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Congenital bilateral absence of vas deferens
CBAVD typically results in male infertility because sperm cannot be transported from the testes. It is often associated with genetic changes in the CFTR gene, which also causes cystic fibrosis (CF).
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Overview
Congenital bilateral absence of vas deferens (CBAVD) is a condition where the vas deferens are not present from birth. These are the tubes that transport sperm from the epididymis (where sperm mature) to the ejaculatory ducts [PMID:33671239]. Their absence means that, even though sperm are produced, they cannot be released during ejaculation, leading to infertility. CBAVD is a form of obstructive azoospermia, meaning no sperm are found in the ejaculate due to a blockage or absence of the transport mechanism. This condition affects approximately 1-2% of males experiencing infertility [PMID:34790082]. It is often considered a genitourinary form of cystic fibrosis, as many individuals with CBAVD have genetic changes in the CFTR gene.
Symptoms & clinical features
The primary symptom of CBAVD is male infertility. Affected individuals typically do not experience any other noticeable symptoms beyond the inability to conceive naturally. They will usually have normal puberty, sexual function, and libido [PMID:33671239]. A physical examination might reveal that the vas deferens cannot be felt in the scrotum. Semen analysis often shows azoospermia, meaning there is an absence of sperm in the ejaculate, despite normal sperm production in the testes. Other fluid levels in the semen, such as fructose, might be abnormal.
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Affected organs
The organs directly affected in CBAVD are the vas deferens, which are part of the male reproductive system. In many cases, other structures derived from the Wolffian duct during embryonic development, such as the epididymis and seminal vesicles, may also be underdeveloped or absent. Although the testes usually function normally and produce sperm, their connection to the outside world is incomplete. Given the strong association with the CFTR gene, individuals with CBAVD may also have subtle involvement of other organs typically affected in cystic fibrosis, such as the lungs and pancreas, though symptoms are often mild or absent in CBAVD-only cases [PMID:34790082].
Risks & severity
The main risk associated with CBAVD is male infertility, as sperm cannot be transported for natural conception. The condition itself is not life-threatening and typically does not impact overall health beyond the reproductive system. However, due to its genetic link with cystic fibrosis (CF), there is a potential for individuals with CBAVD to have milder CF-related symptoms, or for their partners and offspring to be at risk of classic CF if the partner also carries a CFTR gene variant. The severity of reproductive impairment is consistent among individuals with CBAVD, as the absence of the vas deferens uniformly prevents natural sperm transport. There is no typical 'age of onset' for CBAVD symptoms, as the condition is present from birth, but it is usually identified when a couple seeks treatment for infertility.
Genetic causes
CBAVD is predominantly caused by genetic changes in the CFTR gene (cystic fibrosis transmembrane conductance regulator) [PMID:33671239]. The CFTR gene provides instructions for making a protein that acts as a channel on the surface of cells, controlling the movement of chloride ions and water. This function is crucial for maintaining the fluidity of mucus and other secretions in various organs. Pathogenic variants in the CFTR gene can lead to a dysfunctional CFTR protein, resulting in thick, sticky secretions. In the context of CBAVD, this altered function is thought to disrupt the normal development of the vas deferens during foetal growth, causing them to degenerate or fail to form [PMID:34790082]. While many individuals with CBAVD have two CFTR gene variants, some may have one identified CFTR variant and other genetic factors contributing to the condition.
- CFTR CF transmembrane conductance regulatorThe CFTR gene provides instructions for the CFTR protein, a chloride channel crucial for maintaining fluid balance and the production of thin, free-flowing mucus in various bodily systems.
Inheritance pattern
CBAVD is inherited in an autosomal recessive pattern. This means that an individual must inherit two altered copies of a gene, one from each parent, to develop the condition. If a person inherits only one altered copy, they are a carrier and typically do not show symptoms of CBAVD. For two carrier parents, there is a 25% chance with each pregnancy that their child will inherit two altered gene copies and develop CBAVD. There is also a 50% chance the child will be a carrier, and a 25% chance the child will inherit two working copies of the gene. Genetic counselling is often recommended for couples affected by CBAVD to understand the inheritance risks for their offspring and family members.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
Diagnosis & testing
Diagnosis of CBAVD typically begins when a couple presents with male infertility. A physical examination may identify the absence of the vas deferens. A semen analysis confirming azoospermia is a key finding. The definitive diagnosis often involves genetic testing for variants in the CFTR gene [PMID:34790082]. This testing is usually performed through an NHS Genomic Medicine Service pathway, often initiated by a referral from a fertility specialist or a clinical geneticist. The relevant NHS National Genomic Test Directory R-code for CF germline testing for investigation of male infertility is R235. Genetic testing helps confirm the diagnosis and also informs reproductive planning, especially for assisted reproductive technologies.
Management & lifestyle
Management of CBAVD focuses on addressing infertility. Since sperm are typically produced in the testes, surgical procedures such as testicular sperm extraction (TESE) or epididymal sperm aspiration can be used to retrieve sperm directly. These retrieved sperm can then be used in assisted reproductive technologies like intracytoplasmic sperm injection (ICSI) with in vitro fertilisation (IVF). Individuals with CBAVD are often offered genetic counselling to understand the implications of their CFTR genetic variants for themselves and their family, including the risk of cystic fibrosis in potential offspring if their partner is also a carrier.
UK care pathway
In the UK, individuals suspected of having CBAVD largely follow pathways within the NHS Genomic Medicine Service. Referral to a clinical geneticist or a fertility specialist is typically the first step. Genetic testing, specifically for CFTR gene variants, is available via the National Genomic Test Directory, utilising relevant R-codes such as R235 for male infertility. Individuals and couples will have access to genetic counsellors who can provide detailed information about the genetic basis of CBAVD, inheritance patterns, and reproductive options.
Frequently asked questions
Can men with CBAVD still have biological children?
Yes, men with CBAVD can often have biological children through assisted reproductive technologies. Sperm can usually be retrieved directly from the testes or epididymis and then used with IVF and ICSI.
Is CBAVD related to cystic fibrosis?
Yes, CBAVD is strongly linked to cystic fibrosis (CF). Most individuals with CBAVD have genetic changes in the CFTR gene, which also causes CF. It is sometimes considered a form of CF that mainly affects the reproductive system.
Will my children inherit CBAVD if I have it?
CBAVD is inherited in an autosomal recessive pattern. If you have CBAVD, your children will inherit one altered copy of the CFTR gene from you. If your partner is also a carrier for a CFTR variant, there is a risk their child could develop CBAVD or classic CF. Genetic counselling can provide specific risk information.
Do I need any other health checks if I have CBAVD?
While CBAVD primarily affects fertility, due to its link with the CFTR gene, some men may be advised to have basic checks for other mild CF-related symptoms, such as lung or pancreatic function, although significant issues are rare in CBAVD-only cases. Your doctor or genetic counsellor can advise if these checks are recommended for you.
What is the typical age of diagnosis for CBAVD?
CBAVD is present from birth, but it is typically diagnosed in adulthood when a man and his partner seek medical help for infertility. This usually occurs when trying to conceive and finding difficulty.
References
- Cioppi F, Rosta V, Krausz C. Genetics of Azoospermia. International journal of molecular sciences. 2021. PMID: 33806855
- Kuroda S, Usui K, Sanjo H. Genetic disorders and male infertility. Reproductive medicine and biology. 2020. PMID: 33071633
- Kamiński P, Baszyński J, Jerzak I. External and Genetic Conditions Determining Male Infertility. International journal of molecular sciences. 2020. PMID: 32722328
- Cornud F, Belin X, Delafontaine D. Imaging of obstructive azoospermia. European radiology. 1997. PMID: 9265680
- Chen H, Ruan YC, Xu WM. Regulation of male fertility by CFTR and implications in male infertility. Human reproduction update. 2012. PMID: 22709980
- Ferlin A, Stuppia L. Diagnostics of CFTR-negative patients with congenital bilateral absence of vas deferens: which mutations are of most interest? Expert review of molecular diagnostics. 2020. PMID: 31854215
- Gokhale S, Kochhar K. Epididymal Appearance in Congenital Absence of Vas Deferens. Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine. 2021. PMID: 32955739
- Beka M, Leal T. Nasal Potential Difference to Quantify Trans-epithelial Ion Transport in Mice. Journal of visualized experiments : JoVE. 2018. PMID: 30035761