ESX1 gene expression as a robust marker of residual spermatogenesis in azoospermic men.

BACKGROUND: It would be of value to identify ongoing spermatogenesis molecular markers which can predict successful sperm recovery in patients with non-obstructive azoospermia undergoing conventional or microsurgical testicular sperm extraction (TESE/microTESE). ESX1 is an X-linked homeobox gene expressed in testis, placenta, brain and lung in humans and specifically in pre- and post-meiotic germ cells of the testis in mice. METHODS: We investigated the sequence, expression (by RT-PCR) and epigenetic status (by promoter pyrosequencing) of ESX1 in testicular tissue samples, obtained from 81 azoospermic subjects in the context of surgical sperm extraction, to check a possible association between ESX1 alterations and impaired spermatogenesis, as determined by histological analysis. RESULTS: The ESX1 transcript was detected in 100% of cases diagnosed as obstructive azoospermia (33), hypospermatogenesis (18) and incomplete maturation arrest (MA) (2), and sperm recovery was also successful in 100% of these cases. ESX1 mRNA was also detected in 5 of 6 patients with incomplete Sertoli cell-only syndrome, in 4 of 6 subjects with complete MA but in only 3 of 16 cases of complete Sertoli cell-only syndrome (cSCOS), whereas sperm recovery was successful in 4 of 6, 2 of 6 and 5 of 16 of these patients, respectively. In cases of focal spermatogenesis, ESX1 expression and sperm retrieval were concordant in 14 of 19 (74%) cases subjected to TESE, but in only 3 of 11 (27%) men who underwent microTESE. With TESE, but not with microTESE, both samples originated from adjacent testicular areas. The pyrosequencing of the ESX1 CpG island revealed methylation levels that were significantly lower in ESX1 expressors when compared with non-expressors. CONCLUSIONS: ESX1 emerges as a potentially reliable spermatogenesis molecular marker, whose clinical value as a predictor of successful sperm retrieval warrants further studies.

Sperm retrieval for intra-cytoplasmic sperm injection in non-obstructive azoospermia.

Surgical testicular sperm retrieval for intra-cytoplasmic sperm injection (ICSI) purposes is the only possibility of biological fathering in case of non-obstructive azoospermia (NOA). Successful retrieval only correlates with histology, not with FSH values or testicular volume. Concurrent AZFa and AZFb microdeletion predict unsuccessful recovery. Testicular sperm extraction (TESE) (mean of successful retrievals in literature: 52.7%) is the technique of choice: we had successful retrievals in 100% of cases of hypospermatogenesis with > 5 spermatids/tubule (spd/tub), 81.8% of cases of hypospermatogenesis with < 4 spd/tub, 50% of cases of maturation arrest, and 25% of cases of histologically pure Sertoli cell-only syndrome. Microsurgical TESE (mTESE) has been reported to increase successful retrievals: from 16.7-45% for standard TESE to 42.9-63.6% for mTESE, depending on the distribution of testicular histology in the various case studies; from 9 to 14 cases out of 22, respectively, in the only study in which TESE and mTESE were performed simultaneously on the same testis. Improvements in biological procedures for TESE retrievals can increase positive findings. TeFNA does not appear to be indicated in NOA, both because of its low success rates--which, in practice, are only positive in hypospermatogenesis--and because it is unable to detect any carcinomas in situ. Previous surgery of left varicocele in NOA could increase the chances of subsequent recovery. ICSI from TESE has lower birth rates in NOA than in obstructive azoospermia (OA) (19% vs 28%). Abortion rates are significantly higher following ICSI from NOA (11.5%) than from OA (2.5%) (P=0.001). Therefore, the prognostic fertility of a couple with an NOA male is quite lower than for a couple with an OA male.

Sildenafil citrate vs intracavernous alprostadil for patients with arteriogenic erectile dysfunction: a randomised placebo controlled study.

We compared the effectiveness of sildenafil citrate and alprostadil in improving arterial penile inflow (peak systolic velocity (PSV)) and penile rigidity in 55 patients with erectile dysfunction caused by atherosclerosis. A total of 35 patients with pure vasculogenic impotency were randomly assigned to alprostadil (Av group; n=11), sildenafil (Sv group; n=12), or placebo (P group; n=12), and 20 patients with nonvasculogenic impotency were randomly assigned to alprostadil (A group; n=10) or Sildenafil (S group; n=10): Av and A used alprostadil injection (capable of giving a full erection) once a week for 1 month, Sv and S took daily oral sildenafil (25 mg) for 1 month, and P took daily oral placebo for one month. The PSV was measured with Duplex sonography and penile rigidity was assessed using the IIEF-15 questionnaire, both of which were administered before and after treatment. Although both treatments improved penile rigidity, they increased PSV only in the Av and Sv groups. Our results suggest that alprostadil and oral therapy should be the starting therapy in men with vasculogenic impotency, whereas alprostadil should be avoided as the first-line approach in men with nonvasculogenic impotency.

Testicular function following chemo-radiotherapy.

Improvements in cancer survival raise infertility issues in young patients suffering from malignancies. The aim of the study is to review current knowledge on the effect of chemotherapy (CT) and radiotherapy (RT) for testis and hematological neoplasms on testicular function. Cisplatin-based regimens for testis neoplasm induce temporary azoospermia; permanent damage can occur with high doses (400-600 mg/m(2)). Alkylating agents are very effective for hematological neoplasm therapy but extremely dangerous to germinal epithelium. Damage can be irreversible. Spermatozoa cannot tolerate irradiation doses higher than 6 Gy. Leydig cells are damaged by doses higher than 15 Gy. A-Spermatogonia have been shown to survive after CT and RT and their recovery for post-treatment graft has been recently developed in animal models. Infertility counselling before treatment in young oncological patients is mandatory. Cryopreservation is the best option for fertility protection.

[Humoral markers of iron status in patients on maintenance hemodialysis]. / Indici umorali di accumulo di ferro nei pazienti in emodialisi periodica.

In forty-nine patients on regular dialysis treatment (RDT) we evaluated following parameters for a period of twenty-four months: serum ferritin (SF), transferrin, T.I.B.C. percental saturation (Fe/TIBC%), haemoglobin (Hb). Twenty-five patients had received more than 5 g intra-venous iron or several blood transfusions, before the beginning of the study, while the other twenty four patients had never received iron treatment nor transfusions. Serum ferritin and Fe/TIBC% proved to be a good estimate of iron stores in RDT patients. In fact both parameters showed significantly higher levels in iron loaded patients than in never treated patients. Furthermore, in patients who no longer received iron loads during the study period, both SF and Fe/TIBC% showed a significant decrease, without changes in haematologic values. This study demonstrated that oral ferritinic iron (40 mg/day for 6 months) doesn't increase either SF and Fe/TIBC% levels, or modifies haematologic values.

[Acute renal insufficiency caused by diflunisal. Description of a case]. / Insufficienza renale acuta da diflunisal. Descrizione di un caso.

A case of kidney failure in a patient with cirrhosis of the liver in the ascitic stage after treatment of a non-steroid anti-inflammatory drug, diflunisal, is reported. The pathogenesis of the kidney impairment, quickly reversed by withdrawal of the drug, is attributed to pharmacological inhibition of cyclo-oxygenase and prostaglandin synthesis with consequent alterations of intrarenal haemodynamics and renal blood flow.

[Doppler color ultrasonography in the diagnosis of erectile dysfunction of vascular origin]. / Eco-color Doppler nella diagnosi del deficit erettile di origine vascolare.

The aim of this paper is to evaluate whether echo-color Doppler diagnostics allows to detect the different evolutionary stages of arteriopathy affecting the cavernous arteries of the penis. 124 patients with erectile deficiency were examined. All of them were evaluated by andrologic and psychologic anamnesis. An echo-color Doppler examination was performed on cavernous arteries before (basal) and after (dynamic) an injection of Prostaglandin E1 (10 micrograms). The penile circulation has been observed for twenty minutes after the injection to detect anomalous collateral vessels of the cavernous arteries. The population was divided into 4 groups according to the basal and dynamic peak systolic velocity (PSV). Cardiovascular risk factor incidence in patients with normal basal and dynamic PSV values (group A) and in patients with pathologic basal and dynamic PSV values (group C) is 10% and 44% respectively (p < 0.002). Psychologic disorder in group A and C is 41% and 26% respectively (p < 0.05). Patients with pathologic basal PSV and normal dynamic PSV (group B) show an intermediate (26%) incidence of cardiovascular disorders as compared to A and C. Anomalous side branches are equally represented in A and B (41% and 38%) and to a lesser extent in C (26%). Based on anamnestic and instrumental data, Group B ranges at an intermediate position between A and C. In this group, the presence of incipient arteriopathy affecting the penile circulation may be suspected. The ability to detect patients with vascular diseases still at a subclinical stage, as it already happens for other organs, would allow a prompt therapeutic action.