What conditions are associated with absent vas deferens?

Conditions Associated with Absent Vas Deferens

Absent vas deferens is primarily associated with cystic fibrosis (CF) gene mutations, occurring either as congenital bilateral absence of the vas deferens (CBAVD) in patients with or without clinical CF, or as congenital unilateral absence of the vas deferens (CUAVD) associated with ipsilateral renal anomalies. 1, 2

Primary Genetic Condition: Cystic Fibrosis-Related

CBAVD as a CF Phenotype

• CBAVD represents a primarily genital form of cystic fibrosis, with 78% of patients carrying at least one CFTR mutation and 46% having two identifiable mutations 2, 3
• Clinical CF with pulmonary and pancreatic dysfunction includes bilateral absence of the vasa and seminal vesicles in nearly 95% of cases, making CBAVD the most sensitive indicator of biallelic CFTR gene abnormalities 1, 2
• The incidence in males of northern European heritage is 1:2,000 for clinical CF, with an equal frequency presenting as isolated CBAVD without significant respiratory or pancreatic disease 1, 2

Genetic Mechanism

• The severity of disease expression depends on which specific CFTR mutations are inherited on both alleles 1
• Severe mutations like c.1521_1523delCTT (F508del) severely impair CFTR protein quantity or function, while milder abnormalities like the 5T polymorphism in intron 8 only mildly impair function 1
• ADGRG2 mutation is the second most common genetic cause after CFTR 4
• Between 10-20% of CBAVD cases remain without a genetic diagnosis despite comprehensive CFTR and ADGRG2 testing 2

Unilateral Absence: Renal Anomaly Association

CUAVD with Urogenital Malformations

• Congenital unilateral absence of the vas deferens is associated with ipsilateral renal anomalies in 26-75% of cases, compared to only 10% in bilateral vasal agenesis 2, 5
• This represents a distinct embryologic defect occurring during organogenesis, separate from the CF-related mechanism 6
• The term "agenesis" should be used for CBAVD cases associated with urogenital abnormalities where regional defects occur during organogenesis, while "atresia" or "inspissation" applies to CF-related cases 6

Clinical Distinction

• CUAVD may also be CF-related, especially when there is occlusion of the palpable vas on the contralateral side 7
• Up to 20% of CBAVD cases are associated with urinary tract malformations and are not related to CF 7

Clinical Presentation

Characteristic Findings

• CBAVD presents with low volume ejaculate (<1.4 mL), acidic pH (<7.0), and azoospermia 2, 8
• Physical examination demonstrates bilateral absence of the vasa deferentia, which can be diagnosed definitively by palpation 2, 8
• Testes typically have normal size and spermatogenic function despite inability to release sperm 4

Critical Diagnostic Workup

Mandatory Genetic Testing

• CFTR mutation analysis should be performed on all men with CBAVD prior to any therapeutic procedure 1
• CFTR gene testing for the female partner is mandatory before proceeding with assisted reproduction, as couples are at increased risk of having children with CF and/or CBAVD 1, 8, 4
• Karyotype testing is mandatory for azoospermia or severe oligospermia (<5 million/mL) 8, 9

Essential Imaging

• Abdominal imaging is essential regardless of CFTR status to assess for renal anomalies, particularly in unilateral cases 2
• Renal ultrasonography should be performed in all patients with absent vas deferens to assess renal anomalies 5

Important Clinical Pitfalls

Distinguishing CF-Related from Non-CF Cases

• In couples with CBAVD not related to CF (those with urinary tract malformations), there is no increased risk of CF children, but the risk of sons inheriting CBAVD remains unknown 7
• The presence of urogenital malformations suggests a non-CF etiology requiring different genetic counseling 7, 6

Surgical Considerations

• Surgeons who encounter unilateral absence of the vas deferens should assess for bilateral absence by palpation in adults or laparoscopic exploration of the contralateral inguinal canal in pediatric patients 5
• For fertility treatment, proceed directly to sperm retrieval (TESE/MESA) with ICSI, as no medical or surgical treatment restores ejaculatory volume 8