Central role of ultrasound in the evaluation of testicular function and genital tract obstruction in infertile males.

BACKGROUND: Scrotal color Doppler ultrasonography and transrectal ultrasonography provide crucial information about the clinical status of testes and male accessory glands. OBJECTIVE: To analyze the impact of ultrasound in the evaluation of infertile males. MATERIALS AND METHODS: A total of 1120 records from infertile men were retrospectively evaluated (from January 2016 up to June 2020). Data on physical examination, semen analysis, sperm culture, scrotal color Doppler ultrasonography and transrectal ultrasonography, as well as sex hormones were analyzed. Among them, 238 reports from oligozoospermic/azoospermic infertile patients (P) fulfilling the inclusion criteria were considered for data analysis. Patients were subdivided into two groups according to follicle-stimulating hormone (FSH) values (Pa with FSH < 8 U/L and Pb with FSH ≥ 8 U/L). Sixty-three fertile volunteers (mean ± SD years) were enrolled as controls (C). RESULTS: A higher prevalence of ultrasound abnormalities was recorded in P compared to C. Pb group had significantly lower bitesticular volume compared to Pa and C. Pa had a higher prevalence of transrectal ultrasonography abnormalities than Pb (69.9% vs. 38.4%), whereas Pb had a higher prevalence of abnormalities at scrotal color Doppler ultrasonography (60.0% vs. 28.3%, both p < 0.01). Bitesticular volume was inversely proportional to the number of altered seminal parameters and able to predict gonadotropin levels. A bitesticular volume <17 cc was associated with a higher risk of azoospermia (odds ratio = 1.799). Intratesticular vascularization was inversely correlated with gonadotropin levels and directly correlated with sperm count. A higher prevalence of prostate and seminal vesicle alterations was detected in patients and in Pa group, when compared with Pb group. DISCUSSION AND CONCLUSION: Ultrasound abnormalities are correlated with seminal parameters and may guide the clinician in the diagnostic workflow of male infertility, suggesting spermatogenesis impairment or genital tract obstructions.

Efficacy of penile low-intensity shockwave treatment for erectile dysfunction: correlation with the severity of cavernous artery disease.

We analyzed the efficacy of penile low-intensity extracorporeal shockwave treatment for erectile dysfunction (ED) combined with cavernous artery disease (CAD). ED was evaluated by the International Index of Erectile Function, subdividing patients into mild and moderate/severe forms. CAD was assessed using penile color Doppler ultrasonography. Patients (n = 111) with a positive outcome after treatment, based upon the minimal clinically important difference of the International Index of ED, were followed up for 3 months and 6 months. We found a significant mean increase in the index of erectile function, with an overall improvement in hemodynamic parameters of the cavernous artery. In particular, 93.9% of the patients with mild ED without CAD responded to treatment and 72.7% resumed normal erectile function. Only 31.2% of the patients with moderate/severe ED and CAD responded to treatment, and none resumed normal erectile function. All patients with mild ED and no CAD maintained the effects of therapy after 3 months, while no patients with moderate/severe ED and CAD maintained the benefits of treatment after 3 months. Thus, patients with mild ED and no CAD have better and longer lasting responses to such treatment, with a higher probability of resuming normal erectile function than patients with moderate/severe ED and CAD.

Sperm Count and Hypogonadism as Markers of General Male Health.

BACKGROUND: Some evidence suggests that infertile men, who are at increased risk for hypogonadism, metabolic derangements, and osteoporosis, have higher long-term morbidity and mortality than controls, but data are scarce and not conclusive. OBJECTIVE: We tested whether semen quality and reproductive function could represent a marker of general male health. DESIGN, SETTING, AND PARTICIPANTS: A retrospective study of 5177 individuals from a prospectively collected database of 11516 males of infertile couples who had semen analysis in a tertiary university center. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Of them, 5177 had all data for reproductive hormones, testis ultrasound, and biochemical determinations for glucose and lipid metabolism. Hypogonadism was defined as testosterone <10.5nmol/l and/or luteinizing hormone >9.4 IU/l. Individuals with a total sperm count of <10 million had genetic testing (karyotype, Y chromosome microdeletions, and CFTR gene mutations) and those with hypogonadism underwent dual-energy x-ray absorptiometry for bone mineral density. Descriptive statistics and odds ratio (OR) calculation were used. RESULTS AND LIMITATIONS: Men with a low sperm count (<39 million/ejaculate) are at a high risk of hypogonadism (OR 12.2, 95% confidence interval [CI] 10.2-14.6) and have higher body mass index, waist circumference, systolic pressure, low-density lipoprotein cholesterol, triglycerides, and homeostatic model assessment (HOMA) index; lower high-density lipoprotein cholesterol; and a higher prevalence of metabolic syndrome (OR 1.246, 95 CI 1.005-1.545). All data are worse in men with hypogonadism, but a low sperm count per se is associated with a poor metabolic parameter. Men with hypogonadism have lower bone mineral density and 51% prevalence of osteoporosis/osteopenia. Longitudinal studies are necessary to support these data. CONCLUSIONS: This is the largest study with comprehensive evaluation of semen quality and reproductive function, etiology and risk factor determination, and metabolic, cardiovascular, and osteoporosis risk assessment, performed in men referred for fertility evaluation. A low sperm count is associated with poorer metabolic, cardiovascular, and bone health. Hypogonadism is mainly involved in this association, but a low sperm count in itself is a marker of general health. PATIENT SUMMARY: This large study evaluated semen quality, reproductive function, and metabolic risk in men referred for fertility evaluation, and showed that a man's semen count is a marker of his general health. Men with low sperm counts are more likely than those with normal sperm counts to have greater body fat, higher blood pressure, higher "bad" (low-density lipoprotein) cholesterol and triglycerides, and lower "good" (high-density lipoprotein) cholesterol. They also have a higher frequency of metabolic syndrome and insulin resistance, a condition that can lead to diabetes. Men with low sperm counts had a 12-fold increased risk of hypogonadism or low testosterone levels, and half of them had osteoporosis or low bone mass. Fertility evaluation gives men the unique opportunity for health assessment and disease prevention.

Increased risk of testis failure in testicular germ cell tumor survivors undergoing radiotherapy.

Testicular germ cell tumors (TGCTs) are prevalent in males of reproductive age. Among the available therapeutic choices, pelvic radiotherapy (RT) and simple surveillance (SURV) are usually pursued. However, RT is considered to have life-threatening effects on testicular functions. In this study we sought to clarify this issue by evaluating sperm parameters and sex hormones in 131 TGCTs RT-treated-patients at both baseline (T0) and 12 (T1) and 24 months (T2) of follow-up. An age-matched group of 61 SURV patients served as control. Sperm parameters were comparable between SURV and RT at T0. The RT group showed a significant reduction of all sperm parameters at T1 (all P values < 0.05 vs T0 and vs SURV at T1) and increased levels of sperm aneuploidies, with some degree of recovery at T2. On the other hand, despite normal levels of total testosterone being detected in both groups, luteinizing hormone (LH) levels in the RT group progressively increased at T1 and T2 with a relative risk of developing subclinical hypogonadism of 3.03 (95% CI: 1,50-6,11) compared to SURV. Again, compared to SURV, exposure to RT was associated with a 5.78 fold (95% CI: 2,91-11,48) risk of developing vitamin D insufficiency. These data suggest a likely RT-dependent impairment of the Leydig cell compartment.

Impact of Bep or Carboplatin Chemotherapy on Testicular Function and Sperm Nucleus of Subjects with Testicular Germ Cell Tumor.

Young males have testicular germ cells tumors (TGCT) as the most common malignancy and its incidence is increasing in several countries. Besides unilateral orchiectomy (UO), the treatment of TGCT may include surveillance, radiotherapy, or chemotherapy (CT), basing on tumor histology and stage of disease. It is well known that both radio and CT may have negative effects on testicular function, affecting spermatogenesis, and sex hormones. Many reports investigated these aspects in patients treated with bleomycin, etoposide, and cisplatin (BEP), after UO. In contrast no data are available on the side effects of carboplatin treatment in these patients. We included in this study 212 consecutive subjects who undergone to sperm banking at our Andrology and Human Reproduction Unit after UO for TGCT. Hundred subjects were further treated with one or more BEP cycles (BEP-group), 54 with carboplatin (CARB group), and 58 were just surveilled (S-group). All patients were evaluated for seminal parameters, sperm aneuploidy, sperm DNA, sex hormones, volume of the residual testis at baseline (T0) and after 12 (T1) and 24 months (T2) from UO or end of CT. Seminal parameters, sperm aneuploidies, DNA status, gonadic hormones, and testicular volume at baseline were not different between groups. At T1, we observed a significant reduction of sperm concentration and sperm count in the BEP group versus baseline and versus both Carb and S-group. A significant increase of sperm aneuploidies was present at T1 in the BEP group. Similarly, the same group at 1 had altered sperm DNA integrity and fragmentation compared with baseline, S-group and Carb group. These alterations were persistent after 2 years from the end of BEP treatment. Despite a slight improvement at T2, the BEP group had still higher percentages of sperm aneuploidies than other groups. No impairment of sperm aneuploidies and DNA status were observed in the Carb group both after 1 and 2 years from the end of treatment. Despite preliminary, these data demonstrate that in selected patients with TGCTs CT with carboplatin represents a therapeutic option that that seems to not affect sex hormones, spermatogenesis, and sperm nucleus.

Metabolic syndrome and erectile dysfunction: the ultrasound evaluation of cavernosal atherosclerosis.

OBJECTIVE: To study the relation between metabolic syndrome (MS), cavernosal morphological vasculopathy, and peripheral vascular alterations (carotid and femoral wall) in patients with erectile dysfunction. RESEARCH DESIGN AND METHODS: A total of 207 patients and 50 control subjects were evaluated for cardiovascular risk factors, physical examination, reproductive hormones, ultrasound analysis of cavernosal, carotid and femoral arteries (intima-media thickness), and cavernosal flow measurement (peak systolic velocity). RESULTS: A total of 28% of patients had MS, and they presented with a high prevalence of cavernosal alterations (70.3%) and systemic vascular impairment (59.3%), whereas patients with cavernosal alterations (44%) showed the higher prevalence of MS (48.9%). The number of MS components was related to the prevalence of penile vasculopathy. However, multivariate analysis showed that MS is not an independent predictor for cavernosal vasculopathy. CONCLUSIONS: Patients with cavernosal vasculopathy have an increased cardiometabolic risk, and screening for MS components might identify individuals with a higher risk for cavernosal and systemic atherosclerosis.

Testicular contrast harmonic imaging to evaluate intratesticular perfusion alterations in patients with varicocele.

PURPOSE: To determine whether changes in intratesticular microcirculation perfusion affect spermatogenesis in patients with left varicocele we performed testicular contrast harmonic imaging. MATERIALS AND METHODS: A total of 90 patients with left varicocele (oligospermia in 50 and normozoospermia in 40) and 36 controls without varicocele (oligospermia in 16 and normozoospermia in 20) were enrolled in the study. Before contrast harmonic imaging all participants were evaluated by clinical examination, hormonal analysis, semen sample and scrotal ultrasound. We calculated contrast material arrival time in the arteriolar circulation (wash-in), time to peak in arterial circulation, arrival time in the venular circulation (washout) and mean transit time in each testis on contrast harmonic imaging. RESULTS: We found no difference in the distribution rate of varicocele grade in patients with vs without oligospermia. All contrast harmonic imaging parameters were significantly higher in patients with varicocele plus normozoospermia or oligospermia and controls. We found no significant differences in contrast harmonic imaging parameters in patients with lower varicocele grading with respect to the higher grades. In patients with varicocele we found a negative linear correlation between total sperm count and left mean transit time (r = -0.29). In a multivariate model left mean transit time was the only independent predicting parameter of oligospermia (p <0.05). Mean transit time greater than 36 seconds predicted oligospermia in patients with left varicocele with 78% sensitivity and 58% specificity. CONCLUSIONS: To our knowledge we report for the first time that testicular contrast harmonic imaging may be a new diagnostic tool able to improve our knowledge about the influence of varicocele on intratesticular microcirculation.

The ENDOTRIAL study: a spontaneous, open-label, randomized, multicenter, crossover study on the efficacy of sildenafil, tadalafil, and vardenafil in the treatment of erectile dysfunction.

INTRODUCTION: The three effective, commercially available drugs for the treatment of erectile dysfunction-sildenafil, vardenafil, and tadalafil-inhibit the same substrate, the erectolytic enzyme phosphodiesterase type 5 (PDE5). Although there are pharmacological differences between these three compounds, few comparative studies have been conducted to date. AIM: The aim of this study was to determine the efficacy of sildenafil, tadalafil, and vardenafil in a randomly assigned 8-week fixed regimen. METHODS: This was a spontaneous, open-label, randomized, multicenter, crossover study where the patients were randomized to receive sildenafil 50 mg, sildenafil 100 mg, tadalafil 20 mg, or vardenafil 20 mg. MAIN OUTCOME MEASURES: The primary outcome included the posttreatment analysis of erectile function domains of the abridged International Index of Erectile Function (IIEF5+1). The secondary objectives included the analysis of peak-systolic velocities (PSVs), end-diastolic velocities (EDVs), and resistive index (RI), and the estimate of the percentage of men with normal penile hemodynamic parameters after each treatment. RESULTS: In all groups of patients taking sildenafil 50 mg, sildenafil 100 mg, tadalafil 20 mg, and vardenafil 20 mg at a frequency reflecting the common treatment regimens in real life, there was a statistically significant baseline-to-end point improvement in subjective perception of erectile function measured by IIEF5+1. When the four groups were compared, the treatments were not different in modifying IIEF5+1 and penile flow parameters. However, the within-group analysis showed that PSV improved in the sildenafil 50 mg group and that PSV together with RI significantly ameliorated in patients receiving 100 mg of sildenafil. Regression analysis confirmed an independent effect of sildenafil on hemodynamic efficacy parameters. CONCLUSIONS: An overall equivalence was demonstrated in the subjective perception of treatment benefits for all the PDE5i tested. However, sildenafil, in a dose-dependent manner, was the unique PDE5i able to ameliorate some of the penile flow parameters within the 8-week treatment period. These findings should be interpreted conservatively because of the observational nature of the study.

Cavernous artery intima-media thickness: a new parameter in the diagnosis of vascular erectile dysfunction.

INTRODUCTION: A precise characterization of erectile dysfunction (ED) of vascular origin has not yet been achieved. Although cavernous peak systolic velocity (PSV) is generally considered a major parameter, it has many false positives and negatives because of anatomic variations of the cavernous artery course, challenging site of sampling, insufficient caracterization of an early phase of vascular disease, and significant influence of adrenergic tone. AIM: We performed a high magnification ultrasonographic study in order to compare functional and morphological parameters of the cavernous artery to PSV and their relation with penile and systemic atherosclerosis. METHODS: A total of 109 subjects (84 ED patients and 25 controls) evaluated in our andrological center from March 2007 to January 2008 were enrolled in the study. MAIN OUTCOME MEASURES: All subjects underwent medical history, erectile function domain of the International Index of Erectile Function, physical examination, routine and sex hormone blood tests, and high resolution echo color doppler evaluation of carotid, femoral and penile districts (acceleration time, intima media thickness [IMT], intima adventitia thickness, caliper before and after intracavernous alprostadil injection [Delta-cavernous calliper]). RESULTS: Cavernous parameters were significantly different between ED and controls. Multivariate model showed that IMT was the only predicting parameter for ED of vascular origin. Cavernous IMT showed a strong direct correlation with carotid and femoral IMT. ED patients with two or more cardiovascular risk factors had a significantly higher cavernous IMT. CONCLUSIONS: An increased cavernous IMT (>or=0.3 mm) might predict ED of vascular origin with more accuracy than PSV and could be a sensitive predictor also for systemic atherosclerosis at an earlier phase.

Asymmetric development of peripheral atherosclerosis in patients with erectile dysfunction: an ultrasonographic study.

Recent literature focused on erectile dysfunction (ED) as a reliable predictive parameter of cardiovascular diseases. ED patients have a higher prevalence of atherosclerotic lesions (increased intima-media thickness and plaques) at carotid site, but data on femoral site are still lacking. Nevertheless, there is accumulating evidence concerning a significant involvement of femoral atherosclerosis in other clinical conditions associated to ED, such as diabetes mellitus and coronary disease. Therefore, we investigated the prevalence of carotid and femoral atherosclerotic lesions and penile peak systolic velocity (PSV) in 238 ED patients by Eco-Colour Doppler ultrasonography (US). We found - irrespective of the presence of cardiovascular risk factors - a significant increase of atherosclerotic lesions in ED group with respect to 52 controls (66.4% versus 36.5%) and a higher prevalence of atherosclerosis at the femoral site (23.1% versus 5.7%), also with respect to the carotid site (8%). Moreover, PSV was significantly lower in ED patients with atherosclerosis compared to those without atherosclerotic lesions (41.9+/-15.3 cm/s versus 55.2+/-17.7 cm/s), and it was particularly low in those with combined carotid and femoral atherosclerosis (34.8+/-13.3 cm/s) and those with isolated carotid atherosclerosis (37.9+/-13.0 cm/s). These data confirm the strong relation between atherosclerosis and ED, an asymmetric development of atherosclerotic lesions in ED patients and suggest to perform an US study of both femoral and carotid district in these subjects.

Fine-needle and large-needle percutaneous aspiration biopsy of testicles in men with nonobstructive azoospermia: safety and diagnostic performance.

OBJECTIVE: To assess by ultrasonography the safety of the association fine-needle aspiration (FNA) plus a new percutaneous large-needle aspiration biopsy technique (LNAB), and to compare the results obtained with the two techniques in the same testicle and with FNA in the two testicles of the same patient. DESIGN: Retrospective analysis of clinical, ultrasonographic, and pathologic data. SETTING: Clinical and academic research environment. PATIENT(S): Three hundred and eighty-seven testicles of 233 patients (ages 19 to 57 years) with nonobstructive azoospermia were consecutively examined with FNA (154) or FNA + LNAB (233); 54 patients (89 testicles) examined with FNA + LNAB underwent a second ultrasonography up to 63 days after. INTERVENTION(S): Ultrasonography, FNA, LNAB. MAIN OUTCOME MEASURE(S): Hypoechoic area at ultrasonography; cytologic picture at FNA or LNAB of only Sertoli cells (category 1), spermatogenetic cells different from elongated spermatids or spermatozoa (category 2), and elongated spermatids and/or spermatozoa (category 3). RESULT(S): Among the 54 patients monitored by ultrasonography 48 (88.9%) showed no difference and 6 (11.1%) showed an hypoechoic area < or =1 cm in the second image. Category 1 occurred at FNA or LNAB in a very similar number of testicles (36% vs. 36.9%). Categories 2 and 3 were more frequent at LNAB (29.9% vs. 9.8%) and at FNA (54.2% vs. 33.2%), respectively. One hundred and sixty-six patients had both testicles examined by FNA; 147 pair of testicles were concordant for the presence or the absence of spermatozoa or elongated spermatids. In the remaining 19 patients (11.4%), these spermatogenetic cells were shown only in the specimen from one of the two testicles. These 19 patients accounted for 20.0% of 93 patients with spermatogenetic cells in at least one of the two testicles. CONCLUSION(S): The combination of FNA and LNAB did not produce clinically or subclinically relevant complications. No important differences in the identification of category 1 with FNA or LNAB were found. Fine-needle aspiration was more adequate in identifying category 3, which was particularly relevant in 20% of the men who had these cells in at least one of the two testicles.