Assessing the necessity of screening ≤ 5 Mb segmental aneuploidy in routine preimplantation genetic testing for aneuploidy

Abstract

Research Question

Does routine clinical practice require an increase in the resolution of preimplantation genetic testing for aneuploidy (PGT-A) to detect segmental aneuploidies (SAs) ≤ 5 Mb?

Design

This retrospective study analyzed 963 trophectoderm (TE) biopsies from 346 couples undergoing PGT between 2019 and 2023. SAs ≥ 1 Mb were reported. Characteristics, clinical interpretation and concordance of ≤ 5 Mb SAs were analyzed.

Results

The incidence of SAs was 15.1% (145/963) in blastocysts, with SAs of 5 Mb or smaller accounting for 2.3% (22/963). The size of SAs showed a skew distribution. For SAs ≤ 5 Mb, they were found to occur more frequently on the q arm of the chromosome, compared to the p arm. Losses of ≤ 5 Mb SAs were more prevalent than gains, with 17 deletions compared to 5 duplications, respectively. 63.6% (14/22) ≤ 5 Mb SAs were of de novo and 50.0% (7/14) de novo SAs were pathogenic/likely pathogenic (P/LP) CNVs, accounting for 0.7% of 963 blastocysts. For these blastocysts carrying ≤ 5 Mb SAs, reanalysis of backup biopsy samples showed that 35.7% of de novo SAs (5/14) were not detected in the backup samples. Cases were reported that prenatal diagnosis (amniocentesis) revealed the absence of the embryonic ≤ 5 Mb SA detected at blastocyst stage.

Conclusions

The incidence of P/LP de novo ≤ 5 Mb SAs in human blastocysts is extremely low. There is no compelling need to increase the resolution of PGT-A to 5 Mb in routine clinical practice.