Natural vs. programmed cycles for frozen embryo transfer: study protocol for an investigator-initiated, randomized, controlled, multicenter clinical trial
Sheriza Baksh, Anne Casper, Mindy S. Christianson, Kate Devine, Kevin J. Doody, Stephan Ehrhardt, Karl R. Hansen, Ruth B. Lathi, Fatmata Timbo, Rebecca Usadi, Wendy Vitek, David Shade, James H. Segars, Valerie L. Baker, NatPro Study Group, Lusine Aghajanova, Ruben Alvero, Mary Andrews, Diego Arévalo, Emily Barnard, Aracely Casillas, Morgan Copeland, La Tasha B. Craig, K.M. Doody, Ashley M. Eskew, Alma Patricia González, Gretchen L. Hoelscher, Arthur J. Vaught, Lynda Kochman, Andie Lears, Gaya Murugappan, Anna C Nackley, Tasha L. Newsome, Natalie Quintana, Bhuchitra Singh, Anna Sokalska, Michelle Starkey-Scruggs, Robin L. Thomas, Deveine Toney, Irene Trueheart, Kisha Turner, Rebecca Usadi, Sally Villalobos, Anjali Wignarajah, Virginia D. Winn, Christy Zones
Abstract
BACKGROUND: Randomized trials of assisted reproductive technology (ART) have been designed for outcomes of clinical pregnancy or live birth and have not been powered for obstetric outcomes such as preeclampsia, critical for maternal and fetal health. ART increasingly involves frozen embryo transfer (FET). Although there are advantages of FET, multiple studies have shown that risk of preeclampsia is increased with FET compared with fresh embryo transfer, and the reason for this difference is not clear. NatPro will compare the proportion of preeclampsia between two commonly used protocols for FET,modified natural and programmed cycle. METHODS: In this two-arm, parallel-group, multi-center randomized trial, NatPro will randomize 788 women to either modified natural or programmed FET and follow them for up to three FET cycles. Primary outcome will be the proportion of preeclampsia in women with a viable pregnancy assigned to a modified natural cycle FET (corpus luteum present) protocol compared to the proportion of preeclampsia in pregnant women assigned to a programmed FET (corpus luteum absent) protocol. Secondary outcomes will compare the proportion of live births and the proportion of preeclampsia with severe features between the protocols. CONCLUSION: This study has a potential significant impact on millions of women who pursue ART to build their families. NatPro is designed to provide clinically relevant guidance to inform patients and clinicians regarding maternal risk with programmed and modified natural cycle FET protocols. This study will also provide accurate point estimates regarding the likelihood of live birth with programmed and modified natural cycle FET. TRIAL REGISTRATION: ClinicalTrials.gov NCT04551807 . Registered on September 16, 2020.