title: Total fertilization failure and molecular abnormalities in metaphase II oocytes.
abstract: Total fertilization failures (TFF) are rare events of IVF by intracytoplasmic sperm injection (ICSI). When male factor is excluded, the lack of identifiable aetiological criteria raises the question of the reliable clinical management. The goal of this study was to identify molecular abnormalities in metaphase II (MII) oocytes yielding TFF. The nuclear mature MII oocytes mRNA expression profiles were compared between a 30-year-old patient who had experienced three successive TFF (egg number = 39) and control patients with fertile cohorts diagnosed with tubal or male infertility. The mRNA abundance for the 30,000 genes of the genome was evaluated by microarray and, for selected genes, by quantitative-polymerase chain reaction analysis. Transcriptional analysis of unfertilized MII oocytes revealed an altered gene expression profile associated with TFF. Meiosis, cell growth and apoptosis controlling genes were mis-expressed with important fold changes. The results reveal that, despite passing the pre-IVF morphological examination, high-grade oocytes may carry substantial molecular abnormalities at the gene expression level associated with failure of MII oocyte activation. In the absence of an identifiable defect causing TFF, this microarray approach allows improvement of clinical therapeutic management: informed counselling about alternate therapeutic solutions could be proposed.
authors.affiliation: CHU Montpellier, IRB, Institute for Research in Biotherapy, Hôpital Saint-Eloi, Montpellier, F 34295, France.
authors.forename: Stéphan
authors.initials: S
authors.lastname: Gasca
authors.forename: Lionel
authors.initials: L
authors.lastname: Reyftmann
authors.forename: Franck
authors.initials: F
authors.lastname: Pellestor
authors.forename: Thierry
authors.initials: T
authors.lastname: Rème
authors.forename: Said
authors.initials: S
authors.lastname: Assou
authors.forename: Tal
authors.initials: T
authors.lastname: Anahory
authors.forename: Hervé
authors.initials: H
authors.lastname: Dechaud
authors.forename: Bernard
authors.initials: B
authors.lastname: Klein
authors.forename: John
authors.initials: J
authors.lastname: De Vos
authors.forename: Samir
authors.initials: S
authors.lastname: Hamamah
mesh_terms: D000328:Adult; D017209:Apoptosis; D005260:Female; D005298:Fertility; D005306:Fertilization; D005307:Fertilization in Vitro / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D007246:Infertility / Q000628:therapy*; D008297:Male; D008540:Meiosis; D008677:Metaphase; D020411:Oligonucleotide Array Sequence Analysis; D009865:Oocytes / Q000378:metabolism*; D011247:Pregnancy; D020554:Sperm Injections, Intracytoplasmic / Q000379:methods