Experts in Preimplantation Genetic Diagnosis

In a recent presentation, a PGD laboratory where SNP arrays are used instead of array CGH for diagnosis of aneuploidies in embryos, the accuracy of array CGH was questioned and it was incorrectly stated that the test classifies 8% of embryos as normal when in fact they are polyploid.

Reprogenetics has recently published the validation of array CGH (link to Gutierrez Mateo et al. 2011, Fertil Steril, 95:953–8 in pubmed) for aneuploidy diagnosis.  Our results indicate that after reanalysis of embryos that were screened by array CGH, only 1.8% were found to have been misdiagnosed and none of those were polyploid. In that same study, although we acknowledge that some cases of polyploidy cannot be detected by array CGH, our experience with 92,000 previously analyzed embryos shows that only 0.2%* are erroneously classified as normal.

Reprogenetics is currently validating a new protocol that allows detection of all polyploid and haploid embryos with array CGH and the test will be available for clinical use soon. In the meantime, our 1.8% published error rate based on embryo reanalysis is the lowest error rate ever published.


* Polyploidy Detection: Array-CGH cannot detect some triploidies, such 69,XXX, and tetraploidies, such 92,XXXX or 92,XXYY, but it does detect trisomy for gender triploidy 69,XXY and tetraploidy 92,XXXY and 92,XYYY. In addition, any embryo with polyploidy not detectable by array CGH will nonetheless be classified as aneuploid if there is another aneuploidy present in the cell. To determine how many of these pure polyploidies are missed by array-CGH, our database of embryos analyzed by FISH (using 9–12 probes) was queried. We found that 7.5% (6,898/92,018) embryos were polyploid or haploid. However, the majority of these embryos had other abnormalities detectable by CGH or array-CGH, and only 2.3% (2,136/91,073) of the embryos was homogeneously polyploid or haploid. Of those homogeneously polyploid or haploid, only 1.7% (1,587/92,018) were not detectable by array-CGH (i.e., 69,XXX or 92,XXYY). Furthermore, 87% of these embryos were arrested or showed abnormal morohology and consequently would not have been transferred to the patient. (From Gutierrez Mateo et al. 2011, Fertil Steril, 95:953–8)