2/3 A randomized controlled trial of frozen embryo transfers performed in modified natural versus programmed cycles (NatPro)

项目总结 在全球一年内实施的估计160万个辅助生殖技术周期中， 近三分之一被归类为冷冻胚胎移植(FET)。在美国，超过一半的艺术品 周期包括对所有胚胎进行FET或冷冻。鉴于FET的广泛使用，令人严重关切的是 多项研究表明，FET与高血压疾病的风险增加有关 怀孕，包括先兆子痫。将这种风险降到最低是至关重要的，因为先兆子痫与 对母亲和婴儿都有严重的短期和长期后果，包括产妇死亡和胎儿死亡 死亡。此外，最近的几项荟萃分析强调，指导临床医生 使用FET优化活出生率的方案选择很差。 我们小组最近完成了一项由美国国立卫生研究院赞助的项目拨款，其发现强烈表明 一种常用的FET方案解释了FET所见的先兆子痫风险的增加。 在一项前瞻性队列研究中，一种方案(程序化FET)与显著更高的发病率相关 与替代方案(自然周期FET)相比，先兆子痫的发生率更高。此外，通过详细的 在两个不同的人群中对孕妇心血管适应的检查，扰动 人们关注的是程序化FET，而不是自然周期FET。 考虑到这些数据和文献中的其他发现，我们的中心假设是怀孕是由 自然周期中的FET与程序化周期中的FET相比，先兆子痫的发生率较低 周而复始。为了验证这一假设，我们将在6个地点进行随机临床试验。我们的主要具体目标 用自然周期和程序周期来确定先兆子痫的发生率。我们的第二个 假设在自然周期中转移后的活出生率类似于编程FET中的出生率， 通过第二个特定的目标进行测试，在这个目标中，我们将活出生率与自然出生率和 程控循环。所有胚胎都将在试验登记之前被创造出来，没有胚胎将被创造出来 在这项研究过程中面临更大的风险。 随着这个方案的成功完成，我们将建立自然周期FET的活产率 与编程FET周期相比，使用当代标准化协议。如果自然周期是 这项研究被证实与先兆子痫风险较低有关，这项研究将提高数百万人接受抗逆转录病毒治疗的安全性 全世界正在接受FET的女性。这项研究提案高度响应了RFA和 NICHD和NIH的总体任务，因为它不仅将比较与两个通常情况下的 使用了当代的FET协议，但可能更重要的是，它将比较这些FET的安全性 与产妇保健有关的议定书。

PROJECT SUMMARY Of the estimated 1.6 million cycles of assisted reproductive technology (ART) performed globally in one year, nearly one third are categorized as frozen embryo transfer (FET). In the United States, over half of the ART cycles involve FET or freezing of all embryos. Given this widespread use of FET, it is of serious concern that multiple studies have demonstrated an association of FET with an increased risk for hypertensive disorders of pregnancy, including 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, including maternal mortality and fetal death. Furthermore, several recent meta-analyses emphasized that the evidence to guide clinicians about protocol choice for optimizing live birth rate with FET is poor. Our group has recently completed an NIH-sponsored Program Project Grant, with findings that strongly implicate one commonly performed FET protocol as an explanation for the increased risk of preeclampsia seen with FET. In a prospective cohort study, one protocol (the programmed FET) was associated with significantly higher rates of preeclampsia compared with an alternative protocol (the natural cycle FET). Furthermore, through detailed examination of maternal cardiovascular adaptation to pregnancy in two separate populations, perturbations of concern were seen with programmed FET, but not with natural cycle FET. Given these data and other findings in the literature, our central hypothesis is that pregnancy resulting from an FET in a natural cycle will have a lower rate of preeclampsia compared to an FET in a programmed cycle. To test this hypothesis, we will conduct a randomized, clinical trial at 6 sites. Our Primary Specific Aim is to determine the incidence of preeclampsia with the natural versus the programmed cycle. Our second hypothesis is that the live birth rate following transfer in a natural cycle is similar to that in a programmed FET, to be tested through a Second Specific Aim in which we compare the live birth rate with the natural versus the programmed cycle. All embryos will have been created prior to enrollment in the trial and no embryo will be subjected to increased risk in the course of this research. With successful completion of this protocol, we will have established the live birth rates for natural cycle FET compared to a programmed FET cycle, utilizing contemporary standardized protocols. If the natural cycle is confirmed to be associated with a lower risk of preeclampsia, this study will enhance the safety of ART for millions of women who are undergoing FET worldwide. This research proposal is highly responsive to the RFA and the overall mission of NICHD and NIH, as it will not only compare the live birth rates associated with two commonly used contemporary FET protocols, but it will perhaps even more importantly, compare the safety of these FET protocols with respect to maternal health.