HOW DO DIFFERENT CUT-OFFS FOR MOSAICISM AFFECT CLINICAL OUTCOMES OF PGT-A?

This study aims to identify how different euploid – mosaic cut-off ratios affect the availability of euploid embryos for transfer and their clinical impact in a single ART center setting spanning a time frame of more than five years. This retrospective study covers a period from January 2017 to October 2022 and includes 6063 PGT-A cycles. A total of 18425 blastocysts were biopsied and analyzed with NGS. From January 2017 to December 2020, the cut-off value for reporting mosaicism and euploidy was 20%; the rate of which was increased to 30% after January 2021. Chromosomes with PGT-A profiles that deviate from 2 copies by less than 30% were then reported as normal. A total number of 12751 and 5674 blastocysts were biopsied between January 2017-December 2020 and January 2021-October 2022, respectively. PGT-A was performed on Ion Torrent S5 (Thermo Fisher Scientific). Mann-Whitney U for continuous and chi-square test for categorical data were used for statistical significance testing. Between January 2017 and December 2020, the percentage of top-quality embryos according to Gardner classification was not significantly different for <30% mosaic embryos and euploid embryos (55.0% vs 59.7%, p=0.118). However, in the same period, top quality embryos were significantly lower in ≥30% mosaic embryos when compared to euploids (49.7% vs 59.7%, p<0.001). For PGT-A cycles with female age <=38, cycles with at least one euploid embryo in the 30% cut-off group increased from 74.0% to 77.5% whereas cycles with at least one mosaic embryo decreased from 40.8% to 37.0% (p=0.021; p=0.027). Cycles with at least one mosaic embryo without any euploid embryos decreased by 2% (9.2% to 7.2%) (p=0.052). The euploidy percentage out of all tested biopsies was significantly increased from 40.4% to 45.8% (p<0.001). For cycles with female age >38, ratio of PGT-A cycles with at least one euploid embryo increased from 28.1% to 30.3% in the 30% cut-off group but this was not statistically significant (p=0.28). Cycles with at least one mosaic embryo were decreased from 15.1% to 10.8% and cycles with at least one mosaic embryo without any euploid embryo decreased from 9.5% to 5.6% in the 30% cut-off group (p=0.006; p=0.001). The euploidy percentage was increased by 2.8% from 15.1% to 18.1% (p=0.011). The pregnancy outcomes were significantly higher for euploid embryos with the 30% cut-off compared to 20%, as clinical pregnancy was 64.5% vs. 59.1% and clinical pregnancy loss was 7.9% vs. 12.4% (p=0.002; p=0.001). For mosaic embryo transfers, ongoing pregnancy was 5.2% higher in 30% cut-off group, but this was non-significant (59.2% vs 54.0%, p=0.41). Relaxing the mosaicism calling rate by 10% may have added some better-quality blastocysts to the euploid pool giving the opportunity to embryologists of transferring blastocysts with higher implantation potential.