Congenital Bilateral Absence of the Vas Deferens: genetic etiologies and treatment options
Rhea Sindvani, MD, Amanda R. Swanton, MD/PhD, Robert D. Oates, MD.
Boston Medical Center, Boston, MA, USA.
BACKGROUND: Congenital bilateral absence of the vas deferens (CBAVD) is a rare cause of obstructive azoospermia among male infertility patients. While CBAVD is most often associated with mutations in the CFTR gene, other etiologies of CBAVD exist including abnormal development of the mesonephric ducts during embryogenesis or, rarely, mutations in ADGRG2 -- an X-linked gene encoding a G-couple protein receptor expressed in the efferent ducts. Understanding the etiology of this disease is important with regard to work up for the patient and his siblings, the couple, and the offspring. This study aims to characterize a large series of patients with CBAVD presenting to a single infertility practice highlighting the etiology and management.
METHODS: This is a retrospective analysis of new patients presenting to an infertility specialist between January 2015 and March 2023 who were diagnosed with CBAVD. The medical record was reviewed to obtain demographic and medical information, including physical exam, test results, and operative notes.
RESULTS: Eighty patients with a mean age of 34 years old (SD = 6) at presentation were identified. Most patients were referred by reproductive endocrinologists (55%) or urologists (17%) with the indication being azoospermia (59%) or previously diagnosed CBAVD (20%) or known Cystic Fibrosis (CF ; 10%). Of the patients without previously diagnosed clinical CF, 21% (n = 15/70) had history of respiratory symptoms. Nearly all patients underwent CFTR testing (98%) with the most commonly identified mutations being p.Phe508del (45%), 5T (25%), and p.Arg117His (9%). Six patients (8%) were diagnosed with unilateral renal agenesis. None of the patients with renal agenesis that underwent CFTR testing had mutations identified (n = 0/4). On exam, 4/6 (67%) of patients with renal agenesis had bilaterally absent vasa. One patient with a negative CFTR analysis and normal renal anatomy was found to have a mutation in the gene ADGRG2. Sperm extraction was performed in 81% (n = 58/65) of patients with 89% of patients undergoing microsurgical epididymal sperm aspiration in the operating room with cryopreservation of the harvested sample at the IVF group the couple was working with.
CONCLUSIONS: This series demonstrates that the majority of CBAVD cases were on the biallelic CFTR mutation spectrum, although other etiologies do exist. Patients who test negative for CFTR mutations on full gene sequencing should have upper tract evaluation. Additionally, ADGRG2 sequencing may reveal a genetic cause for patients with an otherwise negative workup, though this test is not always readily available and may require a genetics referral. CBAVD patients can undergo successful sperm extraction, most commonly with MESA in this practice.
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