title: Clinical relevance of Y-linked CNV screening in male infertility: new insights based on the 8-year experience of a diagnostic genetic laboratory.
abstract: AZF microdeletion screening is routinely performed in the diagnostic work-up for male infertility; however, some issues remain debated. In this study, we provide insights into the sperm concentration cutoff value for routine testing, the predictive value of AZFc deletion for testicular sperm retrieval and the Y-background contribution to the interpopulation variability of deletion frequencies. In the Spanish population, partial AZFc rearrangements have been poorly explored and no data exist on partial duplications. In our study, 27/806 (3.3%) patients carried complete AZF deletions. All were azoo/cryptozoospermic, except for one whose sperm concentration was 2 × 10(6)/ml. In AZFc-deleted men, we observed a lower sperm recovery rate upon conventional TESE (9.1%) compared with the literature (60-80% with microTESE). Haplogroup E was the most represented among non-Spanish and hgr P among Spanish AZF deletion carriers. The analysis of AZFc partial rearrangements included 330 idiopathic infertile patients and 385 controls of Spanish origin. Gr/gr deletion, but not AZFc partial duplications, was significantly associated with spermatogenic impairment. Our data integrated with the literature suggest that: (1) routine AZF microdeletion testing could eventually include only men with ≤2 × 10(6)/ml; (2) classical TESE is associated with low sperm recovery rate in azoospermic AZFc-deleted men, and therefore microTESE should be preferred; (3) Y background could partially explain the differences in deletion frequencies among populations. Finally, our data on gr/gr deletion further support the inclusion of this genetic test in the work-up of infertile men, whereas partial AZFc duplications do not represent a risk for spermatogenic failure in the Spanish population.
authors.affiliation: 1] Molecular Biology Laboratory, Fundació Puigvert, Universitat Autònoma de Barcelona, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Barcelona, Spain [2] Andrology Service, Fundació Puigvert, Universitat Autònoma de Barcelona, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: Deborah
authors.initials: D
authors.lastname: Lo Giacco
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Chianese
authors.affiliation: Andrology Service, Fundació Puigvert, Universitat Autònoma de Barcelona, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: Josvany
authors.initials: J
authors.lastname: Sánchez-Curbelo
authors.affiliation: Andrology Service, Fundació Puigvert, Universitat Autònoma de Barcelona, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: Lluis
authors.initials: L
authors.lastname: Bassas
authors.affiliation: Molecular Biology Laboratory, Fundació Puigvert, Universitat Autònoma de Barcelona, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Ruiz
authors.affiliation: Andrology Service, Fundació Puigvert, Universitat Autònoma de Barcelona, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Rajmil
authors.affiliation: Andrology Service, Fundació Puigvert, Universitat Autònoma de Barcelona, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Sarquella
authors.affiliation: Andrology Service, Fundació Puigvert, Universitat Autònoma de Barcelona, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Vives
authors.affiliation: Andrology Service, Fundació Puigvert, Universitat Autònoma de Barcelona, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Ruiz-Castañé
authors.affiliation: 1] Human Genetics Research Group, IDIBAPS, Faculty of Medicine, University of Barcelona, Casanova 143, 08036 Barcelona, Spain [2] Biochemistry and Molecular Genetics Service, Clinic Hospital, Villarroel 170, 08036 Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Oliva
authors.affiliation: Molecular Biology Laboratory, Fundació Puigvert, Universitat Autònoma de Barcelona, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Ars
authors.affiliation: 1] Andrology Service, Fundació Puigvert, Universitat Autònoma de Barcelona, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Barcelona, Spain [2] Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Csilla
authors.initials: C
authors.lastname: Krausz
mesh_terms: D002872:Chromosome Deletion; D041322:Chromosomes, Human, Y / Q000235:genetics*; D056915:DNA Copy Number Variations; D056426:Genetic Loci / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007248:Infertility, Male / Q000175:diagnosis* / Q000235:genetics*; D059785:Karyotype; D008297:Male; D009845:Oligospermia / Q000235:genetics; D010641:Phenotype; D013030:Spain; D013076:Sperm Count; D013091:Spermatogenesis / Q000235:genetics