title: Genetic risk factors in infertile men with severe oligozoospermia and azoospermia.
abstract: BACKGROUND
  Male infertility due to severe oligozoospermia and azoospermia has been associated with a number of genetic risk factors.
  
  
  METHODS
  In this study 150 men from couples requesting ICSI were investigated for genetic abnormalities, such as constitutive chromosome abnormalities, microdeletions of the Y chromosome (AZF region) and mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
  
  
  RESULTS
  Genetic analysis identified 16/150 (10.6%) abnormal karyotypes, 8/150 (5.3%) AZFc deletions and 14/150 (9.3%) CFTR gene mutations. An abnormal karyotype was found both in men with oligozoospermia and azoospermia: 9 men had a sex-chromosomal aneuploidy, 6 translocations were identified and one marker chromosome was found. Y chromosomal microdeletions were mainly associated with male infertility, due to testicular insufficiency. All deletions identified comprised the AZFc region, containing the Deleted in Azoospermia (DAZ) gene. CFTR gene mutations were commonly seen in men with congenital absence of the vas deferens, but also in 16% of men with azoospermia without any apparent abnormality of the vas deferens.
  
  
  CONCLUSIONS
  A genetic abnormality was identified in 36/150 (24%) men with extreme oligozoospermia and azoospermia. Application of ICSI in these couples can result in offspring with an enhanced risk of unbalanced chromosome complement, male infertility due to the transmission of a Y-chromosomal microdeletion, and cystic fibrosis if both partners are CFTR gene mutation carriers. Genetic testing and counselling is clearly indicated for these couples before ICSI is considered.
authors.affiliation: Andrology Unit, Department of Urology, Erasmus University Medical Centre, Rotterdam, The Netherlands. Dohle@urol.azr.nl
authors.forename: G R
authors.initials: GR
authors.lastname: Dohle
authors.forename: D J J
authors.initials: DJ
authors.lastname: Halley
authors.forename: J O
authors.initials: JO
authors.lastname: Van Hemel
authors.forename: A M W
authors.initials: AM
authors.lastname: van den Ouwel
authors.forename: M H E C
authors.initials: MH
authors.lastname: Pieters
authors.forename: R F A
authors.initials: RF
authors.lastname: Weber
authors.forename: L C P
authors.initials: LC
authors.lastname: Govaerts
mesh_terms: D002869:Chromosome Aberrations; D003550:Cystic Fibrosis / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D000075364:Deleted in Azoospermia 1 Protein; D017353:Gene Deletion; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease; D006801:Humans; D007713:Klinefelter Syndrome / Q000235:genetics; D008297:Male; D009154:Mutation; D009845:Oligospermia / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics; D012307:Risk Factors; D012729:Sex Chromosome Aberrations; D020554:Sperm Injections, Intracytoplasmic; D014178:Translocation, Genetic; D014649:Vas Deferens / Q000002:abnormalities; D014998:Y Chromosome
chemical_list: C505032:CFTR protein, human; C095668:DAZ1 protein, human; D000075364:Deleted in Azoospermia 1 Protein; D016601:RNA-Binding Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator