Effects of phosphodiesterase-5 inhibitor vardenafil on testicular androgen-binding protein secretion, the maintenance of foci of advanced spermatogenesis and the sperm fertilising capacity in azoospermic men.

We evaluated the effects of vardenafil on testicular androgen-binding protein secretion (ABP). Bilaterally obstructed azoospermic (OA)-men (n = 19) (group A) underwent unilateral testicular biopsy. A group of nonobstructed azoospermic (NOA)-men (n = 68) (group B) underwent bilateral testicular biopsy. ABP secretion in vitro by testicular tissue was assessed in each participant of every group. In addition, intracytoplasmic sperm injection (ICSI) cycles were performed in several couples of group A or group B using frozen/thawed spermatozoa from the biopsy material. Ten OA-men (group A1), 14 NOA-men (group B1), and nine different NOA-men (group B2) had been positive for spermatozoa in the biopsy but pregnancies were not achieved in the respective female partners. Men of groups A1, B1 and B2 were treated with vardenafil, vardenafil and L-carnitine respectively. Then, the men of groups A1, B1 and B2 underwent a second testicular (unilateral) biopsy. Within the group A1 and within the group B1, ABP secretion rate was significantly larger after vardenafil treatment than prior to vardenafil treatment. In addition, fertilisation rates in ICSI cycles within groups A1 or B1 were not affected by vardenafil administration. Vardenafil administration in NOA-men increased ABP secretion and did not affect detrimentally the presence of testicular foci of advanced spermatogenesis.

Gynecomastia as a first clinical sign of nonseminomatous germ cell tumor.

INTRODUCTION: Gynecomastia is a common clinical sign in several diseases. In this report we present a case of gynecomastia with underlying testicular tumor which remained misdiagnosed for a prolonged period of time. CASE REPORT: A 16-year-old adolescent noticed unilateral painless swelling of the left breast. He was referred to the Department of General Surgery and examined by a breast surgeon. A diagnosis of mastitis was made and a treatment with an oral antibiotic drug began. After failure of the initial antibiotic treatment, the patient was referred to the Department of Endocrinology and left testicular cancer was diagnosed. Unilateral high inguinal orchidectomy and subsequent chemotherapeutic treatment were performed. CONCLUSION: Primary care physicians should be aware of the possibility of a concomitant presence of gynecomastia and testicular cancer. We suggest a physical examination as well as a laboratory investigation, and testicular ultrasonography of the testes in all patients with gynecomastia.

Effects of phosphodiesterase-5 inhibitors on sperm parameters and fertilizing capacity.

The aim of this review study is to elucidate the effects that phosphodiesterase 5 (PDE5) inhibitors exert on spermatozoa motility, capacitation process and on their ability to fertilize the oocyte. Second messenger systems such as the cAMP/adenylate cyclase (AC) system and the cGMP/guanylate cyclase (GC) system appear to regulate sperm functions. Increased levels of intracytosolic cAMP result in an enhancement of sperm motility and viability. The stimulation of GC by low doses of nitric oxide (NO) leads to an improvement or maintenance of sperm motility, whereas higher concentrations have an adverse effect on sperm parameters. Several in vivo and in vitro studies have been carried out in order to examine whether PDE5 inhibitors affect positively or negatively sperm parameters and sperm fertilizing capacity. The results of these studies are controversial. Some of these studies demonstrate no significant effects of PDE5 inhibitors on the motility, viability, and morphology of spermatozoa collected from men that have been treated with PDE5 inhibitors. On the other hand, several studies demonstrate a positive effect of PDE5 inhibitors on sperm motility both in vivo and in vitro. In vitro studies of sildenafil citrate demonstrate a stimulatory effect on sperm motility with an increase in intracellular cAMP suggesting an inhibitory action of sildenafil citrate on a PDE isoform other than the PDE5. On the other hand, tadalafil's actions appear to be associated with the inhibitory effect of this compound on PDE11. In vivo studies in men treated with vardenafil in a daily basis demonstrated a significantly larger total number of spermatozoa per ejaculate, quantitative sperm motility, and qualitative sperm motility; it has been suggested that vardenafil administration enhances the secretory function of the prostate and subsequently increases the qualitative and quantitative motility of spermatozoa. The effect that PDE5 inhibitors exert on sperm parameters may lead to the improvement of the outcome of assisted reproductive technology (ART) programs. In the future PDE5 inhibitors might serve as adjunct therapeutical agents for the alleviation of male infertility.

[Current trend in the diagnosis and treatment of primary non refluxing megaureter]. / Orientamenti attuali nella diagnosi e nel trattamento del megauretere primitivo non refluente.

BACKGROUND: The terms megaureter or hydroureteronephrosis are non-specific because indicate various pathologic entities recognise different causes (obstruction, reflux, obstruction-reflux, primary and secondary). An undeveloped renal function in neonatal period makes more difficult the therapeutic approach. Actually the problem is to find the indicators that consent us the individualization of patients more suitable for nonoperative management. METHODS: From 1996 to 2002, we observed 60 patients with 74 megaureters. In 24 cases the diagnosis was antenatal, 6 cases were diagnosed immediately after birth, 13 in the first year of life and 17 after the first year (2y-10y). Patients were classified in two groups based on age; 43 cases diagnosed in the first year of life and 17 after. Both of them were classified in two further groups based on ureteral size and renal function, scintigraphically evaluated. RESULTS: In the first group (A) ureters with 10 mm of dilatation improved in 38.9% of the cases. Were stationary 50% and impaired 11,1% of them. Ureters with dilatation between 7 and 10 mm improved in 24%, were stationary in 72% and impaired in in 4% of the cases. Ureters with less than 7mm dilatation improved in 35.2% and were stationary in 64.8%. In the group A renal scintigraphy MAG3 demonstrated, in the patients with acceptable renal function and washout, an improvement in 65% of the cases. Was stationary in 30% and impaired in 10%. CONCLUSIONS: The grade of dilatation evaluated with ultrasonographic exam and the study of renal function with diuresis renal scintigraphy using Tc-99m MAG3 and washout grade with diuresis renal scintigraphy are remarkable markers for the treatment choice.

The lipidosterolic extract of Serenoa repens in the treatment of benign prostatic hyperplasia: a comparison of two dosage regimens.

This 6-month double-blind, randomized, parallel-group study compared two dose regimens of Libeprosta, the lipidosterolic extract of Serenoa repens in 100 male outpatients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH). The patients received two 80-mg tablets twice daily or two 80-mg tablets three times daily. Baseline evaluations included maximum and mean urinary flow rates, postvoid residual urine volume, and International Prostate Symptom Score (I-PSS) total and quality-of-life scores. Both regimens significantly reduced the I-PSS mean total score from baseline values (P<.001); improvements achieved statistical significance after month 3 and were maintained for the duration of the study. Significant improvements from baseline also occurred in quality-of-life scores, maximum and mean urinary flow rates, and residual urine volume (P<.05). The decrease in residual urine with both regimens was highly significant (P<.001). No significant differences in efficacy were noted between the two dose groups, and no treatment-related complications or clinical adverse events occurred. In this clinical study, the lipidosterolic extract of Serenoa repens was a well-tolerated agent that may significantly improve lower urinary tract symptoms and flow measurements in men with BPH.

Massive haemorrhage of inoperable bladder carcinomas: treatment by intravesical formalin solution.

Numerous modalities of treatment have been used in the past to control massive bladder haematuria, with varying degrees of success. Formalin has been used in urology only for the treatment of intractable haematuria of inoperable bladder carcinomas, usually as the last resort when all other nonsurgical attempts have failed and before more aggressive surgical measures are considered. Eight patients with bladder tumours classified T2 (2 cases), T3 (2 cases) or T4 (4 cases) and 2 patients with radiation cystitis were assessed as being beyond the scope of even palliative surgery, severe haemorrhage being present in all cases. The treatment was instituted in all cases by intravesical instillation of a 10 per cent formalin solution under general anaesthesia. Four patients received 4 and 6 instillations, respectively, the former over 4 weeks and the latter over 10 months. The bladder was filled completely and an indwelling-catheter introduced, the formalin solution being left in the bladder for 5 to 30 min (mean: 12 min). Haematuria was absent after 1 to 25 days (mean: 11 days) in 9 cases. The 10th patient died before arrest of haemorrhage. Survival after instillation was 65 days to 27 months (mean: 11.5 months). The outcome was fatal within 4 months or less in 3 cases and 4 patients died of renal failure within 3 months, one within 65 days after instillation. In 4 cases, treatment with formalin reduced bladder capacity to less than 100 ml. Other complications included retroperitoneal fibrosis (1 case), urinary incontinence (3 cases) and severe frequency and nocturia (3 cases). This procedure should therefore be reserved for terminal cases unable to support more aggressive therapy.

Large infectious bladder stone after long delay in removing ureteral stent.

We herein present a case of formation of a large infectious bladder calculous resulted from placement of a double pigtail catheter for an extensive period. The concomitant poor function of the corresponding renal unit made selection of nephroureterectomy unavoidable in the management of our patient.

Bladder cancer mortality in the Epirus district population (Greece).

OBJECTIVE: To describe the pattern of bladder cancer mortality in the Epirus district population (North-Western Greece) and to establish some relationships with cigarette smoking. PATIENTS AND METHODS: Mortality rates of bladder cancer in the Epirus district population were analysed according to the official data from the Department of Statistics of the University Hospital of Ioannina during the last decade (January 1990-January 2000). Age standardization of death rates was done by the direct method, using the world population as a standard. Fisher's test was used as a significance test for linear regression coefficient in time trend analysis of mortality. RESULTS: The average annual standardized mortality rates from bladder cancer during the study period were 5.23 per 100,000 population (96% Confidence Interval--Cl 4.02-5.63) in males and 1.63 per 100,000 population (96% Confidence Interval--CI 1.18-1.96) in females. Significantly increasing trends of the rates were observed in males (y = 2.421 + 0.231x; p < 0.01), but not in females (y = 1.263 + 0.027x: p > 0.05). The greatest increase in age - specific rates in males was observed in the age group of 70 and more years (y = 25.602 + 3.673x; p < 0.01). In females, all age--specific rates except for the group 60-69 years showed significantly increasing tendency. The increasing tendency of bladder cancer mortality is followed by the rise of per capita cigarette consumption among the Epirus district population. CONCLUSION: Further studies are needed for the explanation of the irregularities in the age-specific rates.

[Varicocele at a prepubertal age. Adolescent varicocele]. / Il varicocele nell'età pre-adolescenziale. Adolescential varicocele.

Varicocele is a dilatation of the spermatic veins, particularly on the left side, and represents one of the most frequent causes of male infertility. Its frequency in pre-adolescence varies from 10% to 15%. Even today varicocele pathogenesis is not clear. In the period from August 1990 to August 1999, 35 males between 10 and 16 years of age were treated surgically in our Institution via interruption of the internal spermatic vein using Palomo's technique. Patients that reached the age of 18 after surgery have had a spermiogramm. The problem of varicocele therapy in pre-adolescence has not yet been resolved with regard to surgical therapy and follow-up.

In vitro spermatogenesis as a method to bypass pre-meiotic or post-meiotic barriers blocking the spermatogenetic process: genetic and epigenetic implications in assisted reproductive technology.

Pregnancies achieved by assisted reproduction technologies and particularly by ooplasmic injections of either in vivo or in vitro generated immature male germ cells are susceptible to genetic risks inherent to the male population treated with assisted reproduction and additional risks inherent to these innovative procedures. The documented, as well as the theoretical risks, are discussed in this review. These risks represent mainly the consequences of genetic abnormalities underlying male infertility and may become stimulators for the development of novel approaches and applications in the treatment of infertility. Recent data suggest that techniques employed for in vitro spermatogenesis, male somatic cell haploidization, stem cell differentiation in vitro and assisted reproductive technology may also affect the epigenetic characteristics of the male gamete, the female gamete, or may have an impact on early embryogenesis. They may be also associated with an increased risk for genomic imprinting abnormalities. Production of haploid male gametes in vitro may not allow the male gamete to undergo all the genetic and epigenetic alterations that the male gamete normally undergoes during in vivo spermatogenesis.

Efforts to create an artificial testis: culture systems of male germ cells under biochemical conditions resembling the seminiferous tubular biochemical environment.

Induction of meiotic and post-meiotic alterations of male germ cells in vitro has been the target of several research efforts since 1960. However, to date, the establishment of an ideal culture system in which spermatogonial stem cells can be maintained and directed to proliferate and undergo meiosis and complete spermiogenesis does not exist. This is attributed to the difficulties concerning the isolation and purification of defined subpopulations of germ cells and the establishment of male germ cell lines. In addition, there is no adequate knowledge regarding the optimal biochemical conditions that promote the survival and differentiation of germ cells in long-term cultures. This review focuses on the methodologies that have been proved sufficient to achieve differentiation of cultured male germ cells. Furthermore, the factors regulating spermatogenesis and the technical prerequisites to achieve differentiation of cultured male germ cells are described. Finally, the role of in vitro cultures of immature diploid germ cells in the therapeutic management of men negative for haploid cells in their testes and the subsequent potential genetic and epigenetic risks are discussed.

Is the risk of hypertension an indication for prophylactic nephrectomy in patients with unilateral multicystic dysplastic kidney?

OBJECTIVE: Surgery is still proposed by some as the treatment of choice for unilateral multicystic dysplastic kidney (UMCDK) because of the potential complications of hypertension, infection and malignant change. The purpose of this study is to demonstrate that the risk of hypertension does not justify routine nephrectomy. MATERIAL AND METHODS: We report 41 cases of UMCDK, treated between 1980 and 2001, 28 of whom were male (68%). Twenty-one patients were nephrectomized (51%). Twenty patients (49%) underwent clinical and ultrasound follow-up. Blood pressure was controlled every 3-4 months (over a period ranging from 9 months to 6 years) and an ultrasound scan was performed every 6 months during the first 2 years, and annually thereafter. RESULTS: In the patients treated non-operatively we observed a progressive spontaneous involution of their multicystic dysplastic kidneys and the total absence of complications such as hypertension or malignancy. CONCLUSION: It is reasonable to conservatively manage patients with UMCDK by means of repeated ultrasound examinations and blood pressure control.

Role of testicular tissue telomerase assay for the prediction of the presence of testicular spermatozoa in azoospermic men with varicoceles, pre- and post-varicocelectomy.

We evaluated the reproductive potential of frozen/thawed testicular spermatozoa of azoospermic men with left varicocele. The role of testicular tissue telomerase assay (TTA) in the prediction of the presence of testicular spermatozoa pre- and post-varicocelectomy was investigated, as well. Therapeutic testicular biopsy and TTA were performed in 82 nonobstructed azoospermic (NOA) men with varicoceles. Testicular spermatozoa were found in 33 men and processed for cryopreservation. Oocytes were later recovered from the spouses of the latter azoospermic men with varicoceles and injected with frozen/thawed testicular spermatozoa. Among the 49 men who were negative for testicular spermatozoa, 22 men underwent subsequently subinguinal microsurgical varicocelectomy. A total of 198 mature oocytes were successfully injected and 101 were normally fertilized and subsequently cleaved. Transfer of these 101 embryos in 26 women resulted in nine full-term pregnancies. Thirteen healthy babies were delivered. A cut-off value of TTA of 39 TPG U microg(-1) protein had an overall diagnostic accuracy equal to 90.2% to predict the presence of testicular spermatozoa pre-varicocelectomy. Within the group of men who were negative for testicular spermatozoa a cut-off value of TTA equal to 28 TPG U microg(-1) protein (pre-varicocelectomy) had a 84.2 % diagnostic accuracy to recognize the men who would become positive for either ejaculated or testicular spermatozoa post-varicocelectomy. Testicular spermatozoa can be found in 40% of NOA men with left varicocele. Ooplasmic injections with frozen/thawed testicular spermatozoa have a role in the therapeutic management of non-obstructive azoospermia associated with varicocele. Pre-varicocelectomy, a TTA cut-off value equal to 39 TPG U microg(-1) protein has a 90.2% diagnostic accuracy to indicate the men positive/negative for testicular spermatozoa. In addition, pre-varicocelectomy, a cut-off value equal to 28 TPG U microg(-1) protein has a 84.2% diagnostic accuracy to identify those men with varicoceles without testicular spermatozoa, who will become positive/negative for spermatozoa (either ejaculated or testicular) post-varicocelectomy.

Effects of paternal cigarette smoking on testicular function, sperm fertilizing capacity, embryonic development, and blastocyst capacity for implantation in rats.

We evaluated the effects of paternal smoking on testicular function, sperm fertilizing capacity, embryonic development, and blastocyst capacity for implantation. Rats of group A were exposed to cigarette smoke for 10 weeks. Rats of group B were exposed to the smoke of incense sticks for 10 weeks. Rats of group C served as a control group. Rats of group D were exposed to cigarette smoke for 7 weeks only. Experimental period was 10 weeks in all groups. At the end of the experimental period serum testosterone responses to human chorionic gonadotropin stimulation, androgen-binding protein activity in testicular cytosols, epididymal sperm motility, and oocyte fertilization rate, oocyte cleavage rate, and blastocyst development rate after in vitro fertilization (IVF) trials were significantly smaller in group A compared with groups B and C. In contrast, fertilization rate, cleavage rate, and blastocyst development rate after intracytoplasmic sperm injection (ICSI) procedures were not significantly different among groups A, B, C, and D. Both after IVF trials and ICSI techniques, the proportion of the alive offspring to the number of transferred oocytes was significantly smaller in group A than in groups B and C. Cigarette smoke-exposure results in a secretory deficiency of Leydig and Sertoli cells leading to an impaired epididymal sperm maturation process and diminished capacity of spermatozoa to penetrate oocytes. In addition paternal cigarette smoke exposure affects the embryonic ability for implantation.

Pre-decondensed sperm head injections into female pronuclei result in chromosomal mingling, zygotic cleavage, and adequate embryonic and fetal development up to delivery of healthy offspring: a novel method of assisted syngamy.

Investigation of the developmental potential post-injection of a pre-decondensed or non-pre-decondensed sperm head into the female pronucleus of a pre-activated oocyte. Rat pre-activated oocytes were treated with intrapronuclear pre-decondensed sperm head injections (IPSHI) (n = 133) or intrapronuclear non-pre-decondensed sperm head injections (INPSHI) (n = 138). All injected oocytes were transferred to pseudopregnant female recipients. Rat IPSHI techniques resulted in the delivery of five healthy offspring. Rat INPSHI techniques did not result in any pregnancies. Rat IPSHI techniques can result in delivery of healthy offspring. Successful performance of human IPSHI techniques might serve as a novel method to manage cases of intracytoplasmic sperm injection failure due to lack of development of male pronucleus or due to failure in pronuclei fusion.

The role of ultrasonographically guided puncture of the human rete testis in the therapeutic management of nonobstructive azoospermia.

We attempted to characterize the cells collected from the rete testis via ultrasonographically guided puncture. Unilateral puncture of the rete testis was performed in nine men with obstructive azoospermia and 51 men with nonobstructive azoospermia. All the aspirated samples from the rete testis were observed via confocal scanning laser microscope and some of them after fluorescent in situ hybridization techniques. Then therapeutic testicular biopsy was performed in the punctured testis of each man. Spermatozoa were found in all rete testis samples and all biopsy samples from obstructed men. Twenty-two nonobstructed men demonstrated absence of spermatozoa in biopsy samples. Twenty-nine nonobstructed men showed spermatozoa in biopsy material and 24 of these men (82%) had demonstrated spermatozoa in rete testis samples. There were no significant differences in fertilization and cleavage rate between intracytoplasmic sperm injection trials using biopsy spermatozoa and rete testis spermatozoa both in obstructed and nonobstructed men. Considering that puncture of the rete testis does not reduce the volume of testicular parenchyma, is less invasive and apparently causes less detrimental effect on testicular vasculature than biopsy, puncture of rete testis is recommended as first line approach for the treatment of azoospermic men. If puncture is negative for spermatozoa in nonobstructed men, biopsy is indicated.