Guidelines for Sexual Health Care for Prostate Cancer Patients: Recommendations of an International Panel.

BACKGROUND: Patients with prostate cancer suffer significant sexual dysfunction after treatment which negatively affects them and their partners psychologically, and strain their relationships. AIM: We convened an international panel with the aim of developing guidelines that will inform clinicians, patients and partners about the impact of prostate cancer therapies (PCT) on patients' and partners' sexual health, their relationships, and about biopsychosocial rehabilitation in prostate cancer (PC) survivorship. METHODS: The guidelines panel included international expert researchers and clinicians, and a guideline methodologist. A systematic review of the literature, using the Ovid MEDLINE, Scopus, CINAHL, PsychINFO, LGBT Life, and Embase databases was conducted (1995-2022) according to the Cochrane Handbook for Systematic Reviews of Interventions. Study selection was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Each statement was assigned an evidence strength (A-C) and a recommendation level (strong, moderate, conditional) based on benefit/risk assessment, according to the nomenclature of the American Urological Association (AUA). Data synthesis included meta-analyses of studies deemed of sufficient quality (3), using A Measurement Tool to Assess Systematic Reviews (AMSTAR). OUTCOMES: Guidelines for sexual health care for patients with prostate cancer were developed, based on available evidence and the expertise of the international panel. RESULTS: The guidelines account for patients' cultural, ethnic, and racial diversity. They attend to the unique needs of individuals with diverse sexual orientations and gender identities. The guidelines are based on literature review, a theoretical model of sexual recovery after PCT, and 6 principles that promote clinician-initiated discussion of realistic expectations of sexual outcomes and mitigation of sexual side-effects through biopsychosocial rehabilitation. Forty-seven statements address the psychosexual, relationship, and functional domains in addition to statements on lifestyle modification, assessment, provider education, and systemic challenges to providing sexual health care in PC survivorship. CLINICAL IMPLICATIONS: The guidelines provide clinicians with a comprehensive approach to sexual health care for patients with prostate cancer. STRENGTHS & LIMITATIONS: The strength of the study is the comprehensive evaluation of existing evidence on sexual dysfunction and rehabilitation in prostate cancer that can, along with available expert knowledge, best undergird clinical practice. Limitation is the variation in the evidence supporting interventions and the lack of research on issues facing patients with prostate cancer in low and middle-income countries. CONCLUSION: The guidelines document the distressing sexual sequelae of PCT, provide evidence-based recommendations for sexual rehabilitation and outline areas for future research. Wittmann D, Mehta A, McCaughan E, et al. Guidelines for Sexual Health Care for Prostate Cancer Patients: Recommendations of an International Panel. J Sex Med 2022;19:1655-1669.

The relationship between genitourinary microorganisms and oxidative stress, sperm DNA fragmentation and semen parameters in infertile men.

An imbalance in the genitourinary microbiome is emerging as a contributing factor to male infertility. The purpose of this study was to determine whether there is an association between genitourinary microorganisms and seminal oxidative stress, sperm DNA fragmentation and semen parameters. It included 770 men attending for diagnostic testing for subfertility. Genitourinary microorganisms were identified in 43.0% men; 20.1% had microorganisms in semen; 18.7% in urine; and 5.8% had microorganisms in urine and semen. Enterococcus faecalis was the most prevalent organism in semen (22.0% samples; 61.5% organisms) with Ureaplasma spp. (16.9% samples; 53.3% organisms) and Gardnerella vaginalis (11.4% samples; 37.4% organisms) most prevalent in urine. Semen parameters were unaffected by microorganisms (p > 0.05). Seminal ROS were significantly higher in men with microorganisms compared to those without (p < 0.001), particularly when present in both urine and semen (p < 0.01). Microorganisms were associated with significantly higher DNA fragmentation, irrespective of whether they were in semen or urine (p < 0.001). An imbalance in the genitourinary microbiome is associated with DNA damage and oxidative stress which may have considerable consequences for achieving an ongoing pregnancy. This highlights the need for incorporating genitourinary microorganism screening for all men as part of diagnostic evaluation prior to undergoing treatment for infertility.

Age-related urologic problems in the complex urologic patient.

PURPOSE: Improved medical care throughout childhood and adolescence has enabled patients with complex urological abnormalities to live longer into adulthood. These patients are now at risk of developing common, age-related, urological conditions. This review aims to review existing data and make recommendations in areas where expert opinion is currently lacking METHODS: This review represents the joint SIU-ICUD (Société Internationale d'Urologie-International Consultation on Urological Disease) consultation on congenital lifelong urology. The results of this analysis were first presented at a joint consultation of the ICUD and SIU at the 2018 SIU annual conference in Seoul, South Korea. RESULTS: BPH may present differently in patients with neurogenic bladder. Thorough assessment of neurological status, bladder and sphincter function is required before offering any bladder outlet surgery. Prostate specific antigen screening should be offered to men aged 50-69 with neurogenic bladders if they have good life expectancy. Multi-parametric MRI and transperineal biopsy would be the investigations of choice if feasible. Surgery for localized disease should only be done by surgeons with the relevant expertise. Bladder cancer in this patient group is more likely to present at a later stage and have a worse prognosis. Parenthood is achievable for most, but often requires assistance with conception. Pregnant women who have had previous urogenital reconstructive surgery should be managed in appropriate obstetric units with the involvement of a reconstructive urologist. CONCLUSIONS: Most evidence regarding complex urogenital abnormalities comes from the pediatric population. Evidence regarding common, age-related urological issues is generally from the 'normal' adult population. As patients with complex congenital urological conditions live longer, more data will become available to assess the long-term benefits of intervention.

Redox potential in human semen: Validation and qualification of the MiOXsys assay.

Seminal oxidative stress (OS) is a major contributing factor to male infertility. Semen analysis cannot identify reactive oxygen species (ROS), which can be measured using a chemiluminescence assay. Measurement of redox potential provides a more comprehensive assessment of OS, although the test has yet to be fully validated. This study aimed to validate the MiOXsys analyser for measuring static oxidation-reduction potential (sORP). Results demonstrated that duplicate measurements must be taken, sensors must be batch tested, and sockets should be regularly changed to avoid inconsistency in measurement. Measurement of sORP using MiOXsys exhibited good reproducibility across different operators (p = 0.469), analysers (p = 0.963) and days (p = 0.942). It is not affected by mechanical agitation (p = 0.522) or snap freezing and thawing (p = 0.823). The stability of sORP over time requires further verification, particularly in samples with high initial sORP. Measurement is temperature sensitive between 2 and 37°C, significantly increasing with increasing temperature (p = 0.0004). MiOXsys is a more stable assay for assessing OS than chemiluminescence methods and permits greater flexibility for sample handling. MiOXsys could be implemented to complement semen analysis as part of routine diagnostic testing for male infertility and may be useful in identifying contributing factors to idiopathic infertility.

Novel use of COMET parameters of sperm DNA damage may increase its utility to diagnose male infertility and predict live births following both IVF and ICSI.

STUDY QUESTION: Do the Comet parameters of the proportions of sperm with low or high DNA damage improve the power of the test in the diagnosis of male infertility and/or prediction of IVF and ICSI live birth rates? SUMMARY ANSWER: The mean Comet score and the scores for proportions of sperm with high or low DNA damage were useful in diagnosing male infertility and provided additional discriminatory information for the prediction of both IVF and ICSI live births. WHAT IS KNOWN ALREADY: Sperm DNA damage impacts adversely on male fertility and IVF outcomes. STUDY DESIGN, SIZE, DURATION: A retrospective study was performed involving a total of 457 participants (381 patients and 76 fertile donors). Data was collected from a fertility clinic between 2015 and 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 381 consecutive male partners of couples attending for ART and 76 fertile donors were included in the study. DNA fragmentation was measured by the alkaline Comet assay. Receiver operator characteristic curve analysis (area under the ROC curve (AUC)) was used to determine the value of average Comet score (ACS), low Comet score (LCS) and high Comet score (HCS) to diagnose male factor infertility. In total, 77 IVF and 226 ICSI cycles were included to determine thresholds for each parameter (AUC analysis) and to compare live birth rates (LBRs) following each ART. MAIN RESULTS AND THE ROLE OF CHANCE: ACS, HCS and LCS were predictive of male infertility (AUC > 0.9, P < 0.0001). IVF LBRs declined once DNA damage exceeded the threshold levels. HCS showed the sharpest decline. Following ICSI, the highest LBRs were in men whose DNA damage levels approached the fertile range. Trends differed in IVF. LBRs decreased as damage increased whereas in ICSI the LBRs decreased but then remained stable. LIMITATIONS, REASONS FOR CAUTION: Since this is the first study to show the impact of sperm DNA damage on ICSI live births, a prospective study should be performed (stratifying patients to IVF or ICSI based on these thresholds) to validate this study. WIDER IMPLICATIONS OF THE FINDINGS: Our study presents novel information towards elucidating the genetic basis of male infertility and secondly on relevance of the extent of DNA damage as an impending factor in both IVF and ICSI success. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by Examenlab Ltd, The Lister Clinic, Cryos International and Imperial College London NHS Trust. No external funding was obtained for this study. SL and KL are employees of Examenlab Ltd, a university spin-out company with a commercial interest in sperm DNA damage. No other author has a conflict of interest to declare. TRIAL REGISTRATION NUMBER: Non-applicable.

Fertility managment in testicular cancer: the need to establish a standardized and evidence-based patient-centric pathway.

OBJECTIVES: The aim of the present paper was to determine the impact of testicular cancer (TC) and its treatments on fertility and to review the current management options for the infertile patient with TC, both before diagnosis and after treatment, with the aim of providing practical recommendations to update contemporary guidelines and standardize clinical practice. PATIENTS AND METHODS: Searches were conducted for relevant articles on Pubmed and Google Scholar between 2000 and 2017, with additional articles sourced from reference lists of included publications. RESULTS: At time of diagnosis, 6-24% of patients with TC were reported to be azoospermic and 50% oligozoospermic. Without conducting semen analysis at diagnosis, these patients cannot be identified and may be at further risk of subfertility. Gonadotoxic therapies cause an overall decrease in male fertility by 30% and there is currently no method to predict which patients will become azoospermic after treatment. Patients with larger, more invasive tumours, however, are at greater risk of infertility from local tumour effects, and are also more likely to undergo several different type of therapy, which has further detrimental effects on conception rates. Most treatment-induced infertility recovers 2 years post-treatment, but paternity can be delayed during a couple's peak reproductive years. Semen cryopreservation remains the procedure of choice in preserving fertility, but the service is underused, with only 24% of patients banking sperm. Microdissection testicular sperm extraction (microTESE) at the time of orchidectomy (onco-microTESE) is a successful infertility treatment option for those found to be azoospermic or severely oligozoospermic at diagnosis, while microTESE may still retrieve sperm in azoospermic patients after chemotherapy. CONCLUSION: The underutilisation of semen analysis and sperm cryopreservation results in the failure to identify the azoospermic or severely oligozoospermic patient at diagnosis who may benefit from fertility-preserving procedures, for example, onco-microTESE at the time of orchidectomy. Fertility preservation and counselling needs to be broached earlier in the TC treatment pathway and made a greater priority. Given the advances in treatment, more patients with TC are surviving and looking to return to a normal life. Preserving their future fertility plays an important role in achieving this.

Fertility preservation in testicular cancer - predictors of spermatogenesis.

OBJECTIVES: To determine the frequency of spermatogenesis in patients with testicular cancer and to assess for any predictors of spermatogenesis. PATIENTS AND METHODS: We retrospectively reviewed 103 testicular germ cell tumours (TGCTs) in men who underwent radical orchidectomy conducted at Guy's Hospital, London, between 2011 and 2015. Primary outcome measures included: the presence and characteristics of spermatogenesis (widespread/focal/proximity to tumour). Secondary outcome measures included: the presence of testicular microlithiasis, tumour characteristics (size, stage, and type), and tumour markers. Secondary outcome measures as potential predictors of spermatogenesis were assessed using univariate and multivariate logistic regression analyses. RESULTS: Spermatogenesis was present in 70% (72/103) of the patients; it was widespread in 63% (45/72) and focal in 38% (27/72). Neither tumour type, stage, presence of microcalcification nor tumour markers predicted spermatogenesis. Men with a percentage testis tumour occupation (PTTO) of >50% of their testis were 82% (95% confidence interval 73.2-98.4) less likely to have spermatogenesis than a PTTO of <50%. CONCLUSIONS: Spermatogenesis is present in most testes affected by TGCTs; it is widespread in two-thirds of patients, and located away from the tumour in 94%. These findings can help predict and guide successful surgical sperm retrieval in testes with TGCTs. The finding of focal spermatogenesis in a third of patients would support a microsurgical approach to sperm retrieval at the time of orchidectomy to maximise success.

A study into the association between local recurrence rates and surgical resection margins in organ-sparing surgery for penile squamous cell cancer.

OBJECTIVE: To evaluate the significance of close surgical margins in organ-sparing surgery (OSS) in the treatment of penile squamous cell carcinoma (pSCC) and clinicopathological factors that may influence local recurrence. PATIENTS AND METHODS: At our tertiary referral centre, between March 2001 and September 2012, 332 patients treated with OSS for pSCC had clear surgical margins. As the focus was the impact of close clear margins on local recurrence, patients with positive margins were excluded for the purpose of this study. Our overall positive margin rate for OSS in penile cancer is 7.6% (42 patients). Analysis was carried out on an on-going prospective database, including prospective accurate pathological recording of surgical margins. Patients underwent OSS after multidisciplinary team (MDT) discussion. Local recurrence was the primary outcome measured and Fisher's exact test and time-to-recurrence curves were used in the analysis. All local recurrences were scrutinised by the MDT and were categorised into: true recurrences or metachronous new occurrences (i.e. tumours arising from a background of penile intraepithelial neoplasia and forming on an epithelial surface not related to the site of initial resection). A multivariate analysis was also conducted to elucidate other factors influencing local recurrence. RESULTS: In all, 64% of the patients had a <5 mm clear deep surgical margin, with 16% clear by <1 mm. Overall, 4% of patients had a true local recurrence, with a median time to recurrence of 6 months. In all, 53% were due to embolic spread, with residual occult local disease accounting for 47%. There was a statistically significant relationship between cavernosal involvement (P = 0.014) and lymphovascular invasion (LVI; P = 0.001) and local recurrence. Although multivariate analysis revealed that the extent of clear margin was not a predictor of disease (P = 0.405), we found an increased risk of local recurrence in the clear margin cohort of <1 mm compared to those of >1 mm (P < 0.001). Those patients considered to have metachronous tumours were scrutinised by our MDT, and eight patients (2.4%) were found to have new occurrences. Our overall proportion of patients therefore needing further treatment for either new occurrences or recurrent disease after OSS stands at 6.4%. CONCLUSIONS: Overall the presence of local recurrent disease in OSS in our experience is low (4%). We report an embolic mechanism of local recurrence, strongly suggested by the presence of cavernosal involvement and LVI. We conclude that a deep clear margin of >1 mm has a very low risk of local recurrence in penile OSS.

Recovery of Baseline Erectile Function in Men Following Radical Prostatectomy for High-Risk Prostate Cancer: A Prospective Analysis Using Validated Measures.

INTRODUCTION: Recovery of baseline erectile function (EF) after robotic radical prostatectomy in men with high-risk prostate cancer is under-reported. Published studies have selectively reported on low-risk disease using non-validated and poorly defined thresholds for EF recovery. AIM: To assess return to baseline EF in men after robotic radical prostatectomy for high-risk prostate cancer. MATERIALS: Five hundred thirty-one men underwent robotic radical prostatectomy for high-risk prostate cancer from February 2010 through July 2014. Pre- and postoperative EF was prospectively assessed using the International Index of Erectile Dysfunction (IIEF-5) questionnaire. Multivariate logistic regression analysis determined the effect of age, preoperative function, comorbidities, body mass index, prostate-specific antigen level, cancer stage or grade, nerve-sparing status, adjuvant therapy, and continence on EF return (defined as postoperative return to baseline EF with or without use of phosphodiesterase type 5 inhibitors). Kaplan-Meier analysis and log-rank test were used to analyze return over time. Mann-Whitney U-test was used to compare IIEF-5 scores. MAIN OUTCOME MEASURES: Pre- and postoperative EF was assessed using the IIEF-5 Sexual Health Inventory for Men at 3 months, 6 months, 1 year, 2 years, 3 years, and 4 years postoperatively. RESULTS: Overall, return of EF was seen in 23.5% of patients at 18 months. This was significantly increased in men no older than 60 years (P = .024), with a preoperative IIEF-5 score of at least 22 (P = .042), and after undergoing neurovascular bundle preservation (34.9% of patients, P < .001). There was no significant change in IIEF-5 scores from 3 to 36 months in patients who were treated with phosphodiesterase type 5 inhibitors in the non-neurovascular bundle preservation group (P = .87), although there was significant improvement in those receiving second- or third-line therapies (P = .042). Other than preoperative hypertension (P = .03), none of the other comorbidities predicted return of EF. CONCLUSION: In this study, 23.5% of men recovered to baseline EF. Of those who underwent bilateral neurovascular bundle preservation robotic radical prostatectomy, 70% recovered baseline EF; however, this accounted for only 9.6% of all patients. Only 4% of men who underwent non-neurovascular bundle preservation had baseline recovery with phosphodiesterase type 5 inhibitors up to 36 months. There was significant improvement after use of second- or third-line therapies, indicating the need for earlier institution of these treatment modalities.

Does Testicular Sperm Improve Intracytoplasmic Sperm Injection Outcomes for Nonazoospermic Infertile Men with Elevated Sperm DNA Fragmentation? A Systematic Review and Meta-analysis.

CONTEXT: For nonazoospermic infertile men with elevated sperm DNA fragmentation (SDF), it is unclear whether the use of testicular sperm for intracytoplasmic sperm injection (ICSI) may offer advantages over ejaculated sperm. OBJECTIVE: To determine whether ICSI outcomes (fertilisation rate, pregnancy rate, miscarriage rate, and live birth rate) are better with testicular sperm than with ejaculated sperm for men with elevated SDF. EVIDENCE ACQUISITION: We searched the Cochrane Central, EMBASE, MEDLINE, Web of Science, and Scopus databases (1946-2023) in February 2023 for relevant human comparative studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. EVIDENCE SYNTHESIS: Out of 2032 records, nine studies (more than 536 participants, mean age range 33-40.5 yr for males and 30.1-37.9 yr for females) were included in the systematic review and meta-analysis. Pooled estimates demonstrated that the pregnancy rate was significantly higher with testicular than with ejaculated sperm according to a sperm chromatin structure assay (SCSA)/sperm chromatin integrity test (SCIT) (odds ratio [OR] 2.51; p = 0.001) and terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assays (OR 3.65; p = 0.005). The live birth rate was significantly higher according to SCSA/SCIT (OR 2.59; p = 0.005). There were no significant differences in the fertilisation rate or miscarriage rate. CONCLUSIONS: Although significant improvements in pregnancy and live birth rates were observed with testicular sperm, the strength of findings is limited by availability and quality of evidence, both of which undermine recommendations for clinical practice. Standardised randomised controlled trials are needed to definitively determine whether the use of testicular sperm improves ISCI outcomes for men with high SDF. Until such evidence exists, ICSI after testicular sperm extraction or aspiration should not be routinely performed. PATIENT SUMMARY: Our review showed that for infertile men with a high level of DNA damage in their sperm, use of sperm extracted from the testicles may give better results than ejaculated sperm for a particular IVF (in vitro fertilisation) technique. However, there is a lack of high-quality data.

Third-generation salvage cryotherapy for radiorecurrent prostate cancer: a centre's experience.

INTRODUCTION: The experience of a tertiary centre in the management of recurrent prostate cancer after radiotherapy by salvage cryotherapy is presented. PATIENTS AND METHODS: Between February 2006 and August 2008, 19 patients underwent salvage cryotherapy for radiorecurrent prostate cancer. Post-radiotherapy recurrence was confirmed by prostatic biopsy. The 'Phoenix definition' was used to define biochemical failure after salvage cryotherapy. RESULTS: The mean age at cryotherapy was 69.2 years and the mean time from radiotherapy to cryotherapy was 72.3 months. Patient characteristics prior to cryotherapy included a mean PSA level of 6.84 ng/ml and a median Gleason score of 7. The mean post-cryotherapy follow-up was 33.3 months. The 2-year biochemical disease-free survival rate was 58%. The median post-cryotherapy PSA nadir was 0.20 ng/ml (range 0.005-8.260). There were no procedure-related or cancer-related deaths. Complications included incontinence (10.5%), erectile dysfunction (89%) and fistula formation (5.3%). CONCLUSIONS: The relatively high rates of biochemical response support the use of cryotherapy as a salvage procedure for radiorecurrent prostate cancer.

Erectile dysfunction: Is platelet-rich plasma the new frontier for treatment in patients with erectile dysfunction? A review of the existing evidence.

Erectile dysfunction (ED) is one of the commonest disorders in adult males and affects 12-19% of men of reproductive age. Only few studies have evaluated the impact of ED on men and couples with infertility-these studies report higher rates of ED in this sub-group of men compared to the general population, with the prevalence of ED in men diagnosed with male infertility ranging from 6.7 to 61.6%. Nevertheless, ED is considered a rare cause of male infertility, accounting for about 0.4-5% of all causes of male infertility. ED remains a poorly treated condition globally and current therapies, like oral medication, offer only temporary symptomatic relief and do not influence disease progression-patients are potentially on lifelong treatment, with ED worsening over time. In contrast, regenerative medicine may potentially reverse or halt the progression of ED processes. In this article, we review the evidence for intracavernosal injections of platelet-rich plasma (PRP) in the treatment of ED.

Detailing Sexual Outcomes After Focal Therapy for Localised Prostate Cancer: A Systematic Review and Meta-analysis.

CONTEXT: Focal therapy has emerged as a promising option to treat well-selected men with localised prostate cancer while preserving healthy prostate tissue and key structures, such as the urethral sphincter and neurovascular bundles. However, how this tissue preservation may translate into improved outcomes, particularly into improved sexual outcomes, is still an active research field. OBJECTIVE: We conducted a systematic review and meta-analysis of the literature to summarise the existing evidence, in order to provide patients with updated data on what to expect after treatment and help identify gaps in current knowledge that may warrant future research. EVIDENCE ACQUISITION: A systematic literature search was conducted on Medline, EMBASE, Scopus, and Web of Science. The search strategy was defined using the "litsearchr" function in R based on a preliminary "naïve" search using the following terms on Medline: (("focal therapy" OR "focal treatment") AND ("prostate cancer") AND ("sexual function" OR "erectile function")). A total of 42 studies, comprising 3117 patients treated and 2352 with available sexual outcomes, were included in the qualitative data synthesis and 26 in a random-effect meta-analysis. EVIDENCE SYNTHESIS: The five-item International Index of Erectile Function (IIEF-5) was the most frequently used questionnaire (30/42 studies), with completion rates ranging from 24% to 100% at 18-24 mo. A decrease was noted at 3 mo (IIEF-5 decrease estimate -3.70 [95% confidence interval -4.43, -2.96]), with improvements at 6 mo (-2.18 [-2.91, -1.46]) and 12 mo (-2.14 [-2.96, -1.32]). Studies in which patients had an altered baseline sexual function were more likely to report a significant and durable postoperative decrease in erectile function scores. The patient-reported outcome questionnaires used were not designed for a diverse population. Functional outcomes were not the primary endpoint and have not been reported consistently in most studies considered. CONCLUSIONS: Focal therapy led to changes in erectile function in most cases under the significance threshold of the patient-reported outcome questionnaires used. However, patients should be counselled according to their baseline erectile function. More research is warranted to detail aspects other than erectile function, such as ejaculation or orgasm. The early postoperative period appears key to study sexual changes after focal therapy, while only a moderate decrease is expected at 12 mo. PATIENT SUMMARY: We reviewed the published literature detailing the sexual consequences of focal therapy for localised prostate cancer using patient-reported outcome questionnaires. Patients were likely to describe a significant decrease in their erectile function at 3 mo, with improvements noted at 6 and 12 mo. The results obtained may not be reproducible in a more diverse population, and further research is warranted to better study aspects other than erectile function, such as ejaculation or orgasm.

Does hormonal therapy improve sperm retrieval rates in men with non-obstructive azoospermia: a systematic review and meta-analysis.

BACKGROUND: The beneficial effects of hormonal therapy in stimulating spermatogenesis in patients with non-obstructive azoospermia (NOA) and either normal gonadotrophins or hypergonadotropic hypogonadism prior to surgical sperm retrieval (SSR) is controversial. Although the European Association of Urology guidelines state that hormone stimulation is not recommended in routine clinical practice, a significant number of patients undergo empiric therapy prior to SSR. The success rate for SSR from microdissection testicular sperm extraction is only 40-60%, thus hormonal therapy could prove to be an effective adjunctive therapy to increase SSR rates. OBJECTIVE AND RATIONALE: The primary aim of this systematic review and meta-analysis was to compare the SSR rates in men with NOA (excluding those with hypogonadotropic hypogonadism) receiving hormone therapy compared to placebo or no treatment. The secondary objective was to compare the effects of hormonal therapy in normogonadotropic and hypergonadotropic NOA men. SEARCH METHODS: A literature search was performed using the Medline, Embase, Web of Science and Clinicaltrials.gov databases from 01 January 1946 to 17 September 2020. We included all studies where hormone status was confirmed. We excluded non-English language and animal studies. Heterogeneity was calculated using I2 statistics and risk of bias was assessed using Cochrane tools. We performed a meta-analysis on all the eligible controlled trials to determine whether hormone stimulation (irrespective of class) improved SSR rates and also whether this was affected by baseline hormone status (hypergonadotropic versus normogonadotropic NOA men). Sensitivity analyses were performed when indicated. OUTCOMES: A total of 3846 studies were screened and 22 studies were included with 1706 participants. A higher SSR rate in subjects pre-treated with hormonal therapy was observed (odds ratio (OR) 1.96, 95% CI: 1.08-3.56, P = 0.03) and this trend persisted when excluding a study containing only men with Klinefelter syndrome (OR 1.90, 95% CI: 1.03-3.51, P = 0.04). However, the subgroup analysis of baseline hormone status demonstrated a significant improvement only in normogonadotropic men (OR 2.13, 95% CI: 1.10-4.14, P = 0.02) and not in hypergonadotropic patients (OR 1.73, 95% CI: 0.44-6.77, P = 0.43). The literature was at moderate or severe risk of bias. WIDER IMPLICATIONS: This meta-analysis demonstrates that hormone therapy is not associated with improved SSR rates in hypergonadotropic hypogonadism. While hormone therapy improved SSR rates in eugonadal men with NOA, the quality of evidence was low with a moderate to high risk of bias. Therefore, hormone therapy should not be routinely used in men with NOA prior to SSR and large scale, prospective randomized controlled trials are needed to validate the meta-analysis findings.

Nicorandil-induced penile ulcerations: a case series.

OBJECTIVE: To report on the largest series to date of ulceration of the external genitalia, related to treatment with nicorandil - a vasodilator for the prevention and long-term treatment of angina - and to review the literature on the subject, focusing on the clinical features and the pathogenesis of this rare, yet marked, side-effect. PATIENTS AND METHODS: Three patients (aged 71-83 years) were referred for severe ulceration of the penis. A complete work-up was performed to exclude potential underlying causes, including malignancy and sexually transmitted diseases. After a careful review of the patients' medical history, a potentially causal relationship was noted; all patients had been taking nicorandil for at least 2 years before the development of penile ulceration. RESULTS: Penile ulcers associated with nicorandil are characteristically large, deep, painful and have punched-out edges. They usually involve the prepuce or the penile shaft skin. Higher doses of nicorandil (at least 40 mg daily) and surgical procedures seem to increase the risk for nicorandil-related ulceration. Response to topical steroids is poor, but complete healing is achieved by discontinuation of nicorandil, while surgical treatment should be discouraged. CONCLUSION: The growing body of literature showing the link between treatment with nicorandil and ulceration at multiple sites has led to the recognition of this side-effect by the World Health Organization. Nicorandil-related ulcers rarely involve the penile skin and constitute a diagnostic and therapeutic challenge. The pathogenesis of this rare side-effect is largely unknown, but mechanisms such as the 'vascular steal phenomenon' and the direct toxic effect of the drug or its metabolites have been implicated.

18 F-FDG PET/CT use in functional assessment of the testes: A systematic review.

INTRODUCTION: Our study analysed previous studies employing positron emission tomography with co-registered computer tomography (PET/CT) in andrological patient evaluation and assessed the differences in 2-[18 F]F-fluoro-2'-deoxyglucose (FDG) uptake between three groups: healthy testes, benign and malignant testicular pathology. METHODS: Medline and Embase were systematically searched for studies involving FDG-PET/CT imaging of testes with results expressed as mean standardised uptake value (SUVmean ). A one-way ANOVA was used to compare SUVmean between three groups. All papers assessing andrological parameters were pooled to compare fertility data. RESULTS: Seventeen studies, including three relating to fertility diagnosis, with a total of 830 patients, were included in the review. One-way ANOVA showed a statistical difference between mean values of tracer SUVmean in healthy and malignant testes (Dif. = -2.77, 95% CI = -4.32 to 1.21, p < 0.01) as well as benign and malignant (Dif. = -2.95, 95% CI = -4.33 to -1.21, p < 0.01) but no difference between healthy and benign (Dif. = 0.19, 95% CI = -0.96 to 1.33, p = 0.90). There is some evidence to suggest that FDG uptake and testicular volume are positively correlated to total sperm count, sperm concentration and sperm motility and that germ cells are likely to account for the majority of testicular FDG accumulation. CONCLUSION: Our findings indicate that malignant testicular lesions demonstrate a significantly higher FDG uptake than benign testicular lesions or healthy testes. Some evidence also suggests that FDG-PET could visualise metabolic activity and thus spermatogenesis; however more studies are required to determine whether FDG-PET could also be used to diagnose infertility. Further studies should focus on correlating both sex hormone-serum levels and semen analysis results with imaging data.

Should the current guidelines for the treatment of varicoceles in infertile men be re-evaluated?

Male infertility is a major health burden worldwide. In the United Kingdom, the diagnostic and treatment pathway for male factor fertility is fragmented with wide variance in management and funding protocols. There is now a focus on potential overtreatment of couples with IVF and failure to treat male factors before considering assisted reproductive technology (ART). Despite this, contemporary Urological guidelines are not definitive in the indications for varicocele treatment, whilst the current National Institute for Health and Care Excellence (NICE) guidelines do not advocate surgical intervention. While controversy exists concerning the effects of varicocele treatment on natural pregnancy rates, there is growing evidence that varicocele treatment can have additional positive effects on fertility by reducing their impact on sperm DNA fragmentation and improving ART outcomes. Studies have demonstrated that azoospermic men may become oligospermic following varicocele intervention, obviating the need for surgical sperm retrieval. Sperm retrieval rates also increase following varicocele treatment in men with non-obstructive azoospermia. The contemporary literature demonstrates a clear clinical benefit for treating varicoceles in infertile men, which may be more cost-effective than proceeding to immediate ART. This review comprehensively evaluates the current indications for varicocele treatment, and it is proposed that these should be redefined in contemporary guidelines to reflect current advances in male fertility research.

The semen microbiome and its impact on sperm function and male fertility: A systematic review and meta-analysis.

BACKGROUND: Male factor is attributable in up to 50% of cases of infertility. In vitro studies demonstrate that bacteria can negatively impact sperm function. The use of next-generation sequencing techniques has provided a better understanding of the human microbiome, and dysbiosis has been reported to impact health. Evidence regarding the impact of the semen microbiome on sperm function and fertility remains conflicting. MATERIALS AND METHODS: A systematic search was conducted in accordance with the Preferred Reporting Items for Reviews and Meta-analysis (PRISMA) statement. The databases MEDLINE, OVID and PubMed were searched to identify English language studies related to the identification of bacteria in the semen of infertile and fertile men, between 1992 and 2019. Fifty-five observational studies were included, with 51 299 subjects. We included studies identifying bacteria using next-generation sequencing, culture or polymerase chain reaction. RESULTS: The semen microbiome was rich and diverse in both fertile and infertile men. Three NGS studies reported clustering of the seminal microbiome with a predominant species. Lactobacillus and Prevotella were dominant in respective clusters. Lactobacillus was associated with improvements in semen parameters. Prevotella appeared to exert a negative effect on sperm quality. Bacteriospermia negatively impacted sperm concentration and progressive motility, and DNA fragmentation index (DFI; MD: 3.518, 95% CI: 0.907 to 6.129, P = .008). There was an increased prevalence of ureaplasma urealyticum in infertile men (OR: 2.25, 95% CI: 1.47-3.46). Ureaplasma urealyticum negatively impacted concentration and morphology. There was no difference in the prevalence of chlamydia trachomatis between fertile and infertile men and no significant impact on semen parameters. Enterococcus faecalis negatively impacted total motility, and Mycoplasma hominis negatively impacted concentration, PM and morphology. DISCUSSION AND CONCLUSIONS: Ureaplasma urealyticum, Enterococcus faecalis, Mycoplasma hominis and Prevotella negatively impact semen parameters, whereas Lactobacillus appears to protect sperm quality. These findings may facilitate the development of novel therapies (eg probiotics), although the evidence regarding the impact of the seminal microbiome on fertility is inconclusive and further studies are needed to investigate this association.

Assessment of Return to Baseline Urinary and Sexual Function Following Primary Focal Cryotherapy for Nonmetastatic Prostate Cancer.

BACKGROUND: The oncological outcomes in men with clinically significant prostate cancer following focal cryotherapy are promising, although functional outcomes are under-reported. OBJECTIVE: To determine the impact of focal cryotherapy on urinary and sexual function, specifically assessing return to baseline function. DESIGN, SETTING, AND PARTICIPANTS: Between October 2013 and November 2016, 58 of 122 men who underwent focal cryotherapy for predominantly anterior clinically significant localised prostate cancer within a prospective registry returned patient-reported outcome measure questionnaires, which included International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF-15) questionnaires. INTERVENTION: Standard cryotherapy procedure using either the SeedNet or the Visual-ICE cryotherapy system. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome was return to baseline function of IPSS score and IIEF erectile function (EF) subdomain. Cumulative incidence and Cox-regression analyses were performed. RESULTS AND LIMITATIONS: Probability of returning to baseline IPSS function was 78% at 12 mo and 87% at both 18 and 24 mo, with recovery seen up to 18 mo. For IIEF (EF domain), the probability of returning to baseline function was 85% at 12 mo and 89% at both 18 and 24 mo, with recovery seen up to 18 mo. Only the preoperative IIEF-EF score was associated with a poor outcome (hazard ratio 0.96, 95% confidence interval 0.93-0.999, p = 0.04). The main limitation was that only half of the patients returned their questionnaires. CONCLUSIONS: In men undergoing primary focal cryotherapy, there is a high degree of preservation of urinary and erectile function with return to baseline function occurring from 3 mo and continuing up to 18 mo after focal cryotherapy. PATIENT SUMMARY: In men who underwent focal cryotherapy for prostate cancer, approximately nine in 10 returned to their baseline urinary and sexual function. Keeping in mind that level 1 evidence and long-term data are still needed, in men who wish to preserve urinary and sexual function, focal cryotherapy may be considered an alternative treatment option to radical therapy.