Luca Boeri

Infertility as a proxy of general male health: results of a cross-sectional survey

OBJECTIVE To evaluate the prevalence, and clinical and seminal impact of comorbidities in white European men presenting for couple infertility. DESIGN Cross-sectional study. SETTING Academic reproductive medicine outpatient clinic. PATIENT(S) Cohort of 2,100 consecutive infertile men (noninterracial infertile couples). INTERVENTION(S) Obtaining complete demographic, clinical, and laboratory data from 2,100 consecutive infertile men with health-significant comorbidities scored via the Charlson comorbidity index (CCI; categorized 0 vs. 1 vs. ≥2) and semen analysis values assessed based on 2010 World Health Organization reference criteria. MAIN OUTCOME MEASURE(S) Assessment of the rate of comorbidities by means of CCI scores and possible associations between CCI, semen and hormonal parameters. RESULT(S) Descriptive statistics and regression models tested the associations among semen parameters, clinical characteristics, and CCI. When assessing general comorbidity prevalence, CCI 0, CCI 1, and CCI ≥2 was found in 1,921 (91.5%), 102 (4.9%), and 77 (3.6%) patients, respectively. Patient age and follicle-stimulating hormone levels increased as the general health status decreased. Conversely, the total testosterone levels and sperm concentration decreased as CCI scores increased. A higher rate of oligozoospermia and nonobstructive azoospermia was observed in patients with CCI ≥1. No differences were observed among the considered comorbidity groups in terms of testicular volume or further hormonal or seminal parameters. Both continuously coded and categorized sperm concentrations were independent predictors of CCI ≥1. Patients with sperm concentration <45.6 million/mL (most informative cutoff value) had a 2.74-fold increased risk of having a CCI ≥1. CONCLUSION(S) Decreased general health status appears to be associated with impaired male reproductive health, including lower sperm concentration, lower total testosterone levels, and higher follicle-stimulating hormone values.

Orgasmic Dysfunction After Robot-assisted Versus Open Radical Prostatectomy.

UNLABELLED Several alterations of orgasmic function that occur after radical prostatectomy (RP) have never been assessed in robot-assisted RP (RARP) series. We sought to assess the prevalence and predictors of recovery from orgasm-associated incontinence (climacturia) and painful orgasm (PO) after RARP and open RP (ORP). Following surgery, sexually active patients who had undergone either RARP or ORP prospectively completed a 28-item questionnaire including sensitive issues regarding sexual function (eg, climacturia and PO). Rates of postoperative climacturia and PO were compared for RARP and ORP patients. Kaplan-Meier analysis was applied to assess estimated rates of recovery from either climacturia or PO after both procedures. Cox regression models tested predictors of recovery from those conditions. Overall, 221 (29.5%) of 749 patients reported climacturia, without differences between RARP and ORP. Conversely, PO was significantly more frequently reported after ORP than after RARP (46 [11.6%] vs 25 [7.1%] patients, respectively; p=0.04). At Kaplan-Meier analysis, recovery from climacturia over time was faster and greater after RARP than after ORP (8.5% vs 5%, respectively, at 24-mo assessment and 48% vs 15%, respectively, at 84-mo assessment; p<0.01). Conversely, no differences were found between groups in terms of postoperative recovery from PO. At multivariable analysis, only RARP achieved independent predictor status for recovery from climacturia after adjusting for other functional outcomes. Conversely, no variables were significantly associated with recovery from postoperative PO. PATIENT SUMMARY Orgasmic modifications such as climacturia and painful orgasm (PO) are frequently reported after radical prostatectomy. Robotic surgery was associated with a lower rate of postoperative PO and with greater and faster recovery from climacturia.

Adipose-derived Stem Cells Counteract Urethral Stricture Formation in Rats

BACKGROUND A medical treatment for urethral stricture (US) is not yet available. OBJECTIVE To evaluate if local injection of human adipose tissue-derived stem cells (hADSC) prevents urethral fibrosis in a rat model of US. DESIGN, SETTING, AND PARTICIPANTS Male rats were divided into three groups: sham, US, and hADSC (n=12 each). Sham rats received a vehicle injection in the urethral wall. US and hADSCs were incised and injected with the fibrosis-inducer transforming growth factor-β1 in the urethral wall. INTERVENTION One day later, hADSCs were injected in the urethral wall of hADSC rats whereas sham and US rats were injected with the vehicle. After 4 wk, the rats underwent cystometries and tissues were then harvested for functional and molecular analyses. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Cystometry, microultrasound, histochemistry, organ bath studies, reverse transcription polymerase chain reaction, and western blot. RESULTS AND LIMITATIONS US rats exhibited 49-51% shorter micturition intervals, 35-51% smaller micturition volumes and bladder capacity, 33-62% higher threshold pressures and flow pressures, and 35-37% lower bladder filling compliance compared with hADSC-treated rats and sham rats (p<0.05). By ultrasound, US rats had hyperechogenic and thick urethral walls with narrowed lumen compared with sham rats, whereas hADSC rats displayed less extensive urethral changes. Isolated detrusor from US rats exhibited 34-55% smaller contractions than detrusor from sham rats (p<0.05). Corresponding values were 11-35% for isolated detrusors from hADSC rats. Collagen and elastin protein expression were increased in the penile urethras of US rats compared with sham and hADSC groups (p<0.05). Endothelial and inducible nitric oxide synthase expressions were higher (p<0.05) in the hADSC group. Compared with US rats, hADSC rats demonstrated decreased expression of several fibrosis-related genes. Administration of hADSCs was performed at an early stage of US development, which we consider a limitation of the study. CONCLUSIONS Local injection of hADSCs prevents stricture formation and urodynamic complications in a new rat model for US. PATIENT SUMMARY Stem cell therapy is effective for preventing urethral stricture in an experimental setting.

Peyronie's Disease and Autoimmunity—A Real-Life Clinical Study and Comprehensive Review

INTRODUCTION Although heavily investigated over the last decades, Peyronies disease (PD) pathogenesis remains unclear. AIM We sought to investigate the association between PD and autoimmune diseases (ADs) in men seeking medical help for sexual dysfunction in the real-life setting. METHODS Complete sociodemographic and clinical data from a homogenous cohort of 1,140 consecutive Caucasian-European men were analyzed. Health-significant comorbidities were scored with the Charlson Comorbidity Index and ADs were stratified according to International Classification of Diseases, Ninth Revision classification. MAIN OUTCOME MEASURES Descriptive statistics and multivariate logistic regression models tested the association between ADs and PD. RESULTS PD was diagnosed in 148 (13%) of the 1,140 men; of PD patients, 14 (9.5%) had a comorbid AD; conversely, the rate of ADs in non-PD patients was significantly lower (χ(2) = 24.7; P < 0.01). Both patient age and AD comorbidity achieved multivariable independent predictor status for PD (odds ratio [OR]: 1.05; P < 0.01 and OR: 4.90; P < 0.01, respectively). CONCLUSIONS Our observational findings showed that ADs are highly comorbid with PD in a large cohort of same-race individuals seeking medical help for sexual dysfunction in the real-life setting.

Serenoa repens, selenium and lycopene to manage lower urinary tract symptoms suggestive for benign prostatic hyperplasia

ABSTRACT Introduction: Benign prostatic hyperplasia (BPH) is a disease affecting most of the elderly male. α1-blockers and 5-alpha reductase inhibitors are currently used to target lower urinary tract symptoms (LUTS). Moreover phytotherapeutic agents, including Serenoa Repens (SeR), have shown to have a role in ameliorating BPH/LUTS alone or in combination of other elements like Selenium (Se) and Lycopene (Ly). Areas covered: A literature review was performed using data from articles assessing the role of of SeR+Se+Ly in the management of LUTS secondary to BPH. Diverging evidence on SeR’s efficacy is available. On one hand several studies have shown SeR efficacy in treating BPH/LUTS. SeR is effective in reducing prostate size, urinary frequency, dysuria, nocturia and in improving maximum urine flow-rate. On the other hand two long-term trials reported that SeR did not improve prostate size or urinary flow. SeR+Se+Ly in combination with tamsulosin is more effective than single therapies in improving IPSS and increasing maximal urinary flow-rate in patients affected by LUTS/BPH. Expert opinion: Despite great amount of preclinical and clinical studies, the use of SeR in BPH/LUTS is not sustained by clear evidence for a therapeutic efficacy but current data hint higher efficacy of of SeR+Se+Ly compared to SeR alone.

Efficacy and safety of dapoxetine in treatment of premature ejaculation: an evidence-based review.

Premature ejaculation (PE) is a major issue in male sexual health, with a global prevalence estimated to be between 20% and 40%, making it the most common sexual dysfunction in men. PE causes distress and reduced quality of life for patients and has a negative impact on interpersonal relationships. Historically, it has been treated with cognitive therapy, behavioural methods and off‐label use of selective serotonin reuptake inhibitors (SSRIs) usually used to treat depression and other psychological disorders. Dapoxetine is the only SSRI specifically designed to treat PE.

Metabolic syndrome in white European men presenting for primary couple's infertility: investigation of the clinical and reproductive burden.

Despite complex interactions between obesity, dyslipidemia, hyperinsulinaemia, and the reproductive axis, the impact of metabolic syndrome on human male reproductive function has not been analysed comprehensively. Complete demographic, clinical, and laboratory data from 1337 consecutive primary infertile men were analysed. Health‐significant comorbidities were scored with the Charlson Comorbidity Index (categorised 0 vs. 1 vs. 2 or higher). NCEP‐ATPIII criteria were used to define metabolic syndrome. Semen analysis values were assessed based on the 2010 World Health Organisation (WHO) reference criteria. Descriptive statistics and logistic regression models tested the association between semen parameters and clinical characteristics and metabolic syndrome. Metabolic syndrome was found in 128 (9.6%) of 1337 men. Patients with metabolic syndrome were older (p < 0.001) and had a greater Charlson Comorbidity Index of 1 or higher (chi‐square: 15.6; p < 0.001) compared with those without metabolic syndrome. Metabolic syndrome patients had lower levels of total testosterone (p < 0.001), sex hormone‐binding globulin (p = 0.004), inhibin B (p = 0.03), and anti‐Müllerian hormone (p = 0.009), and they were hypogonadal at a higher rate (chi‐square: 32.0; p < 0.001) than patients without metabolic syndrome. Conversely, the two groups did not differ significantly in further hormonal levels, semen parameters, and rate of either obstructive or non‐obstructive azoospermia. At multivariate logistic regression analysis, testicular volume (OR: 0.90; p = 0.002) achieved independent predictor status for WHO pathological semen concentration; conversely, age, Charlson Comorbidity Index scores, metabolic syndrome, and inhibin B values did not. No parameters predicted normal sperm morphology and total progressive motility. Metabolic syndrome accounts for roughly 9% of men presenting for primary couples infertility. Although metabolic syndrome patients have a lower general male health status, semen analysis values seem independent of the presence of metabolic syndrome.

Metabolic syndrome in White-European men presenting for secondary couple's infertility: An investigation of the clinical and reproductive burden

We aimed to determine the impact of metabolic syndrome (MetS) on reproductive function in men with secondary infertility, a condition that has received relatively little attention from researchers. Complete demographic, clinical, and laboratory data from 167 consecutive secondary infertile men were analyzed. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI; categorised 0 vs 1 vs 2 or higher). NCEP-ATP III criteria were used to define MetS. Semen analysis values were assessed based on the 2010 World Health Organization (WHO) reference criteria. Descriptive statistics and logistic regression models tested the association between semen parameters and clinical characteristics and MetS. MetS was found in 20 (12%) of 167 men. Patients with MetS were older (P < 0.001) and had a greater BMI (P < 0.001) compared with those without MetS. MetS patients had lower levels of total testosterone (P = 0.001), sex hormone-binding globulin, inhibin B, and anti-Mόllerian hormone (all P ≤ 0.03), and they were hypogonadal at a higher prevalence (P = 0.01) than patients without MetS. Moreover, MetS patients presented lower values of semen volume, sperm concentration, and sperm normal morphology (all P ≤ 0.03). At multivariate logistic regression analysis, no parameters predicted sperm concentration, normal sperm morphology, and total progressive motility. Our data show that almost 1 of 8 White-European men presenting for secondary couple′s infertility is diagnosed with MetS. MetS was found to be associated with a higher prevalence of hypogonadism, decreased semen volume, decreased sperm concentration, and normal morphology in a specific cohort of White-European men.

Detrusor Muscle in TUR-Derived Bladder Tumor Specimens: Can We Actually Improve the Surgical Quality?

INTRODUCTION Published series of transurethral resection of bladder tumor (TURBT) show high rates (18%-52%) of procedures resulting in no detrusor muscle (DM) layer being present in the pathologic specimen. This is of clinical importance since DM inclusion in surgical specimens is invariably associated with better oncologic results and is considered a surrogate marker of surgical quality. We sought to assess rates and predictors of DM absence (DM-) at a final pathology report in a series of consecutive TURBTs performed at a single tertiary-referral academic center. MATERIALS AND METHODS We retrospectively collected data from 437 TURBTs performed over 1 year. Complete endoscopic perioperative data were available for all patients; surgeons were categorized as either staff physicians or residents. Likewise, pathologic data, including tumor grade and stage, and DM status (present vs absent) were recorded. Only procedures with bladder cancer (BCa) at final pathology were included in the analyses. Logistic regression analyses tested potential predictors of DM-. Kaplan-Meier analyses were applied to assess the impact of DM- on postoperative tumor recurrence. RESULTS Overall, BCa was found in 302 (69.1%) specimens at final pathology; DM- occurred in 29 (9.6%) cases. A comparable rate of DM- was observed for procedures conducted by staff physicians and residents (9% [23/232] vs 12.8% [6/41], respectively; p = 0.6). Flat morphology emerged as the most informative predictor of DM- after adjusting for tumor size, number of lesions, tumor stage and grade, surgeon experience, and resection modality. At Kaplan-Meier analysis, DM- was not associated with worse outcomes in terms of postoperative recurrence-free survival. CONCLUSIONS Current findings showed a rate of roughly 10% of DM- at TURBT. Flat morphology emerged as the most significant predictor of DM-, whereas surgeon experience was not associated with DM-.

Long-term sexual outcomes after holmium laser enucleation of the prostate: which patients could benefit the most?

Assess rate and predictors of erectile function (EF) outcomes at long-term follow-up (FU) after holmium laser enucleation of the prostate (HoLEP). Cross-sectional analyses were performed on 135 patients with a mean FU of 12 years post HoLEP. Patients completed both a baseline and a FU International Index of Erectile Function (IIEF)-EF domain and the International Prostatic Symptoms Score (IPSS). Postoperative EF outcomes, including rate and predictors of EF improvement considering minimal clinically important differences (MCIDs) criteria, were assessed. Logistic regression models tested the association between predictors and EF. At a mean (median) FU of 152.1 (163) months, patients showed a significant decrease in the IIEF-EF score P<0.01) and significant IPSS improvement (P<0.01). Overall, 50 (37%) patients worsened by at least one IIEF-EF category. Conversel, 23 (17%) patients reported an improvement in postoperative IIEF-EF score; 75 (55.6%) and 10 (7.4%) patients maintained and eventually improved their IIEF-EF category, respectively. Patients reporting a decrease in the postoperative IIEF-EF score were significantly older (P=0.03) and showed a significantly longer mean FU (P<0.01) than those reporting postoperative improvements of IIEF-EF. Nine (6.7%) patients showed significant EF improvement according to MCIDs criteria. Both higher IPSS scores (odds ratio (OR): 1.12; P=0.02) and lower IIEF-EF (OR: 0.88; P<0.01) at baseline, emerged as independent predictors of postoperative EF improvement. HoLEP was associated with a decrease in EF and a persistent amelioration of BPH-related urinary symptoms at long-term FU. Almost one third of patients worsened by at least one IIEF-EF category. However, a clinically meaningful EF improvement was observed in roughly 7% of the individuals. Patients with more severe preoperative urinary symptoms and ED benefited more from HoLEP in terms of EF.