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

1/3 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: 10480775
• 负责人: Valerie Lynn Baker
• 金额: $ 202.55万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 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/10480775
• 关键词: Address; Affect; Assisted Reproductive Technology; Autologous; Birth Rate; Blinded; Blood Circulation; Cardiovascular system; Child; Clinical; Clinical Data; Cryopreservation; Data; Development; Diagnosis; 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; Hypertension; 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.

项目概要 全球一年内估计进行了 160 万次辅助生殖技术 (ART) 周期， 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 周期涉及 FET 或冷冻所有胚胎。鉴于 FET 的广泛使用，值得严重关注的是 多项研究表明 FET 与高血压疾病风险增加有关 怀孕，包括先兆子痫。尽量减少这种风险至关重要，因为先兆子痫与 对母亲和婴儿造成严重的短期和长期后果，包括孕产妇死亡和胎儿死亡 死亡。此外，最近的一些荟萃分析强调，指导临床医生的证据 使用 FET 优化活产率的方案选择很差。 我们的小组最近完成了一项由美国国立卫生研究院 (NIH) 赞助的项目资助项目，其研究结果强烈表明 一种常用的 FET 方案，作为 FET 导致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（编程 FET）与显着较高的发生率相关 与替代方案（自然周期 FET）相比，先兆子痫的发生率。此外，通过详细 检查两个不同人群中母亲心血管对妊娠的适应情况， 人们对编程 FET 表示担忧，但对自然循环 FET 则不然。 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 与程序化周期中的 FET 相比，自然周期中的 FET 的先兆子痫发生率较低 循环。为了检验这一假设，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 目的是确定自然周期与程序周期的先兆子痫的发生率。我们的第二个 假设自然循环中转移后的活产率与程序化 FET 中的活产率相似， 通过第二个具体目标进行测试，其中我们将活产率与自然出生率和自然出生率进行比较 编程循环。所有胚胎都将在参加试验之前创建，并且不会 在本研究过程中面临更大的风险。 成功完成该协议后，我们将确定自然周期 FET 的活产率 与利用当代标准化协议的编程 FET 周期相比。如果自然循环是 这项研究被证实与降低先兆子痫风险相关，将提高数百万人接受 ART 的安全性 全球接受 FET 治疗的女性人数。该研究提案对 RFA 和 NICHD 和 NIH 的总体使命，因为它不仅会比较两种常见疾病的活产率 使用当代 FET 协议，但也许更重要的是，比较这些 FET 的安全性 关于孕产妇健康的协议。