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

2/3 以改良的自然周期与程序周期进行冷冻胚胎移植的随机对照试验 (NatPro)

• 批准号: 10252914
• 负责人: Karl Richard Hansen
• 金额: $ 30.9万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-26 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10252914
• 关键词: Address; Affect; Assisted Reproductive Technology; Autologous; Birth Rate; Blinded; Blood Circulation; Cardiovascular system; Child; Clinical; Clinical Data; Cryopreservation; Data; Development; Diagnosis; Disease; Embryo; Embryo Transfer; Endometrial; Endometrial Cycles; Enrollment; Ensure; Estradiol; Fertilization in Vitro; Fetal Death; Fetal Growth; Fetus; Freezing; Future; Gonadal Steroid Hormones; Hormonal; Hormones; Human; Hypothalamic structure; Incidence; Infant; Lead; Literature; Live Birth; Maternal Health; Maternal Mortality; Maternal Physiology; Maternal and Child Health; Medical Records; Meta-Analysis; Methods; Mission; Mothers; National Institute of Child Health and Human Development; Outcome; Ovulation; Participant; Physiological; Pituitary Gland; Play; Population; Pre-Eclampsia; Pregnancy; Preimplantation Diagnosis; Preparation; Procedures; Progesterone; Program Research Project Grants; Prospective cohort study; Protocols documentation; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Relaxin; Research; Research Proposals; Risk; Role; Safety; Site; Spontaneous abortion; Standardization; Testing; Treatment Protocols; United States; United States National Institutes of Health; Vascular Endothelial Growth Factors; Woman; adjudicate; arm; assisted reproduction; base; corpus luteum; design; egg; embryo cryopreservation; implantation; predictive marker; pregnancy disorder; randomized trial; response; risk minimization; treatment group

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.

项目摘要 据估计，全球一年内进行的辅助生殖技术（ART）周期为160万个， 近三分之一被归类为冷冻胚胎移植（FET）。在美国，超过一半的ART 周期包括FET或冷冻所有胚胎。鉴于FET的广泛使用，令人严重关切的是， 多项研究表明FET与高血压疾病风险增加相关， 妊娠，包括先兆子痫。至关重要的是，这种风险应尽量减少，因为先兆子痫是相关的 对母亲和婴儿造成严重的短期和长期后果，包括产妇死亡率和胎儿死亡率。 死亡此外，最近的几项荟萃分析强调，指导临床医生的证据 用FET优化活产率的方案选择很差。 我们的团队最近完成了一项NIH赞助的计划项目资助，其发现强烈暗示了 一种通常执行的FET方案作为FET所见先兆子痫风险增加的解释。 在一项前瞻性队列研究中，一种方案（程控FET）与显著更高的发生率相关 先兆子痫与替代方案（自然周期FET）的比较。此外，通过详细 在两个不同的人群中检查母体对妊娠的心血管适应性， 对编程FET有顾虑，但对自然周期FET没有。 鉴于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于 自然周期中的FET与程序周期中的FET相比， 周期为了检验这一假设，我们将在6个研究中心进行随机临床试验。我们的主要具体目标 是确定自然周期和程序周期的先兆子痫的发病率。我们的第二 假设在自然周期中转移后的活产率与程序FET中的活产率相似， 将通过第二个具体目标进行测试，在该目标中，我们将活产率与自然出生率和 编程周期所有胚胎将在入组试验之前产生，并且没有胚胎将在试验期间产生。 在这项研究中面临的风险越来越大。 随着本方案的成功完成，我们将确定自然周期FET的活产率 与编程的FET周期相比，使用当代标准化方案。如果自然循环是 证实与先兆子痫的风险较低有关，这项研究将提高数百万人ART的安全性 全世界接受FET的女性。这项研究建议是高度响应RFA和 NICHD和NIH的总体使命，因为它不仅将比较与两种常见疾病相关的活产率， 使用当代FET协议，但它可能更重要的是，比较这些FET的安全性， 关于产妇保健的议定书。