Outcomes of Infertility Treatments in Clinic and Population-Based Cohorts

描述（由申请人提供）：不孕症，定义为在没有避孕的情况下性交一年内无法怀孕，是夫妇常见的健康状况。不孕症的治疗范围从侵入性较小的医学治疗（包括促排卵和人工授精）到辅助生殖技术（ART），后者在体外完成人类生殖的早期阶段。抗逆转录病毒治疗在短期内产生高怀孕率，使其成为一种有吸引力的治疗方法。然而，流行病学研究表明，与自然怀孕的儿童相比，通过抗逆转录病毒治疗怀孕的儿童早产、低出生体重和出生缺陷的发生率更高，即使分析仅限于单胎妊娠。主要的问题仍然是这些不良结果是否与治疗有关，还是与不孕的潜在原因有关。由于大多数关于不孕症治疗和结果的数据是基于临床的，而不是基于人群的，因此很难解决这些问题。这项研究将在接受各种治疗的夫妇中解决这些问题。我们建议对35岁以下有男性伴侣和原发性不孕症的女性进行一项以临床为基础和以平行人群为基础的回顾性观察性研究。该研究将包括问卷设计和试点、数据链接、参与者招募以及通过记录审查和对妇女治疗和怀孕情况的调查收集数据。结局包括活产的累积概率、活产时间、早产、低出生体重、多胎妊娠、出生缺陷和新生儿发病率。为了组建一个以临床为基础的队列，我们将使用犹他州生殖医学中心（UCRM）的临床治疗记录来确定潜在的参与者。为了建立一个平行的基于人群的队列，我们将使用UPDB的结婚证、出生证明和胎儿死亡证明来确定潜在的参与者。对于这两个队列，我们将通过电话筛选确定最终资格。在联系、最终资格和同意后，两个队列的妇女将被要求完成一份调查问卷，以收集和核实关于不孕症治疗选择和尝试怀孕时间的信息。为了确定出生结果，我们将两个队列的个人记录链接到两个来源：犹他州人口数据库（UPDB）的犹他州出生证明数据和犹他州出生缺陷网络（UBDN）主动监测的出生缺陷数据。最终，我们预计将有大约1000名妇女参加这项研究，每个队列500名，大约130名妇女（估计有65名活产）接受了抗逆转录病毒治疗，520名妇女（估计有234名活产）接受了微创性不孕症治疗，350名妇女（估计有88名活产）没有接受治疗。这将使我们有能力研究累积怀孕概率和常见的分娩结果；以及探索其他结果的机会。这项研究的结果将描述寻求健康孩子的夫妇的临床相关结果，也将为未来有针对性的随机试验的发展提供信息。公共卫生相关性：不孕症是一个重要的公共卫生问题，因为它影响着美国和其他国家数百万对夫妇

DESCRIPTION (provided by applicant): Infertility, defined as inability to conceive within one year of intercourse without contraception, is a common health condition for couples. Infertility treatments range from less invasive medical treatments (including ovulation induction and artificial insemination) to assisted reproductive technologies (ART), which complete early stages of human reproduction in vitro. ART produces high pregnancy rates in the short term, making it an attractive treatment. However, epidemiologic studies have demonstrated higher incidence of preterm birth, low birth weight, and birth defects among children conceived through ART, when compared to children conceived naturally, even when the analyses are limited to singleton pregnancies. Major questions remain as to whether these adverse outcomes are related to the treatments or to the underlying causes of the infertility. Because most data on infertility treatments and outcomes are clinic-based rather than population-based, it has been difficult to address such questions. This study will address these issues in couples that receive a variety of treatments. We propose to conduct a pilot retrospective observational study in a clinic-based and a parallel population-based cohort of women under age 35 with male partners and primary infertility. The study will include questionnaire design and piloting, data linkage, participant recruitment, and data collection through record reviews and surveys of women about their treatments and pregnancies. Outcomes include cumulative probabilities of live birth, time to live birth, preterm birth, low birth weight, multiple gestation, birth defects, and neonatal morbidity. To assemble a clinic-based cohort, we will use clinical treatment records from the Utah Center for Reproductive Medicine (UCRM) to identify potential participants. To establish a parallel population- based cohort, we will use marriage certificates, birth certificates, and fetal death certificates from the UPDB to identify potential participants. For both cohorts, we will establish final eligibility by telephone screening. Upon contact, final eligibility, and consent, women in both cohorts will be asked to complete a questionnaire to collect and verify information on infertility treatment choices and time attempting pregnancy. To ascertain birth outcomes, we will link the individual records from both cohorts to two sources: Utah state birth certificates data via the Utah Population Database (UPDB) and birth defects data via the active surveillance of the Utah Birth Defects Network (UBDN). Ultimately, we expect that approximately 1000 women will participate in the study, with 500 from each cohort, yielding approximately 130 women (with an estimated 65 live births) who have received ART, 520 women (with an estimated 234 live births) who have received less-invasive infertility treatment, and 350 women (with an estimated 88 live births) who have received no treatment. This will give us power to look at cumulative pregnancy probabilities and common birth outcomes; and the opportunity to explore other outcomes. The results of this study will describe clinically relevant outcomes for couples seeking to have healthy children and will also inform the development of future targeted randomized trials. PUBLIC HEALTH RELEVANCE: Infertility is an important public health issue because it impacts millions of couples in the United States and other countries, and there are growing concerns about poor perinatal outcomes associated with some types of infertility treatment. We propose a pilot retrospective observational study in a clinic-based cohort and parallel population-based cohort of women under age 35 with primary infertility to study the cumulative probabilities of live birth, time to live birth, preterm birth, low birth weight, birth defects, and neonatal morbidity associated with different types of infertility treatment. The results of this study will describe clinically relevant outcomes for couples seeking to have healthy children and will also inform the development of future targeted randomized trials.