P-518 Do mosaic embryos still stand a chance for pregnancy?
Authors: Teng Z.X 
Published: June 2022

Abstract

Study question
To investigate the effect of embryo mosaicism on clinical IVF outcomes in single and double frozen embryo transfer (FET).

Summary answer
There is no statistical difference between the low/high mosaic and euploid embryos in regards to the pregnancy and miscarriage rate, in single and double FETs.

What is known already
During mitosis and meiosis, mis-segregation of chromosomes causes aneuploidy. Recent studies have shown that next-generation sequencing (NGS) based pre-implantation genetic test for aneuploidy (PGT-A) improve clinical IVF outcomes by detecting chromosomal abnormalities in human embryos. Euploid embryos have been confirmed to achieve a higher pregnancy, implantation and live birth rate than aneuploid embryos. However, mosaic embryos, which contain two or more cell lines with different chromosomal set, are yet controversial in the assisted reproductive medical field. Hence, comprehensive studies on the clinical IVF outcomes of mosaic embryo transfers (METs) are necessary to resolve the concerns of embryo mosaicism.

Study design, size, duration
This single centre retrospective study included 93 low mosaic embryos, which were transferred in 64 FET cycles (35 single and 29 double FET), and 27 high mosaic embryos from 18 FET cycles (9 single and 9 double FET), from January 2018 to October 2021. The pregnancy and miscarriage rate of the METs were compared to an euploid control group, which comprised of 184 euploid embryos from 124 FET cycles (64 single and 60 double FET).

Participants/materials, setting, methods
All embryos were cultured to blastocyst stage and trophectoderm (TE) biopsy was performed on day 5 or 6. NGS based PGT-A was conducted to detect chromosomal abnormalities. According to the Preimplantation Genetic Diagnosis International Society guideline, mosaic embryos were categorized into 2 groups: low (20-39% mosaicism) and high mosaic embryos (40-80% mosaicism). Pearson chi-square test was performed to compare the pregnancy and miscarriage rate between low/high METs and euploid group, in single and double FETs.

Main results and the role of chance
In single FET cycles, patients with low mosaic embryos transferred achieved a higher pregnancy rate than the patients with euploid (60% versus 42%) and high mosaic (60% versus 33%) embryos transferred. In addition, the miscarriage rate for low mosaic embryos (9%) was the lowest, compared to the the euploid (11%) and high mosaic (22%) embryos. On the other hand, the highest pregnancy and lowest miscarriage rate in double FET cycles were achieved by patients with euploid embryos transferred. Results showed that patients with euploid embryos transferred possessed a pregnancy rate of 68%, whereas patients with low and high mosaic embryos transferred showed a pregnancy rate of 48% and 56% respectively. As mentioned above, the euploid embryos resulted in a lower miscarriage rate than the low (3% versus 10%) and high mosaic (3% versus 11%) embryos in double FET cycles. However, it is important to highlight that the above mentioned differences between the low/high METs and euploid control group in respect of the pregnancy and miscarriage rate were not statistically significant, in both single and double FET cycles (p &lt; 0.05).

Limitations, reasons for caution
The factors of patient’s age and blastocyst grading were not taken into account in this study. Hence, a larger-scale randomized trial is a need to further identify and resolve the concerns of embryo mosaicism in the assisted reproductive medical field .

Wider implications of the findings
In the PGT-A analysis, only a fraction of the TE within an embryo was tested. Thus, misclassification of embryos might occur. It is suggested that clinical management of mosaic embryos should be carefully reviewed in the case of patients with no euploid embryos to be transferred.

Trial registration number
NA