologic samples, and genetic data to address these gaps in the existing literature. Our long-term goal is to understand whether women who have experienced infertility have adverse long-term health compared to women who never experienced infertility and the factors that underlie these differences. Our specific aims will address: Aim 1: Chronic disease incidence: Evaluate the relationship between infertility (overall and by subtype) and the risk of cardiovascular diseases (myocardial infarction and stroke), type 2 diabetes, and breast cancer. Aim 2: Biomarkers of chronic disease: Investigate whether women who experienced infertility have altered inflammatory, cardiometabolic, and hormonal biomarker profiles compared to women who have not experienced infertility. Aim 3: Shared genetics: Evaluate whether women experiencing infertility have a different genetic profile compared to women never experiencing infertility using bi-directional mendelian randomization. No studies have utilized these combined phenotypic, biologic, and genetic data at the scale required to address fundamental public health questions related to the long-term health of women with infertility – a scientific gap that we address in this proposal. As approximately one in six women experience infertility, the potential public health impact of understanding the relationship between infertility and long-term health demands pursing research in this area. These aims represent a rigorous and efficient opportunity to investigate infertility in relation to women’s overall long-term health trajectory.