Azoospermia and Sertoli-cell-only syndrome: hypoxia in the sperm production site due to impairment in venous drainage of male reproductive system.

Sertoli-cell-only (SCO) syndrome, or germ cell aplasia, is diagnosed on testicular biopsy when germ cells are seen to be absent without histological impairment of Sertoli or Leydig cells. It is considered a situation of irreversible infertility. Recent studies have shown that varicocele, a bilateral disease, causes hypoxia in the testicular microcirculation. Destruction of one-way valves in the internal spermatic veins (ISV) elevates hydrostatic pressure in the testicular venules, exceeding the pressure in the arteriolar system. The positive pressure gradient between arterial and venous system is reversed, causing hypoxia in the sperm production site. Sperm production deteriorates gradually, progressing to azoospermia. Our prediction was that, if genetic problems are excluded, SCO may be the final stage of longstanding hypoxia which deteriorates sperm production in a progressive process over time. This would indicate that SCO is not always an independent disease entity, but may represent deterioration of the testicular parenchyma beyond azoospermia. Our prediction is confirmed by histology of the seminiferous tubules demonstrating that SCO is associated with extensive degenerative ischaemic changes and destruction of the normal architecture of the sperm production site. Adequate treatment of bilateral varicocele by microsurgery or by selective sclerotherapy of the ISV resumes, at least partially, the flow of oxygenated blood to the sperm production site and restored sperm production in 4 out of 10 patients. Based on our findings the following statements can be made: (i) SCO may be related in part of the cases to persistent, longstanding testicular parenchymal hypoxia; (ii) germ cells may still exist in other areas of the testicular parenchyma; and (iii) if genetic problems are excluded, adequate correction of the hypoxia may restore very limited sperm production in some patients.