Discrimination and characterization of Sertoli cell-only syndrome in non-obstructive azoospermia using cell-free seminal DDX4.

Cell-free seminal mRNA (cfs-mRNA) contains testis-specific transcripts from bilateral testes. This study determined the presence of DEAD box polypeptide 4 (DDX4) in cfs-mRNA to identify and characterize the incidence of Sertoli cell-only (SCO) syndrome in men with non-obstructive azoospermia (NOA). DDX4 cfs-mRNA was determined in 315 men with NOA, and compared with testicular samples obtained by microdissection from 19 NOA patients. Karyotype and azoospermia factor microdeletion analysis were performed, and clinical features were evaluated. Negative DDX4 cfs-mRNA suggestive of SCO was found in 13.7% of NOA patients, with a similar incidence in NOA men with known genetic causes and those without known genetic causes. DDX4 cfs-mRNA was absent in 44% of SCO cases diagnosed by testicular histopathology, but present in all patients presenting with maturation arrest or hypospermatogenesis. Furthermore, 84.2% of NOA men with DDX4 cfs-positive mRNA had a DDX4-positive testicular sample. In NOA men without genetic causes, SCO patients discriminated by negative DDX4 cfs-mRNA showed different clinical features when compared with non-SCO cases. These results suggest that the evaluation of DDX4 cfs-mRNA is more accurate than testicular histopathology in discriminating SCO, and also permits the identification of a specific group of NOA men with distinct clinical features.

Onco-testicular sperm extraction: testicular sperm extraction in azoospermic and very severely oligozoospermic cancer patients.

An increased risk of testicular cancer in men with infertility and poor semen quality has been reported. In view of the high cure rates for testicular germ cell tumours, increasing clinical importance is being placed on the protection of fertility. High-dose cytostatic therapy may be expected to cause long-term infertility. Thus, the standard procedure for fertility protection is the cryopreservation of ejaculated spermatozoa or testicular tissue before therapy. Four male patients with azoospermia and two patients with very severe oligozoospermia underwent onco-testicular sperm extraction (TESE). We attempted onco-TESE in patients with azoospermia and very severe oligozoospermia after orchiectomy. Of the patients with testicular germ cell tumours, four had spermatozoa in their testicular tissues. Sertoli cell-only syndrome was found in one patient, and one patient showed maturation arrest without the detection of spermatozoa. Three of six showed seminomatous germ cell tumour, two of six had nonseminomatous germ cell tumour and one patient showed no malignancy. Two patients achieved clinical pregnancy. Fertility challenges in men with cancer are the most straightforward because of the relative ease of obtaining and cryopreserving sperm. Testicular sperm extraction is a useful technique for obtaining spermatozoa before cytotoxic therapy in azoospermic and very severely oligozoospermic cancer patients.

Sperm retrieval and live birth rates in presumed Sertoli-cell-only syndrome in testis biopsy: a single centre experience.

We aimed to investigate sperm retrieval rates (SRR) by testicular sperm extraction (TESE), factors affecting SRR, and fertilization rate (FR), implantation rate (IR), clinical pregnancy rate (CPR) and live birth rate (LBR) in patients with presumed Sertoli-cell-only syndrome in testis biopsy (SCOS). We retrospectively evaluated files of 134 patients with SCOS who underwent TESE. Group I were patients in whom spermatozoa were retrieved and Group II were patients in whom no spermatozoa could be retrieved. SRR, Follicle stimulating hormone (FSH), Luteinizing hormone (LH), and testosterone levels, and the volume of testicles were compared between groups. In addition, FR, IR, CPR and LBR were determined. Sperm retrieval was achieved in 37 (27.6%) patients (Group I), and the remaining 97 (72.4%) patients made Group II. There were no significant differences in age, infertility time, testicular volume, serum FSH, LH and testosterone levels between Groups I and II (p > 0.05). Intracytoplasmic sperm injection (ICSI) was performed in 36 patients. FR, IR, and CPR were 60.86 ± 23.03, 36.53 ± 41.78 and 51.3% respectively. Cycle and patient based LBRs were 37.8 and 45.1% respectively. SRR in SCOS is lower than patients with non-obstructive azoospermia (NOA) in general. No parameters to predict spermatozoa retrieval were determined. In patients with SCOS, ICSI achieves similar live birth rate to other patients with NOA.

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.