Evidence of restorative therapies in the treatment of Peyronie disease: A narrative review.

OBJECTIVE: To describe the evidence of Platelet Rich Plasma (PRP), Stem cells therapy (SCT) and Extracorporeal shockwave therapy (ESWL) for the treatment of Peyronies disease (PD), including information from the main urological society guidelines. MATERIALS AND METHODS: A literature review of PubMed articles published between 2000 and 2023 was conducted, utilizing keywords such as "Peyronie's Disease", "Penile curvature", "Platelet Rich Plasma", "Stem cells", and "Extracorporeal shockwave therapy". Only full-text articles in English were included, excluding case reports and opinions. RESULTS: A considerable number of clinical trials were conducted using PRP penile injections for therapy of PD, showing reduction of curvature, plaque size and improvement in quality of life. Preclinical studies in rats have shown the potential benefit of adipose-derived stem cells, with improvements in erectile function and fibrosis. Human studies with mesenchymal stem cells demonstrated promising results, with reduction of curvature and plaque size. ESWL effects on PD were investigated in randomized clinical trials and demonstrated no significant impact in curvature or plaque size, but reasonable effect on pain control. CONCLUSION: Restorative therapies has emerged as an innovative treatment option for PD and the results from current studies appear to be promising and demonstrated good safety profile. Unfortunately, due to scarce evidence, PRP and SCT are still considered experimental by American Urological Association (AUA) and European Association of Urology (EAU) guidelines. ESWT is recommended, by the same guidelines, for pain control only. More high-quality studies with long-term follow-up outcomes are needed to evaluate efficacy and reproducibility of those therapies.

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.

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.

Testosterone levels increase following bariatric surgery - validation of preceding literature in a large-scale population analysis.

BACKGROUND: The effects of bariatric surgery on testosterone levels in men with obesity and hypogonadism have not been thoroughly explored yet. OBJECTIVES: To investigate the possible effects of bariatric surgery on T levels in obese hypogonadal men by comparing T levels before and after surgery using a comprehensive claims database. MATERIALS AND METHODS: The TriNetX US Collaborative Network database was used to identify men ages 18-80 who underwent a bariatric procedure and had a serum T value of < 350 ng/dL prior to surgery. Men who received testosterone therapy before/or after surgery were excluded. We conducted a retrospective self-matched cohort analysis to examine the difference in serum T levels before and after bariatric surgery. A sub-analysis was carried out to explore differences between men who reached eugonadal status or maintained low T levels following surgery. Descriptive statistics detailed sociodemographic and clinical characteristics, with continuous and categorical data compared using unpaired t-tests and chi-square analysis, respectively. Changes in T levels and body mass index (BMI) before and after surgery were compared using an unpaired t-test with a < 0.05 set for significance. All analyses were conducted using the TriNetX platform which utilizes both Python and R software. RESULTS: The study analyzed 69 hypogonadal men who underwent bariatric surgery and had T levels assessed before and after the procedure. The mean (standard deviation) pre-surgery serum T level was 208 ± 79 ng/dL, which post-surgery increased to 371 ± 164 ng/dL, marking an average increase of 163 ± 164 ng/dL. Likewise, the mean (standard deviation) body mass index decreased from 42.9 ± 9.0 to 38.8 ± 5.7 kg/m2. Post-surgery, 45% (31 men) achieved eugonadal status, while 55% (38 men) continued to have low T levels. A comparison between the post-surgery eugonadal cohort and the persistent low T cohort revealed that the former had higher pre-surgery serum T levels (235 ± 71 ng/dL vs. 184 ± 80.4 ng/dL, p = 0.007), a higher pre-surgery body mass index (45.5 ± 4.5 kg/m2 vs. 41.1 ± 11.5 kg/m2, p = 0.041), and a significantly greater reduction in body mass index post-surgery (7.3 ± 7.2 kg/m2 vs. 2.0 ± 12.8 kg/m2, p = 0.04). Notably, the increase in T was significantly higher in the eugonadal cohort compared to the persistent low testosterone cohort (257 ± 143 ng/dL vs. 95 ± 178 ng/dL, p < 0.0001). CONCLUSION: This study provides evidence of bariatric surgery's positive effect on serum T levels in obese men with baseline low T. Almost one out of two men with low T reached normal T levels after bariatric surgery. As the most comprehensive study to date, it validates and substantiates previous work suggesting that weight loss can improve T levels physiologically.

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.

Detection of microplastics in the human penis.

The proliferation of microplastics (MPs) represents a burgeoning environmental and health crisis. Measuring less than 5 mm in diameter, MPs have infiltrated atmospheric, freshwater, and terrestrial ecosystems, penetrating commonplace consumables like seafood, sea salt, and bottled beverages. Their size and surface area render them susceptible to chemical interactions with physiological fluids and tissues, raising bioaccumulation and toxicity concerns. Human exposure to MPs occurs through ingestion, inhalation, and dermal contact. To date, there is no direct evidence identifying MPs in penile tissue. The objective of this study was to assess for potential aggregation of MPs in penile tissue. Tissue samples were extracted from six individuals who underwent surgery for a multi-component inflatable penile prosthesis (IPP). Samples were obtained from the corpora using Adson forceps before corporotomy dilation and device implantation and placed into cleaned glassware. A control sample was collected and stored in a McKesson specimen plastic container. The tissue fractions were analyzed using the Agilent 8700 Laser Direct Infrared (LDIR) Chemical Imaging System (Agilent Technologies. Moreover, the morphology of the particles was investigated by a Zeiss Merlin Scanning Electron Microscope (SEM), complementing the detection range of LDIR to below 20 µm. MPs via LDIR were identified in 80% of the samples, ranging in size from 20-500 µm. Smaller particles down to 2 µm were detected via SEM. Seven types of MPs were found in the penile tissue, with polyethylene terephthalate (47.8%) and polypropylene (34.7%) being the most prevalent. The detection of MPs in penile tissue raises inquiries on the ramifications of environmental pollutants on sexual health. Our research adds a key dimension to the discussion on man-made pollutants, focusing on MPs in the male reproductive system.

Artificial Intelligence Modeling and Priapism.

PURPOSE OF REVIEW: This narrative review aims to outline the current available evidence, challenges, and future perspectives of Artificial Intelligence (AI) in the diagnosis and management of priapism, a condition marked by prolonged and often painful erections that presents unique diagnostic and therapeutic challenges. RECENT FINDINGS: Recent advancements in AI offer promising solutions to face the challenges in diagnosing and treating priapism. AI models have demonstrated the potential to predict the need for surgical intervention and improve diagnostic accuracy. The integration of AI models into medical decision-making for priapism can also predict long-term consequences. AI is currently being implemented in urology to enhance diagnostics and treatment work-up for various conditions, including priapism. Traditional diagnostic approaches rely heavily on assessments based on history, leading to potential delays in treatment with possible long-term sequelae. To date, the role of AI in the management of priapism is understudied, yet to achieve dependable and effective models that can reliably assist physicians in making decisions regarding both diagnostic and treatment strategies.

Spontaneous erectile function recovery among young men with erectile dysfunction taking tadalafil 5 mg once a day.

BACKGROUND: Daily (once a day [OaD]) tadalafil intake is a valuable option for men favoring spontaneous over scheduled sexual intercourse. AIM: The study sought to assess the rate of and the clinical factors associated with spontaneous, medication-free erectile function (EF) recovery after discontinuation of tadalafil 5 mg OaD in a cohort of young men seeking first medical help for psychogenic erectile dysfunction (ED) as their primary complaint. METHODS: Data from 96 consecutive patients <50 years of age seeking first medical help for ED and prescribed tadalafil 5 mg OaD were analyzed. Patients completed the International Index of Erectile Function (IIEF) and underwent baseline penile color Doppler ultrasound. Follow-up involved clinical assessments or phone interviews. Spontaneous medication-free EF recovery was defined as IIEF EF domain score >22 after tadalafil discontinuation, prompting cessation of follow-up. Descriptive statistics compared tadalafil OaD responders and nonresponders. Cox regression hazard models explored the association between baseline characteristics and EF recovery risk post-drug discontinuation. Kaplan-Meier analyses estimated EF recovery probability over time. OUTCOMES: The primary outcome was EF recovery after discontinuation of tadalafil 5 mg OaD. RESULTS: Overall, median age was 39 (interquartile range [IQR], 32-45) years. Of all, 82 (85.4%) patients achieved EF recovery after tadalafil OaD discontinuation, while 14 (14.6%) patients were identified as nonresponders. Median tadalafil usage time (from beginning to discontinuation) was 3 (IQR, 2-11) months. The most common treatment-emergent adverse event was headache in 9 (9.4%) patients. Nonresponders were older (43 [IQR, 42-45] years vs 38 [IQR, 31-44] years; P = .03), had higher body mass index (25.5 [IQR, 23.4-29.9] kg/m2 vs 23.6 [IQR, 21.8-25.9] kg/m2; P = .04), and reported lower baseline IIEF EF domain scores (12 [IQR, 7-15] vs 15 [IQR, 10-22]; P = .02) than responders. Nonresponders and responders did not differ in terms of baseline ED severity, Charlson comorbidity index, smoking, alcohol consumption, regular physical exercise, and color Doppler ultrasound parameters. Upon Cox regression analysis, younger age (hazard ratio, 0.95; 95% confidence interval, 0.92-0.99; P = .01) was associated to EF recovery, after adjusting for baseline ED severity, body mass index, smoking, and Charlson comorbidity index ≥1. The Kaplan-Meier analysis displays the probability of EF recovery over time, indicating rates of 43%, 60%, and 72% at 3-, 6-, and 12-month follow-up intervals, respectively. CLINICAL IMPLICATIONS: Tadalafil 5 mg OaD is an effective short-term treatment for psychogenic ED, allowing its discontinuation after achieving a normal medication-free EF. STRENGTHS AND LIMITATIONS: The main limitations are the limited number of participants and the potential neglect of confounding factors. CONCLUSION: Almost 1 out of 2 young men with primary psychogenic ED who were prescribed with tadalafil 5 mg OaD recovered spontaneous medication-free EF after 3 months of treatment. Overall, the younger the patient was, the higher the chance there was of spontaneous EF recovery after drug discontinuation.

Role of Follicle-stimulating Hormone, Inhibin B, and Anti-Müllerian Hormone in Predicting Sperm Retrieval from Men with Nonobstructive Azoospermia Undergoing Microdissection Testicular Sperm Extraction: A Systematic Review and Meta-analysis.

Background and objective: No clear-cut markers for predicting positive sperm retrieval (+SR) at microdissection testicular sperm extraction (mTESE) have been identified thus far. Our aim was to conduct a systematic review and meta-analysis to evaluate the ability of follicle-stimulating hormone (FSH), inhibin B (InhB), and anti-Müllerian hormone (AMH) to predict +SR in men with nonobstructive azoospermia (NOA) undergoing mTESE. Methods: We performed a search in the PubMed, EMBASE, Web of Science, and Scopus databases according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Thirty-four publications were selected for inclusion in the analysis. Key findings and limitations: Overall, the mean +SR rate was 45%. Pooled standardized mean difference (SMD) values revealed significant hormonal differences between the +SR and -SR groups, with lower FSH (SMD -0.30), higher InhB (SMD 0.54), and lower AMH (SMD -0.56) levels in the +SR group. Pooled odds ratios (Ors) revealed no significant prediction of +SR by either FSH (OR 1.03, 95% confidence interval [CI] 1.00-1.06) or InhB (OR 1.01, 95% CI 1.00-1.02), despite variations in baseline levels and study heterogeneity. Conversely, AMH had significant predictive value (OR 0.82, 95% CI 0.73-0.92), with lower baseline levels in the +SR group. InhB and FSH levels were higher in the +SR group, while InhB exhibited the opposite trend. Conclusions and clinical implications: Despite study heterogeneity, our meta-analysis findings support the ability of AMH to predict +SR for men with NOA undergoing mTESE. Patient summary: We conducted a review and analysis of results from previous studies. Our findings show that for men with an infertility condition called nonobstructive azoospermia, blood levels of anti-Müllerian hormone can predict successful extraction of sperm using a microsurgical technique. Levels of two other hormones did not predict successful sperm extraction.

Eligibility for the medical therapy among men with non-obstructive azoospermia-Findings from a multi-centric cross-sectional study.

BACKGROUND: Existing literature does not provide accurate epidemiological data regarding the true prevalence of men with non-obstructive azoospermia (NOA) who would be eligible for hormonal optimization therapy, according to specific pre-treatment criteria. OBJECTIVES: To investigate the characteristics of those men with NOA who would qualify for the medical therapy prior to any SR procedure in a large multi-centric cross-sectional study. MATERIALS AND METHODS: Complete data from 1644 NOA patients seeking medical help for primary infertility at three tertiary referral centers from USA, Brazil, and Italy were analyzed. Baseline serum hormone levels were collected for all patients. NOA was confirmed after two consecutive semen analyses. Genetic tests, including karyotype analysis and Y microdeletions, were performed on all patients. Patients with secondary hypogonadism (total testosterone (T) levels less than 300 ng/dL and luteinizing hormone (LH) levels less than 8 mIU/mL) were earmarked as potential candidates for receiving clomiphene citrate (CC) and/or human chorionic gonadotropin (hCG). Patients with a T to 17ß-estradiol (E2) ratio < 10 were classified as eligible for aromatase inhibitors (AIs) therapy (e.g., anastrazole). A third sub-cohort was created by combining the criteria of the first two sub-cohorts. Descriptive statistics was used to detail overall characteristics and differences between the different sub-cohorts. RESULTS: Among the 1,644 men, 28% (n = 460) had T < 300 ng/dL and LH < 8 mIU/mL, thereby being potentially suitable for CC and/or hCG, while 37% (n = 607) had a T to E2 ratio < 10 thus potentially suitable for AIs. Lastly, 17.7% (n = 280) met the criteria for potential eligibility for both CC and/or hCG and AIs. CONCLUSIONS: Findings from this multicentric cross-sectional study reveal that about 30% of men with NOA were eligible for hormonal treatment with CC and/or hCG while 37% were found to be potential candidates for AIs, and 17% for both therapies. Therefore, these findings show that a only a small subset of NOA patients can benefit from medical therapy prior to considering any SR procedures.

Early versus late penile prosthesis surgery: a cross-sectional real-life study unveiling predictive factors.

Penile prosthesis implantation (PP surgery) is a well-established solution for severe, medication-refractory erectile dysfunction (ED). Despite its effectiveness, limited data exists on patient characteristics influencing the timing of PP surgery after ED onset. We aimed to investigate predictors for early PP surgery and compare preoperative factors in men who had early (<12 months) vs. late PP surgery (≥12 months). We analyzed data from 210 men undergoing inflatable PP surgery for medication-refractory ED to investigate predictors for early PP surgery. Men with early PP surgery were older (64 vs. 61 years), had more comorbidities, (97.2% vs. 63.3% CCI ≥ 1). Linear regression analysis showed that more comorbidities were associated with an earlier time to PP surgery (Coeff: -1.82, 95% CI: -3.08 to -0.56, p = 0.004). At multivariate Cox regression analysis, CCI ≥ 1 emerged as the sole predictor of early PP surgery (OR: 1.29, 95% CI: 1.07-1.56, p = 0.007) after adjusting for age, ED etiology, and ethnicity. Our study sheds light on factors influencing decisions for early vs. late PP surgery post-medication-refractory ED. Men with more comorbidities were more likely to receive early PP surgery, emphasizing the importance of preoperative counseling and personalized treatment plans.

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.

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.

Low Birth Weight is Associated with Sperm DNA Fragmentation and Assisted Reproductive Technology Outcomes in Primary Infertile Men: Results of a Cross-Sectional Study.

PURPOSE: To assess the relationship between clinical and semen characteristics and assisted reproductive technology (ART) outcomes with different birth weight (BW) categories in a cohort of infertile men. MATERIALS AND METHODS: Data from 1,063 infertile men were analyzed. Patients with BW ≤2,500, 2,500-4,000, and ≥4,000 g were considered as having low BW (LBW), normal BW (NBW), and high BW (HBW), respectively. Testicular volume (TV) was assessed with a Prader orchidometer. Serum hormones were measured in all cases. Semen analyses were categorized based on 2021 World Health Organization reference criteria. Sperm DNA fragmentation (SDF) was tested in every patient and considered pathological for SDF >30%. ART outcomes were available for 282 (26.5%) patients. Descriptive statistics and logistic regression analyses detailed the association between semen parameters and clinical characteristics and the defined BW categories. RESULTS: Of all, LBW, NBW, and HBW categories were found in 79 (7.5%), 807 (76.0%), and 177 (16.5%) men, respectively. LBW men had smaller TV, presented higher follicle-stimulating hormone (FSH) but lower total testosterone levels compared to other groups (all p<0.01). Sperm progressive motility (p=0.01) and normal morphology (p<0.01) were lower and SDF values were higher (all p<0.01) in LBW compared to other groups. ART pregnancy outcomes were lower in LBW compared to both NBW and HBW categories (26.1% vs. 34.5% vs. 34.5%, p=0.01). At multivariable logistic regression analysis, LBW was associated with SDF >30% (odd ratio [OR] 3.7; p<0.001), after accounting for age, Charlson Comorbidity Index (CCI), FSH, and TV. Similarly, LBW (OR 2.2; p<0.001), SDF >30% (OR 2.9; p<0.001) and partner's age (OR 1.3; p=0.001) were associated with negative ART outcomes, after accounting for the same predictors. CONCLUSIONS: LBW was associated with impaired clinical and semen characteristics in infertile men compared to both NBW and HBW. SDF and ART outcomes were significantly worse in the LBW group.

A Systematic Review and Meta-analysis on the Impact of Infertility on Men's General Health.

CONTEXT: Male infertility has been associated with increased morbidity and mortality. OBJECTIVE: To perform a systematic review and meta-analysis to provide the most critical evidence on the association between infertility and the risk of incident comorbidities in males. EVIDENCE ACQUISITION: A systematic review and meta-analysis was performed according to the Meta-analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and registered on PROSPERO. All published studies on infertile versus fertile men regarding overall mortality and risks of cancer, diabetes, and cardiovascular events were selected from a database search on PubMed, EMBASE, Google Scholar, and Cochrane. Forest plot and quasi-individual patient data meta-analysis were used for pooled analyses. A risk of bias was assessed using the ROBINS-E tool. EVIDENCE SYNTHESIS: Overall, an increased risk of death from any cause was found for infertile men (hazard risk [HR] 1.37, [95% confidence interval {CI} 1.04-1.81], p = 0.027), and a 30-yr survival probability of 91.0% (95% CI 89.6-92.4%) was found for infertile versus 95.9% (95% CI 95.3-96.4%) for fertile men (p < 0.001). An increased risk emerged of being diagnosed with testis cancer (relative risk [RR] 1.86 [95% CI 1.41-2.45], p < 0.001), melanoma (RR 1.30 [95% CI 1.08-1.56], p = 0.006), and prostate cancer (RR 1.66 [95% CI 1.06-2.61], p < 0.001). As well, an increased risk of diabetes (HR 1.39 [95% CI 1.09-1.71], p = 0.008), with a 30-yr probability of diabetes of 25.0% (95% CI 21.1-26.9%) for infertile versus 17.1% (95% CI 16.1-18.1%) for fertile men (p < 0.001), and an increased risk of cardiovascular events (HR 1.20 [95% CI 1.00-1.44], p = 0.049), with a probability of major cardiovascular events of 13.9% (95% CI 13.3-14.6%) for fertile versus 15.7% (95% CI 14.3-16.9%) for infertile men (p = 0.008), emerged. CONCLUSIONS: There is statistical evidence that a diagnosis of male infertility is associated with increased risks of death and incident comorbidities. Owing to the overall high risk of bias, results should be interpreted carefully. PATIENT SUMMARY: Male fertility is a proxy of general men's health and as such should be seen as an opportunity to improve preventive strategies for overall men's health beyond the immediate reproductive goals.

Unrecognised orgasmic phase disorders in men presenting with new-onset erectile dysfunction-Findings from a real-life, cross-sectional study.

BACKGROUND: Orgasmic phase disorders in men worsen the burden of erectile dysfunction on sexual satisfaction. OBJECTIVES: To investigate the prevalence of and predictors of unreported orgasmic phase disorder in a cohort of men looking for their first urological assessment for new-onset erectile dysfunction in a real-life setting. MATERIALS AND METHODS: Data from 1107 heterosexual, sexually active men consecutively assessed for new-onset erectile dysfunction were analysed. Throughout a comprehensive medical and sexual history, all patients were asked to self-report any orgasmic phase disorder and to complete the International Index of Erectile Function and the Beck's Inventory for Depression (depressive symptoms scored as Beck's Inventory for Depression ≥11). Men self-reporting orgasmic phase disorder during the interview were excluded from further analyses. The median value of the International Index of Erectile Function-orgasmic function domain was arbitrarily used to categorise men with (International Index of Erectile Function-orgasmic function ≤5) and without unreported orgasmic phase disorder (International Index of Erectile Function-orgasmic function >5). Circulating hormones were measured in every patient. Descriptive statistics and logistic regression models were used to test the association between clinical variables and unreported orgasmic phase disorder. RESULTS: Of 1098 patients with non-self-reporting orgasmic phase disorder, 314 (28.6%) had International Index of Erectile Function-orgasmic function ≤5. Patients with erectile dysfunction + unreported orgasmic phase disorder were older (median [interquartile range]: 58 [44-66] years vs. 51 [40-60] years), had higher body mass index [25.8 (23.7-28.1) kg/m2 vs. 25.2 (23.3-27.4) kg/m2 ], higher prevalence of type 2 diabetes (36 [11.5%] vs. 45 [5.7%]) and lower International Index of Erectile Function-erectile function scores (6 [2-10] vs. 18 [11-24]) than men with erectile dysfunction-only (all p < 0.05). Patients with erectile dysfunction + unreported orgasmic phase disorder depicted higher rates of severe erectile dysfunction (75.5% vs. 25%) and Beck's Inventory for Depression ≥11 (22.6% vs. 17.9%) (all p < 0.05). In the multivariable logistic regression analysis, older age (odds ratio: 1.02) and lower International Index of Erectile Function-erectile function scores (odds ratio: 0.83) were independently associated with unreported orgasmic phase disorder (all p < 0.05). CONCLUSIONS: Almost one in three men seeking first medical help for erectile dysfunction depicted criteria suggestive of unreported orgasmic phase disorder. Men with unreported orgasmic phase disorder were older and had higher rates of severe erectile dysfunction and concomitant depressive symptoms. These real-life findings outline the clinical relevance of a comprehensive investigation of concomitant sexual dysfunction in men only complaining of erectile dysfunction to more effectively tailor patient management.