title: Preimplantation genetic diagnosis and sperm analysis by fluorescence in-situ hybridization for the most common reciprocal translocation t(11;22).
abstract: In this study we describe the pre-clinical development and clinical application of preimplantation genetic diagnosis (PGD) by fluorescence in-situ hybridization (FISH) for two non-related carriers (one 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 the embryos was also indicated (husband: 47,XXY karyotype). Four-colour FISH analysis was performed on six blastomeres from three embryos. No embryo transfer was possible because all the embryos were unbalanced. Three PGD cycles, with two-colour FISH, were carried out for the couple with the male translocation carrier. A total of 35 embryos were biopsied and diagnosed by FISH; nine out of the 35 embryos (25. 7%) were normal and seven of them were transferred (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%) were triploid or polyploid, 10 out of 35 embryos (28.6%) were mosaic and seven out of 35 embryos (20%) were chaotic. Diagnosis failed in 2.9% of the embryos. The spermatozoa of the male carrier were also analysed using three-colour FISH. Only 29.1% of the sperm cells seemed to be balanced or normal. By choosing probes lying on both sides of the breakpoints and by using a combination of sub-telomeric or locus-specific probes and centromeric probes, the use of three-colour FISH enabled detection of all the imbalances in sperm and/or cleavage-stage embryos in the patients. This may improve risk assessment and genetic counselling in the future for translocation carriers.
authors.affiliation: Centre for Medical Genetics, University Hospital, Dutch-speaking Free University of Brussels (Vrije Universiteit Brussel) Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Van Assche
authors.forename: C
authors.initials: C
authors.lastname: Staessen
authors.forename: W
authors.initials: W
authors.lastname: Vegetti
authors.forename: M
authors.initials: M
authors.lastname: Bonduelle
authors.forename: M
authors.initials: M
authors.lastname: Vandervorst
authors.forename: A
authors.initials: A
authors.lastname: Van Steirteghem
authors.forename: I
authors.initials: I
authors.lastname: Liebaers
mesh_terms: D001755:Blastocyst / Q000166:cytology*; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002892:Chromosomes, Human, Pair 22; D005260:Female; D005307:Fertilization in Vitro; D006580:Genetic Carrier Screening / Q000379:methods; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008214:Lymphocytes / Q000166:cytology*; D008297:Male; D008677:Metaphase; D009030:Mosaicism; D013094:Spermatozoa / Q000166:cytology*; D014178:Translocation, Genetic