Prevalence and authenticity of de-novo segmental aneuploidy (>16 Mb) in human blastocysts as detected by next-generation sequencing.
RESEARCH QUESTION
What is the prevalence and authenticity of de-novo segmental aneuploidies (>16 Mb) detected by next-generation sequencing (NGS) in human preimplantation blastocysts?


DESIGN
Between April 2013 and June 2016, 5735 blastocysts from 1854 couples (average age 33.11 ± 5.65 years) underwent preimplantation genetic testing for chromosomal structural rearrangement (PGT-SR) or for aneuploidy (PGT-A) using NGS on trophectoderm (TE) biopsy samples. The prevalence of de-novo segmental aneuploidy was calculated from these results. Forty blastocysts with de-novo segmental aneuploidy detected by NGS, which had been donated for research, were warmed for further fluorescence in-situ hybridization (FISH) analysis to confirm their authenticity.


RESULTS
The frequency of de-novo segmental aneuploidies in blastocysts was 10.13% (581/5735); the phenomenon was not related to maternal age and occurred on all chromosomes. Of the 40 donated blastocysts, 39 were successfully warmed and fixed for FISH analysis at the single-cell level. The de-novo segmental aneuploidies identified by NGS were confirmed by FISH in all 39 blastocysts. However, the de-novo segmental aneuploidies in these blastocysts were not all pure patterns, with 66.67% (26/39) of blastocysts exhibiting mosaic patterns varying from 8.30% to 92.86% of cells with de-novo segmental aneuploidy. The concordance rate between NGS and FISH in TE and inner cell mass (ICM) samples was 47.69% (31/65).


CONCLUSIONS
De-novo segmental aneuploidy above 16 Mb occurred in blastocysts and could be detected by NGS, while some aneuploidies existed as mosaics in both TE and ICM.
['Zhou|Shuang|S|', 'Cheng|Dehua|D|', 'Ouyang|Qi|Q|', 'Xie|Pingyuan|P|', 'Lu|Changfu|C|', 'Gong|Fei|F|', 'Hu|Liang|L|', 'Tan|Yueqiu|Y|', 'Lu|Guangxiu|G|', 'Lin|Ge|G|']
D000328:Adult D000782:Aneuploidy D001755:Blastocyst D053624:Blastocyst Inner Cell Mass D006801:Humans D017404:In Situ Hybridization, Fluorescence D008423:Maternal Age D009030:Mosaicism D019836:Preimplantation Diagnosis D017421:Sequence Analysis
De-novo segmental aneuploidy Next-generation sequencing Mosaic