Male partners of infertile couples with congenital unilateral absence of the vas deferens are mainly non‐azoospermic

Abstract

Background: Men with congenital unilateral absence of vas deferens were reported to be mainly azoospermic, with both unilateral renal absence and mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) but some have neither. Objectives:To assess whether in infertile couples the male partners with congenital unilateral absence of vas deferens are mainly azoospermic men. Material and Methods: Retrospective study in a unique university hospital; reproductive, clinical, CFTR analysis and seminal data of male partners of infertile couples (from 1998 to 2018) were analysed. Diagnosis of congenital unilateral absence of vas deferens was based on transrectal ultrasounds (TRUS): complete or partial absence of one vas deferens with complete contralateral vas deferens confirmed in 63 men. Distribution of sperm count in three classes: azoospermia, oligozoospermia or normozoospermia. Ultrasound determination of renal status; seminal biomarkers assays; and search for CFTR mutations.Results: Among the 63 men, 39.7% displayed azoospermia, 27% oligozoospermia and 33.3% normozoospermia; 42% of the non-azoospermic men (16/38) had previously obtained a natural pregnancy. We found unilateral renal absence in 17/59 patients (29%). Among 50 men with CFTR testing, five carried an allele associated with cystic fibrosis belonging to the 29 men without renal anomalies, indicating a high allelic frequency (8.6%). The 63 patients displayed high rates of surgical histories for undescended testicles or inguinal hernia, low values of semen volume and of total seminal glycerophosphocholine. Conclusions:Our results indicate that men with congenital unilateral absence of vas deferens mainly display oligozoospermia or normozoospermia and that they were previously fertile. They clearly confirm, first, that CFTR testing is recommended in congenital unilateral absence of vas deferens men and it should be mandatory for those with normal kidneys; and, second, that TRUS is needed for the diagnosis of congenital unilateral absence of vas deferens. As congenital unilateral absence of vas deferens may be present whatever the sperm count, biological warnings are represented by semen volume and seminal epididymal markers and clinical warnings by surgical histories of undescended testes or inguinal hernia.

Genetics of the congenital absence of the vas deferens

“…As early as 1870, a Swiss surgeon, Reverdin, described unilateral renal absence (URA) in a man with CUAVD and an ipsilateral absence of SV (Reverdin 1870). Since then, numerous studies (Schlegel et al 1996;Casals et al 2000;Weiske et al 2000;Patat et al 2016;Mieusset et al 2017Mieusset et al , 2020 have confirmed that URA is found with CAVDs at a high rate of 5-40%, while the prevalence of URA at birth is nearly 1,000 times lower (4/10,000) (Laurichesse Delmas et al 2017). It is important to note that URA is found twoto-three times more frequently in patients with CUAVD (20-40% of the cases, with URA being predominantly ipsilateral) than in those with CBAVD (5-10% of cases).…”

“…Therefore, for approximately a quarter of the iCBAVD patients, the responsibility of CFTR cannot be definitively proven, whereas for CF patients, the two mutated alleles can be characterized in 99% of the cases (Table 1 ). For CUAVDs, 30–50% of the subjects carry at least one CFTR mutation after comprehensive gene scanning, which means that more than half of the CUAVDs are not CFTR- related (Schlegel et al 1996 ; Casals et al 2000 ; Cai et al 2019 ; Mieusset et al 2020 ). The presence of a renal abnormality is very significantly more frequent in CAVD patients in whom only one or no CFTR abnormality has been detected (Augarten et al 1994 ; Schwarzer & Schwarz 2012 ).…”

“… Percentages are calculated from compilations of data from large series (the main ones are referenced). These average frequencies are given as an indication to highlight differences related to ethnicity and CAVD forms [CF] CF-causing allele, [NCF] non-CF-causing allele including mutations that result in a CFTR-RD and variations of unknown significance (VUS), [0] no pathogenic variants ([CF] or [NCF]) detected by full CFTR screening, NA non-applicable (various rare mutations) a Claustres et al ( 2017 ) b Claustres et al ( 2000 ) c Cai et al ( 2019 ); Mieusset et al ( 2020 ) d Tian et al ( 2016 ) e Yuan et al ( 2019 ) …”

“…6 ). However, the most common comorbidity of CAVD is probably the association with the other defects of the urogenital system, notably the solitary kidney (URA) which was found in about one-third of the CUAVD cases (Akinsal et al 2018 ; Mieusset et al 2020 ). Thus, an abdominal ultrasound for renal imaging is strongly recommended for all men with iCAVD (Fig.…”

“…In all cases, azoospermia is present. In case of CUAVD, the diagnosis is very often made when azoospermia is present (by acquired obstruction of the only permeable seminal duct), but it should be emphasized that in infertile couples, men with CUAVD are mainly non-azoospermic (Mieusset et al 2020 ). Indeed, in the absence of contralateral obstruction in case of CUAVD, the semen is more or less rich in spermatozoa.…”