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

A. Mertzanidou, L. Wilton, J. Cheng, , E. Vanneste, Y. Moreau, J.R. Vermeesch,
Published: 9 October 2012

Abstract: STUDY QUESTIONWhat are the aneuploidy rates and incidence of mosaicism in good-quality human preimplantation embryos.SUMMARY ANSWERHigh-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 ALREADYHumans, 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 DURATIONThe 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 METHODSThere 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 CHANCEThe 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 FINDINGSFinding 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.
Keywords: aneuploidy / array-CGH / mosaicism / preimplantation embryo / chromosomal abnormalities

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