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Background  Chromosomal mosaicism is observed as the presence of both euploid and aneuploid cells in a particular blastocyst. Recent studies have reported that the implantation rate of mosaic embryo transfer is remarkably lower than the euploid embryos. The superior capability of next-generation sequencing (NGS) to detect chromosomal mosaicism in preimplantation genetic screening (PGS) remains controversial, and several data displayed similar implantation and pregnancy rates using NGS or array comparative genomic hybridization (aCGH).    Results  In this study, the main inconsistency of aneuploidy detection and clinical performance between the NGS and aCGH were assessed. The phase I consisted of a parallel comparison in 182 blastocysts from 45 selected PGS patients for both the NGS and aCGH platforms. The phase II retrospectively compared the clinical outcomes of 90 patients with NGS-screened euploid embryo transfer to that of 129 patients with aCGH-screened euploid embryo transfer. The parallel comparison showed that the inconsistency of embryo euploidy was 11.8% ( p  = 0.01). Chromosomal mosaicism (10.7% with NGS  vs.  3.9% with aCGH) and segmental aneuploidy (10.7% with NGS  vs.  6.7% with aCGH) contributed to the discrepancy mainly. The chromosomally mosaic embryos (20%–50% of aneuploidy) and several embryos with segmental aneuploidy (≥10 Mbp) were hard to distinguish using the aCGH platform, but could be clearly identified using the NGS platform. After the first euploid embryo cryotransfer, the β-HCG(+) rate and implantation rate significantly increased in the PGS/NGS patients (HCG[+] rate: 73.3% in PGS/NGS  vs.  60.5% in PGS/aCGH,  p  = 0.048; implantation rate: 53.2% in PGS/NGS  vs.  45.0% in PGS/aCGH,  p  = 0.043). The clinical and ongoing pregnancy rates appeared higher in the NGS group, but did not reached statistical significance.    Conclusions  The results demonstrated that the NGS platform can identify embryos with chromosomal mosaicism and segmental aneuploidy more precisely than the aCGH platform, and the following clinical performance of NGS was more favorable.

molecular cytogenetics

Identification of mosaic and segmental aneuploidies by next-generation sequencing in preimplantation genetic screening can improve clinical outcomes compared to array-comparative genomic hybridization