title: Validation of array comparative genome hybridization for diagnosis of translocations in preimplantation human embryos.
abstract: Fluorescent in-situ hybridization (FISH) for preimplantation genetic diagnosis (PGD) of structural chromosome abnormalities has limitations, including carrier testing, inconclusive results and limited aneuploidy screening. Array comparative genome hybridization (CGH) was used in PGD cases for translocations. Unbalances could be identified if three fragments were detectable. Smallest detectable fragments were ∼6 Mbp and ∼5 Mbp for blastomeres and trophectoderm, respectively. Cases in which three or more fragments were detectable by array CGH underwent PGD by FISH and concordance was obtained in 53/54 (98.1%). The error rate for array CGH was 1.9% (1/54). Of 402 embryos analysed, 81 were normal or balanced, 92 unbalanced but euploid, 123 unbalanced and aneuploid and 106 balanced but aneuploid. FISH with additional probes to detect other aneuploidies would have missed 28 abnormal embryos in the reciprocal group and 10 in the Robertsonian group. PGD cases (926) were retrospectively reviewed for reciprocal translocations performed by FISH to identify which could have been analysed by array CGH. This study validates array CGH in PGD for translocations and shows that it can identify all embryos with unbalanced reciprocal and Robertsonian translocations. Array CGH is a better approach than FISH since it allows simultaneous screening of all chromosomes for aneuploidy.
authors.affiliation: Reprogenetics, Livingston, NJ 07039, USA. pere.colls@reprogenetics.com
authors.forename: Pere
authors.initials: P
authors.lastname: Colls
authors.forename: Tomas
authors.initials: T
authors.lastname: Escudero
authors.forename: Jill
authors.initials: J
authors.lastname: Fischer
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Cekleniak
authors.forename: Snunit
authors.initials: S
authors.lastname: Ben-Ozer
authors.forename: Bill
authors.initials: B
authors.lastname: Meyer
authors.forename: Miguel
authors.initials: M
authors.lastname: Damien
authors.forename: Jamie A
authors.initials: JA
authors.lastname: Grifo
authors.forename: Avner
authors.initials: A
authors.lastname: Hershlag
authors.forename: Santiago
authors.initials: S
authors.lastname: Munné
mesh_terms: D000328:Adult; D001755:Blastocyst; D055028:Comparative Genomic Hybridization / Q000379:methods*; D003951:Diagnostic Errors; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D011247:Pregnancy; D011256:Pregnancy Outcome; D019836:Preimplantation Diagnosis / Q000379:methods*; D012189:Retrospective Studies; D014178:Translocation, Genetic