Werner M Neuhausser1,2,3,4,5, Denis A Vaughan6,7,8, Denny Sakkas8, Michele R Hacker6,7, Tom Toth6,7,8, Alan Penzias6,7,8. 1. Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA, USA. wneuhaus@bidmc.harvard.edu. 2. Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA, USA. wneuhaus@bidmc.harvard.edu. 3. Boston IVF, Waltham, MA, USA. wneuhaus@bidmc.harvard.edu. 4. Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, USA. wneuhaus@bidmc.harvard.edu. 5. Broad Institute of MIT and Harvard, Cambridge, USA. wneuhaus@bidmc.harvard.edu. 6. Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA, USA. 7. Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA, USA. 8. Boston IVF, Waltham, MA, USA.
Abstract
BACKGROUND: With improvements in in vitro culture techniques there has been a steady shift in practice to transfer embryos at the blastocyst stage (post fertilization day (p.f.d.) 5-7), when embryos reach the endometrial cavity during natural conception. For patients with > 5 zygotes on day 1 of embryo development, fresh blastocyst embryo transfer (ET) increases live birth rates when compared to cleavage stage (p.f.d. 3) transfer. In poorer prognosis patients (≤ 5 zygotes) cleavage stage ET is commonly performed to reduce the risk of cycle cancellation if no embryo survives to the blastocyst stage. However, there is a dearth of randomized controlled trial (RCT) data demonstrating improved live birth rates per cycle for cleavage vs blastocyst stage ET in this subgroup of patients. The hypothesis of the PRECiSE (PooR Embryo Yield Cleavage Stage Versus blaStocyst Embryo Transfer) trial is that blastocyst ET is not inferior to cleavage stage ET with regard to live birth rates per retrieval in poorer prognosis patients. The adoption of routine blastocyst culture for all patients would result in higher rates of single embryo transfers (SET), reduced incidence of multiple pregnancies and simplified laboratory protocols, thereby reducing costs. METHODS/ DESIGN: Multicenter, non-inferiority randomized controlled trial (RCT) comparing blastocyst to cleavage stage embryo transfer in poorer prognosis patients with ≤5 zygotes on day 1 after fertilization. The primary outcome is live birth per retrieval. Secondary outcomes include: time to pregnancy, clinical pregnancy, ongoing pregnancy, miscarriage and multiple pregnancy rate (per retrieval). This trial will enroll 658 women with ≤5 zygotes on day 1 at 6 IVF centers over the course of 22 months. DISCUSSION: If the hypothesis is proven true, the data from this trial may facilitate the adoption of uniform blastocyst culture in all IVF patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03764865. Registered 5 December 2019, Protocol issue date: 4 December 2018, Original.
RCT Entities:
BACKGROUND: With improvements in in vitro culture techniques there has been a steady shift in practice to transfer embryos at the blastocyst stage (post fertilization day (p.f.d.) 5-7), when embryos reach the endometrial cavity during natural conception. For patients with > 5 zygotes on day 1 of embryo development, fresh blastocyst embryo transfer (ET) increases live birth rates when compared to cleavage stage (p.f.d. 3) transfer. In poorer prognosis patients (≤ 5 zygotes) cleavage stage ET is commonly performed to reduce the risk of cycle cancellation if no embryo survives to the blastocyst stage. However, there is a dearth of randomized controlled trial (RCT) data demonstrating improved live birth rates per cycle for cleavage vs blastocyst stage ET in this subgroup of patients. The hypothesis of the PRECiSE (PooR Embryo Yield Cleavage Stage Versus blaStocyst Embryo Transfer) trial is that blastocyst ET is not inferior to cleavage stage ET with regard to live birth rates per retrieval in poorer prognosis patients. The adoption of routine blastocyst culture for all patients would result in higher rates of single embryo transfers (SET), reduced incidence of multiple pregnancies and simplified laboratory protocols, thereby reducing costs. METHODS/ DESIGN: Multicenter, non-inferiority randomized controlled trial (RCT) comparing blastocyst to cleavage stage embryo transfer in poorer prognosis patients with ≤5 zygotes on day 1 after fertilization. The primary outcome is live birth per retrieval. Secondary outcomes include: time to pregnancy, clinical pregnancy, ongoing pregnancy, miscarriage and multiple pregnancy rate (per retrieval). This trial will enroll 658 women with ≤5 zygotes on day 1 at 6 IVF centers over the course of 22 months. DISCUSSION: If the hypothesis is proven true, the data from this trial may facilitate the adoption of uniform blastocyst culture in all IVFpatients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03764865. Registered 5 December 2019, Protocol issue date: 4 December 2018, Original.
Authors: Lisa A Vrooman; Eric A Rhon-Calderon; Kashviya V Suri; Asha K Dahiya; Yemin Lan; Richard M Schultz; Marisa S Bartolomei Journal: Front Cell Dev Biol Date: 2022-04-25