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

行政请求项目摘要

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.