Genomic changes detected by array CGH in human embryos with developmental defects

• Published in: Molecular human reproduction 2010-02, Vol.16 (2), p.125-134
• Main Authors: Rajcan-Separovic, E., Qiao, Y., Tyson, C., Harvard, C., Fawcett, C., Kalousek, D., Stephenson, M., Philipp, T.
• Format: Article
• Language: English
• Subjects: Abortion, Spontaneous - genetics; array comparative genomic hybridization; Biological and medical sciences; Chromosomes, Artificial, Bacterial - genetics; Comparative Genomic Hybridization - methods; DNA copy number variants; DNA Copy Number Variations - genetics; Embryo, Mammalian - metabolism; Embryology: invertebrates and vertebrates. Teratology; embryonic developmental defects; embryoscopy; Female; Fundamental and applied biological sciences. Psychology; Humans; miscarriages; Pregnancy
• ISSN: 1360-9947; 1460-2407
• DOI: 10.1093/molehr/gap083

Developmental abnormalities of human embryos can be visualized in utero using embryoscopy. Our previous embryoscopic and genetic evaluations detected developmental abnormalities in the majority of both euploid (74%) and aneuploid or polyploid (90%) miscarriages. Since we found the pattern of morphological changes to be similar in euploid and non-euploid embryos, we proposed that lethal submicroscopic changes, not detected by standard chromosome testing, may be responsible for miscarriage of euploid embryos. Whole genome oligo and bacterial artificial chromosome array comparative genome hybridization (CGH) was used to screen for submicroscopic chromosomal changes (DNA copy number variants or CNVs) in 17 euploid embryonic miscarriages, with a range of developmental abnormalities documented by embryoscopy. The CNV breakpoints were refined using a custom array (Agilent) with high resolution coverage of the CNVs. Six unique CNVs, previously not reported, were identified in 5 of the 17 embryos (29% of all cases or 50% of cases studied with higher resolution arrays). All six unique CNVs were