Abstract
BACKGROUND: There is a considerable proportion of false positive results when the result of preimplantation genetic testing for aneuploidy is chromosomal mosaicism. The aim of this study was to assess the concordance among clinical trophectoderm biopsy, second trophectoderm biopsy, and inner cell mass biopsy in mosaic human embryos with segmental deletion and evaluate a modified biopsy protocol. METHODS: This retrospective study included 100 pretested blastocysts, which were classified as segmental deletion mosaics with one to two chromosomes were affected, donated by 84 couples in a single, high-volume fertility center in Beijing China. Re-biopsy was taken from the inner cell mass and two symmetrical trophectoderm sites near the inner cell mass in each embryo. Samples from the inner cell mass and one of the two trophectoderm were prepared for modified protocol, which isolated portions into single cells, the cells with normal morphology were collected and cell debris were removed. Re-biopsy samples were analyzed by next-generation sequencing. Main outcome measures were concordance between clinical biopsy and blastocyst, and segmental mosaicism in modified protocol. RESULTS: Only six (6.5%) of 92 inner cell mass samples presented with concordant chromosomal aberrations, four (4.3%) presented with de novo segmental abnormalities, and 82 (89.1%) did not show any segmental abnormalities. For the trophectoderm samples, 62 (66.7%) of 93 s biopsies and 76 (80%) of 95 modified biopsies did not show any segmental deletion or duplication. The modified biopsy protocol was associated with fewer segmental abnormalities (20% versus 33.3%; odds ratio: 0.5, 95% confidence interval: 0.26 to 0.97) and fewer segmental deletion mosaics (10.5% versus 23.7%; odds ratio: 0.38, 95% confidence interval: 0.17 to 0.85) compared with the second biopsy. CONCLUSIONS: A clinical mosaic embryo with simple segmental deletion was extremely low predictive of the embryo. Removal of cell debris from biopsy samples may reduce the incidence of segmental deletion mosaics.