Non-invasive biomarkers for sperm retrieval in non-obstructive patients: a comprehensive review.

Recent advancements in reproductive medicine have guided novel strategies for addressing male infertility, particularly in cases of non-obstructive azoospermia (NOA). Two prominent invasive interventions, namely testicular sperm extraction (TESE) and microdissection TESE (micro-TESE), have emerged as key techniques to retrieve gametes for assisted reproduction technologies (ART). Both heterogeneity and complexity of NOA pose a multifaceted challenge to clinicians, as the invasiveness of these procedures and their unpredictable success underscore the need for more precise guidance. Seminal plasma can be aptly regarded as a liquid biopsy of the male reproductive tract, encompassing secretions from the testes, epididymides, seminal vesicles, bulbourethral glands, and prostate. This fluid harbors a variety of cell-free nucleic acids, microvesicles, proteins, and metabolites intricately linked to gonadal activity. However, despite numerous investigations exploring potential biomarkers from seminal fluid, their widespread inclusion into the clinical practice remains limited. This could be partially due to the complex interplay of diverse clinical and genetic factors inherent to NOA that likely contributes to the absence of definitive biomarkers for residual spermatogenesis. It is conceivable that the integration of clinical data with biomarkers could increase the potential in predicting surgical procedure outcomes and their choice in NOA cases. This comprehensive review addresses the challenge of sperm retrieval in NOA through non-invasive biomarkers. Moreover, we delve into promising perspectives, elucidating innovative approaches grounded in multi-omics methodologies, including genomics, transcriptomics and proteomics. These cutting-edge techniques, combined with the clinical and genetics features of patients, could improve the use of biomarkers in personalized medical approaches, patient counseling, and the decision-making continuum. Finally, Artificial intelligence (AI) holds significant potential in the realm of combining biomarkers and clinical data, also in the context of identifying non-invasive biomarkers for sperm retrieval.

A complete dissection of the whole testicular parenchyma is required in most patients with nonobstructive azoospermia to obtain enough good quality testicular spermatozoa for ICSI.

BACKGROUND: Due to the heterogeneous distribution of seminiferous tubules (STs) in patients with nonobstructive azoospermia (NOA), retrieving enough good quality spermatozoa for ICSI may require a complete testicular dissection. According to the only available study in this field, spermatozoa may be found in the testis surface in 34.2% of patients, while a deeper testicular dissection is able to provide spermatozoa for ICSI in 28% of those without spermatozoa in the testis surface. OBJECTIVES: To determine the probability of finding enough spermatozoa for ICSI at the initial wide incision of the testis in a cohort of men with NOA undergoing microdissection testicular spermatozoa extraction (mTESE). MATERIALS AND METHODS: We evaluated 276 patients, aged 37 (20-62) years, who underwent unilateral (86, 31.15%) or bilateral (190, 68.8%) mTESE from January 2018 through December 2021. During mTESE, the entire surface of the testicular parenchyma was explored first in search for dilated STs: if no/ not enough spermatozoa were retrieved, the deeper portion of the parenchyma was explored. RESULTS: Spermatozoa were retrieved in 137 patients (49.6%). Histopathology demonstrated Sertoli-cell only syndrome in 65.6% of operated testes, while maturation arrest was found in 19.5%, hypospermatogenesis (HS) in 12.7%, and hyalinosis in 2%. Spermatozoa were obtained from the testis surface in 46 of 276 patients (16.6%), and after a complete dissection in 91 subjects (32.9%). On multivariate logistic regression, only the histopathological subcategory HS was predictive of the chance of retrieving spermatozoa from the surface of the testis (OR 3.24, 95% CI 1.37-7.69, p = 0.007). DISCUSSION: Most patients with NOA, particularly those with unfavorable histopathological patterns, require a complete dissection of the testicular parenchyma to obtain enough good quality for ICSI. CONCLUSIONS: By enabling the complete exploration of the testicular parenchyma, mTESE is to be preferred to cTESE to retrieve spermatozoa in patients with NOA.

Prediction Models for Successful Sperm Retrieval in Patients with Non-Obstructive Azoospermia Undergoing Microdissection Testicular Sperm Extraction: Is There Any Room for Further Studies?

Several prediction models for successful sperm retrieval (SSR) in patients with azoospermia due to spermatogenic dysfunction (also termed non-obstructive azoospermia-NOA) have been developed and published in the past years, however their resulting prediction accuracy has never been strong enough to translate their results in the clinical practice. This notwithstanding, the number of prediction models being proposed in this field is growing. We have reviewed the available evidence and found that, although patients with complete AZFc deletion or a history of cryptorchidism may have better probability of SSR compared to those with idiopathic NOA, no clinical or laboratory marker is able to determine whether a patient with NOA should or should not undergo microdissection testicular sperm extraction (mTESE) to have his testicular sperm retrieved. Further research is warranted to confirm the utility of evaluating the expression of noncoding RNAs in the seminal plasma, to individuate patients with NOA with higher probability of SSR.

Levels of uric acid in erectile dysfunction of different aetiology.

Erectile dysfunction is a common disease characterized by endothelial dysfunction. The aetiology of ED is often multifactorial but evidence is being accumulated in favor of the proper function of the vascular endothelium that is essential to achieving and maintaining penile erection. Uric acid itself causes endothelial dysfunction via decreased nitric oxide production. This study aims to evaluate the serum uric acid (SUA) levels in 180 ED patients, diagnosed with the International Index of Erectile Function-5 (IIEF-5) and 30 non-ED control. Serum uric acid was analyzed with a commercially available kit using ModularEVO (Roche, Monza, Italy). Within-assay and between-assay variations were 3.0% and 6.0%, respectively. Out of the ED patients, 85 were classified as arteriogenic (A-ED) and 95 as non-arteriogenic (NA-ED) with penile-echo-color-Doppler. Uric acid levels (median and range in mg/dL) in A-ED patients (5.8, 4.3-7.5) were significantly higher (p < .001) than in NA-ED patients (4.4, 2.6-5.9) and in control group (4.6, 3.1-7.2). There was a significant difference (p < .001) between uric acid levels in patients with mild A-ED (IIEF-5 16-20) and severe/complete A-ED (IIEF-5 ≤ 10) that were 5.4 (range 4.3-6.5) mg/dL and 6.8 (range 6.4-7.2) mg/dL, respectively. There was no difference between the levels of uric acid in patients with different degree of NA-ED. Our findings reveal that SUA is a marker of ED but only of ED of arteriogenic aetiology.

Evaluation of high sensitive troponin in erectile dysfunction.

BACKGROUND: Evidence is accumulating in favour of a link between erectile dysfunction (ED) and coronary artery diseases. We investigated the presence of cardiac injury in patients who have had arteriogenic and nonarteriogenic ED using the hs-Tn levels. METHODS: The diagnosis of ED was based on the International Index of Erectile Function 5-questionnaire (IIF-5) and patients were classified as arteriogenic (A-ED, n = 40), nonarteriogenic (NA-ED, n = 48), and borderline (BL-ED, n = 32) patients in relation to the results of echo-color-Doppler examination of cavernous arteries. The level of hs-TnT and hs-TnI was measured in 120 men with a history of ED of less than one year with no clinical evidence of cardiac ischemic disease. RESULTS: The levels of both hs-TnT and hs-TnI were within the reference range and there was no significant (P > 0.05) difference between patients of the three groups. The hs-CRP values were higher in A-ED men compared with NA-ED (P = 0.048) but not compared with BL-ED (P = 0.136) and negatively correlated with IIF-5 (r = -0.480; P = 0.031). CONCLUSIONS: In ED patients of the three groups the measurement of hs-Tn allows us to exclude the presence of cardiac involvement at least when the history of ED is less than one year and the men are without atherosclerotic risk factors.

Peyronie's disease: a "triple oxygenant therapy".

OBJECTIVES: To evaluate the effects of upregulators of nitric oxide in one patient with Peyronie's disease, after non significant improvement following intracavernosal verapamil. METHODS: A 20-years-old Caucasian male presented with penile induration in flaccid state, persistent during erection and associated with mild pain at third middle of penis. After treatment with intracavernosal verapamil for 4 months with relief of penile discomfort, followed by counseling on the use of penile extender for at least 6 hours per day, he was prescribed pentoxifylline associated with tadalafil plus levo-arginine, propionil-carnitine and Vitamin B3. RESULTS: After almost 2 years, the septal thickness was reduced at ultrasound evaluation after this “triple oxygenant therapy”. CONCLUSION: NO-iNOS biology in Peyronie patients is the very protagonist in modulating penile fibrosis through up-regulation of NO-cGMP pathway that influences penile health by preventing and reversing fibrosis in the tunical albuginea.

Surgical subinguinal approach to varicocele combined with antegrade intraoperative sclerosis of venous vessels.

Varicocele is treated by different surgical techniques, none of which is yet acknowledged as the "gold standard." Some of these techniques, especially microsurgical techniques, are very time consuming and thus expensive, and the treatment of varicocele still causes some complications and recurrences. Marmar and Kim's technique presents some indisputable advantages: it allows the preservation of the arteries and seems to offer the highest percentage of success and lowest number of complications. The authors modified and simplified the microsurgical technique of Marmar and Kim, using a subinguinal approach with intraoperative antegrade sclerotherapy of dilated veins. After the cord has been clamped, 1.5 to 3 mL of 3% aetoxisclerol mixed with 0.5 mL of air is injected. Commonly, minor complications can occur. The most common complication is transient penile lymphangitis, the cause of which is unclear. As the procedure allows selective sparing of the lymphatic vessels, it avoids hydrocele due to the performed procedure.

Erectile dysfunction and amatorial cycling.

Today cycling is considered a useful form of exercise for reducing cardiovascular risk, but it may also represent a risk factor for erectile dysfunction and perineal-genital paresthesia. These disorders are attributed to the local reduction of oxygen in the perineal-genital area, secondary to the perineal compression. Numerous studies have been carried out measuring the penile oxygen pressure or penile blood flow by echo-colour-Doppler: a reduced inflow of blood and oxygen to the cavernous tissue was demonstrated. The attention of the specialist is therefore concentrated on the compression of the perineum on the bicycle saddle and how to reduce this through the position of the cyclist on the bicycle (i.e. height and tilt of the saddle), the different shapes of saddle available (i.e. noseless, grooved, wide, etc.) and the padding materials of the saddle. In order to reduce perineal compression, the posterior part of the saddle should be as wide as the distance between the two ischiatic tuberosities. In addition, the saddle should be studied on the basis of the biotype of the cyclist: ectomorphic, mesomorphic or endomorphic. However, in the genesis of the erectile dysfunction of the cyclist, apart from the above-mentioned factors, an "individual predisposition to developing erectile dysfunction" linked to the perineal-genital anatomy (i.e. type of insertion of the perineum into the root of the penis, number of layers of the tunica albuginea of the corpus cavernosum) cannot be excluded.

Conservative surgical therapy for leydig cell tumor.

PURPOSE: We performed a long-term evaluation of conservative surgical treatment of benign Leydig cell tumor. MATERIALS AND METHODS: A multicenter retrospective clinical study was performed at 6 European centers. Case files of all patients diagnosed with Leydig cell tumor and treated with conservative surgery were examined. Patients underwent physical examination, hormone and tumor marker assays, scrotal and abdominal ultrasound, chest x-ray, and an endocrinological examination. RESULTS: From 1987 to 2006, 22 patients with Leydig cell tumor underwent conservative surgery. Mean patient age was 35 years (range 5 to 61). Mean followup was 47 months (range 1 to 230). No local recurrence or metastasis was observed. Patients presented with a palpable testicular nodule (3 patients, 13.7%) or a nodule diagnosed by ultrasound (15 patients, 68.2%), gynecomastia (2 patients, 9.1%), precocious pseudopuberty (1 patient, 4.5%) or scrotal pain (1 patient, 4.5%). Three patients were monorchid after contralateral orchiectomy for inguinal hernia repair (1 patient, 28 years before surgery) and nonseminomatous germ cell tumor (2 patients, 1 month and 6 years before surgery). Diagnosis after frozen section examination was Leydig cell tumor in 20 of 22 cases (91.0%). Mean histological size of the nodule was 1.11 cm (range 0.5 to 2.5). Preoperative FSH and LH levels were high in 4 patients. Tumor markers were normal before and after surgery. Followup was conducted for all patients every 3 to 6 months with physical examination, tumor markers, scrotal and abdominal ultrasound, chest x-ray. Six patients (27.3%) underwent abdominal computerized tomography. CONCLUSIONS: When diagnosed early Leydig cell tumors present a favorable followup. In select cases with motivated patients, conservative surgery proved to be a feasible and safe choice.

Testicular sperm extraction in cancerous testicle in patients with azoospermia: a case report.

The aim of this study is to evaluate the feasibility of testicular sperm extraction (TESE) in a cancerous testicle during orchiectomy for testicular neoplasm. This is a retrospective study and includes case histories of four azoospermic patients with incidental testicular cancer. None of the patients had fathered children prior to surgery and all patients were strongly motivated by the desire to have offspring. Patients underwent surgical exploration via inguinotomy and spermatic cord clamping. After nodule excision, micro-TESE was performed from the same albugineal incision, under microscopic guidance. Frozen section examination was not performed in the case of large nodules (>3 cm in diameter). Two patients showed classic seminoma and underwent orchiectomy. In two patients, a Leydig cell tumour was found (one patient underwent orchiectomy for large nodule size). Micro-TESE was performed in four patients. Spermatozoa were found in three patients and the retrieved sperm was cryopreserved. One ICSI cycle was performed, but pregnancy failed. In azoospermic patients with testicular nodules, TESE in the cancerous testis is feasible and may avoid further surgery, without any oncological risk.

Long-term followup and clinical characteristics of testicular Leydig cell tumor: experience with 24 cases.

PURPOSE: The natural history of Leydig cell testicular tumors is not well known, and differentiation between malignant and benign forms is not easy. We performed a retrospective multicenter evaluation of clinical and histological characteristics as well as followup of Leydig cell tumors. MATERIALS AND METHODS: From 1990 to August 2004 surgery was performed on 24 Leydig cell tumors. Before surgery all patients underwent clinical examination, tumor markers (alpha-fetoprotein, beta-human chorionic gonadotropin, lactate dehydrogenase), scrotal ultrasound and chest x-ray. Surgery was performed under ultrasound or palpation guidance via inguinotomy with clamping of the spermatic cord. Lesions less than 3 cm in diameter were resected and sent for frozen section examination. Histological criteria were considered. Abdominal computerized tomography or ultrasound and chest x-ray were performed postoperatively every 3 months for the first 2 years and every 6 months thereafter. RESULTS: Patient age range was 22 to 61 years (mean 37.75). In 7 patients (29.2%) the lesion was palpable and incidental diagnosis was made in 10 patients (41.7%). In the other patients diagnosis was made by ultrasound performed for testicular pain (4 patients, 16.6%) or the appearance of gynecomastia (3 patients, 12.5%). Frozen section examination was done in 20 of 24 patients (83%). In 17 of 20 patients (85%) Leydig cell tumor was diagnosed on frozen section examination. All patients underwent radical orchiectomy. All definitive diagnoses interpreted the neoplasia as benign. Average followup was 117 months (range 11 to 241). There was no disease recurrence or progression and all patients are currently disease-free. CONCLUSIONS: In our case study all Leydig cell tumors were interpreted as benign and long-term followup was negative.

Surgical treatment of varicocele by a subinguinal approach combined with antegrade intraoperative sclerotherapy of venous vessels.

OBJECTIVE: To evaluate the efficacy, in terms of recurrences, complications and operative duration, of a new technique for treating varicocele. PATIENTS AND METHODS: Between September 1999 and December 2002 we evaluated 307 men aged 17-51 years with varicocele. In all of the men the clinical diagnosis was confirmed by ultrasonography. The men were treated by a variant of the microsurgical technique described in 1994. A 2-3 cm distal subinguinal incision was made at the level of the superficial inguinal ring and the spermatic cord was exposed. The largest vein in the spermatic cord fat was cannulated. A 7-9 cm segment of the spermatic cord was clamped for 8-10 min; at the start of the ischaemia time, 1.5-3 mL of 3% atoxysclerol was injected into the cannulated vein. After sclerotherapy, the vein was ligated at the injection site, and the blood flow to the cord was restored. RESULTS: The mean operative duration was 25 min. Follow-up at 3 and 6 months after surgery, with objective examination and scrotal ultrasonography, revealed one case of clinical recurrence/persistence. The most common complication was penile lymphangitis (nine men) that regressed spontaneously; three men had temporary orchialgia. There were no cases of secondary hydrocele or testicular atrophy. CONCLUSIONS: The modified technique appears to be relatively easy and safe, and to of low cost. Given the promising results in terms of complications and persistence, the treatment appears to be a suitable first-line approach for the surgical treatment of varicocele.

Vas deferens endoscopy (vasoscopy): a new diagnostic tool?

PURPOSE: To assess whether an experimental endoscopic study of the vasa deferentia is feasible. PATIENTS AND METHODS: Endoscopic study of the seminal tracts was carried out during three vasectomies performed prior to open prostatectomy. A flexible endoscope, 0.56 mm in diameter, with a depth of field of 5 mm and a 3000 fiberoptic light source was used for the procedure. RESULTS: Endoscopy was possible for the inguinoscrotal segment of the vas deferens. The curvature at the opening of the internal inguinal ring proved impassable. CONCLUSIONS: Endoscopy of the vas deferens is possible with a 0.56-mm flexible endoscope, but because of the extreme curvature of the vas at the inguinal ring, the complete vas cannot be evaluated in an antegrade manner.

Prognostic parameters in adult impalpable ultrasonographic lesions of the testicle.

PURPOSE: Through an analysis of individual published data we assessed whether prognostic criteria exist for adult impalpable testicular sonographic lesions. MATERIALS AND METHODS: We performed a bibliographic search on PubMed, MEDLINE, EMBASE online databases from 1990 to May 2004 using search words such as sonographic lesions of the testicle, impalpable tumors of the testicle and impalpable testicular lesions. Six articles were found that presented a description of the histological characteristics, patient age, lesion dimensions, presence of cryptorchidism and association with tumors in other parts of the body. A multivariate analysis was performed comparing the characteristics that appeared more interesting from a univariate analysis. RESULTS: The characteristics of the 48 impalpable sonographic lesions were examined. Histologically 15 of the lesions were Leydig cell tumors (31%), 12 (25%) seminomas, 7 (14.5%) nonseminomatous germ cell tumors, 2 (4.5%) Sertoli cell tumors, 12 (25%) benign forms (fibrosis, infarct, lipoma, mesothelial hyperplasia, adenomatoid tumor). The average age was 37.5, average dimension was 10.11 mm. The lesions were hypoechoic in 85% of the cases. Of the patients 31% were infertile. Multivariate analysis showed that histological data were correlated with lesion dimensions and presence of infertility. Dimension was particularly related to germ cell tumors (for dimensions between 16 and 32 mm relative risk ratio [RRR] = 13.97, p=0.0449). Infertility proved significant in defining stromal tumors (RRR = 9,681, p=0.022) CONCLUSIONS: Although with the limits of a retrospective study consisting in an analysis of individual data, interesting correlations between malignant pathologies and the initial characteristics of impalpable sonographic lesions were revealed. In particular an interesting correlation was found between the dimensions of the lesion and the malignant pathology and between Leydig cell tumor and infertility.

Testicular-sparing microsurgery for suspected testicular masses.

OBJECTIVE: To describe a microsurgical technique for removing suspected testicular masses with sparing of the testicular parenchyma, and to describe case studies. PATIENTS AND METHODS: Six men were referred with testicular lesions (3-6 mm) detected on ultrasonography (US); in one, the lesion was palpable. US showed hypoechoic lesions and in two cases were mixed hypoechoic and anechoic. In these men, the testicular lesion was identified by US before surgery, giving three-dimensional coordinates to facilitate intraoperative recognition. A traditional inguinal incision was used and the funiculus clamped subinguinally without opening the canal. The testicle was isolated after sectioning the gubernaculum testis. In a separate operative field, an equatorial incision of the albuginea was made in a plane orthogonal to the major axis of the testicle, sparing the subtunical vasa. The parenchymal lobuli were dislodged and the seminiferous tubules dissociated, the nodule identified and completely removed, together with approximately 1 mm of surrounding healthy tissue. This technique can also be used for microsurgical testicular sperm extraction (MicroTESE), to retrieve sperm in infertile men. RESULTS: In two infertile men MicroTESE was also performed. Histology revealed one case each of seminoma, Leydig-cell tumour, Leydig cell hyperplasia, atrophy, normality in the incidental forms, and complicated cysts of the albuginea. In the follow-up for infertility reasons, no scarring was observable on the tunica albuginea in the men who had conservative therapy. One year later the patient with seminoma was free of disease. CONCLUSIONS: The increasingly frequent detection of benign testicular lesions, particularly in infertile men, calls for a surgical approach that must be as conservative as possible for the testicular parenchyma. We think that microsurgery should be the first-line technique in small suspected testicular lesions in infertile men.

Detection of testicular ultrasonographic lesions in severe male infertility.

PURPOSE: We retrospectively assessed the number and histology of testicular lesions diagnosed clinically and by ultrasonography in a population of infertile men. MATERIALS AND METHODS: From October 2000 to January 2003, 560 infertile men underwent physical examination, hormonal assessment (follicle-stimulating hormone, luteinizing hormone, testosterone) and scrotal ultrasonography. Eight men were diagnosed with focal testicular ultrasonographic lesions. In 4 cases there was a palpable lesion and in the other 4 cases the lesion was not palpable, diagnosed by ultrasonography (1 was cryptorchid). Only cases of lesions with clear-cut ultrasonographic edges and no history of recent genital infections were considered for explorative surgery through the groin. Microcalcifications were reported if present. The testicle was only preserved when frozen section examination revealed a benign lesion and the margins were negative. RESULTS: Gynecomastia was not present in any patient. No microcalcifications were observed. Follicle-stimulating hormone was high in all patients (range 19.8 to 66.0 mUI/ml, mean 34.4). Luteinizing hormone levels were variable (range 1.32 to 28 mUI/ml, mean 12.3). Testosterone was normal in all cases (range 2.82 to 6.25 ng/ml, mean 4.2). Ultrasonographic features of the lesions were hypoechoic area (6 patients) and mixed hyper-hypoechoic area (2 patients). Histological outcomes of Leydig cell tumor (in 3 patients), focal Leydig cell hyperplasia (1 patient), fibrosis (1 patient), diffuse Leydig cell hyperplasia (1 patient), classic seminoma (1 patient) and embryonal carcinoma (in 1 patient) were observed. CONCLUSIONS: Of 560 infertile patients 8 (1.4%) showed focal testicular lesions, 2 (0.4%) were diagnosed with germ cell tumors and 3 (0.5%) with interstitial cell neoplasms. The malignant tumors were both palpable and in 2 of 3 cases Leydig cell tumors were diagnosed only with ultrasonography.

The contractile wall of the caput epididymidis in men affected by congenital or postinflammatory obstructive azoospermia.

The transport and storage of spermatozoa in the epididymis depend on the contractile activity of its tubular wall. It is not known what differences exist in the contractile wall of the human epididymis in cases of obstructive azoospermia. The contractile wall in the tubules of the caput epididymidis was analyzed by light microscopy and transmission electron microscopy in 10 azoospermic men, 5 with a bilateral congenital absence of vas deferens (CBAVD) and 5 with a bilateral postinflammatory congestive obstruction of the epididymis. Five specimens from the same region of the caput epididymidis, obtained from fertile men who had undergone an orchidectomy because of testicular cancer, served as controls. No differences were observed between congenital and congestive obstructions. The contractile wall in caput tubules proximal to the obstructed level was strongly thickened when compared with controls (62.98 +/- 5.84 micro; 80.82 +/- 7.72 micro vs 19.59 +/- 2.23 micro, respectively, for congestive and congenital obstructions vs controls; P <.0001 vs controls), and the spindle-shaped myoid cells, which formed the contractile wall in normal cases, were replaced by large smooth muscle cells (SMCs) that showed features of coexisting contractile and secretory functions. The former included crowded cytoplasmic bundles of thin myofilaments (5-6 nm in diameter) converging to a large number of dense bodies, numerous micropinocytotic vesicles of the plasma membrane, and a continuous cell basement membrane. The presence of a developed rough endoplasmic reticulum and a Golgi complex, associated with the accumulation of thick layers of pericellular basement membrane-like material and ground substance, was indicative of a secretory phenotype of SMCs. The increased mechanical forces on the epididymal wall upstream from the obstruction might eventually activate the differentiation of myoid cells into SMCs, leading to an altered physiology of the contractile wall that could have possible clinical relevance in the case of microsurgical epididymovasostomy.

High incidence of benign testicular neoplasms diagnosed by ultrasound.

PURPOSE: We evaluated the clinical and histological significance of incidental ultrasonographic focal testicular lesions and assessed whether a conservative surgical approach may put the patient at higher oncological risk due to insufficient surgical eradication. MATERIALS AND METHODS: From October 2000 to May 2002 all patients with infertility, scrotal swelling, scrotal pain, varicocele, scrotal trauma or erectile dysfunction underwent scrotal ultrasonography. A total of 1,320 patients were investigated. Focal testicular lesions were found in 27 patients (2%), palpable nodules were present in 17 (63%) and nonpalpable incidental lesions were diagnosed in 10. Nodule diameter was 3 to 24 mm. All patients underwent explorative surgery via inguinotomy and preventive clamping of the spermatic cord. The nodules were completely removed with biopsy of the resection margins. Nonpalpable lesions were removed under ultrasonographic guidance. The testicle was only preserved when frozen section revealed a benign lesion and margins were negative. RESULTS: Of the 17 cases of palpable lesions (diameter 3 to 24 mm) conservative surgery was performed in 8 (47%). Definitive histological diagnosis showed Leydig cell tumor in 2 (25%), and large cell calcifying Sertoli's cell tumor, adenomatoid tumor, pseudofibrotic tumor of the tunica albuginea, epidermoid cyst, tubular fibrosis and non-Hodgkin's lymphoma in each 1 (12.5%). The remaining 9 patients (53%) underwent orchidectomy. Definitive histological examination revealed pure seminoma in 4 patients (44%), embryonal carcinoma in 4 (44%) and diffuse Leydig cell hyperplasia in 1 (12%). Seven of the 10 pts (70%) with nonpalpable nodules (diameter 4 to 16 mm) underwent conservative surgery. Histological study revealed focal Leydig cell hyperplasia in 1 case (10%), fibrosis in 3 (30%), infarction in 2 (20%) and mesothelial hyperplasia in 1 (10%). Orchiectomy was performed in the remaining 3 pts. Histology showed diffuse Leydig cell tumor in 2 pts (20%) and adenomatoid tumor with abscessed areas in 1 (10%). Neither atrophy nor local relapse was observed in pts who underwent conservative treatment during followup (mean: 1 month, range 19 to 9). CONCLUSIONS: The incidental diagnosis of testicular ultrasound alterations is increasing and 80% show a benign histology. In these cases a conservative surgical approach is the best option and it does not expose the patient to the risk of relapse.