Multicentre randomised comparative effectiveness trial of cleavage-stage versus blastocyst-stage embryo transfer in patients with few embryos (PRECISE): implementation of a study protocol in reproductive medicine
Werner M Neuhausser, Denis A Vaughan, Denny Sakkas, Alan Penzias, Raymond M Anchan, Mark D Hornstein, Harrison T Reeder, Kurt T Barnhart, Elizabeth A Stewart, Marcelle Cedars, Cihan Halicigil, Hugh S Taylor, Michelle Beck, Michele R Hacker, Erica Marsh, Clarisa R Gracia, Zev Rosenwaks, Zev Williams, Dustin J Rabideau, , , , , ,Background
With improvements in in vitro culture techniques, there has been a steady shift in practice to transfer in vitro fertilisation (IVF) embryos at the blastocyst-stage to increase pregnancy rates per embryo transfer (ET) and reduce the risk of multiple pregnancy. In patients with fewer embryos (≤5 zygotes), fresh cleavage-stage ET is still commonly performed to reduce the risk of cycle cancellation if no embryo survives to the blastocyst-stage in vitro. However, evidence for improved outcomes with cleavage-stage embryo transfer in this subgroup of patients is lacking. We will compare blastocyst-stage to cleavage-stage ET with regard to cumulative live birth rates (CLBR) per oocyte retrieval and other patient-centred cycle outcomes in patients with ≤5 zygotes.
Methods and analysis
Multicentre, randomised pragmatic comparative effectiveness trial with superiority design comparing blastocyst-stage to cleavage-stage ET in patients with ≤5 zygotes. This trial will enrol and randomise 1126 women aged 18–44 undergoing IVF to either fresh cleavage-stage or blastocyst-stage ET at eleven IVF centres. Surplus embryos will be vitrified at the blastocyst-stage. The primary outcome is the CLBR per oocyte retrieval. Secondary outcomes include: multiple pregnancy, pregnancy loss <20 weeks and cycle cancellation. Exploratory outcomes include: live birth per fresh ET, ectopic pregnancy, time to pregnancy, stillbirth, preterm birth, financial burden, patient distress and facilitators and barriers for patient involvement and implementation. All primary analyses will be conducted according to the intent-to-treat principle. We also will report per-protocol analyses as a sensitivity analysis. A multidisciplinary stakeholder team, including a 5-patient stakeholder panel, will participate in study design, conduct and oversight.
Ethics and dissemination
The Institutional Review Board at Beth Israel Deaconess Medical Center (BIDMC) provides central regulatory oversight. Results will inform timing of embryo transfer in patients with ≤5 zygotes and will be disseminated through academic publications, meeting presentations and communications to advocacy groups and patient participants.
Trial registration number