CFTR variants and renal abnormalities in males with congenital unilateral absence of the vas deferens (CUAVD): a systematic review and meta-analysis of observational studies

Cai, Hong-Cai; Qing, Xingrong; Niringiyumukiza, Jean Damascene; Zhan, Xia; Mo, Dun-Sheng; Zhou, Yuanzhong; Shang, Xue‐Jun

doi:10.1038/s41436-018-0262-7

Cited by 25 publications

(18 citation statements)

References 55 publications

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“…In all included men, CUAVD diagnosis was uniquely based on scrotal US and TRUS, the only possibility to discriminate unilateral from bilateral absence of VD . Semen characteristics were reported, preventing a bias of selection when men are mainly azoospermic or a loss of crucial information when values of sperm count are missing . The sensitivity of the different methods used for CFTR mutation detection was indicated and presence of CF mutations was made clear.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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“…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 ).…”

Section: Genetics Of Cavdmentioning

confidence: 99%

“… 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 ) …”

Section: Genetics Of Cavdmentioning

confidence: 99%

Genetics of the congenital absence of the vas deferens

2020

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Congenital absence of the vas deferens (CAVD) may have various clinical presentations depending on whether it is bilateral (CBAVD) or unilateral (CUAVD), complete or partial, and associated or not with other abnormalities of the male urogenital tract. CBAVD is usually discovered in adult men either during the systematic assessment of cystic fibrosis or other CFTR-related conditions, or during the exploration of isolated infertility with obstructive azoospermia. The prevalence of CAVDs in men is reported to be approximately 0.1%. However, this figure is probably underestimated, because unilateral forms of CAVD in asymptomatic fertile men are not usually diagnosed. The diagnosis of CAVDs is based on clinical, ultrasound, and sperm examinations. The majority of subjects with CAVD carry at least one cystic fibrosis-causing mutation that warrants CFTR testing and in case of a positive result, genetic counseling prior to conception. Approximately 2% of the cases of CAVD are hemizygous for a loss-of-function mutation in the ADGRG2 gene that may cause a familial form of X-linked infertility. However, despite this recent finding, 10-20% of CBAVDs and 60-70% of CUAVDs remain without a genetic diagnosis. An important proportion of these unexplained CAVDs coexist with a solitary kidney suggesting an early organogenesis disorder (Wolffian duct), unlike CAVDs related to CFTR or ADGRG2 mutations, which might be the result of progressive degeneration that begins later in fetal life and probably continues after birth. How the dysfunction of CFTR, ADGRG2, or other genes such as SLC29A3 leads to this involution is the subject of various pathophysiological hypotheses that are discussed in this review.

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“…In most cases, CBAVD is a clinical manifestation of CF rather than an isolated event (Chillón et al, 1995;Lewis-Jones et al, 2000); therefore, the clinical manifestations can be diverse (Bombieri et al, 2011). In addition to infertility due to the absence of the bilateral vas deferens, CBAVD may be accompanied by abnormalities of the genitourinary system, mainly including abnormalities in or the absence of the seminal vesicles and kidneys (Casals et al, 2000;Radpour et al, 2008;Cai et al, 2019). The volume of the testis is typically normal or small (Boucher et al, 1999).…”

Section: Clinical Featuresmentioning

confidence: 99%

Congenital Bilateral Absence of the Vas Deferens

Cai

2022

Front. Genet.

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Congenital bilateral absence of the vas deferens (CBAVD) is clinically characterized by the absence of the bilateral vas deferens; the main clinical manifestation is infertility, accounting for 1–2% of male infertility cases. CBAVD may be accompanied by congenital abnormalities in the urogenital system and cystic fibrosis (CF)-related clinical manifestations. CBAVD can develop as a mild manifestation of CF or can be isolated. The main pathogenic mechanism of CBAVD is gene mutation, and CBAVD and CF have a common genetic mutation background. CFTR mutation is the main pathogenic cause of CBAVD and CF, and ADGRG2 mutation is the second most common cause. Although lack of the vas deferens in CBAVD patients causes infertility due to the inability to release sperm, the testes of CBAVD patients have spermatogenic function. Therefore, CBAVD patients can achieve fertility through sperm retrieval surgery and assisted reproductive technology (ART). However, gene mutations in CBAVD patients can have an impact on the ART outcome, and there is a risk of passing on gene mutations to offspring. For CBAVD patients and their spouses, performing genetic counseling (which currently refers mainly to CFTR mutation screening) helps to reduce the risks of genetic mutations being passed on to offspring and of offspring having CF with concomitant CBAVD.

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CFTR variants and renal abnormalities in males with congenital unilateral absence of the vas deferens (CUAVD): a systematic review and meta-analysis of observational studies

Abstract: CFTR variants are common in CUAVD, and the 5T allele may be associated with increased CUAVD risk. CUAVD patients bear a higher RA risk than CBAVD patients, but this is not associated with CFTR variants.

Cited by 25 publications

References 55 publications

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

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

Genetics of the congenital absence of the vas deferens

Congenital Bilateral Absence of the Vas Deferens

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