Microarray analysis reveals abnormal chromosomal complements in over 70% of 14 normally developing human embryos

Hum Reprod. 2013 Jan;28(1):256-64. doi: 10.1093/humrep/des362. Epub 2012 Oct 9.

Abstract

Study question: What are the aneuploidy rates and incidence of mosaicism in good-quality human preimplantation embryos.

Summary answer: High-level mosaicism and structural aberrations are not restricted to arrested or poorly developing embryos but are also common in good-quality IVF embryos.

What is known already: Humans, compared with other mammals, have a poor fertility rate, and even IVF treatments have a relatively low success rate. It is known that human gametes and early preimplantation embryos carry chromosomal abnormalities that are thought to lower their developmental potential.

Study design, size and duration: The embryos studied came from nine young (age <35 years old) IVF patients and were part of a cohort of embryos that all resulted in healthy births. These 14 embryos inseminated by ICSI and cryopreserved on Day 2 of development were thawed, cultured overnight and allowed to succumb by being left at room temperature for 24 h. Following removal of the zona pellucida, blastomeres were disaggregated and collected.

Participants/materials, setting and methods: There were 91 single blastomeres collected and amplified by multiple displacement amplification. Array-comparative genomic hybridization was performed on the amplified DNA. Array-data were normalized and aneuploidy was detected by the circular binary segmentation method.

Main results and the role of chance: The good-quality embryos exhibited high rates of aneuploidy, 10 of 14 (71.4%) of the embryos being mosaic. While none of the embryos had the same aneuploidy pattern in all cells, 4 of 14 (28.6%) were uniformly diploid. Of the 70 analysed blastomeres, 55.7% were diploid and 44.3% had chromosomal abnormalities, while 29% of the abnormal cells carried structural aberrations.

Wider implications of the findings: Finding such a high rate of aneuploidy and mosaicism in excellent quality embryos from cycles with a high implantation rate warrants further research on the origin and significance of chromosomal abnormalities in human preimplantation embryos.

Study funding/competing interest(s): This research was supported by the Instituut voor de aanmoediging van innovatie door Wetenschap en Technologie in Vlaanderen (IWT-Vlaanderen). A.M. is a PhD student at the IWT-Vlaanderen. C.S. is a postdoctoral fellow at the FWO Vlaanderen. There are no competing interests.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aneuploidy
  • Blastomeres / pathology*
  • Chromosomal Instability*
  • Chromosome Aberrations / embryology*
  • Cohort Studies
  • Comparative Genomic Hybridization
  • Cryopreservation
  • Diploidy
  • Ectogenesis
  • Female
  • Humans
  • Infertility, Female / pathology
  • Infertility, Female / therapy
  • Mosaicism / embryology*
  • Oligonucleotide Array Sequence Analysis
  • Preimplantation Diagnosis
  • Reproducibility of Results
  • Sperm Injections, Intracytoplasmic
  • Zygote