Preimplantation genetic diagnosis and sperm analysis by fluorescence in-situ hybridization for the most common reciprocal translocation t(11;22)

In this study we describe the pre-clinical development and clinical applica tion of preimplantation genetic diagnosis (PGD) by fluorescence in-situ hyb ridization (FISH) for two non-related carriers tone male and one female) of the most common balanced reciprocal translocation: t(11;22)(q25;q12). For the couple with the female carrier, enumeration of the sex chromosomes in t he embryos was also indicated (husband: 47,XXY karyotype). Four-colour FISH analysis was performed on six blastomeres from three embryos. No embryo tr ansfer was possible because all the embryos were unbalanced. Three PGD cycl es, with two-colour FISH, were carried out for the couple with the male tra nslocation carrier. A total of 35 embryos were biopsied and diagnosed by FI SH; nine out of the 35 embryos (25.7%) were normal and seven of them were t ransferred (two embryos from the first and four from the third cycle), six out of 35 embryos (17%) were unbalanced, three out of 35 embryos (5.7%) wer e triploid or polyploid, 10 out of: 35 embryos (28.6%) were mosaic and seve n out of 35 embryos (20%) were chaotic. Diagnosis failed in 2.9% of the emb ryos. The spermatozoa of the male carrier were also analysed using three-co lour FISH. Only 29.1% of the sperm cells seemed to be balanced or normal. B y choosing probes lying on both sides of the breakpoints and by using a com bination of sub-telomeric or locus-specific probes and centromeric probes, the use of three-colour FISH enabled detection of all the imbalances in spe rm and/or cleavage-stage embryos in the patients. This may improve risk ass essment and genetic counselling in the future for translocation carriers.