Variation in the Incidence and Type of Full versus Mosaic Segmental Aneuploidies Identified in Blastocysts Undergoing PGT-A

Abstract

Objectives: The primary aim of this study was to investigate the incidence of segmental aneuploidies (full vs. mosaic) in embryos biopsied for Preimplantation Genetic Testing with Aneuploidy (PGT-A) screening using low-coverage whole genome sequencing (WGS). The secondary aim was to investigate factors that may be associated with segmental aneuploidy rates, including blastocyst developmental stage and quality. Methods: This study involved a retrospective analysis of cycle and PGT-A data from 8,153 blastocysts biopsied from 2,522 patients at four Monash IVF Victorian clinics between January 2015 and June 2021. All biopsies were processed using the Veriseq PGS Kit (Illumina) and analyzed using Bluefuse Multi software (Illumina) with a conclusive PGT-A result. Segmental aneuploidy was reported with a minimum resolution of greater than or equal to 10[Formula: see text]Mb. The reporting range for mosaicism was 20%–70% loss/gain in copy number. Statistical significance was established at a P-value of less than 0.05. Results: Segmental aneuploidies (full and/or mosaic) were reported in 682/8,153 (8.4%) biopsied embryos. Analysis of the types of segmental aneuploidy showed a higher proportion of deletions (423/8,153; 5.2%) compared to duplications (210/8,153; 2.6% [[Formula: see text]] plus a small portion with both duplications and deletions detected 49/8153; 0.6% [[Formula: see text]]). The incidence of segmental aneuploidies appeared to increase in correlation with chromosome size. Segregation of embryos by blastocyst stage indicated an increase in the incidence of segmental aneuploidies in early blastocysts (9/64; 14.1%) compared with expanding/expanded (39/475, 8.2%, [[Formula: see text]] and hatching/hatched blastocysts [634/7614, 8.3%; [Formula: see text]]). Furthermore, the incidence of segmental aneuploidies significantly increased as blastocyst overall grade decreased (Grade A 71/1,429, 5.0%; Grade B 298/3,764, 7.9%; Grade C 313/2,960, 10.6%; [Formula: see text]). Of the segmental aneuploidies detected, 425/682 (62.3%) were present at a mosaic level. Conclusions: Segmental aneuploidy rates varied between blastocyst stage and grades, with a significant proportion of segmental aneuploidies being detected at the mosaic level. Our data highlights that segmental aneuploidies, both at the full and mosaic level, are associated with lower blastocyst quality and poorer embryo development.