Age, Sperm Retrieval, and Testicular Histology in Klinefelter Syndrome.

PURPOSE: We sought to examine sperm retrieval and testicular histology in males of different ages with Klinefelter syndrome. MATERIALS AND METHODS: We identified all males with Klinefelter syndrome who underwent microdissection testicular sperm extraction at our institution from 1995 to 2020. Patients were divided into adolescent (<20 years) and adult (≥20 years) cohorts. Histology and sperm retrieval were compared using chi-square statistics. Multivariable logistic regression models were used to examine factors associated with successful sperm retrieval. RESULTS: We identified 217 males with Klinefelter syndrome, of whom 59 were adolescents and 158 were adults. Adults were stratified into 10-year groupings (20-29 years, n = 62; 30-39 years, n = 88; ≥40 years, n = 8). Approximately 17% of adolescents had testis histology containing germ cells compared with 15% of the 20 to 29-year cohort, 14% of the 30 to 39-year cohort, and 0% over 40 years. In comparison to adolescents (53%), the sperm retrieval rate was significantly higher in the 20 to 29-year cohort (71%, P = .04) and lower in the ≥40-year cohort (13%, P = .03). In multivariable analysis, the presence of hypospermatogenesis on testis biopsy (OR 5.8, P = .03) was associated with higher odds of successful sperm retrieval. CONCLUSIONS: Younger males more frequently had germ cell-containing testis histology, however this finding was not associated with a higher odds of sperm retrieval. Reproductive urologists should counsel azoospermic males with Klinefelter syndrome that sperm retrieval during adolescence for fertility preservation is not required and can be performed in young adulthood.

Fertility assessment and treatment in adolescent and young adult cancer survivors.

In the survivorship setting, adolescent and young adult (AYA) cancer survivors frequently demonstrate little knowledge of infertility risk, are unclear regarding their fertility status, and may under- or overestimate their treatment-related risk for infertility. In female AYA survivors, ovarian function usually parallels fertility, and can be assessed with serum hormone levels and ultrasonography. Posttreatment fertility preservation may be appropriate for survivors at risk for primary ovarian insufficiency. In male AYA survivors, fertility and gonadal function are not always equally affected, and can be assessed with a semen analysis and serum hormones, respectively. As reproductive health issues are commonly cited as an important concern by survivors of AYA cancer, multidisciplinary care teams including oncology, endocrinology, psychology, and reproductive medicine are advocated, with the aim of optimal provision of fertility advice and care for AYA cancer survivors.

The use of fresh compared to frozen ejaculated sperm has no impact on fresh embryo transfer cycle reproductive outcomes.

PURPOSE: To compare the reproductive outcomes of fresh embryo transfer (ET) cycles utilizing fresh versus frozen ejaculated sperm. METHODS: First autologous fresh embryo transfer cycles at a single high-volume academic institution between 2013 and 2019 were retrospectively reviewed. IVF cycles using ejaculated sperm were included, and cycles using donor or surgically retrieved sperm were excluded. Sperm concentration was stratified as ≥ 5 and < 5 million/ml. The primary outcome was live birth, and the secondary outcomes were clinical intrauterine pregnancy (IUP) and miscarriage. A multivariable logistic regression model for the aforementioned outcomes was adjusted a priori for sperm concentration as well as maternal and paternal age. RESULTS: A total of 6128 couples were included. Of these, 5780 (94.3%) utilized fresh sperm, and 348 (5.7%) frozen sperm. A total of 5716 (93.2%) had sperm concentrations ≥ 5 million/ml and 412 (6.7%) had sperm concentrations < 5 million/ml. On multivariable logistic regression, the use of freshly ejaculated sperm was not associated with significantly different odds of clinical IUP, miscarriage, or live birth when compared to cycles using frozen sperm. CONCLUSION: For couples conceiving via fresh ET, the use of fresh versus frozen ejaculated sperm is not associated with reproductive outcomes.

Immune Deficiency Does Not Increase Inflatable Penile Prosthesis Reoperation Rates.

INTRODUCTION: Immunocompromised patients are postulated to have higher rates of post-operative infection. We sought to determine if inflatable penile prosthesis (IPP) reoperation rates (due to infection, erosion, device malfunction or patient dissatisfaction) are higher among immunocompromised men. METHODS: We analyzed men who underwent initial IPP insertion from 2000 to 2016 in the New York Statewide Planning and Research Cooperative System database. Immunocompromised patients were propensity-score matched in a 1:3 fashion with immunocompetent patients. We estimated and compared reoperation rates (including removal, reoperation due to infection, revision, or replacement of an IPP after an index procedure) at 30 days, 90 days, 1 year and 3 years of follow up between immunocompromised men and controls by performing a Kaplan Meier analysis and Log-rank tests. Cox proportional hazards models were built to examine the overall association between immune deficient status and the risk of reoperation. MAIN OUTCOME MEASURE: Reoperation rate and time to reoperation after index IPP placement. RESULTS: A total of 245 immunocompromised patients who received an initial IPP between 2000 and 2016 were identified. After propensity score matching, we analyzed 235 immunocompromised men and 705 controls. There was no difference in overall reoperation rates between immunocompromised men and controls within any time period assessed (30 days, 90 days, 1 year, or 3 years). In our Cox proportional hazards model, the hazards of overall reoperation, removal, or revision/replacement (HR 1.11 [95% CI 0.74-1.67], HR 1.58 [95% CI 0.90-2.79)], and HR 0.83 [95% CI 0.47-1.45], respectively) were not significant different between immunocompromised men and controls. Reoperation due to infection was also not significantly different between immunocompromised and immunocompetent men (HR 2.06 [95% CI 0.97-4.40]). STRENGTHS & LIMITATIONS: This study is strengthened by its size as the largest cohort of immunocompromised men treated with IPP to date in the literature, but is limited by the retrospective nature of the database which may introduce selection bias and by the low event rate for IPP reoperation. CONCLUSIONS: Reoperation rates, including those due to infection, are not significantly different between immunocompromised men and immunocompetent controls. Therefore, immune status in appropriately selected candidates does not appear to place patients at substantially higher risk of explant or revision. Gaffney CD, Fainberg J, Aboukhshaba A, et al. Immune Deficiency Does Not Increase Inflatable Penile Prosthesis Reoperation Rates. J Sex Med 2021;18:1427-1433.

Predictors of varicocele-associated pain and its impact on semen parameters following microsurgical repair.

Our study aimed to assess for predictors of varicocele-associated pain and whether it predicts semen parameters after microsurgical varicocelectomy. We assessed all men diagnosed with a varicocele by two surgeons from 2017 to 2020, excluding those who did not undergo surgical treatment. Patients were stratified based on the presence of pain at clinical assessment, and these groups were compared. Logistic regression models were utilised to assess for predictors of pain. A total of 313 men were included, with relatively similar proportions completed by both surgeons (48.2% and 51.8%). A total of 98 (31.3%) had typical varicocele-associated pain at the time of assessment. The pain group was younger than the no pain group (30.5 versus. 35.0, respectively, p < .01), and those with pain had greater varicocele grades (p = .008). Although not statistically different, there was a greater portion of left-sided only varicoceles in the pain group (p = .09). No significant differences were demonstrated between sperm concentration, motility, volume or morphology pre-operatively, or post-operatively between groups. Younger age and varicocele grade were predictive of varicocele-associated pain. In conclusion, almost 1/3 of men presented with varicocele-associated pain. Pain does not predict response to varicocelectomy, but these men tend to be younger, and have higher grade varicoceles.

Prostatic irradiation-induced sexual dysfunction: A review and multidisciplinary guide to management in the radical radiotherapy era (Part II on Urological Management).

Prostate cancer is the most common malignancy in men and the second leading cause of cancer-related death in men. Radiotherapy is a curative option that is administered via external beam radiation, brachytherapy, or in combination. Sexual dysfunction is a common toxicity following radiotherapy, similar to men undergoing radical prostatectomy, but the etiology is different. The pathophysiology of radiation-induced sexual dysfunction is multi-factorial, and the toxicity is a major cause of impaired quality of life among long-term prostate cancer survivors. Management of a patient's sexual function during and after radiotherapy requires multidisciplinary coordination of care between radiation oncology, urology, psychiatry, pharmacy, and dermatology. This review provides a framework for clinicians to better understand prostatic radiotherapy-induced sexual dysfunction diagnosis, evaluation, and a patient-centered approach to toxicity preventive strategies and management.

Prostatic irradiation-induced sexual dysfunction: a review and multidisciplinary guide to management in the radical radiotherapy era (Part I defining the organ at risk for sexual toxicities).

Prostate cancer is the most common malignancy and the second leading cause of cancer-related death in men. Radiotherapy is a curative option that is administered via external beam radiation, brachytherapy, or in combination. Erectile, ejaculatory and orgasm dysfunction(s) is/are known potential and common toxicities associated with prostate radiotherapy. Our multidisciplinary team of physicians and/or scientists have written a three (3) part comprehensive review of the pathogenesis and management radiation-induced sexual dysfunction. Part I reviews pertinent anatomy associated with normal sexual function and then considers the pathogenesis of prostate radiation-induced sexual toxicities. Next, our team considers the associated radiobiological (including the effects of time, dose and fractionation) and physical (treatment planning and defining a novel Organ at Risk (OAR)) components that should be minded in the context of safe radiation treatment planning. The authors identify an OAR (i.e., the prostatic plexus) and provide suggestions on how to minimize injury to said OAR during the radiation treatment planning process.

A Contemporary Analysis of Dual Inflatable Penile Prosthesis and Artificial Urinary Sphincter Outcomes.

PURPOSE: Inflatable penile prostheses and artificial urinary sphincters are used to treat men with erectile dysfunction and stress urinary incontinence, respectively. After prostate cancer treatment men often experience erectile dysfunction and stress urinary incontinence. Dual prosthetic implantation can improve the quality of life of these men. We evaluated reoperation outcomes in men who underwent dual implantation compared to each device implanted individually. MATERIALS AND METHODS: We queried the SPARCS (New York State Department of Health Statewide Planning and Research Cooperative) database for men who underwent inflatable penile prosthesis and/or artificial urinary sphincter insertion between 2000 and 2014. The primary outcomes were the inflatable penile prosthesis and artificial urinary sphincter reoperation rates (revision, replacement or removal). Multivariable regression analysis was performed to assess the association of dual implantation with reoperation. Adjusted time to event analysis was also performed. RESULTS: Median followup in the inflatable penile prosthesis cohort was 66 months (IQR 25-118) and in the artificial urinary sphincter cohort it was 69 months (IQR 27-121). Compared with men who received a penile prosthesis alone those with a penile prosthesis and an artificial urinary sphincter had a higher likelihood of undergoing inflatable penile prosthesis reoperation at 1 year (OR 2.08, 95% CI 1.32-3.27, p <0.01) and 3 years (OR 2.60, 95% CI 1.69-3.99, p <0.01). Compared with an artificial urinary sphincter alone patients with an inflatable penile prosthesis and an artificial urinary sphincter did not have a higher likelihood of undergoing artificial urinary sphincter reoperation at 1 year (p = 0.76) or 3 years (p = 0.73). CONCLUSIONS: Combined inflatable penile prosthesis and artificial urinary sphincter insertion portends a higher likelihood of inflatable penile prosthesis reoperation at 1 and 3 years. However, artificial urinary sphincter outcomes remain comparable. These findings should be used to better counsel patients about the risk of reoperation when undergoing dual implantation.

Impact of Pelvic Radiation Therapy on Inflatable Penile Prosthesis Reoperation Rates.

INTRODUCTION: Considering that radiation therapy (RT) compromises soft tissue microvasculature, impairs wound healing, and causes cavernosal fibrosis, inflatable penile prosthesis (IPP) outcomes may be adversely affected in men treated with RT. AIM: To compare IPP outcomes among those who had undergone prior RT vs a cohort who underwent radical prostatectomy (RP) before insertion of IPP. METHODS: The Surveillance, Epidemiology, and End Results (SEER)-Medicare Database was queried for men with prostate cancer (PCa) who underwent RT (n = 83,277) or RP (n = 32,608) with subsequent IPP insertion between 2002 and 2013. Men who had undergone both RT and RP were excluded from the analysis. MAIN OUTCOME MEASURE: The primary outcome was reoperation, defined by removal, revision, or replacement of the IPP. RESULTS: We identified 350 men who received an IPP following RT and 653 who received an IPP following RP. Men who underwent RT were older (P < .01) and had more comorbidities (P < .01). There were no significant differences in overall reoperation rates at 90 days (P = .78), 1 year (P = .52), or 3 years (P = .48). Time-to-event analysis demonstrated that RT was not associated with an increased likelihood of overall reoperation (hazard ratio [HR] 1.46, 95% confidence interval [CI] 0.94-2.29, P = .09). There was no association between time from RT to IPP and overall reoperation rates. CLINICAL IMPLICATIONS: Prior RT for the treatment of PCa does not impact the revision or removal rates of IPPs as compared with a cohort of non-radiated patients who underwent RP. STRENGTH & LIMITATIONS: The strength includes the analysis of outcomes among a contemporary, nationwide cohort with robust follow-up. Using diagnosis and procedure codes, we were thoroughly able to capture reoperations. Limitations include the lack of specific indications for reoperation and inability to control for surgeon experience or technique. CONCLUSION: IPP is a safe and effective treatment of erectile dysfunction that should be offered to men with a history of pelvic radiation who have failed medical therapy. Golan R, Patel NA, Sun T, et al. Impact of pelvic radiation therapy on inflatable penile prosthesis reoperation rates. J Sex Med 2018;15:1653-1658.

Trends in Penile Prosthetics: Influence of Patient Demographics, Surgeon Volume, and Hospital Volume on Type of Penile Prosthesis Inserted in New York State.

INTRODUCTION: Penile prostheses (PPs) are a discrete, well-tolerated treatment option for men with medical refractory erectile dysfunction. Despite the increasing prevalence of erectile dysfunction, multiple series evaluating inpatient data have found a decrease in the frequency of PP surgery during the past decade. AIMS: To investigate trends in PP surgery and factors affecting the choice of different PPs in New York State. METHODS: This study used the New York State Department of Health Statewide Planning and Research Cooperative (SPARCS) data cohort that includes longitudinal information on hospital discharges, ambulatory surgery, emergency department visits, and outpatient services. Patients older than 18 years who underwent inflatable or non-inflatable PP insertion from 2000 to 2014 were included in the study. OUTCOMES: Influence of patient demographics, surgeon volume, and hospital volume on type of PP inserted. RESULTS: Since 2000, 14,114 patients received PP surgery in New York State; 12,352 PPs (88%) were inflatable and 1,762 (12%) were non-inflatable, with facility-level variation from 0% to 100%. There was an increasing trend in the number of annual procedures performed, with rates of non-inflatable PP insertion decreasing annually (P < .01). More procedures were performed in the ambulatory setting over time (P < .01). Important predictors of device choice were insurance type, year of insertion, hospital and surgeon volume, and the presence of comorbidities. CLINICAL IMPLICATIONS: Major influences in choice of PP inserted include racial and socioeconomic factors and surgeon and hospital surgical volume. STRENGTHS AND LIMITATIONS: Use of the SPARCS database, which captures inpatient and outpatient services, allows for more accurate insight into trends in contrast to inpatient sampling alone. However, SPARCS is limited to patients within New York State and the results might not be generalizable to men in other states. Also, patient preference was not accounted for in these analyses, which can play a role in PP selection. CONCLUSIONS: During the past 14 years, there has been an increasing trend in inflatable PP surgery for the management of erectile dysfunction. Most procedures are performed in the ambulatory setting and not previously captured by prior studies using inpatient data. Kashanian JA, Golan R, Sun T, et al. Trends in Penile Prosthetics: Influence of Patient Demographics, Surgeon Volume, and Hospital Volume on Type of Penile Prosthesis Inserted in New York State. J Sex Med 2018;15:245-250.

Pediatric Oncology Providers' Attitudes and Practice Patterns Regarding Fertility Preservation in Adolescent Male Cancer Patients.

BACKGROUND: The aim of this study was to evaluate pediatric oncology providers' attitudes toward fertility preservation (FP), their use of educational materials, their approach to FP discussion, and their FP knowledge specifically pertaining to adolescent males. METHODS: A 40-item online survey was distributed to physicians, advanced practice nurses (APN), and nurses within pediatric oncology. RESULTS: About 78.7% of physicians, 81.4% of APN, and 51.9% of nurses reported high levels of comfort in discussing FP options with adolescent males (P<0.05). Fifty-one percent of physicians and 54.2% of APN reported using educational materials, compared with 38.9% of nurses (P<0.05). Regarding knowledge of FP technologies, 48.7% of physicians, 52.5% of APN, and 81.1% of nurses reported being unfamiliar with intracytoplasmic sperm injection (P<0.05). An overwhelming majority (92.9%) of respondents reported having no formal training in discussing FP. Finally, 84.8% of respondents believed formal training on this issue would be useful to them. CONCLUSIONS: This study illustrates an unmet need in the education of pediatric oncology providers, as knowledge gaps and discomfort are common themes reported by health care professionals within the context of adolescent male FP care. In addition, this study reveals a high level of receptiveness to FP training by these same providers.

Real-world practice in Peyronie's disease management: Results from a national survey of urologists.

BACKGROUND: Despite many available treatments for Peyronie's disease (PD), practice patterns of available therapeutics are not well characterized. OBJECTIVE: We conducted a national survey of urologists to characterize real-world practice patterns of PD management and to characterize the use of therapies discouraged by the American Urological Association guidelines on PD management. MATERIALS AND METHODS: A 34-item survey was distributed via RedCap to urologists who treat patients with PD in all American Urological Association sections. Questions elicited demographic information as well as practices in the diagnosis and treatment of PD. Comparisons were made with Pearson's chi-squared test. The primary outcome was reported use of therapies discouraged by the American Urological Association guidelines on PD. RESULTS: A total of 145 respondents completed the survey, of whom 19% were fellowship trained in andrology/sexual medicine, 36% practiced in an academic setting, and 50% had at least 20 years in practice. Only 60% of respondents reporting performing in-office curvature assessment prior to commencing intralesional injection or surgical treatment, with higher prevalence in andrology/sexual medicine fellowship-trained versus non-fellowship-trained urologists (85% vs. 54%, p = 0.003). The most popular treatment modalities were collagenase clostridium histolyticum (61% of respondents), phosphodiesterase-5 inhibitors (54%), and penile traction (53%). Twenty-one percent of respondents reported currently using a treatment that is explicitly discouraged by the American Urological Association guidelines (extracorporeal shockwave therapy for curvature, L-carnitine, omega-3 fatty acids, or vitamin E). DISCUSSION: Patients seeking PD treatment may be offered different therapies, some of which are not evidence-based, depending on the treating urologist. This study is limited by self-selection and response bias. Its strength is that it represents a cross-sectional overview of real-world practice patterns in PD management, which has not been previously described. CONCLUSIONS: A significant proportion of urologists reported PD management practices that are not evidence-based and not guideline-supported.

Trends in Antimicrobial Prophylaxis for Inflatable Penile Prosthesis Surgery From a Large National Cohort.

OBJECTIVE: To assess changes in antibiotic prophylaxis for inflatable penile prosthesis surgery following publication of the American Urological Association (AUA) Best Practice Statement in April 2008. MATERIALS AND METHODS: The Premier Healthcare Database was queried for inflatable penile prosthesis surgeries from January 2000 to March 2020. The primary outcome was administration of an AUA-adherent antimicrobial regimen and secondary outcome was 90-day explant. Piecewise linear regression was used to compare antimicrobial trends before vs after guideline publication. Multivariable logistic regression models were constructed for primary and secondary outcomes. RESULTS: A total of 26,574 patients who underwent inflatable penile prosthesis surgery were identified, of whom 17,754 (67%) received AUA-adherent antibiotics. After guideline publication, there was a 42% relative increase in AUA-adherent regimen usage, with an increase in the usage trend on piecewise linear regression (from 0.1% to 0.8% of encounters per quarter, R2 = 0.75, P < .001). Increased usage trends were also observed for gentamicin (from 0.0% to 1.0% of encounters per quarter, R2 = 0.84, P < .001) and vancomycin (0.1%-0.7%, R2 = 0.77, P < .001). On multivariable regression, odds of AUA-adherence increased after guideline publication (OR: 1.67, 95% CI: 1.54-1.80, P < .001) and with surgery by a high-volume surgeon (OR: 2.21, 95% CI: 2.07-2.35, P < .01). Nonadherence to an AUA-recommended regimen with use of nonstandard antibiotics (OR: 1.16, 95% CI: 0.78-1.71, P = .5) or excess antibiotics (OR: 0.91, 95% CI: 0.62-1.30, P = .6) was not independently associated with increased risk of 90-day explant. CONCLUSIONS: Publication of the AUA Best Practice Statement was associated with subsequent increases in the usage of guideline-adherent antibiotic regimens, particularly vancomycin and gentamicin, despite absence of level-1 evidence supporting this combination.

Utility of evaluating semen samples from adolescents with Klinefelter Syndrome for cryopreservation: A multi-institution evaluation.

INTRODUCTION: Klinefelter Syndrome (KS) is the most common genetic condition cause of non-obstructive azoospermia (NOA). KS also often results in decreased testicular growth and testosterone production. Because of this, exogenous testosterone therapy is commonly prescribed for KS patients to treat hypogonadism, but this may have additional impacts to future fertility potential. KS adolescent patients may be asked to provide multiple semen samples to identify potential sperm for early cryopreservation. OBJECTIVE: To develop a multi-institutional database to evaluate the prevalence of sperm in the ejaculate of adolescent KS patients. METHODS: A retrospective study was performed of all adolescent KS patients seen at two high-volume tertiary male infertility clinics between 2015 and 2020. Adolescence was defined as individuals aged 12-19 years, as per the World Health Organization. Demographic information data including weight, height, medical comorbidities, and concurrent medications were collected. Serum hormone levels including FSH, LH, and testosterone were collected, as well as any available semen analysis data. RESULTS: A total of 116 patients were identified and included in the database. A total of 100 (86.2%) had hormone data available and 48 (41.3%) had semen analysis data. Of the 48 patients with semen analyses, only 4 (8.3%) patients had rare sperm in the ejaculate while the remaining had azoospermia (91.7%). None of the specimens were suitable for cryopreservation. The average serum total testosterone level of adolescent KS patients was 181 ± 216 ng/dL. FSH levels were 14.3 ± 18.8 IU/L (normal 0.3-10.0 IU/L) and LH levels were 7.8 ± 12.4 IU/L (normal 1.2-7.8 IU/L). A total of 17 patients repeated a semen analysis, and in no instance did this result in sperm where there was none previously. CONCLUSION: The findings from a large multicenter retrospective cohort of adolescent KS patients suggest that a single semen analysis is sufficient for attempted cryopreservation purposes, and that multiple semen analyses is not needed.