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

摘要 建议的补充将基于NIH正在进行的怀孕研究在线(Presto)的数据。 资助的前瞻性队列研究，招募试图怀孕的女性并跟踪她们的先入为主 产后6个月(R01HD086742)。符合条件的女性参与者年龄为21-45岁，居民 北美，试图怀孕，注册时不使用避孕或生育治疗。之后 登记时，女性参与者邀请她们的男性伴侣完成基线调查问卷。2013年6月- 7/2022，Presto已经招募了超过16,750名女性参与者和近4,000名男性伴侣。全 在新冠肺炎大流行期间，问卷在网上完成，数据收集继续进行。2020年4月， 我们为双方合作伙伴增加了关于新冠肺炎感染和与疫情相关的压力源的新问题， 包括生活方式、行为和医疗保健的改变，在2021年1月，我们增加了关于这两个方面的问题 合作伙伴接种SARS-CoV-2疫苗(接种过疫苗、疫苗类型和每次接种日期)。在11月 2021年，我们增加了关于强化注射的问题。我们还获得了女性报告的男性SARS-CoV-2数据 在男性伴侣未报名的情况下接种疫苗和新冠肺炎感染数据。因为这项研究 一开始，参与者报告了关于社会人口统计、生活方式、 人体测量学和医学史。在每两个月一次的调查问卷上(最长实施12个月)， 女性参与者报告关于她们怀孕状态的额外数据，以及她们暴露在或 协变量。我们将使用上述前瞻性收集的数据来检查SARS-CoV-2病毒的程度 双方接种疫苗和感染新冠肺炎与自然流产有关，包括 早期SAB(妊娠8周)。我们将考虑疫苗接种的各种可能影响的窗口和 感染，检查疫苗剂量(包括加强剂)的数量，并通过其他可能的方式识别差异 效果修饰符(例如，年龄)。我们将控制几个混杂因素，包括新冠肺炎相关的压力源，以及 另外，在妊娠早期和晚期分别给出结果(妊娠8周与≥相比)。最后，我们将检查 夫妻双方共同接触的影响(例如，双方都接种了疫苗，女性伴侣 接种了疫苗，男性伴侣接种了疫苗，而不是配偶接种了疫苗)。在至少1600名美国参与者中， 报告了2020年12月14日之后的研究相关概念，我们将估计危险比和95%的可信度 区间采用COX比例风险回归模型。我们的跨学科研究团队已经发表了 关于疫苗相关影响和生殖结果的广泛报道，其中许多基于Presto数据， 我们拥有研究这些研究问题所需的专业知识。鉴于我们正在进行的预期数据 在整个流行病期间收集，我们成功地招募了大量和多样化的夫妇，以及 我们预期的怀孕数据收集，Presto是分析疫苗接种数据的独特位置 和SAB，并向科学界和公众提供有关疫苗安全性的基本信息。

ABSTRACT The proposed supplement will be based on data from Pregnancy Study Online (PRESTO), an ongoing NIH- funded prospective cohort study that enrolls women trying to conceive and follows them from preconception through 6 months after delivery (R01HD086742). Eligible female participants are aged 21-45 years, residents of North America, trying to conceive, and not using contraception or fertility treatment at enrollment. After enrollment, female participants invite their male partners to complete a baseline questionnaire. During 6/2013- 7/2022, PRESTO has enrolled more than 16,750 female participants and nearly 4,000 of their male partners. All questionnaires are completed online and data collection continued during the COVID-19 pandemic. In April 2020, we added new questions for both partners on COVID-19 infection and stressors related to the pandemic, including changes in lifestyle, behaviors and health care, and in January 2021, we added questions for both partners on SARS-CoV-2 vaccination (ever vaccinated, type of vaccine, and date of each shot). In November 2021, we added questions about booster shots. We also obtained female-reported data on male SARS-CoV-2 vaccination and COVID-19 infection data in the event that the male partner did not enroll. Since the study’s inception, participants have reported detailed baseline data about socio-demographics, lifestyle, anthropometrics, and medical history. On each bimonthly questionnaire (administered for up to 12 months), female participants report additional data about their pregnancy status and any changes in their exposures or covariates. We will use the above prospectively-collected data to examine the extent to which SARS-CoV-2 vaccination and COVID-19 infection in both partners are associated with spontaneous abortion (SAB), including early SAB (<8 weeks of gestation). We will consider various windows of possible effects of vaccination and infection, examine the number of vaccine doses (including boosters), and identify differences by other possible effect modifiers (e.g., age). We will control for several confounders, including COVID-19-related stressors, and also present results separately by early and late SAB (<8 vs. ≥8 weeks of gestation). Finally, we will examine the effects of joint exposures in both members of a couple (e.g., both partners vaccinated, female partner vaccinated, male partner vaccinated, vs. neither partner vaccinated). Among at least 1,600 U.S. participants who reported a study-related conception after 12/14/2020, we will estimate the hazard ratio and 95% confidence interval using Cox proportional hazards regression models. Our interdisciplinary research team has published extensively on vaccine-related effects and reproductive outcomes, many of which are based on PRESTO data, and we have the expertise necessary to study these research questions. Given our ongoing prospective data collection throughout the pandemic, our successful recruitment of a large and diverse population of couples, and our prospective collection of pregnancy data, PRESTO is uniquely-positioned to analyze data on vaccination and SAB and provide essential information to the scientific community and the public on vaccine safety.