Basic and Clinical Andrology最新文献

Background: Gonadotropin dysregulation seems to play a potential role in the carcinogenesis of testicular germ cell tumor (TGCT). The aim of this study was to explore the expression of specific genes related to sex hormone regulation, synthesis, and metabolism in TGCT and to define specific hormonal clusters. Two publicly available databases were used for this analysis (TCGA and GSE99420). By means of hard-threshold regularized KMEANS clustering, we assigned TGCT samples into four clusters defined in respect to different expression of the sex hormone-related genes. We analysed clinical data, protein and gene expression, signaling regarding hormonal clusters. Based on whole-transcriptome gene expression, prediction of anti-cancer drug response was made by RIDGE models.

Results: Cluster #1 (12-16%) consisted primarily of non-seminomatous germ cell tumor (NSGCT), characterized by high expression of PRL, GNRH1, HSD17B2 and SRD5A1. Cluster #2 (42-50%) included predominantly seminomas with high expression of SRD5A3, being highly infiltrated by T and B cells. Cluster #3 (8.3-18%) comprised of NSGCT with high expression of CGA, CYP19A1, HSD17B12, HSD17B1, SHBG. Cluster #4 (23-30%), which consisted primarily of NSGCT with a small fraction of seminomas, was outlined by increased expression of STAR, POMC, CYP11A1, CYP17A1, HSD3B2 and HSD17B3. Elevated fibroblast levels and increased extracellular matrix- and growth factor signaling-related gene signature scores were described in cluster #1 and #3. In the combined model of progression-free survival, S2/S3 tumor marker status, hormonal cluster #1 or #3 and teratoma histology, were independently associated with 25-30% increase of progression risk. Based on the increased receptor tyrosine kinase and growth factor signaling, cluster #1, #3 and #4 were predicted to be sensitive to tyrosine kinase inhibitors, FGFR inhibitors or EGFR/ERBB inhibitors. Cluster #2 and #4 were responsive to compounds interfering with DNA synthesis, cytoskeleton, cell cycle and epigenetics. Response to apoptosis modulators was predicted only for cluster #2.

Conclusions: Hormonal cluster #1 or #3 is an independent prognostic factor regarding poor progression-free survival. Hormonal cluster assignment also affects the predicted drug response with cluster-dependent susceptibility to specific novel therapeutic compounds.

Background: Sperm cryopreservation in patients with testicular germ cell tumours (GCTs) is traditionally performed after orchiectomy. But, some evidence suggests preoperative semen quality to be superior. We aimed to clarify the optimal time-point of cryopreservation.In a retrospective study, semen quality of 163 patients analysed preoperatively was compared with 242 patients analysed shortly after orchiectomy. Descriptive statistical methods with standard tests for comparisons were employed along with stratified analyses regarding the influence of clinical factors.

Results: All major semen parameters were significantly better in the preoperative group: median ejaculate volume (3 ml preoperatively vs. 2 ml postoperatively); median total sperm count (56.9 x10⁶vs.13 x 10⁶), median progressive motility (40% vs. 25%); azoospermia (4.9% vs. 14.9%). Stratified analysis of subgroups did not reveal significant impact of particular clinical factors on the superiority of preoperative semen quality. Limitations relate to the design of group comparison rather than intraindividual longitudinal comparisons and to selective inclusion of patients opting for cryopreservation.

Conclusions: In GCT patients, semen quality before orchiectomy is significantly superior to that found immediately after surgery. This superiority encompasses all major semen quality parameters. Of particular note is a threefold increase of azoospermia postoperatively. GCT patients are best advised to have cryopreservation performed before orchiectomy.

Context: Malignant tumours of the penis are rare. Their incidence varies around the world and increases with age. Treatment is essentially surgical. Surgery may be conservative or radical. We report the anatomoclinical aspects of 5 cases of penile cancer observed in our department.

Case presentations: A 44-year-old patient with a circumcised penis, diagnosed with a fusosarcoma (a rare type of sarcoma) of the penis. Three patients (ages 61, 59, and 70) were diagnosed with squamous cell carcinoma, the most common type of penile cancer. These patients also had circumcised penises. The last case was a metastatic squamous cell carcinoma of the penis in a 68-year-old patient. All patients were immunocompetent and had a circumcised penis. They refused surgery in any form.

Conclusion: The clinical aspects of penile cancer are polymorphous and misleading. Any bulging or indurated lesions on the penis should be biopsied.

Background: To the best of our knowledge, there is a gap in the review of literature about the most suitable varicocelectomy technique in isolating and ligating adherent periarterial vein(s). Consequently, leaving the artery intact or ligating it together with the adherent vein may pose a challenge. We conducted a comparative prospective study to assess the outcomes of the three techniques namely Fisch, sclerotherapy and microvaricoclectomy (MSV).

Results: The patients who underwent MSV showed the longest operative time (66.29 ± 2.78 min), followed by Fisch technique (56.94 ± 3.07 min) then sclerotherapy (55.45 ± 1.99). Thus, the difference in the operative time between the three techniques was statistically significant (P < 0.001). Regarding the postoperative right vein diameter, MSV group showed the largest diameter (2.14 ± 0.15 mm), followed by Fisch technique (2.13 ± 0.15 mm) then sclerotherapy (1.75 ± 0.42 mm). Regarding the postoperative left vein diameter, MSV group showed again the largest diameter (2.17 ± 0.21 mm), followed by Fisch technique (2.14 ± 0.15 mm) then sclerotherapy (1.75 ± 0.42 mm). Moreover, the patients who underwent sclerotherapy showed the highest postoperative progressive sperm motility percent (25.27 ± 4.00%), followed by Fisch technique (21.56 ± 7.30%) then MSV group (19.85 ± 6.33%). Post hoc pair wise comparisons revealed that sclerotherapy and Fisch technique had a significantly higher effectiveness in reducing operative time than MSV. Additionally, it revealed that sclerotherapy technique had a significantly higher effectiveness in reducing postoperative vein diameters measurement than MSV and Fisch technique. Post hoc pair wise comparisons revealed that sclerotherapy technique had a significantly higher effectiveness in improving the postoperative progressive sperm motility percent than MSV. Patients who underwent the 3 techniques demonstrated statistically significant differences between baseline and post-operative vein diameter, reflux duration, sperm concentration, progressive sperm motility, progressive motile count/ejaculate and sperm abnormal forms.

Conclusion: The 3 techniques showed significant improvement in the semen parameters after 3 months in the studied patients. However, sclerotherapy technique showed a significantly higher effectiveness in improving the postoperative progressive sperm motility percent compared to MSV.

The serendipitous discovery that inhibiting type 5 phosphodiesterase (PDE5) using sildenafil, a potent PDE5 inhibitor (PDE5i) initially developed for cardioprotection, introduced the possibility of orally managing erectile dysfunction (ED) led to an increase in research data, which are currently considered groundbreaking for the new discipline of sexual medicine. Findings from a number of laboratories and clinics around the world unanimously demonstrated the following: (i) the major cause of ED is directly or indirectly related to cardiovascular disease (CVD); (ii) ED and CVDs share the same risk factors, which are related mainly to lifestyle choices; (iii) the first therapeutic approach to both ED and CVDs is to transform harmful lifestyles into virtuous lifestyles; and (iv) PDE5is in general, particularly sildenafil, are very safe, if not protective, for use in CVD patients. However, the use of PDE5is has faced several challenges. Many patients and some healthcare providers (HCPs) often share the misconception that using these drugs can increase the risk of CVD. Some patients might desire to fulfill the unmet need for privacy linked to the stigma of being treated for ED or might be enticed by the idea of buying drugs online, either because of shame or cheaper prices, without knowing the risks associated with counterfeit drugs. The aim of this narrative revision of the current literature is to demonstrate that (i) the orodispersible film of sildenafil is safe from a CV perspective; (ii) it is a discreet formulation that respects the need for privacy; and (iii) it is virtually the unique PDE5i formulation too expensive to produce outside the correct channels, making it impossible to be counterfeit.

Background: Hemodynamic alterations in the spermatic vein are implicated in infertility among patients with varicocele (VC). Contrast-enhanced ultrasound (CEUS), a powerful tool for hemodynamic analysis, remains unexplored for VC. This study aimed to demonstrate the feasibility of using CEUS to evaluate spermatic vein hemodynamics in patients with VC and establish a clear correlation between specific hemodynamic patterns and impaired semen parameters. This study included 165 patients with left-sided VC and 50 healthy volunteers. All participants underwent CEUS of the spermatic veins, along with maximum venous diameter and testicular volume measurements and serum sex hormone levels and routine semen analyses. The sperm DNA fragmentation index was measured in 146 patients with VC and 37 healthy controls.

Results: The analyses revealed four distinct blood flow patterns of the spermatic vein: steady flow, intermittent stasis, intermittent reflux, and filling defect. In healthy spermatic veins, the predominant blood flow patterns included steady flow and intermittent stasis. Spermatic veins with VC exhibited a significant increase in the intermittent reflux and filling defect patterns, with the proportion rising as the clinical grade increased. The four patterns were further grouped into the "steady flow & intermittent stasis" and "intermittent reflux & filling defect" patterns for logistic regression analyses; the intermittent reflux & filling defect pattern was revealed as an independent risk factor for impaired sperm concentration, total sperm counts, progressive motility, morphology, and DNA fragmentation index.

Conclusions: This study validated the feasibility of CEUS for assessing the hemodynamics of the spermatic vein and established the intermittent reflux & filling defect pattern as an independent predictor of impaired semen parameters.

Purpose: To investigate the therapeutic potential of Acrorus tatarinowii in oligoasthenozoospermia and its related mechanism through modulation of the BCL2/Bax/Caspase3 signaling pathway.

Methods: Initially, using the TCMSP and Disgenet databases, active ingredients of Acrorus tatarinowii were identified and their target genes associated with sperm-related diseases were elucidated.Subsequently, an oligoasthenozoospermia mouse model was induced and treated with Acrorus tatarinowii. Serum hormone levels were assessed by ELISA, testicular histopathology by HE staining, and target gene expression by qPCR and Western blotting.

Results: Acrorus tatarinowii treatment significantly upregulated BCL2 expression in the testes of oligoasthenozoospermic rat. This was accompanied by improved histopathological features in testicular tissues, reduced LH and FSH levels in serum.

Conclusion: Acrorus tatarinowii exerts therapeutic effects in oligoasthenozoospermia by regulating the BCL2/Bax/Caspase3 pathway, maybe by inhibiting apoptosis, and promoting germ cell proliferation. These findings highlight its potential as a natural remedy for male infertility associated with sperm function disorders.

Background: Manual counting for semen analysis is recommended by the World Health Organization. Technicians performing this usually record their results on a paper worksheet and then enter the data into an electronic laboratory information system. One disadvantage of this approach is the chance of post-analytical transcription errors, which can be reduced by checking the computer entries before reporting by another technician. Such practice inevitably increases the running cost and delays the reporting time. The present study was to establish a paperless electronic data entry system for semen analysis and compare its precision with the conventional paper method. During semen analysis, readings on the cell counter were video recorded. The precision of the paper record entries was determined by comparing them with the corresponding video records. Patient characteristics and semen analysis results were input directly into an in-house developed data entry system via a tablet computer immediately after analysis. The same set of data was also handwritten on a paper form and was subsequently input into a standard computerized database according to routine practice. The agreement of the data entries between the two systems was then compared.

Results: A total of 787 semen analyses were included in the study, involving 201 samples in Phase I and 586 samples in Phase II of the study. Phase I was the initial learning period. The overall rate of transcription error of the paper form was 0.07%, whereas that of the paperless system was 0.17%. In phase II, the paperless system was modified according to users' comments. The transcription error rate of the paper form was 0.05%, while that of the paperless system was substantially reduced to 0.01% (p = 0.008).

Conclusion: The paperless system is a reliable tool for recording data from semen analysis compared with the conventional paper form. However, training is needed to reduce the error rate of the paperless system.

Background: To evaluate the effects of penile revascularization surgery on penile vascular hemodynamics and to assess the utility of the resistive index (RI) as an objective parameter for postoperative patient follow-up.

Methods: This study included a total of 35 patients who underwent penile revascularization. Penile color Doppler ultrasonography was performed preoperatively and at the third postoperative month to evaluate cavernosal arteries, dorsal arteries, deep dorsal vein, and inferior epigastric artery. During these evaluations, peak systolic velocity, end diastolic velocity, and resistive index were measured. The International Index of Erectile Function questionnaire was administered before surgery and at the third postoperative month. In addition, corpus cavernosum electromyography and cavernosometry tests were performed in all cases preoperatively. Anastomotic patency was assessed using computed tomography angiography at the end of the follow-up period.

Results: The mean preoperative resistive index values were determined to be 0.74 ± 0.07 and 0.73 ± 0.09 cm/s for the right and left cavernosal arteries, respectively, and these values increased to 0.95 ± 0.09 and 0.96 ± 0.06 cm/s, respectively, at the last postoperative control. The mean International Index of Erectile Function-5, 15 scores for the right and left cavernosal arteries were 8.52 ± 4.83 and 19.4 ± 8.54, respectively, preoperatively, and these scores improved to 15.26 ± 4.50 and 35.76 ± 13.65, respectively, at the last postoperative follow-up.

Conclusion: The results of this study suggest that the resistive index can be used as an objective parameter in the diagnosis of erectile dysfunction of vascular origin and in the follow-up and management of the disease following penile revascularization.

Trial registration: NCT06350019/04/03/2024 (retrospectively registered).

Background: Primary ciliary dyskinesia (PCD) is a heterogenous disease caused by mutations of miscellaneous genes which physiologically play an important role in proper structure and/or function of various cellular cilia including sperm flagella. Besides male infertility, the typical phenotypes, based on decreased mucociliary clearance, are lifelong respiratory issues, i.e., chronic bronchitis leading to bronchiectasis, chronic rhinosinusitis, and chronic otitis media. Moreover, since motile cilia are important during embryological development in the sense of direction of gut rotation, 50% of affected individuals develop situs inversus - so-called Kartagener's syndrome.

Case presentation: We present two cases of PCD as a rare cause of male infertility.

Conclusions: Primary ciliary dyskinesia should be suspected in infertile males having (sub)normal sperm concentration values with persistent zero motility together with patient's and/or family history of respiratory symptoms like bronchiectasis, chronic cough, rhinitis, recurrent sinusitis, and otitis media. Due to more than 50 identified mutations until now, the causal mechanism of male infertility is miscellaneous and not in all cases known in detail. Besides impaired sperm motility, other mechanisms significantly decreasing efficacy of assisted reproduction techniques play a pivotal role. Thus, proper diagnostic work-up including, among others, sperm DNA fragmentation, is mandatory to avoid ineffective treatment burden.