Biopsy vs comprehensive embryo/blastocyst analysis: a closer look at embryonic chromosome evaluation.

Study question: Compared with embryonic cytogenetic constitution of biopsied samples in human pre-implantation embryos, are there any differences in whole embryos?

Summary answer: Whole embryos exhibit a significantly higher euploidy rate and reduction in mosaic aneuploidy rate compared to biopsied samples.

What is known already: Much of the existing evidence of cytogenetic constitution of human pre-implantation embryos is based on biopsied cells obtained from blastomeres or trophectoderm biopsies. The mosaic rate of biopsies taken from blastocyst trophectoderm ranges widely, from 2% to 25%.

Study design size duration: We investigated the embryonic cytogenetic constitution of 221 whole human embryos/blastocysts from 2019 to 2022, including 41 high-quality blastocysts, 57 low-quality blastocysts, and 123 arrested embryos/blastocysts.

Participants/materials setting methods: The cytogenetic constitution of whole embryos/blastocysts was assessed using next-generation sequencing. Mosaicism was diagnosed using a cut-off threshold of 30-70%, with embryos displaying 30-70% aneuploid cells classified as mosaic.

Main results and the role of chance: Among high-quality blastocysts, the euploidy rate was 82.9%, with a remarkably low mosaic aneuploidy of only 2.5%. The euploidy rates of viable low-quality blastocysts and arrested embryos/blastocysts were 38.6% and 13.0%, respectively. The mosaic aneuploidy rate decreased progressively with embryonic development, from 93.2% at the cleavage stage to 40% at the blastocyst stage. Chaotic aneuploidy was the primary factor (66.1%, 39/59) contributing to embryonic arrest at the cleavage stage. Additionally, 26.1% of embryos/blastocysts exhibited segmental aneuploidy, with segmental duplications (30.6%, 22/72) and deletions (54.2%, 39/72) being the most common types of segmental aneuploidy.

Limitations reasons for caution: The sample size in this study is relatively small, especially in the subgroup analysis. Furthermore, whole-embryo analysis is not a foolproof diagnostic method, since it may underestimate the presence of mosaicism.

Wider implications of the findings: The cytogenetic constitution of whole embryos provides a more accurate reflection of their physiological state compared to biopsied samples. The low mosaic aneuploidy rate in high-quality blastocysts supports the practice of transferring mosaic embryos in patients without euploid embryos. If blastocysts reach stage III by Day 6 post-fertilization, nearly half are euploid, suggesting that extending embryo culture to Day 7 may be beneficial in cases where high-quality embryos are lacking.

Study funding/competing interests: This study was supported by the Natural Science Foundation of Guangdong Province (No. 2023A1515010250) and Pilot Program-China Reproductive Health Public Welfare Fund Project (No. SZ202413). The authors report no conflicts of interest.

Trial registration number: N/A.