Clinical application of oligo array-CGH for detecting balanced translocations in preimplantation genetic diagnosis

Array comparative genomic hybridization (array-CGH), which facilitates to detect unbalanced reciprocal translocation and allows screening aneuploidy for chromosomes, has been repeatedly verified to be valid for diagnosis of translocations in preimplantation human embryos. Currently, the main microarrays used for CGH are bacterial artificial chromosome (BAC)-based arrays. Compared with the BAC-based arrays, oligonucleotide (oligo)-based arrays have a relatively higher resolution and optimal coverage particularly in the subtelomeric regions. Herein, we described the clinical application of a newly designed oligo-based array by Agilent in preimplantation genetic diagnosis (PGD) and aneuploidy screening for balanced translocations. In the study, a total of 144 embryos from 9 couples carrying Robertsonian translocations and 5 carrying reciprocal translocations were biopsied on day 3 for array-CGH analysis. Overall, 135 (93.8%) embryos were successfully diagnosed to be free of either aneuploidies or unbalanced fragments. However, the remained 9 (6.2%) embryos failed to be amplified due to failed cell lysis, DNA damage or the absence of nuclei in the biopsied cells. Collectively, 23 embryos were identified as "euploid and balanced" and suitable to be transferred. Finally, 9 embryos of satisfactory quality were transferred to 6 women, among which 4 recipients exhibited positive hCG level. Fortunately, one recipient with positive hCG level has delivered one baby, and two pregnancies were continuing. Our study served as the first clinical application of oligo-based array CGH technology in PGD for both reciprocal and Robertsonian translocations concomitant with comprehensive aneuploidy screening.