O-291 Cumulative pregnancy rates of two strategies: day 3 fresh embryo transfer followed by day 3 or day 5 frozen embryo transfer, a Randomized Controlled Trial
Authors: Mengels A , Peeraer K , Spiessens C , Debrock S 
Published: June 2022

Abstract

Study question
Are cumulative pregnancy rates different if supernumerary embryos are vitrified on day 5 instead of day 3?

Summary answer
Results do not show a significant difference in cumulative pregnancy rates between the vitrification day 3 and day 5 group.

What is known already
The pregnancy and live birth rates following IVF or ICSI treatment are higher after extended embryo culture and blastocyst transfer (day 5) compared to cleavage-stage (day 3) embryo transfer (Glujovski et al 2016). Cumulative pregnancy rates after fresh and frozen embryo transfers show no significant difference after one oocyte retrieval (OR) but only one study used vitrification for the cryopreservation of supernumerary embryos while four studies used a slow freezing protocol (Fernandez-Shaw et al., 2014). A retrospective analysis by De Vos et al., 2016 concluded significantly less embryo transfers were necessary until live birth for blastocyst-stage embryos.

Study design, size, duration
A Randomized Controlled Trial was performed in an academic center between 01/01/2018 and 31/07/2020. Patients were randomized in the vitrification day 3 or day 5 group. Primary outcome is the number of embryo transfers needed to reach ongoing pregnancy. Power calculation revealed that 75 patients were needed in each group, assuming a median of 4 transfers in the day 3 group versus a median of 2 transfers in the day 5 group to achieve pregnancy.

Participants/materials, setting, methods
Patients &lt;38 years undergoing their first/second OR were randomized at the start of the cycle. Embryos with ≥6 cells, &lt;25% fragmentation and equal blastomeres and blastocysts with expansion grade ≥2 with inner cell mass and trophectoderm score A/B were vitrified. A time-to-event analysis was performed with ongoing pregnancy as the event of interest and the number of embryo transfers as the time component. The statistical comparison was performed by a Cox proportional hazards model.

Main results and the role of chance
By December 2021, 234 transfers (96 fresh and 138 frozen) of 78 patients were performed in the vitrification day 3 group and 207 transfers (83 fresh and 113 frozen) of 80 patients in the vitrification day 5 group. The time-to-event analysis did not show a difference between both arms with regards to ongoing pregnancy as the primary study outcome (HR 1.25, 95% CI 0.81; 1.91, p = 0.31). The cumulative ongoing pregnancy rate after 8 transfers was 56% in the day 3 group versus 57% in the day 5 group. Median number of transfers till pregnancy was 6 versus 4, respectively. Similar results were found for the secondary study outcome (clinical pregnancy with fetal heart rate, HR 1.19, 95% CI 0.80; 1.80, p = 0.407). A total of 225 transfers (93 fresh and 132 frozen) of 78 patients were performed in the vitrification day 3 group and 201 transfers (92 fresh and 109 frozen) in the vitrification day 5 group. The cumulative clinical pregnancy rate after 8 transfers was 62% in the day 3 group versus 59% in the day 5 group. Median number of transfers till pregnancy was 6 versus 4, respectively.

Limitations, reasons for caution
Although power calculation revealed 75 patients are needed in each study group (β = 0.87, α &lt; 0.05), numbers remain low.

Wider implications of the findings
A recent systematic review and cumulative meta-analysis of Marconi et al. (2021) suggests day 5 embryo transfer is associated with higher risk of preterm birth although evidence was low. Health/economic analyses should be taken into account to determine the most cost-effective strategy for patient and hospital/society.

Trial registration number
NCT04196036