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

摘要 大约15%的美国夫妇经历不孕不育(怀孕12个月)，超过20%的夫妇 夫妇经历自然流产(SAB，妊娠丢失和妊娠20周)。疾病的流行 在过去的十年里，生殖力受损的人数有所增加，研究表明，精子数量一直在增加 在过去的40年里呈下降趋势。男性因素导致50%的不育症，但流行病学研究表明 男性不育症的预测指标很少，男性参与生殖健康研究的比例也很低。连 较少的研究探讨了父亲对围产期和儿科健康结果的影响。有了来自 NICHD，我们于2013年6月在网上推出了怀孕研究(Presto)，以评估进行 北美基于网络的先入为主队列研究，以评估饮食、生活方式和医学决定因素 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，男性暴露在环境中，如男性睡眠和 含糖饮料的摄入量是生育能力的重要决定因素。在我们由NICHD支持的可行性补助金中 (R21-HD094322)，我们证明了家庭精液检测是可行的，400名男性提供至少一项精液检测 三年内的精液样本。一般人口中男性的先入为主的入学呈现出一种 独特的机会来研究男性因素如何影响精液质量，以及精液质量的程度 选定的男性因素预测生育和围产期的结果。我们现在建议再招聘一名 2,000名男性--包括精液测试子研究中的800名--评估一组更广泛的目标：1)评估 选定的行为因素与不良精液质量的关系，重点关注常见但未被研究的因素 对于那些研究有限或不确定的(例如，睡眠不佳或不充分，骑自行车，使用大麻，电子烟 使用/蒸发，以及摄入含糖、咖啡因和酒精饮料)；2)评估 哪种质量差的精液预示着不育、SAB和不良的围产儿结局(较短的妊娠长度 和较低的婴儿出生体重)；以及3)评估男性因素与SAB风险和不良围产儿的关系 结果，以及这些关联在多大程度上受到精液质量的影响。重要的是，我们将评估 与女性因素联合暴露，以更好地调查因果路径。提高睡眠的粒度和 将通过一个试点目标收集活动暴露情况，以检查传播FitBit活动图的可行性 给100名参与者的子集。我们已经表明，有相当数量的男性愿意参加 我们的先入为主的队列研究表明，男性愿意在家进行精液检测，而精液数据 在普通人群的预期范围内。使用创新且经济实惠的精液 测试方法，前瞻性研究设计，Presto已建立的基础设施，以及综合 收集男性和女性伴侣的风险因素数据是额外的优势。建议的结果 这项研究将对男性生殖健康具有重要的公共卫生和临床意义。

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.