Cystic Fibrosis, CFTR Carriers, and Male Fertility

For many men, an infertility evaluation is the first time they learn they carry a CFTR gene mutation. Congenital bilateral absence of the vas deferens (CBAVD), the reproductive hallmark of cystic fibrosis gene involvement, can occur in men who have no respiratory symptoms and no family history of CF. Understanding the connection between CFTR, CBAVD, and fertility is essential for making informed decisions about family building.

The CFTR-CBAVD Connection

The vas deferens is the tube that carries sperm from the testicle to the urethra. In CBAVD, both vas deferens fail to develop, meaning sperm is produced but has no pathway out. This accounts for 1 to 2% of male infertility cases and is present in approximately 98% of men with classical cystic fibrosis.

What surprises many patients is that CBAVD can also occur in CFTR carriers, people with only one or two mild mutations who do not have CF by any clinical definition. The vas deferens appears to be among the most sensitive structures to CFTR dysfunction, failing to develop even when lung and pancreatic function remain entirely normal.

Diagnosis and Genetic Testing

CBAVD is typically diagnosed during a physical exam and confirmed with transrectal ultrasound showing absence of the vas deferens and seminal vesicles. The semen analysis shows azoospermia (no sperm) with low volume and acidic pH, reflecting the missing contribution from the vas deferens and seminal vesicles.

Once CBAVD is identified, comprehensive CFTR genetic testing is the next step. Standard carrier screening panels test for 23 to 40 common mutations, but they miss rarer variants. Full CFTR gene sequencing is recommended for men with CBAVD, as it identifies mutations in roughly 80% of cases.

Sperm Retrieval: MESA and TESE

Men with CBAVD produce sperm normally. The problem is purely one of transport. Surgical sperm retrieval bypasses the missing plumbing entirely.

MESA (microsurgical epididymal sperm aspiration) is the preferred technique for CBAVD. Performed under anesthesia with an operating microscope, it involves opening the epididymis and aspirating fluid containing motile sperm. MESA typically yields enough sperm for multiple IVF cycles, and excess sperm can be frozen for future use.

TESE (testicular sperm extraction) is the alternative when MESA is not feasible. It involves removing small pieces of testicular tissue and extracting sperm from them. TESE sperm may be less mature than MESA sperm but are still fully usable with ICSI.

IVF with ICSI: The Treatment Path

Because surgically retrieved sperm cannot fertilize eggs on their own in a lab dish, intracytoplasmic sperm injection (ICSI) is required. A single sperm is injected directly into each mature egg. Fertilization rates with ICSI using MESA-retrieved sperm are comparable to those achieved with ejaculated sperm.

The IVF cycle is coordinated so the female partner's egg retrieval occurs on the same day as (or close to) the sperm retrieval, though freezing either component allows flexibility in timing.

PGT-M: Testing Embryos for CF

If both partners carry CFTR mutations, preimplantation genetic testing for monogenic conditions (PGT-M) can identify embryos without two disease-causing mutations. This testing adds to the cost and complexity of IVF but allows couples to avoid passing CF to their children.

The PGT-M probe workup requires DNA samples from both partners and takes 4 to 8 weeks to develop. Planning this before starting the IVF cycle avoids delays.

Heritability and What It Means for a Son

A son conceived via ICSI by a man with CBAVD will inherit at least one CFTR mutation from his father. If the mother is also a carrier, the son could have CF or CBAVD himself. If the mother is not a carrier, the son will be a carrier and may or may not have CBAVD depending on the specific mutation inherited and whether additional variants exist.

This is another reason genetic counseling with a specialist who understands reproductive genetics is an integral part of the process, not an add-on.