Mutations of the Cystic Fibrosis Gene and Congenital Absence of the Vas Deferens

Abstract

It is estimated that about 30 to 40% of couples seeking fertility treatments are diagnosed with male factor infertility. These males have a range of gonadal dysfunctions which include azoospermia (i.e., no sperm in the ejaculate); oligozoospermia (i.e. sperm count less than 20 million/ml), asthenozoospermia (i.e.sperm motility less than 50%) and teratozoospermia (i.e. sperm with normal morphology less than 30%). The group of patients with azoospermia represent about 25% of the total and, of these, about 30% have an obstructive process (obstructive azoospermia) while the remaining have a primary testicular failure (non-obstructive azoospermia). In the obstructive azoospermia group, 25% of males have congenital bilateral absence of the vas deferens (CBAVD), while the incidence among all infertile males is about 2%. In the USA, it is estimated that approximately 16000 males are affected by CBAVD. Anatomically, CBAVD is a disorder characterized by regression bilaterally of variable portions of the epididymis, vas deferens, and, in about 80% of cases, absence of the seminal vesicles. In about 10 to 20% of the patients, a renal anomaly is also present. These anatomical hallmarks are so strikingly similar to those observed in men with cystic fibrosis (CF) that, as early as 1971 (Holsclaw et al. 1971), these two apparently unrelated disorders were hypothesized to have the same genetic origin. The hypothesis was proven when mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene (Kerem et al. 1989; Riordan et al. 1989;Rommens et al. 1989) were found in patients with CF as well patients with isolated CBAVD (Dumur et al. 1990; Anguiano et al. 1992; Patrizio et al. 1993).