A 34-Year-Old Man with Azoospermia, Normal Testicular Volume and a Normal FSH
A 34-year-old man and his 31-year-old partner present after 2 years of primary infertility. He has a normal libido and potency, testicular volumes of 18 mL bilaterally, and no history of cryptorchidism, orchitis, chemotherapy or pelvic surgery. Two semen analyses show azoospermia with low volume (1.1 mL) and acidic pH (6.4); fructose is absent. FSH is 4.2 IU/L, LH 3.1 IU/L, testosterone 14 nmol/L and prolactin normal. Examination reveals a small, soft right testis and a palpable cord on the left; the right epididymis is not clearly felt.
1. Interpret the semen and hormonal findings, and generate a differential diagnosis with the tests you would order.
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Interpretation: Azoospermia with low volume, acidic pH and absent fructose points to failure of seminal vesicle contribution, which in a man with normal testicular volume and normal FSH/LH/testosterone suggests ejaculatory duct obstruction or congenital bilateral absence of the vas deferens (CBAVD) rather than primary testicular failure. Normal FSH and testicular volume argue against non-obstructive azoospermia.
Differential diagnosis:
- CBAVD (CFTR-related), suggested by absent vasa on examination and low-volume, acidic, fructose-negative ejaculate.
- Ejaculatory duct obstruction (Mullerian duct cyst, utricle cyst, stones, previous infection), which may give low-volume ejaculate with fructose present or absent depending on completeness.
- Hypogonadotropic hypogonadism is excluded by normal gonadotrophins.
- Retrograde ejaculation would give low volume and absent sperm but fructose is usually present and post-ejaculate urine contains sperm.
- Kartagener syndrome if there are respiratory symptoms (immotile cilia).
Tests:
- Post-ejaculate urine for sperm.
- Transrectal ultrasound to look for seminal vesicle dilatation, ejaculatory duct cysts, utricle, and to assess the vasa.
- CFTR genetic testing (and partner testing) if CBAVD is suspected; also renal ultrasound, as unilateral renal agenesis can occur.
- Hormonal profile already normal; consider inhibin B if there is doubt about spermatogenesis.
- Karyotype and Y-chromosome microdeletion testing are not first-line here but can be added if testicular failure is suspected.
2. If CBAVD is confirmed, what are the reproductive options, and what counselling points matter most?
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Options:
- Surgical sperm retrieval (microsurgical epididymal sperm aspiration or testicular sperm extraction) combined with intracytoplasmic sperm injection (ICSI). Sperm can be retrieved from the epididymis or testis even in CBAVD because spermatogenesis is usually intact.
- Donor sperm if the couple prefers to avoid ICSI or if retrieval fails.
- Adoption or child-free living, discussed without pressure.
Counselling points:
- Genetic implications: CBAVD is usually due to CFTR mutations; the man may have a mild CFTR-related phenotype and the partner should be screened. If the partner is a carrier, the offspring risk of cystic fibrosis is 50% per pregnancy, and preimplantation genetic testing or prenatal diagnosis should be offered.
- Associated renal anomalies: unilateral renal agenesis occurs in a minority; ultrasound is needed.
- Success rates: ICSI outcomes are generally good when sperm is retrieved, but the couple should understand the need for repeated cycles, the possibility of failed retrieval, and the physical and emotional burden.
- Natural conception is essentially impossible without intervention, and the couple should not be offered empirical hormonal treatment.
- Long-term health: men with CFTR-related disease should be aware of possible respiratory or pancreatic issues and be referred if symptomatic.
- Consent and documentation for sperm storage and use, and the legal framework for assisted reproduction in their jurisdiction.