Congenital bilateral absence of vas deferens (ORPHA:48)
A rare non-syndromic urogenital tract malformation characterized by improper development of the vas deferens leading to male infertility.
Epidemiology
Congenital bilateral absence of vas deferens (CBAVD) affects about 1/1,000 males. It is found in 98% of males with cystic fibrosis and accounts for 6-8% of cases of obstructive azoospermia. In about 50% of cases, the CBAVD is associated with the absence of the seminal vesicles. Unilateral renal agenesis is detected in 5-10% of patients with CBAVD, while is present in 5-40% of congenital unilateral absence of vase deferens (ipsilateral).
Clinical description
CBAVD is usually diagnosed in adult men, either during systematic assessment of cystic fibrosis (CF) or during assessment of isolated infertility (azoospermia). Infertile patients with CBAVD produce small volumes of acidic sperm (< 1 ml with a pH < 7.0). The latter is non-pathognomonic and more common when the seminal vesicles are also absent. CBAVD frequently coexists with kidney anomalies and other comorbidities.
Etiology
In 1990, mutations in the CFTR gene (the causative gene for cystic fibrosis) were identified in 42% of patients in a population of infertile males with CBAVD, suggesting that CBAVD is a genital form of cystic fibrosis. Since then, an exhaustive analysis of the 27 exons of the CFTR gene has led to the classification of CBAVD patients into four groups: I) patients with two mutations in the CFTR gene (19%), II) patients with one mutation in the CFTR gene and having the IVS8-5T allele in the trans position (33%), III) patients with either a mutation in the CFTR gene or having the IVS8-5T allele (27%) and IV) patients with neither the IVS8-5T allele nor a mutation in the CFTR gene (21%).
Diagnostic methods
The diagnosis of CBAVD is clinical. Traditionally, it was based on the absence of the intrascrotal portion of the vas deferens on palpation. The gold standard for diagnosis is scrotal and transrectal ultrasound, which also allows evaluation of the absence of the seminal vesicles. Abdominal ultrasound should be added to rule out a unilateral renal agenesis. Sperm analysis typically shows azoospermia, hypospermia (<1 ml) and acid pH (<7.0). Genetic testing can confirm the mutation in the CFTR gene.
Differential diagnosis
The differential diagnosis includes other causes of azoospermia and obstruction of the seminal tract (e.g. injuries, infections, cysts, etc.).
Genetic counseling
CBAVD patients with CFTR mutations should be informed of the increased risk to develop related diseases and transmit CF to their child. The risk is higher in patient without a solitary kidney. If an affected couple (the male partner is a carrier for a severe CFTR mutation) wishes to have a child with assisted reproductive technology (ART; i.e. surgical sperm retrieval and in vitro fertilization techniques), both partners should be offered genetic testing. If the female partner is not a carrier of one of the CFTR mutations, the risks of having a child affected by CF is <1/1000 (2.5 times higher than in the general population). If a mutation is detected in both partners, the risk of having a child with CF is 25%, and 50% if the mutation is on both alleles in one parent.
Management and treatment
The diagnosis of CBAVD often has implications that go beyond the problem of infertility because of its potential association with renal anomalies and other clinical conditions related to CFTR mutations. Some patients with a CFTR mutation may later present mild CF symptoms such as recurrent respiratory tract infections and could benefit from referral to a pneumologist or CF center for management and follow-up. In the case of solitary kidney, the patient should be followed a nephrologist.
Prognosis
CBAVD has no impact on life expectancy. Nevertheless, associated conditions (namely CF or other CFTR-related conditions) can potentially affect quality of life. If a solitary kidney is present, but renal function otherwise normal, quality of life is usually not impacted.

                            Last update: 
                            June 2023


                            - Expert reviewer(s): 
                            Pr Marco CASTAGNETTI  - Dr Giovanni MOSIELLO | EUROGEN*


                                * European Reference Network