Infertility History and Chronic Disease Profile

项目摘要/摘要 不孕不育是一种常见病，美国每年有150万女性患病。它是 在病因和严重性上都是不同的，不同的生物机制导致不同类型的 不孕不育。虽然众所周知，患有不孕症的妇女有更高的风险进行多次不良妊娠 结果，研究表明，这些女性在晚年患慢性病的风险也可能增加， 美国国立卫生研究院已经将了解不孕不育作为女性整体健康的潜在标志(PA- 17-091，“生育状况作为整体健康的标志”)。既往研究对女性糖尿病患者长期健康的影响 不孕症一直受到随访时间短、统计能力低和无法服用的研究的限制。 考虑不孕不育诊断、生育治疗和慢性病的异质性。我们的建议 结合前瞻性收集的116,430名参与者的广泛表型数据《护士健康研究II》 30多年的随访、生物样本和遗传数据，以弥补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不育的女性是否有长期不利的 与从未经历过不孕不育的女性的健康状况进行比较，以及这些差异的原因。我们的 具体目标将涉及：目标1：慢性病发病率：评估不孕症之间的关系 (总体和分型)和心血管疾病风险(心肌梗死和中风)，类型2 糖尿病和乳腺癌。目标2：慢性病的生物标记物：调查 与有不孕症经历的患者相比，这些患者的炎症、心脏代谢和激素生物标志物特征发生了改变 没有经历过不孕不育的女性。目标3：共享遗传学：评估女性是否经历了 与从未经历过双向不孕的女性相比，不孕不育具有不同的基因特征 孟德尔随机化。还没有研究利用这些表型、生物和遗传数据在 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 不孕不育--我们在这项提案中解决的一个科学鸿沟。大约六分之一的女性经历过 不孕不育对公众健康的潜在影响了解不孕不育与长期 健康需要在这一领域进行研究。这些目标代表着一个严格而高效的机会 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.