Massively parallel sequencing on human cleavage-stage embryos to detect chromosomal abnormality

Eur J Med Genet. 2018 Jan;61(1):34-42. doi: 10.1016/j.ejmg.2017.10.009. Epub 2017 Oct 12.


Purpose: Next-generation sequencing technology like MPS has recently been introduced to perform comprehensive chromosome screening on human trophectoderm samples for preimplantation embryo assessment. However, the potential of MPS in chromosome analysis of single cell from blastomeres has not yet been investigated.

Methods: In this study, 12 couples underwent MPS analysis, including 9 balanced translocation carriers and 3 carriers of numerical chromosomal abnormalities. Cleavage-stage (Day 3) embryos (n = 105) were biopsied with one cell removal. Single cell from blastomeres was processed by whole genome amplification (WGA). WGA products were subjected to both MPS and microarray-based comparative genomic hybridization (array-CGH). Euploid embryos identified as "balanced or normal" were selected for frozen-thawed embryo transfer (FET) cycles.

Results: Reliable MPS-PGD results as well as array CGH-PGD results were obtained for 101 biopsied cleavage-stage embryos. 18.8% (19/101) embryos were identified as "euploid and balanced" by both MPS and array-CGH. 20.8% (21/101) were unbalanced for the translocation but normal for aneuploidy.26.7% (27/101) had aneuploidy and were unbalanced. 33.7% (34/101) showed normal or balanced but still had aneuploidy of chromosomes. In identifications of embryo aneuploidy and imbalance, MPS and array-CGH showed 100% consistency, with the exception of 4 samples. After transferring 12 embryos with normal or balanced for every chromosome, 1 live birth and 5 ongoing clinical pregnancies were achieved.

Conclusion: In conclusion, as a flexible and cost-effective strategy and higher potential accuracy. MPS could be clinically applied to detect numeric abnormality of chromosome segments in day 3 preimplantation blastomeres.

Keywords: Chromosomal abnormality; Cleavage-stage embryo; Massively parallel sequencing (MPS); Microarray-based comparative genomic hybridization (array-CGH); Preimplantation genetic diagnosis(PGD).

MeSH terms

  • Adult
  • Blastocyst / pathology*
  • Chromosome Aberrations*
  • Chromosome Disorders / diagnosis*
  • Chromosome Disorders / genetics
  • Female
  • Genetic Testing / methods*
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Male
  • Reproductive Techniques, Assisted
  • Sequence Analysis, DNA / methods*