1/3 A randomized controlled trial of frozen embryo transfers performed in modified natural versus programmed cycles (NatPro)

管理请求项目摘要 在美国，在368,000个辅助生殖周期中，大约75%进行了辅助生殖 每年都会涉及冷冻胚胎。多项研究表明，冷冻胚胎与 胎盘移植(FET)会增加妊娠高血压疾病的风险，如先兆子痫。 将这种风险降到最低是至关重要的，因为先兆子痫与严重的短缩和 对母亲和婴儿的长期后果。我们需要的是一个严谨的、前瞻性的、 接受体外受精的妇女被随机分成有无周期的随机对照试验 黄体(CL)的存在。NatPro由NICHD资助，作为链接的R01，随机 2019年9月的临床试验旨在明确回答这个问题：高血压 如果在自然周期中使用CL进行FETS，则妊娠障碍会减少 与没有CL的程序化周期相比？不幸的是，NatPro的推出恰逢 新冠肺炎大流行，并根据2020年3月政府的建议，试管受精 诊所被关闭，导致这项研究的启动和登记的延迟。在COVID之后- 19项限制被取消，NatPro稳步招收研究对象，其速度与其 原计划。然而，由于大流行造成了最初的、不可预见的征聘延误， 要在五年资助期内完成这项研究，将需要加快招生步伐。 这一行政副刊的目的有两个：1)迅速增加研究的数量 招聘地点大幅增加招生步伐；以及2)增加人员，使 完成计划招生目标的学习。这两项措施加在一起将使 NatPro领导层“转弯”，加快招生步伐，完成 在资助期内学习。及时完成NatPro研究是最重要的 重要的是与先兆子痫相关的负面健康后果，影响两者 这项研究的结果和由此使用的程序可能会将母亲和孩子的风险降至最低 在胚胎移植之前。虽然这项研究占计划招生人数的53%，但如果 招生的速度，样本大小很可能不足以确定 对患者和提供者的建议。然而，如果研究进行到完成， 这些发现可能成为临床指南的基础，这些指南每年影响36.8万名妇女。 依靠试管受精建立家庭的美国人。

Administrative Request Project Summary In the United States, approximately 75% of the 368,000 assisted reproduction cycles performed annually involve frozen embryos. Multiple studies have suggested an association of frozen embryo transfer (FET) with an increased risk of hypertensive disorders of pregnancy, such as preeclampsia. It is critical that this risk be minimized because preeclampsia is associated with severe short- and long-term consequences for both mother and infant. What is needed is a rigorous, prospective, randomized controlled trial where women undergoing IVF are randomized to cycles with and without the presence of a corpus luteum (CL). NatPro was funded by NICHD as a linked R01, randomized clinical trial in September 2019 designed to definitively answer the question: are hypertensive disorders of pregnancy reduced when FETs are performed in a natural cycle with a CL, when compared to a programmed cycle without a CL? Unfortunately, the launch of NatPro coincided with the COVID-19 pandemic and, in accordance with government recommendations in March 2020, IVF clinics were shutdown leading to a delay in initiation and enrollment for the study. After the COVID- 19 restrictions were lifted, NatPro has steadily enrolled study subjects at a rate very similar to its original plan. However, due to the initial, unforeseen recruitment delay caused by the pandemic, completion of the study within the 5-year funding period will require an increased pace of enrollment. The goals of this administrative supplement are two-fold: 1) to rapidly increase the number of study recruitment sites to substantially increase the enrollment pace; and 2) to increase personnel to enable completion of the study with the planned enrollment targets. Together, these two measures will allow the NatPro leadership to “bend the curve” and accelerate the pace of enrollment and complete the study within the funding period. Completing the NatPro Study in a timely manner is of the utmost importance because the negative health outcomes associated with preeclampsia, affecting both mother and child, may be minimized by the findings of this study and the resulting procedures used prior to embryo transfer. While the study is at 53% of planned enrollment, if there is no change in the pace of enrollment, the sample size is very likely to be insufficient to make definitive recommendations for patients and providers. If the study is carried to completion, however, the findings are likely to form the basis for clinical guidelines affecting the 368,000 women each year in the US that rely on IVF to build their families.