Genetic markers of male infertility: Y chromosome microdeletions and cystic fibrosis transmembrane conductance gene mutations

Today, approximately 15% of couples have reduced fertility. In most cases the reason is male infertility, usually of genetic origin. Thus, in the context of research in genes involved in reproduction and sex determination, genetic defects in gametogenesis are being extensively studied. The most frequent pathogenic causes of male infertility are Y chromosomal microdeletions and obstructive azoospermia due to congenital absence of the vas deferens (CAVD) in the presence of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. We have investigated the most common CFTR gene alterations in Croatian men with CAVD, using Roche research prototype assays. Results revealed that the 5T variant was present in 27% of the subjects. The F508 deletion was found in 21% of the subjects. It was the most frequent mutation, although its incidence was much lower than among patients with cystic fibrosis. The prevalence of microdeletions in the azoospermia factor region (AZF) of the Y chromosome in Croatia was 4.5%. This is the first report of Y microdeletions in the Croatian population. Genetic counseling of all couples with the diagnosis of male infertility is recommended before intrauterine insemination, in vitro fertilization, and intracytoplasmic sperm injection, and should also include AZF and CFTR genotyping. Couples requesting assisted reproductive treatment should be offered molecular analysis of the CFTR gene, if male infertility due to obstructive azoospermia is the underlying cause. Also, men with severe oligozoospermia or non-obstructive azoospermia seeking assisted reproductive treatment should be screened for deletions in the Y chromosome.