A pilot randomized controlled trial of Day 3 single embryo transfer with adjunctive time-lapse selection versus Day 5 single embryo transfer with or without adjunctive time-lapse selection.

STUDY QUESTION: Compared to D5 selection with conventional morphology (CM), does adjunctive use of the Eeva™ test on D3 or D5 improve the clinical pregnancy rate (CPR) per transfer?

SUMMARY ANSWER: The evidence is insufficient to conclude that adjunctive use of the Eeva™ test on D3 or D5 improves CPR per transfer as compared to D5 selection with CM.

WHAT IS KNOWN ALREADY: Time-lapse imaging is increasingly used for embryo selection, despite there being no class I data to support its clinical application.

STUDY DESIGN, SIZE, DURATION: Pilot randomized controlled trial included 163 patients from August 2014 to February 2016.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients up to age 41 years with a planned fresh autologous single embryo transfer (SET), less than four prior oocyte retrievals, and four or more zygotes were blocked according to age (<35, 35-37, 38-40 years) and randomized to one of three study arms: (1) D3 SET + EevaTM, (2) D5 SET + Eeva™ or (3) D5 SET with CM alone. All embryos were cultured in the same time-lapse system under identical conditions. Intention-to-treat (ITT) and as-treated analyses of the primary endpoint (CPR at 7 weeks) and secondary endpoint (ongoing pregnancy rate at 12 weeks) were performed. Multivariate regression analyses adjusted for patient age and ICSI.

MAIN RESULTS AND THE ROLE OF CHANCE: Of 478 eligible patients, 217 consented and 163 were randomized. Demographic characteristics were similar among the three study arms. There were no statistically significant differences in the clinical pregnancy rate or the ongoing pregnancy rate between the study arms for either the ITT or as-treated analyses (CPR ITT: D3 + Eeva™: 41.1% vs. D5 + Eeva™: 38.9% vs. D5 CM: 49.1%).

LIMITATIONS, REASONS FOR CAUTION: This study was designed as a pilot randomized controlled trial and was not powered to detect a statistically significant difference at α < 0.05. Importantly, the study was terminated prematurely by the sponsor due to a change in funding priorities, so the sample size is limited and the results should be interpreted with caution due to the role of chance. Furthermore, these findings may not be generalizable to other time-lapse systems.

WIDER IMPLICATIONS OF THE FINDINGS: Our findings do not support the clinical application of these time-lapse markers.

STUDY FUNDING/COMPETING INTEREST(S): This study was funded by Progyny, Inc. There are no competing interests.

TRIAL REGISTRATION NUMBER: clinicaltrials.gov: NCT02218255.

TRIAL REGISTRATION DATE: 14 August 2014.

DATE OF FIRST PATIENT'S ENROLLMENT: 3 September 2014.