Segmental aneuploid hotspots identified across the genome concordant on reanalysis

Abstract

Abstract The aim of this study was to characterize a large set of full segmental aneuploidies identified in trophectoderm (TE) biopsies and evaluate concordance in human blastocysts. Full segmental aneuploid errors were identified in TE biopsies (n = 2766) from preimplantation genetic testing for aneuploid (PGT-A) cycles. Full segmental deletions (n = 1872; 66.1%) presented twice as many times as duplications (n = 939; 33.9%), mapped more often to the q-arm (n = 1696; 61.3%) than the p-arm (n = 847; 31.0%) or both arms (n = 223; 8.1%; P < 0.05), and were eight times more likely to include the distal end of a chromosome than not (P < 0.05). Additionally, 37 recurring coordinates (each ≥ 10 events) were discovered across 17 different chromosomes, which were also significantly enriched for distal regions (P = 4.1 × 10−56). Blinded concordance analysis of 162 dissected blastocysts validated the original TE PGT-A full segmental result for a concordance of 96.3% (n = 156); remaining dissected blastocysts were identified as mosaic (n = 6; 3.7%). Origin of aneuploid analysis revealed full segmental aneuploid errors were mostly paternally derived (67%) in contrast to whole chromosome aneuploid errors (5.8% paternally derived). Errors from both parental gametes were observed in 6.5% of aneuploid embryos when multiple whole chromosomes were affected. The average number of recombination events was significantly less in paternally derived (1.81) compared to maternally derived (3.81) segmental aneuploidies (P < 0.0001). In summary, full segmental aneuploidies were identified at hotspots across the genome and were highly concordant upon blinded analysis. Nevertheless, future studies assessing the reproductive potential of full (non-mosaic) segmental aneuploid embryos are critical to rule out potential harmful reproductive risks.