P-502 Mosaic embryos result in equivalent live birth rates when compared to euploid embryos following frozen embryo transfer
Authors: Sashitzky S , Bibi M , Stern R , Greene A , Keltz M 
Published: July 2024

Abstract

Study question
Are mosaic embryos associated with a lower live birth rate (LBR) than euploid embryos?

Summary answer
In this adequately powered study, mosaic embryos had nearly identical LBR and similar miscarriage rates (MR) when compared to euploid embryos.

What is known already
While prior data has suggested that mosaic embryos result in almost half the LBR and three-fold higher MR than euploid embryos, all prior data supports mosaic embryo transfers as safe with acceptable LBRs. Recent studies have suggested a revised selection criteria choosing either euploid or mosaic embryos for transfer based on embryo grade, day of freeze, low level (LL) versus high level (HL) mosaicism and segmental versus whole chromosome mosaicism. Given the lower LBR reported with mosaics, we initially offered double embryo transfer (DET). We initiated this study to assess our LBR, MR, aneuploidy and DET outcomes with mosaics.

Study design, size, duration
This was a retrospective case-control cohort study. All mosaic embryos (51) that underwent frozen embryo transfer (FET) between January 2020 and June 2023 were compared to all euploid embryos (706) among all patients with tested embryos that underwent FET in the same time frame. Our Power analysis confirmed that with the 14:1 ratio of 706/51 euploid/mosaic embryos this study is sufficiently powered to exclude a &gt; 20% lower LBR following mosaic transfer.

Participants/materials, setting, methods
All patients seen at our IVF center undergoing FET of mosaic or euploid embryos tested with next generation sequencing during the study period were included. Primary outcome was LBR. Further comparison included age, MR, twin rate, freeze day and grade. Embryos were further analyzed for HL versus LL mosaicism, segmental or whole chromosomal mosaicism, freeze date and grade. Statistics employed chi-squared for categorical and student t-test for continuous data with significance set at p &lt; 0.01

Main results and the role of chance
Mosaic embryos resulted in nearly identical LBR when compared to euploid embryos, 26/51(50.9%) versus 359/706(50.85%). Implantation rate was also equivalent, 29/51(54.6%) and 376/706(53.3%). Both biochemical pregnancy [mosaics, 8/45(17.8%) versus euploid 127/683(18.6)], and MR [mosaics 3/29(10.3%) versus euploids 24/373(6.4%)] were not significantly different.
Among mosaic embryos, the LBR in LL versus HL mosaics were 17/28 (60.7%) and 9/23 (39.1%), respectively. LBR following segmental only versus whole chromosomal defects were 14/27(51.9%) and 11/24(45.8%). LBR following Day 5 versus Day 6/7 freeze were 10/22(45.5%) and 16/29(55.2%) and LBR for favorably graded embryos were 19/34(55.9%) versus fair to poor graded 7/17(41.2%). None of these achieved statistical significance.
While Mosaic embryos were transferred in significantly older patients (37.6 vs 36.1 p &lt; 0.01), there was no difference in mean age associated with LBR (36.1 vs 36.3 p =.4). Additionally, there was no statistically significant difference in LBR between age groups, &lt;35yo 143/259(55.2%), 35-37yo 96/202(47.5%), 38-40yo 96/207(46.4%) or &gt; 40yo 50/90(55.6%) among tested embryos.
DET was performed more often with mosaic 19/45 (42.2%) than euploid embryos 36/683 (5.3%) p &lt; 0.001, resulting in significantly higher twin births/LB 5/22 (23.8%) versus 6/356 (1.7%) p &lt; 0.001. All DET data sets included the 13 DETs where one euploid and one mosaic embryo were transferred.

Limitations, reasons for caution
Our small mosaic numbers may have kept the higher LBR with LL, segmental and good quality mosaic embryos from achieving statistical significance, and may be too small to confirm a higher MR with mosaics.
Prospective trials are needed to confirm which euploid or mosaic embryo should be selected for transfer.

Wider implications of the findings
Given the equivalent LBR, mosaic embryos should be used for transfer prior to repeating IVF retrieval for euploids.
The high rate of twin delivery following mosaic DET suggests only eSET should be utilized with any tested embryos.
Larger prospective trials are needed to further refine euploid versus mosaic embryo selection criteria.

Trial registration number
not applicable