Purpose: Preclinical data increasingly support an impact of low-intensity extracorporeal shockwave therapy (Li-ESWT) on the bladder. We investigated the molecular effects of Li-ESWT on the bladder of a streptozotocin-induced diabetic rat model. Methods: Fifteen 8-week-old male Wistar rats were randomized into 3 groups: a control group (n=5), a group of diabetic rats without treatment (diabetes mellitus [DM], n=5) and a group of diabetic rats treated with Li-ESWT (DM-ESWT, n=5). A single intraperitoneal dose of streptozotocin (60 mg/kg) was used to induce diabetes. Twenty days after diabetes induction, each rat in the DM-ESWT group received 300 shockwaves with an energy flux density of 0.09 mJ/mm2. Sessions were repeated 3 times/week for 2 weeks, followed by a 2-week washout period. Total RNA from bladder tissue was extracted, cDNA was synthesized, and quantitative real-time polymerase chain reaction was performed to analyze the expression pattern of transient receptor potential vanilloid 1 (Trpv1), interleukin-1β (Il1b), and the muscarinic receptors M1, M2, and M3 (Chrm1, Chrm2, and Chrm3). Results: The expression of Trpv1, Il1b, and Chrm2 genes was significantly different between the 3 groups (P=0.002, P<0.0001, and P=0.011, respectively; 1-way analysis of variance). In the DM group, the expression of all genes was higher than in the control group, but statistical significance was observed only for Trpv1 and Il1b (P=0.002 and P<0.0001, respectively). Li-ESWT significantly reduced the expression of Il1b and Chrm2 (P=0.001 and P=0.011, respectively), whereas a nonsignificant tendency for reduced expression was noted for Trpv1 (P=0.069). Conclusions The induction of diabetes was associated with increased expression of genes related to mechanosensation, inflammation/ischemia, and contraction in the rat bladder. Li-ESWT reduced the expression of IL1b, Chrm2, and to a lesser extent Trpv1 toward the control levels, suggesting the therapeutic potential of this treatment modality for diabetic cystopathy.

Purpose: We aimed to develop urodynamic criteria to improve the accuracy of the diagnosis of bladder outlet obstruction (BOO) and detrusor underactivity (DU) in women with lower urinary tract symptoms (LUTS). Methods: Initially, in a group of 68 consecutive women with LUTS and increased postvoid residual (PVR) who had undergone urodynamic investigations, we examined the level of agreement between the operating physician’s diagnosis of BOO or DU and the diagnosis according to urodynamic nomograms/indices, including the Blaivas-Groutz (B-G) nomogram, urethral resistance factor (URA), bladder outlet obstruction index (BOOI), and bladder contractility index (BCI). Based on the initial results, we categorized 160 women into 4 groups using the B-G nomogram and URA (group 1, severe-moderate BOO; group 2, mild BOO and URA≥20; group 3, mild BOO and URA<20; group 4, nonobstructed) and compared the urodynamic parameters. Finally, we redefined women as obstructed (groups 1+2) and nonobstructed (groups 3+4) for subanalysis. Results: The agreement between the B-G nomogram and physician’s diagnosis was poor in the mild obstruction zone (κ=0.308, P=0.01). By adding URA (cutoff value=20), excellent agreement was reached (κ=0.856, P<0.001). Statistically significant differences were found among the 4 groups (analysis of variance) in maximum flow rate (Qmax) (P<0.0001), voided volume (VV) (P=0.042), PVR (P=0.032), BOOI (P<0.0001), and BCI (P<0.0001), with a positive linear trend for Qmax and VV and a negative linear trend for PVR and BOOI moving from groups 1 to 4. In the subanalysis, all parameters showed statistically significant differences between obstructed and nonobstructed women, except BCI (Qmax, P=0.0001; VV, P=0.0091; PVR, P=0.0005; BOOI, P=0.0001). Conclusions The combination of the B-G nomogram with URA increased the accuracy of diagnosing BOO among women with LUTS. Based on this combination, most women in the mild obstruction zone of the B-G nomogram would be considered underactive rather than obstructed.

Purpose: Preclinical data increasingly support an impact of low-intensity extracorporeal shockwave therapy (Li-ESWT) on the bladder. We investigated the molecular effects of Li-ESWT on the bladder of a streptozotocin-induced diabetic rat model. Methods: Fifteen 8-week-old male Wistar rats were randomized into 3 groups: a control group (n=5), a group of diabetic rats without treatment (diabetes mellitus [DM], n=5) and a group of diabetic rats treated with Li-ESWT (DM-ESWT, n=5). A single intraperitoneal dose of streptozotocin (60 mg/kg) was used to induce diabetes. Twenty days after diabetes induction, each rat in the DM-ESWT group received 300 shockwaves with an energy flux density of 0.09 mJ/mm2. Sessions were repeated 3 times/week for 2 weeks, followed by a 2-week washout period. Total RNA from bladder tissue was extracted, cDNA was synthesized, and quantitative real-time polymerase chain reaction was performed to analyze the expression pattern of transient receptor potential vanilloid 1 (Trpv1), interleukin-1β (Il1b), and the muscarinic receptors M1, M2, and M3 (Chrm1, Chrm2, and Chrm3). Results: The expression of Trpv1, Il1b, and Chrm2 genes was significantly different between the 3 groups (P=0.002, P<0.0001, and P=0.011, respectively; 1-way analysis of variance). In the DM group, the expression of all genes was higher than in the control group, but statistical significance was observed only for Trpv1 and Il1b (P=0.002 and P<0.0001, respectively). Li-ESWT significantly reduced the expression of Il1b and Chrm2 (P=0.001 and P=0.011, respectively), whereas a nonsignificant tendency for reduced expression was noted for Trpv1 (P=0.069). Conclusions The induction of diabetes was associated with increased expression of genes related to mechanosensation, inflammation/ischemia, and contraction in the rat bladder. Li-ESWT reduced the expression of IL1b, Chrm2, and to a lesser extent Trpv1 toward the control levels, suggesting the therapeutic potential of this treatment modality for diabetic cystopathy.

Purpose: We aimed to develop urodynamic criteria to improve the accuracy of the diagnosis of bladder outlet obstruction (BOO) and detrusor underactivity (DU) in women with lower urinary tract symptoms (LUTS). Methods: Initially, in a group of 68 consecutive women with LUTS and increased postvoid residual (PVR) who had undergone urodynamic investigations, we examined the level of agreement between the operating physician’s diagnosis of BOO or DU and the diagnosis according to urodynamic nomograms/indices, including the Blaivas-Groutz (B-G) nomogram, urethral resistance factor (URA), bladder outlet obstruction index (BOOI), and bladder contractility index (BCI). Based on the initial results, we categorized 160 women into 4 groups using the B-G nomogram and URA (group 1, severe-moderate BOO; group 2, mild BOO and URA≥20; group 3, mild BOO and URA<20; group 4, nonobstructed) and compared the urodynamic parameters. Finally, we redefined women as obstructed (groups 1+2) and nonobstructed (groups 3+4) for subanalysis. Results: The agreement between the B-G nomogram and physician’s diagnosis was poor in the mild obstruction zone (κ=0.308, P=0.01). By adding URA (cutoff value=20), excellent agreement was reached (κ=0.856, P<0.001). Statistically significant differences were found among the 4 groups (analysis of variance) in maximum flow rate (Qmax) (P<0.0001), voided volume (VV) (P=0.042), PVR (P=0.032), BOOI (P<0.0001), and BCI (P<0.0001), with a positive linear trend for Qmax and VV and a negative linear trend for PVR and BOOI moving from groups 1 to 4. In the subanalysis, all parameters showed statistically significant differences between obstructed and nonobstructed women, except BCI (Qmax, P=0.0001; VV, P=0.0091; PVR, P=0.0005; BOOI, P=0.0001). Conclusions The combination of the B-G nomogram with URA increased the accuracy of diagnosing BOO among women with LUTS. Based on this combination, most women in the mild obstruction zone of the B-G nomogram would be considered underactive rather than obstructed.

Purpose: Augmented adiposity may negatively impact sexual sphere through its metabolic effects and its detrimental impact on reproductive hormones. Moreover, a dysregulated metabolic pathway may promote apoptosis among spermatogenic cells. Based on these premises, a relation between weights loss and ameliorate semen parameters seems beneficial. To investigate if physical activity may affect semen parameters and fertility rate, a systematic literature search on major dataset has been performed. Materials and Methods: The search terms included: “Assisted reproduction therapies,” “fertility,” “semen parameters,” “sperm parameters,” and “physical activity.” This analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines and it was registered on PROSPERO (CRD42023384471). A total of 47 studies have been identified; 1 reference has been eliminated after duplication check. After preliminary screening 32 papers have been excluded. Considering the exclusion criteria, 15 full-text articles were evaluated for eligibility. After a full-text review, six studies published during a span of eight years (2014–2022) have been included in the meta-analysis. Semen parameters, pregnancy and birth rates were investigated. The revised Cochrane risk of bias tool (Rob2) has been used to check the risk of bias. Results: The number of patients enrolled in studies ranges from 17 to 521; in the end, a total of 1,637 patients have been enrolled in the study. Fertility parameters investigated were semen quality parameters and pregnancy rates and live births. A statistically significant relationship between physical exercise and sperm concentration (p=0.02), total sperm motility (p<0.01), total sperm count (p<0.01), normal morphology (p<0.01) has been established. Moreover, the study registered a statistically significant association within physical activity and total pregnancy rate (p<0.01) and live birth rate (p<0.01). Conclusions We demonstrated that physical activity is significantly associated with amelioration of semen parameters and may be crucial in improving or even reverting male infertility.

Diabetes Mellitus ; Humans ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells ; Umbilical Cord ; Wharton Jelly

Purpose: Varicocele has been associated with high seminal oxidative stress (OS), impaired semen quality, and reduced male fertility potential. However, the exact mechanism(s) underlying the development of varicocele-mediated infertility and the cause-effect relationship between varicocele and testicular dysfunction are not fully understood. The aim of this systematic review and meta-analysis (SRMA) is to investigate the impact of varicocele on testicular OS markers and sperm parameters in experimental animals with varicocele as compared to animals without varicocele. Materials and Methods: A literature search was performed using the Scopus and PubMed databases on studies that investigated testicular OS markers and sperm parameters in animals with varicocele. The primary outcomes included malondialdehyde (MDA) (nmol/mg) levels whereas the secondary outcomes included total sperm count (×106), sperm vitality (%), total sperm motility (%), and sperm DNA fragmentation (SDF) (%). Standardized mean difference (SMD) (95% confidence interval [CI]) was chosen to express the effect size. The quality of the included studies was evaluated using the Cambridge Quality Checklist. Results: Out of 76 identified articles, 6 studies on rats were included in the meta-analysis. The analysis showed a significant increase of MDA (SMD: 15.61 [1.93, 29.29]; p=0.03) in rats with varicocele vs. controls. We also observed a significant decrease in total sperm count (SMD: -17.45 [-28.97, -5.93]; p<0.01), sperm vitality (SMD: -16.41 [-26.30, -6.52]; p<0.01), total sperm motility (SMD: -17.67 [-24.90, -10.44]; p<0.01), and a significant increase of SDF (SMD: 7.41 [1.23, 13.59]; p=0.02), in rats with varicocele vs. controls. The quality of the included studies was ranked as high. Conclusions This SRMA indicates a significant increase in levels of testicular MDA and SDF and a reduction of sperm quality in experimental animals with varicocele. These findings support the potential role of testicular OS in the development of varicocele-induced testicular damage.

Purpose: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition. Materials and Methods: An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method. Results: A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4–6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated. Conclusions This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians.