Sertoli-cell-only syndrome and other causes of non-obstructive azoospermia

When a semen test finds no sperm, the first question is whether sperm are being made. If production is normal but a duct is blocked, for example after infection or vasectomy, the problem is obstructive and often treatable by retrieving sperm from the epididymis. If the testis itself is not producing sperm, the problem is non-obstructive, and the options are different.

Blood tests help to tell them apart. A raised follicle-stimulating hormone and small testes point towards a testicular cause, whereas normal hormones and normal-sized testes lean towards obstruction. A testicular ultrasound and a clinical examination add further information.

Inside the testis, narrow tubules contain germ cells that mature into sperm and Sertoli cells that nurture them. In Sertoli-cell-only syndrome, a biopsy shows the Sertoli cells present but germ cells absent in the sampled tubules. The man usually looks and feels typical, with normal masculine development and often normal testosterone, and the diagnosis commonly emerges only when fertility is investigated.

Some men have a complete pattern, others a focal pattern in which only part of the testis is affected. That distinction matters because focal areas elsewhere can still contain sperm, which is what retrieval surgeons are looking for.

Several causes can be behind the picture, and sometimes none is found. The NHS lists damage from infection, cancer, surgery, congenital defects and undescended testicles among the reasons for poor testicular function, and the medicines and treatments that affect sperm production include chemotherapy and anabolic steroids.

• Klinefelter syndrome, an extra X chromosome. The NHS notes that many men are undiagnosed until fertility testing.

• Microdeletions on the Y chromosome that remove genes needed for sperm production.

• Previously undescended testes or testicular torsion.

• Chemotherapy or pelvic radiotherapy.

• Mumps orchitis in adulthood or other severe testicular infection.

• Hormonal causes such as low pituitary signalling, which can respond to medical treatment.

• Unexplained, where no cause can be identified despite a full work-up.

A specialist will usually request at least two semen analyses, hormone profile including FSH, LH and testosterone, a karyotype (chromosome test) and a Y-chromosome microdeletion screen. The results guide both the chance of sperm retrieval and the genetic counselling that follows.

The HFEA recommends genetic testing before ICSI where a clear genetic cause is suspected, because a son conceived through ICSI may inherit his father infertility, particularly with Y chromosome causes. A session with a fertility counsellor or clinical geneticist is part of the pathway.

The HFEA describes several techniques. Needle methods (PESA and TESA) and testicular biopsy (TESE) are used in blockages and some production problems. Micro-TESE uses an operating microscope to find the tubules most likely to contain sperm and is generally considered the approach for men whose sperm production is impaired, such as after chemotherapy, with genetic conditions, or after earlier surgery.

The procedure is done in a hospital, commonly under anaesthesia. The HFEA lists bleeding and infection as rare complications and notes that some men experience changes in testosterone affecting sexual function or mood. The NHS describes surgical extraction as usually under local anaesthetic in some settings, so the type of anaesthetic depends on the technique. Sperm may be frozen at the time so that the female partner or egg donor can be treated later.

Retrieval success depends heavily on the underlying cause and cannot be predicted from semen alone. A complete Sertoli-cell-only pattern on biopsy lowers the chance of finding sperm, while focal patterns or other diagnoses may offer better odds. Specialists generally quote individual probabilities, and men should expect the conversation to include the possibility that no sperm are found.

If retrieval fails or is not wanted, donor sperm, adoption and living child-free are legitimate choices. Emotional support through the fertility clinic or a counsellor is valuable at this stage.

Some of the conditions behind azoospermia also affect testosterone, bone density and long-term health, so a blood testosterone check and periodic review are usually sensible. Low sperm count and testicular lumps or pain in the same person should always be examined, as testicular cancer can occur alongside poor sperm production.