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.

项目摘要 在估计的160万个辅助生殖技术（ART）的循环中，全球一年内的辅助生殖技术（ART） 将近三分之一被归类为冷冻胚胎转移（FET）。在美国，艺术的一半以上 周期涉及FET或所有胚胎的冷冻。鉴于这种广泛使用FET，因此严重关注 多项研究表明，FET的关联与高血压疾病的风险增加 怀孕，包括先兆子痫。至关重要的是，这种风险被最小化，因为先兆子痫与 母亲和婴儿都有严重的短期和长期后果，包括孕产妇死亡和胎儿 死亡。此外，最近的一些荟萃分析强调，指导临床医生的证据 通过FET优化活出生率的协议选择很差。 我们的小组最近完成了一项由NIH赞助的计划项目赠款，其发现强烈暗示 一种通常执行的FET方案是一种解释FET观察到的先兆子痫的风险的解释。 在一项前瞻性队列研究中，一项方案（程序化的FET）与率明显更高有关 与替代方案（自然循环FET）相比，先兆子痫此外，通过详细 检查两个单独人群中母体心血管适应怀孕的适应 在编程的FET中看到了关注，但自然周期FET没有看到。 鉴于文献中的这些数据和其他发现，我们的中心假设是 与程序中的FET相比 循环。为了检验这一假设，我们将在6个地点进行随机的临床试验。我们的主要目标 是确定先兆子痫的发生率与编程周期的发生率。我们的第二个 假设是，自然周期中传递后传递后的活出生率与编程的FET相似， 要通过第二个特定目标进行测试，在该目标中，我们将活产率与自然与自然的生育率进行比较 程序周期。所有胚胎都将在入学之前创建，并且不会胚胎 在这项研究过程中，风险增加。 随着该协议的成功完成，我们将确定自然循环FET的实时出生率 与编程的FET周期相比，利用当代标准化协议。如果自然循环是 这项研究确认与较低的先兆子痫风险有关，将提高数百万的艺术安全性 在全球范围内经历Fet的妇女。该研究建议对RFA和 NICHD和NIH的整体任务，因为它不仅将与两个通常相关的活出生率进行比较 使用了当代的FET协议，但它可能更重要的是，比较这些FET的安全性 关于孕产妇健康的协议。