Congenital Bilateral Absence of the Vas Deferens

Congenital bilateral absence of the vas deferens is a genetic condition where both vasa deferentia are absent from birth, leading to obstructive azoospermia. It is found in about 1 to 2% of infertile men and in about 6% of men with obstructive azoospermia.

It is a mild form of the cystic fibrosis spectrum. Most men have no lung or gut disease, but they carry mutations that matter for their children.

Pathophysiology. Disruption of the CFTR gene impairs development of the Wolffian duct structures in the foetus. In most men, two CFTR mutations are found, often one severe and one mild (for example F508del with the 5T allele), and the rest have a single detectable mutation.

Testes have normal sperm production. The epididymis is often absent in its body and tail, the seminal vesicles are absent or small, and renal anomalies (unilateral renal agenesis) occur in about 10 to 25%.

Infertility with normal libido, erections and virilisation, and normal testicular size. The vasa cannot be palpated, and the epididymal head may be full. Low ejaculate volume (under 1.4 mL), and often chronic sinusitis, recurrent chest infection or bronchiectasis in some men. A history of pancreatitis or a sibling with cystic fibrosis is relevant.

• Genital examination for absent vasa, bilaterally.
• Semen analysis: azoospermia, low volume, acidic pH (under 7.2) and absent fructose.
• Hormones: FSH, LH and testosterone are normal.
• CFTR gene sequencing and testing for deletions, including the 5T allele, in the man, and then in the partner.
• Transrectal ultrasound: hypoplastic or absent seminal vesicles. Scrotal ultrasound for epididymal abnormality.
• Renal ultrasound for renal agenesis or ectopia.
• Sweat chloride test, and lung and sinus assessment when symptoms suggest cystic fibrosis spectrum disease.

Differential diagnosis.

• Unilateral absence of the vas deferens (renal anomaly association)
• Ejaculatory duct obstruction
• Vasectomy or post-surgical obstruction
• Young syndrome
• Cystic fibrosis
• Nonobstructive azoospermia

• Sperm retrieval with intracytoplasmic sperm injection: microsurgical epididymal sperm aspiration, percutaneous epididymal sperm aspiration, or testicular sperm extraction. Retrieval succeeds in almost all men, and cryopreservation of spare sperm avoids repeat surgery.
• Test the female partner for CFTR carrier status before assisted conception, since the carrier frequency varies with ancestry (about 1 in 25 in people of white European ancestry, and lower in many other populations). If the partner is a carrier, offer preimplantation genetic testing, prenatal diagnosis or donor sperm. Children of a man with this condition carry at least one mutation.
• Genetic counselling for the man, and cascade testing of relatives where relevant.
• Perioperative cefazolin 2 g intravenously (3 g if over 120 kg) as a single dose, with paracetamol 1 g every 6 hours (maximum 4 g daily) and ibuprofen 400 mg every 8 hours for 3 to 5 days.
• Reconstruction is not possible because the vasa are absent.
• Surveillance for cystic fibrosis spectrum disease: sinus and respiratory review, with spirometry when symptoms occur, and pancreatitis awareness. Men with two CFTR mutations may need pulmonary and gastroenterology review.

Special groups. Couples from populations with low carrier frequency still need partner testing, since a missed carrier carries a high risk of a child with cystic fibrosis.

Monitoring. Fertility outcomes after intracytoplasmic sperm injection, annual respiratory review where symptoms exist, and renal follow up when a renal anomaly is found.

Referral and escalation. Refer to urology or andrology, a fertility unit and clinical genetics. Urgent referral is rarely needed.