Clinical application of array CGH on PGD/PGS with day 3 embryo biopsy



Array CGH has emerged in the field of preim-plantation genetic diagnosis (PGD) for chromosomal diseases and aneuploid screening (PGS). The aim of this study was to describe our preliminary experience of application to day 3 embryo biopsy. The non-transferred embryos were reanalyzed with multicolor FISH.

Materials and Methods:

There were 7 patients receiving PGD or PGS via array CGH since September of 2011. The indications were repeated abortion (2 couples), female X mosaicism (one couple), advanced maternal age (>37 yrs; two couples) and translocation carriers (two couples). The mean age is 35.3 years old (31 40). One cell from each day 3 embryo underwent whole genome amplification (WGA) using Surplex (BlueGnome Ltd, Cambridge, UK). WGA products and control genomic DNA were labeled in Cy3 and Cy5 fluorophores respectively. Both labeled DNAs were co-hybridizeed in a 24sure array or a 24sure plus array (BlueGnome Ltd, Cambridge, UK). 12 hour protocols with overnight hybridization were adopted. After washing, slides were scanned using Innoscan 710 (Innopsys, Carbonne, France). Data were analyzed by BlueFuse Multi software (BlueGnome Ltd, Cambridge, UK). Suitable embryos (normal or balanced) were transferred back on day 4. Abnormal embryos were fixed and analyzed with FISH via commercial probes (Vysis probes from Abbott, GH & Co. KG.).


A successful WGA was obtained in 44 out of 47 biopsied embryos (93.6%) and all amplified products were labeled successfully. A total of 33 embryos were diagnosed as abnormal or unbalanced in translocation cases (33/44; 75%). After transfer of 9 embryos in 5 cycles, there are 3 ongoing pregnancies including two pairs of twins (pregnancy rate 50% per OPU cycle or 60% per transfer cycle) with an implantation rate of 56%. 15 non-transferred embryos due to abnormal results were reanalyzed on day 4 by FISH with probes to chromosomes 13, 18, 21, X and Y. The mean number of blastomeres to detect was 5. Three of these showed euploidy for the probes used but the abnormalities revealed by array were not belonging to the probes we used. The others of these reanalyzed embryos were abnormal including aneuploidy, mosaicisms or other abnormality. The two aneuploid embryos were compatible with results of array CGH. Interestingly, there were 4 embryos with euploid mosaicism for probes to 13, 18, 21, X and Y. The three embryos without good WGA products revealed mosaicism by reanalysis with FISH.


PGD/PGS on day 3 embryos via FISH has been challenged with high mosaicism rates at this stage and limited number of probes used. The preliminary experience of array CGH applied on PGS and PGD for day 3 embryos chromosome diseases showed promising clinical results. The encouraging data implied a place for day 3 embryo biopsy with array CGH for diagnostic assistance, especially for couples with limited number of embryos and wishing embryo transfer in fresh cycle. Further evaluation is needed for the impact of mosaicism on PGD/PGS with array CGH for day 3 embryos.


C.K. Chen, C.Y. Lin, M.L. Wang, H.Y. Yeh, H.Y. Huang, H.S. Wang, C.L. Lee, Y.K. Soong

  • Department of Obstetrics and Gynecology, Chang-Gung Memorial Hospital and Medical College, TaoYuan, Taiwan


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