Sertoli Cell-Only Syndrome

Sertoli cell only syndrome, or germ cell aplasia, is a histological pattern in which the seminiferous tubules contain only Sertoli cells and no germ cells. It is found in about 10 to 30% of men with nonobstructive azoospermia.

It may involve all tubules (complete) or only some (focal), and focal disease may allow sperm retrieval.

It is diagnosed by testicular biopsy. Men have azoospermia, small testes and a raised FSH, with normal virilisation.

Pathophysiology. Germ cells are absent because they did not migrate to the gonad, or because they were lost.

Causes:

• Y chromosome microdeletions: complete AZFa deletion causes complete Sertoli cell only histology, and AZFb and AZFc deletions give varied patterns.
• Cryptorchidism, radiotherapy and chemotherapy (alkylating agents).
• Klinefelter syndrome and other chromosomal abnormalities.
• Mumps orchitis, and toxins.
• Idiopathic, in many.

Leydig cells usually work normally, so testosterone is normal or mildly low.

Primary infertility with azoospermia. Small, soft testes (volume 10 to 15 mL), normal epididymis and vasa, and normal virilisation and libido. Gynaecomastia or features of androgen deficiency may appear in men with Leydig cell dysfunction.

• Semen analysis on at least two samples with centrifugation: azoospermia with normal volume and pH.
• FSH (often over 2 to 3 times the upper limit), LH, total testosterone and inhibin B (low or undetectable). FSH does not predict retrieval.
• Karyotype and Y chromosome microdeletion testing (AZFa, AZFb, AZFc).
• Scrotal ultrasound: small testes, microlithiasis and masses.
• Testicular biopsy or micro-dissection testicular sperm extraction: tubules with Sertoli cells only and no germ cells, with focal areas of spermatogenesis in some. Immunostaining may be used to confirm germ cell absence.

Differential diagnosis.

• Maturation arrest of spermatogenesis
• Hypospermatogenesis
• Klinefelter syndrome
• Hypogonadotropic hypogonadism
• Obstructive azoospermia (normal FSH)
• Testicular atrophy after orchitis or torsion

• No medical treatment restores sperm production.
• Micro-dissection testicular sperm extraction when focal spermatogenesis may exist: sperm are found in about 20 to 40%, and the retrieved sperm are used for intracytoplasmic sperm injection. Complete AZFa or AZFb deletion makes retrieval nearly impossible, so surgery is not offered.
• Hormone optimisation before extraction is of uncertain value. It is used in selected men with low testosterone (under about 10 nmol/L): clomifene citrate 25 mg orally daily, or anastrozole 1 mg orally daily, or human chorionic gonadotrophin 1500 to 3000 IU two to three times weekly, for about 3 months, off label.
• Perioperative cefazolin 2 g intravenously (3 g if over 120 kg) as a single dose, with paracetamol 1 g every 6 hours (maximum 4 g daily) and ibuprofen 400 mg every 8 hours for 3 to 5 days.
• Counselling about donor sperm, adoption and childfree living when no sperm is found. Genetic counselling: Y chromosome microdeletions are passed to sons conceived with retrieved sperm.
• Androgen deficiency: testosterone replacement only after fertility plans are settled, since it suppresses any remaining sperm production. Preferred options are gel 50 mg daily or intramuscular testosterone undecanoate 1000 mg every 10 to 14 weeks after loading, titrated to mid-normal levels.
• Bone density and metabolic review in androgen deficiency.

Monitoring. Testosterone and FSH 3 to 6 months after micro-dissection extraction, since testosterone falls in some men and usually recovers over 12 months. Yearly testicular ultrasound for cancer surveillance.

Referral and escalation. Refer to urology or andrology, a fertility unit, and genetics. Urgent referral for a testicular mass.