The genetics of male infertility in relation to cystic fibrosis

Abstract

Absence, dysfunction or low levels of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein result in a broad range of clinical manifestations with CF with pancreatic insufficiency at the severe end of the phenotypic spectrum and, at the other end relatively mild clinical conditions, including several forms of male infertility. The condition of congenital bilateral absence of the vas deferens (CBAVD) is in 75-80% of the patients associated with defects in the CFTR gene. In the remaining patients, CBAVD is also associated with urinary tract malformations, and this form of CBAVD is not related to CF. Congenital unilateral absence of the vas deferens also seems to be associated with CF except when associated with renal abnormalities at the ipsilateral side of the absent vas. A possible role of the CFTR protein in the aetiology of infertility due to defects in sperm production and maturation has also been suggested recently. In contrast, Young's syndrome is probably not related to CF. The relation between some conditions of male infertility and CF implies appropriate clinical examination of the patients, CFTR mutation analysis and genetic counselling. Because infertility can now in many cases be treated by artificial reproductive technology couples have an increased risk of having children with CF or infertility if the female partner is also a carrier of a CFTR mutation. Couples should be well informed about these risks and risk prevention including pre-implantation diagnosis. Follow-up studies of children born to these couples are mandatory, whether male infertility is linked to CF or not.