A prospective study of male factors, fertility, and pregnancy outcomes

男性因素、生育力和妊娠结局的前瞻性研究

• 批准号: 10461191
• 负责人: MICHAEL L EISENBERG
• 金额: $ 69.37万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-05 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10461191
• 关键词: Agreement; Alcoholic Beverages; American; Area; Behavioral; Bicycling; Canada; Clinical; Cohort Studies; Collection; Conceptions; Couples; Data; Data Reporting; Enrollment; Etiology; Female; Fertility; Fertility Determinant; Funding; Future; General Population; Gestational Age; Grant; Health; Home; Infant; Infertility; Infrastructure; Intake; Length; Life Style; Male Infertility; Mediating; Medical; Metabolism; Methods; Monitor; National Institute of Child Health and Human Development; North America; Online Systems; Outcome; Participant; Pathway interactions; Patient Self-Report; Perinatal; Physical activity; Pilot Projects; Predictive Factor; Pregnancy; Pregnancy Outcome; Pregnancy loss; Prevalence; Prospective Studies; Public Health; Reporting; Reproductive Health; Research; Research Design; Risk; Risk Factors; Sampling; Selection Bias; Seminal fluid; Sleep; Sleep Deprivation; Sleep Disorders; Sperm Count Procedure; Sperm Motility; Spontaneous abortion; Strenuous Exercise; Subfecundity; Testing; United States; actigraphy; adverse birth outcomes; adverse outcome; base; cigarette smoking; cohort; cost effective; dietary; electronic cigarette use; epidemiology study; experience; fitbit; follow-up; high risk; innovation; male; marijuana use; men; modifiable risk; nutrition; pediatric health outcomes; perinatal outcomes; poor sleep; recruit; reproductive outcome; sedentary lifestyle; sleep quality; sperm cell; study population; subfertility; sugar; sweetened beverage; time-to-pregnancy; vaping

ABSTRACT About 15% of American couples experience infertility (time-to-pregnancy >12 months) and more than 20% of couples experience spontaneous abortion (SAB, pregnancy loss <20 weeks' gestation). The prevalence of impaired fecundity has increased over the last decade and studies indicate that sperm counts have been declining over the last four decades. Male factor contributes to 50% of infertility, yet epidemiologic research on predictors of male infertility is scarce and male participation in reproductive health studies has been low. Even less research has explored paternal influences of perinatal and pediatric health outcomes. With funding from the NICHD, we launched Pregnancy Study Online (PRESTO) in June 2013 to assess the feasibility of conducting a web-based preconception cohort study in North America to evaluate dietary, lifestyle, and medical determinants of fecundity. Since June 2013, we have recruited more than 13,000 females and 3,000 of their male partners from the United States and Canada. In this cohort, we have shown that male exposures, such as male sleep and sugar-sweetened beverage intake, are strong determinants of fertility. In our NICHD-supported feasibility grant (R21-HD094322), we demonstrated that at-home semen testing is feasible, with 400 men providing at least one semen sample during a 3-year period. Preconception enrollment of men from the general population presents a unique opportunity to examine how male factors influence semen quality, and the extent to which semen quality and selected male factors predict reproductive and perinatal outcomes. We now propose to recruit an additional 2,000 men—including 800 in the semen testing substudy—to assess a broader set of aims: 1) to evaluate the association of selected behavioral factors with poor semen quality, focusing on common but understudied factors for which studies are limited or inconclusive (e.g. poor or inadequate sleep, bicycling, marijuana use, e-cigarette use/vaping, and intake of sugar-sweetened, caffeinated, and alcoholic beverages); 2) to assess the extent to which poor semen quality predicts subfertility, SAB, and adverse perinatal outcomes (shorter gestational length and lower infant birthweight); and 3) to evaluate male factors in relation to risk of SAB and adverse perinatal outcomes, and the extent to which these associations are mediated by semen quality. Importantly, we will assess exposures jointly with female factors to better investigate causal pathways. Increased granularity of sleep and activity exposures will be collected through a pilot aim to examine the feasibility of disseminating FitBit actigraphs to a subset of 100 participants. We have already shown that appreciable numbers of men are willing to enroll in our preconception cohort study, that men are willing to perform at-home semen testing, and that the semen data are within the range expected for the general population. The use of an innovative and cost-effective semen testing method, the prospective study design, the established infrastructure of PRESTO, and the comprehensive collection of risk factor data in both male and female partners are added strengths. Results from the proposed study will have important public health and clinical implications for male reproductive health.

摘要 大约15%的美国夫妇患有不孕症（怀孕时间>12个月），超过20%的美国夫妇患有不孕症。 夫妇经历自然流产（SAB，妊娠期<20周的妊娠丢失）。之时尚 在过去的十年中，生育力受损的情况有所增加，研究表明，精子数量已经 在过去的四十年里下降。男性因素导致50%的不孕症，但流行病学研究表明， 男性不育症的预测因素很少，男性参与生殖健康研究的人数很少。甚至 较少的研究探讨父亲对围产期和儿科健康结果的影响。资助下 NICHD，我们于2013年6月推出了妊娠研究在线（PRESTO），以评估进行 一项基于网络的北美孕前队列研究，旨在评估饮食、生活方式和医疗决定因素 繁殖力。自2013年6月以来，我们已经招募了13，000多名女性和3，000名男性伴侣 来自美国和加拿大。在这个队列中，我们已经表明，男性暴露，如男性睡眠和 含糖饮料的摄入量，是生育能力的强有力的决定因素。在我们的NICHD支持的可行性补助金中， （R21-HD 094322），我们证明了家庭精液检测是可行的，400名男性提供了至少一个 三年内的精液样本一般人群中男性的孕前登记呈现出一种 这是一个独特的机会来研究男性因素如何影响精液质量，以及精液质量在多大程度上影响精液质量。 选定的男性因素可预测生殖和围产期结局。我们现建议增聘一名 2，000名男性-包括精液检测子研究中的800名-以评估更广泛的目标：1）评估 选定的行为因素与精液质量差的相关性，重点关注常见但未充分研究的因素 研究有限或不确定（例如睡眠不足或睡眠不足，骑自行车，使用大麻，电子烟） 使用/vaping，摄入含糖，含咖啡因和酒精饮料）; 2）评估 精液质量差预示着生育力低下、SAB和不良的围产期结局（妊娠期较短 3）评估男性因素与SAB的风险和不良围生儿结局的关系 结果，以及这些关联在多大程度上由精液质量介导。重要的是，我们将评估 暴露与女性因素结合，以更好地调查因果途径。增加睡眠的粒度， 将通过试点项目收集活动暴露，以检查推广FitBit活动记录仪的可行性 100名参与者的子集。我们已经表明，相当数量的男性愿意参加 我们的孕前队列研究表明，男性愿意在家中进行精液检测， 在一般人群的预期范围内。使用一种创新的和具有成本效益的精液 测试方法，前瞻性研究设计，PRESTO的既定基础设施，以及 收集男性和女性伴侣的风险因素数据是另一个优势。拟议的结果 研究将对男性生殖健康产生重要的公共卫生和临床意义。