OBJECTIVETo assess the value of array comparative genomic hybridization (array CGH) technique for preimplantation genetic diagnosis (PGD).

METHODSArray CGH was performed on three types of cells, which included 3-5 cells isolated from B2/C38/A1 embryonic stem cell lines, single cells isolated from two discarded normal fertilized embryos, and 10 blastocysts biopsied from 5 couples undergoing PGD for chromosomal translocations. For the 10 blastocysts, 8 were abnormal embryos, 1 appeared to be normal but showed arrested development, and 1 embryo was without any fluorescence signals. 24sure V3 or 24sure+ array chips were applied for CGH analysis. The results were analyzed with a BlueFuse Multi software.

RESULTS(1) The results of cells from B2/C3/A1 embryo stem cells by array CGH were consistent with karyotyping analysis. (2) For the 6 single cell samples from two discarded embryos, 2 blastomeres from one embryo were diagnosed as with aneuploidy and a normal karyotype, respectively. Two out of 4 blastomeres biopsied from another embryo were normal, whilst the remaining two were diagnosed with aneuploidies of -22 and +13. Repeated detection with 24sure+ array was consistent with the 24sure V3 result. (3) Ten cell masses from 10 embryos in PGD cycles were successfully analyzed with array CGH, among which four were confirmed with fluorescence in situ hybridization (FISH) on day 3. In two of them, array CGH confirmed FISH diagnosis. For the remaining two, additional aneuploidies for chromosomes not tested by FISH were discovered by array CGH. Another embryo diagnosed as no signal by FISH was found to have trisomy 13 by array CGH. The remaining 5 embryos also showed discordant results by FISH and array CGH. One embryo from a Robertsonian translocation carrier was found to have monosomy 13 by FISH but trisomy 14 and additional aneuploidies by both 24sure V3 and 24sure+ chips. One embryo with many fragments and arrested development by D5 showed discordant results by FISH and array CGH. However, the FISH and array CGH results for other two embryos from this reciprocal translocation carrier were consistent. Three embryos with inconsistent results by FISH and array CGH had a chromosomal translocation involving q11 region.

CONCLUSIONArray CGH is useful for PGD applications for its capability to detect structural chromosomal abnormalities through screening of aneuploidies. However, the 24sure V3 array may not suit detection of translocations with breakpoints close to the q11 region of chromosomes.