One out of two idiopathic infertile men has pathologic sperm DNA fragmentation values: Potential implications for clinical practice.

OBJECTIVES: To investigate the distribution of sperm DNA fragmentation (SDF) values and their association with clinical and seminal parameters in idiopathic infertile men. DESIGN, PATIENTS, MEASUREMENTS: Data from 3224 primary infertile men (belonging to couples having failed to conceive a pregnancy within 12 months) who underwent a thorough diagnostic work-up were analysed. A SDF value ≥ 30% (according to Sperm Chromatin Structure Assay) was considered pathologic. We excluded: (1) men with genetic abnormalities; (2) men with history of cryptorchidism; (3) men with biochemical hypogonadism; (4) men with clinical varicocele; and (5) men with other possible known aetiological factors. Descriptive statistics and logistic regression analyses were used to describe the whole cohort. RESULTS: Of all, 792 (23%) men with at least one abnormal WHO semen parameter but without any identified aetiologic factor for infertility, were considered as idiopathic infertile men. Of 792, 418 (52.7%) men had SDF ≥30%. Men with pathologic SDF were older (p = .02), had higher Follicle-stimulating hormone (FSH) (p = .04) but lower total testosterone (p = .03) values than those with SDF <30%. The homoeostatic model assessment index for insulin resistance (HOMA-IR) was higher in men with SDF ≥30% (p = .01). Idiopathic infertile men with SDF ≥30% presented with lower sperm concentration (p < .001) and lower progressive sperm motility (p < .01) than those with SDF < 30%. Logistic regression analysis revealed that older age (OR: 1.1, p = .02) and higher HOMA-IR score (OR: 1.8, p = .03) were associated with SDF ≥ 30%, after accounting for FSH and sperm concentration values. CONCLUSIONS: Approximately half of infertile men categorized as idiopathic had pathologic SDF values. Idiopathic infertile men with pathologic SDF showed worse clinical, hormonal and semen parameters than those with normal SDF values. These results suggest that including SDF testing could be clinically relevant over the real-life management work-up of infertile men.

A historical comparison of thulium fiber laser systems for stone lithotripsy: navigating toward safe and effective parameters.

INTRODUCTION AND OBJECTIVES: Medical device companies have introduced new TFL machines, including Soltive (Olympus, Japan), Fiber Dust (Quanta System, Italy), and TFLDrive (Coloplast, France). The primary objective of this study is to compare our initial clinical experiences with TFL using those devices. Through this historical comparison of Thulium Fiber Laser systems for stone lithotripsy, we aim to advance our understanding and approach toward achieving safe and effective TFL parameters. MATERIALS AND METHODS: The data for this comparative analysis were extracted from three distinct prospective series that were previously published, outlining our initial clinical experience with the Soltive (Olympus, Japan), FiberDust laser (Quanta System, Italy), and TFLDrive laser (Coloplast, France). Parameters such as stone size, stone density, laser-on time (LOT), and laser settings were meticulously recorded. Additionally, we assessed critical variables such as ablation speed (expressed in mm3/s) and Joules/mm3 for each lithotripsy procedure. RESULTS: A total of 149 patients were enrolled in this study. Among them, 120 patients were subjected to analysis concerning renal stones. Statistically significant differences were observed in the median (IQR) stone volume: 650 (127-6027) mm3 for TFLDrive, 1800 (682.8-2760) mm3 for Soltive, and 1125 (294-4000) mm3 for FiberDust (p: 0.007); while there were no differences regarding stone density among the groups. Significant variations were identified in median (IQR) pulse energy, frequency, and total power. The Soltive group exhibited lower energy levels (0.3 J vs. 0.6 J, p: 0.002) but significantly higher pulse frequency (100 Hz vs. 17.5 Hz, p: 0.003) and total power (24 W vs. 11W, p: 0.001) compared to the other groups. Laser-on time showed no substantial differences across all three groups. Additionally, a statistically significant difference was observed in median J/mm3, with the TFLDrive group using higher values (24 J/mm3, p: 0.001), while the Soltive group demonstrated a higher median ablation speed of 1.16 mm3/s (p: 0.001). The overall complication rate remained low for all groups, with comparable stone-free rates. CONCLUSION: By reducing pulsed frequency, we improved laser efficiency, but smaller volumes lead to decreased efficiency due to increased retropulsion and fragment movement. Further studies are needed to identify and establish the appropriate laser settings for this new technology.

Endourological society fellowship program: a real contribution to improve surgical outcomes of stone patients treated with ureteroscopy.

PURPOSE: We assessed the impact of the one-year endourological society fellowship program (ESFP) on the achievement of optimal surgical outcomes (OSO) in stone patients treated with ureteroscopy (URS). MATERIALS AND METHODS: We identified 303 stone patients treated with URS from January 2018 to June 2022 by five experienced surgeons (ES). Of those, two attended ESFP. OSO was defined as the presence of residual fragments ≤ 4 mm at 1-month post-operative imaging (Ultrasound + X - Ray or CT scan). Descriptive statistics explored patients' characteristics and the rate of OSO according to the attendance of ESFP. Uni- and multivariate logistic regression analyses (UVA and MVA) tested the impact of stone characteristics, surgical data, ESFP, and imaging technique on the rate of OSO. The LOWESS curve explored the graphical association between stone size and the multivariable-adjusted probability of OSO in the two groups of surgeons. RESULTS: Of 303 patients, 208 (69%) were treated by the two surgeons who attended ESFP. OSO was achieved in 66% and 52% of patients treated by ES with and without ESFP, respectively (p = 0.01). At UVA, ESFP (OR = 1.78; 95% CI = 1.09-2.90), stone diameter (OR = 0.92; 95% CI = 0.88-0.96), stone location (kidney vs. ureter; OR = 0.34; 95% CI = 0.21-0.58), imaging technique (CT scan vs. Ultrasound + X-Ray; OR = 0.28; 95% CI = 0.16-0.47) predicted OSO achievement (all p < 0.05). At MVA analyses, ESFP was associated with OSO (OR = 2.24; 95% CI = 1.29-3.88; p < 0.05), along with the other aforementioned variables. The LOWESS curve showed that the greater the stone size, the greater the difference in OSO in the two groups of surgeons. CONCLUSIONS: ESFP positively affects OSO achievement after URS, especially in patients with a high stone burden.

How much energy do we need to ablate 1 cubic millimeter of stone during Thulium Fiber Laser lithotripsy? An in vitro study.

INTRODUCTION: Both Holmium:yttrium-aluminium-garnet (Ho:YAG) laser and Thulium Fiber Laser (TFL) can effectively treat all urinary stone types. This in vitro study evaluated the ablation volume per pulse (AVP) and required energy needed to ablate 1mm3 (RE, J/mm3) of various stone types at different laser settings with TFL. METHODS: 272-µm core-diameter laser fibers (Boston Scientific©) were connected to a 50 Watts TFL generator (IPG®). An experimental setup immerged human stones of calcium oxalate monohydrate (COM), uric acid (UA), and cystine (CYS) with a single pulse lasing emission (0.5/0.8/1 J), in contact mode. Stones were dried out before three-dimensional scanning to measure AVP and deduce from the pulse energy (PE) and AVP the RE. A direct comparison with known Ho:YAG's AVP and RE was then carried out. RESULTS: AVP for COM stones was significantly greater than those for CYS stones and similar to UA stones (p = 0.02 and p = 0.06, respectively). If AVP increased with PE against COM and UA stones, AVP decreased against CYS stones. 1 J PE resulted in a threefold lower RE compared with other PE for COM stones. On the contrary, RE for CYS increased with PE, whereas PE did not had influence on RE for UA. TFL was associated with greater AVP for COM, but lower for UA and CYS stones compared to Ho:YAG laser. CONCLUSION: This in vitro study firstly describes the ablation volume per pulse and required energy to treat a cubic millimeter of three frequent human stone types, and suggest TFL could not be suited for cystine. Therefore, stone composition could be considered when choosing the laser source for lithotripsy.

Is "Kidney Stone Calculator" efficient in predicting ureteroscopic lithotripsy duration? A holmium:YAG and thulium fiber lasers comparative analysis.

PURPOSE: This study aimed to evaluate the ability of Kidney Stone Calculator (KSC), a flexible ureteroscopy surgical planning software, to predict the lithotripsy duration with both holmium:YAG (Ho:YAG) and thulium fiber laser (TFL). METHODS: A multicenter prospective study was conducted from January 2020 to April 2023. Patients with kidney or ureteral stones confirmed at non-contrast computed tomography and treated by flexible ureteroscopy with laser lithotripsy were enrolled. "Kidney Stone Calculator" provided stone volume and subsequent lithotripsy duration estimation using three-dimensional segmentation of the stone on computed tomography and the graphical user interface for laser settings. The primary endpoint was the quantitative and qualitative comparison between estimated and effective lithotripsy durations. Secondary endpoints included subgroup analysis (Ho:YAG-TFL) of differences between estimated and effective lithotripsy durations and intraoperative outcomes. Multivariate analysis assessed the association between pre- and intraoperative variables and these differences according to laser source. RESULTS: 89 patients were included in this study, 43 and 46 in Ho:YAG and TFL groups, respectively. No significant difference was found between estimated and effective lithotripsy durations (27.37 vs 28.36 min, p = 0.43) with a significant correlation (r = + 0.89, p < 0.001). Among groups, this difference did not differ (p = 0.68 and 0.07, respectively), with a higher correlation between estimated and effective lithotripsy durations for TFL compared to Ho:YAG (r = + 0.95, p < 0.001 vs r = + 0.81, p < 0.001, respectively). At multivariate analysis, the difference was correlated with preoperative (volume > 2000 mm3 (Ho:YAG), 500-750 mm3 SV and calyceal diverticulum (TFL)), operative (fragmentation setting (p > 0.001), and basket utilization (p = 0.05) (Ho:YAG)) variables. CONCLUSION: KSC is a reliable tool for predicting the lithotripsy duration estimation during flexible ureteroscopy for both Ho:YAG and TFL. However, some variables not including laser source may lead to underestimating this estimation.

Ureteroscopic management in cystinuric patients: long-term results from a tertiary care referral center.

OBJECTIVE: To evaluate long-term surgical and functional outcomes of cystinuric patients exclusively treated with Ureteroscopy (URS). METHODS: Data from patients treated for cystine stones at a single academic center were retrospectively analyzed. The management protocol consisted of (i) treating symptomatic or > 7 mm stones, (ii) multi-staged URS for voluminous stones, (iii) referring patients to a dedicated nephrological clinic. The eGFR was calculated according to the MDRD formula. CKD category was assessed according to the NKF classification. Relevant CKD was defined as CKD category ≥ 3a. Descriptive statistics were used to analyze the cohort data. RESULTS: Data from 46 cystinuric patients treated with 332 URS were available. Median age at diagnosis and at first URS in our center were 18 and 32 years, respectively. Median follow-up was 101 months. Median number of URS and recurrences per patient were 6 and 2, respectively. The median interval between the first and the last available creatinine level was 64 months. Median first and last eGFR were 72 and 74 mL/min, respectively. Overall, 83% of patients had stable or improved renal function within the study period. Ureteral stricture occurred in 3 (6.5%) patients. CONCLUSIONS: Cystinuria requires intensive endoscopic management. Most patients treated with URS have stable or improved renal function within a long-term follow-up. CKD is a not neglectable event that potentially occurs at an early stage of life. Current findings should be considered for the surgical management of cystinuric patients.

Temperature profile during endourological laser activation: introducing the thermal safety distance concept.

PURPOSE: To examine temporal-spatial distribution of heat generated upon laser activation in a bench model of renal calyx. To establish reference values for a safety distance between the laser fiber and healthy tissue during laser lithotripsy. METHODS: We developed an in-vitro experimental setup employing a glass pipette and laser activation under various intra-operative parameters, such as power and presence of irrigation. A thermal camera was used to monitor both temporal and spatial temperature changes during uninterrupted 60-second laser activation. We computed the thermal dose according to Sapareto and Dewey's formula at different distances from the laser fiber tip, in order to determine a safety distance. RESULTS: A positive correlation was observed between average power and the highest recorded temperature (Spearman's coefficient 0.94, p < 0.001). Irrigation was found to reduce the highest recorded temperature, with a maximum average reduction of 9.4 °C at 40 W (p = 0.002). A positive correlation existed between average power and safety distance values (Spearman's coefficient 0.86, p = 0.001). A thermal dose indicative of tissue damage was observed at 20 W without irrigation (safety distance 0.93±0.11 mm). While at 40 W, irrigation led to slight reduction in mean safety distance (4.47±0.85 vs. 5.22±0.09 mm, p = 0.08). CONCLUSIONS: Laser settings with an average power greater than 10 W deliver a thermal dose indicative of tissue damage, which increases with higher average power values. According to safety distance values from this study, a maximum of 10 W should be used in the ureter, and a maximum of 20 W should be used in kidney in presence of irrigation.

Acknowledging acute kidney disease following ureteroscopy and laser lithotripsy: results from a tertiary care referral center.

BACKGROUND: Acute kidney disease (AKD) is a recently described syndrome consisting of kidney function abnormalities lasting less than 3 months. Little is known regarding AKD following ureteroscopy (URS) and laser lithotripsy. OBJECTIVE: To evaluate the occurrence and evolution of AKD in stone patients treated with URS. MATERIALS AND METHODS: Data from 284 patients treated with URS for urinary stones were retrospectively analyzed. According to the KDIGO 2020 criteria, AKD was defined as postoperative acute kidney injury (AKI) occurrence, estimated glomerular filtration rate (eGFR) decrease ≥ 35%, or serum creatinine (SCr) increase ≥ 50%. AKI was defined as SCr increase ≥ 0.3 mg/dL or ≥ 50%. AKD evolution was evaluated 60 days post-URS. Data were analyzed using descriptive statistics. Univariable (UVA) and multivariable (MVA) logistic regression analyses tested the association of patients' characteristics and perioperative data with the occurrence of AKD. RESULTS: Overall, postoperative AKD occurred in 32 (11.3%) patients. Recovery from AKD was found in 26 (82%) patients and persistent AKD occurred in 6 (18%) patients. At UVA, age at surgery (p = 0.05), baseline SCr (p = 0.02), baseline CKD category (p = 0.006), Charlson comorbidity index (p = 0.01), operative time (p = 0.04) and postoperative complications (< 0.001) were associated with AKD. At MVA, CKD category (OR 2.99, 95% CI = 1.4-6.3; p = 0.004), operative time (OR 1.01, 95% CI = 1.001-1.018; p = 0.023) and postoperative complications (OR 3.5, 95% CI = 1.46-8.49; p = 0.005) were independent predictors of AKD. CONCLUSIONS: AKD is a frequent complication in patients treated with URS. Moreover, AKD persists in a non-neglectable percentage of patients at medium-term follow-up. Therefore, nephrological assessment should be considered, especially in high-risk patients. Current findings should be considered for the peri-operative management of stone patients.

Ureteral stents: What your eyes can't see! An in vitro study.

OBJECTIVES: To characterize and compare in vitro the surfaces of ureteral stents (STENTS) before utilization. METHODS: Our in vitro experiment included six unused STENTS models: three double-pigtail with side orifices (ImaJin and Stenostent [Coloplast©,France], TriaSoft [BostonScientific©,USA]), two double-pigtail without side orifice (Vortek-TumorStent [Coloplast©,France], Urosoft-TumorStent [Bard-Angiomed©,Germany]) and one single-pigtail (J-Fil [Rocamed©,Monaco]). STENTS were made of polyurethane except for ImaJin (silicone). For all STENTS, four parts of the stent were specifically analyzed under high-resolution scanning electron microscopy (HR-SEM,FEI-XL40 [Philips©,France]): surface core, lateral orifice, ureteral loop, and black marking surface. Each experiment was repeated with three different samples from three different stents. STENTS analysis included multiple imperfection searches, defined as irregularities>10µm. RESULTS: All STENTS presented imperfections with no discernible differences. Imperfections were mainly located on the stent loop and on the lateral orifice. For STENTS without side orifice (J-Fil, Urosoft) imperfections were also reported, on the beveled cut as well as the distal loop orifice. Marking surfaces examinations found defects in the Urosoft and imperfections in the ImaJin and Stenostent. The Triasoft presented a better smoothness on marking surfaces compared to other STENTS. Additional matter was reported on the loop distal orifice for J-Fil and ImaJin but all STENTS presented irregular cross-sectional aeras. CONCLUSION: All ureteral stents are not perfectly smooth even before utilization. Imperfections were noticed regardless to stent composition or shape, and could play a role in the incrustation phenomenon, is association with inner irregularities, infection, and urine composition. Both manufacturing and material could have an impact on the stent external surface's smoothness.

The Importance of Discordant Follicle Stimulating Hormone and Inhibin B Levels in Primary Infertile Men: Findings from a Cross-Sectional Study.

PURPOSE: We aimed to investigate the relationship between follicle stimulating hormone (FSH) and inhibin B (InhB). MATERIALS AND METHODS: Data from 1,230 consecutive men presenting for primary couple's infertility were analyzed. Health-significant comorbidities were scored with Charlson comorbidity index. Quartiles of FSH and InhB were considered to determine threshold values. Descriptive statistics and logistic regression models tested association between FSH and InhB values. RESULTS: Overall, 1,080 (87.8%) men had concordant FSH and InhB values. Conversely, 150 patients (12.2%) had discrepancies in FSH and InhB, with 78 (6.3%) and 72 (5.9%) men reporting both low and high FSH and InhB values, respectively. Infertile men with discordant values were younger (median [interquartile range] 38.0 years [34-41 years] vs. 36.0 years [31-40 years]); had smaller testicular volume (TV) (12 mL [10-15 mL] vs. 15 mL [12-20 mL]); and, had more frequently a sperm DNA fragmentation test >30% (179 [59.1%] vs. 40 [78.4%]) than those with concordant values (all p<0.05). Moreover, a higher frequency of previous cryptorchidism (27.3% vs. 11.9%), lower sperm concentration (3.0 million/mL [0.9-11.0 million/mL] vs. 13.8 million/mL [3.1-36.0 million/mL]), lower progressive sperm motility rates (12.0% [5.0%-25.3%] vs. 20.0% [7.0%-36.0%]), and greater rates of non-obstructive azoospermia (36.4% vs. 23.9%) were found in men with discordant FSH and InhB values (all p≤0.005). At multivariable logistic regression analysis, higher body mass index (odds ratio [OR], 1.08; p=0.001), smaller TV (OR, 0.91; p<0.001), and a history of cryptorchidism (OR, 2.49; p<0.001) were associated with discordant FSH and InhB values. CONCLUSIONS: More than one out of ten infertile men had discordant FSH and InhB values in the real-life setting showing worse clinical profiles than those with concordant levels. Smaller TV and history of cryptorchidism could be used as clinical markers to better tailor the need to test InhB.

PDE5is-naïve versus non-naïve patients at first investigation for erectile dysfunction-findings from a long-term, real-life cross-sectional study.

BACKGROUND: Phosphodiesterase 5 inhibitors (PDE5is) represent a first-line pharmacological therapy for erectile dysfunction (ED). Men could obtain PDE5is for recreational purposes without any proper medical prescription. OBJECTIVE: We aimed to analyze clinical characteristics of patients who already used any PDE5i for ED without previous formal medical prescription. MATERIALS AND METHODS: Data from 2012 heterosexual, sexually active men seeking first medical help for ED at our outpatient clinic between 2005 and 2022 were analyzed. All patients were assessed with a comprehensive sexual and medical history and completed the International Index of Erectile Function (IIEF) at baseline. Comorbidities were scored with the Charlson comorbidity index (CCI). Thereof, according to exposure to any PDE5i before their first visit, patients were subdivided into: PDE5i-naïve and non-PDE5i-naïve patients. Descriptive statistics tested the sociodemographic and clinical characteristics of both groups. A logistic regression model predicted the likelihood of being PDE5i-naïve at the baseline. Linear regression analysis (LRA) estimated the likelihood of being PDE5i-naïve versus non-PDE5i-naïve over the analyzed timeframe. Lastly, local polynomial regression models graphically explored the likelihood of being PDE5i-naïve at the first clinical assessment over the analyzed timeframe, and the sensitivity analyses tested the probability of being PDE5i-naïve at baseline. RESULTS: Overall, 1,491 (70.9%) patients were PDE5i-naïve and 611 (29.1%) were non-PDE5i-naïve at the first assessment. PDE5is-naïve patients were younger, with a lower prevalence of CCI ≥ 1 and of normal erectile function (EF) than non-PDE5i-naïve men (all p < 0.05). Multivariable logistic regression found that patients with lower BMI (OR: 0.99), higher IIEF-EF scores (OR: 1.02), lower rates of severe ED (OR: 0.94), and who had been assessed earlier throughout the study timeframe (OR: 1.27) were less likely to be PDE5i-naïve at baseline. Univariate LRA revealed that younger patients (Coeff: -0.02), with lower CCI (Coeff: -0.29) and higher alcohol intake per week (Coeff: 0.52) were more likely to be PDE5i-naïve over the analyzed timeframe. Moreover, for the same IIEF-EF score, patients with higher CCI had lower probability of being PDE5i-naïve. CONCLUSIONS: Self-prescription of PDE5is is an attitude presents in the general population, despite this phenomenon has decreased overtime. Current data outline the importance to keep promoting educational campaigns to promote PDE5is as effective and safe medicinal products, while avoiding their improper use.

Contemporary Diagnostic Work-Up for Male Infertility: Emphasizing Comprehensive Baseline Assessment.

Infertility is a prevalent issue affecting many couples during their reproductive years, with a significant number facing challenges in conceiving despite regular unprotected intercourse. Male factor infertility (MFI) contributes significantly to these cases, with a significant proportion of men lacking an identifiable etiology. As such, a thorough assessment of MFI has become increasingly vital for personalized management. This position paper from the Andrology team at IRCCS Ospedale San Raffaele emphasizes a comprehensive and individualized approach to MFI work-up, addressing the evolving challenges encountered in clinical practice. Our approach involves a thorough diagnostic work-up to identify the underlying causes of MFI, integrating insights from extensive literature review and our proprietary data. Our data demonstrates that an extensive diagnostic assessment allows us to identify at least one underlying cause of MFI in most infertile men. However, challenges persist in diagnosing less severe phenotypes with unclear etiology. We discuss the importance of individualized MFI work-up and its implications for developing rational therapeutic protocols. Lastly, this paper highlights the necessity for a personalized diagnostic assessment, addressing the daily clinical challenges and emphasizing tailored approaches to try to improve outcomes among couples seeking first medical help for infertility.

Urinary Symptoms Change and Quality of Life After Robotic Radical Prostatectomy: A Secondary Analysis of a Randomized Controlled Trial.

OBJECTIVE: To present the patient-reported quality of life (QoL) outcomes from a prospective, randomized controlled trial comparing the use of pelvic floor muscle training (PFMT) and duloxetine after robot-assisted radical prostatectomy (RARP). METHODS: We identified 213 men with organ-confined disease having post-RARP urinary incontinence who were randomly assigned to received PFMT, duloxetine, combined PFMT-duloxetine and pelvic floor muscle home exercises. Urinary symptoms burden was measured by marked clinical important difference improvement (MCID) defined by using the International Prostate Symptom Score (IPSS) difference of - 8 points (ΔIPSS ≤-8). QoL was assessed according to Visual Analog Scale (VAS), King's Health Questionnaire (KQH), and International Index of Erectile Function (IIEF-5). Multivariable regression analyses aimed to predict MCID, burden of urinary symptoms (IPSS ≥8), and patients reporting to be satisfied (IPSS QoL ≤2) or comfortable (VAS ≤1) post-RARP. RESULTS: Moderate to severe urinary symptoms decreased from 48% preoperatively to 40%, 34%, and 23% at 3, 6, and 12months post-RARP. After surgery, MCID improvement was observed in 19% of patients, and deterioration in 3.3%. Large prostate was the only factor associated to MCID (OR 1.03 [95%CI 1.01-1.05], P = .005). At 6months, patients reached the same degree of preoperative satisfaction. Neurovascular bundle preservation was the only predictor of being comfortable regarding urinary symptoms postoperatively (OR 12.8 [CI95% 1.47-111.7], P = .02 at 3months) and was also associated to higher median postoperative IIEF-5. CONCLUSION: Despite urinary incontinence following RARP, patients with larger prostates experience a reduction of lower urinary tract symptoms within a year, which subsequently elevates QoL. Furthermore, nerve-sparing surgery augments erectile function and urinary outcomes, shaping postoperative QoL.