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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Detailing sexual outcomes after treatment of localised prostate cancer with focal therapy using various energy sources: protocol for a mixed-methods study.

INTRODUCTION: Focal therapy has emerged as a promising treatment option for men with localised prostate cancer. However, most of the evaluation of postoperative function has taken place at a relatively high, non-granular level. Most of the data we use to provide informed consent for our patients is obtained from retrospective series, or derived from prospective studies whose primary outcome was oncological. Finally, most studies have focused on erectile function and overlooked other, presumably important, elements of male sexual function. The present study aims at studying in-depth the sexual consequences of focal therapy with various energy sources. METHODS AND ANALYSIS: This will be a mixed-methods research study based on a retrospective and prospective cohort, recruited in parallel. The retrospective cohort will consist of patients treated with focal irreversible electroporation, and the prospective cohort of patients treated with three focal therapy energies. Participants will be recruited from two UK urology centres, one National Health Service and one private. On consent, patients will fill in self-administered validated questionnaires (International Index of Erectile Function-15 (IIEF-15), Male Sexual Health Questionnaire-Ejaculatory Dysfunction-Short Form (MSHQ-EjD-SF)) and semistructured interviews will be organised to collect patients' expectations and postoperative changes in domains such as erection, ejaculation, orgasm, libido/sexual desire, masculinity/virility, penile morphology, pain or discomfort, regret, shame, cancer-related stress, overall impact and partner satisfaction. An exploratory thematic analysis will be performed to detail recurring themes that will be grouped into clusters of experiences. We will then be able to find clusters of agreement and disagreement that will be illustrated using exemplar patient quotations. ETHICS AND DISSEMINATION: Ethical approval was obtained (Regional Ethics Committee reference 20/NW/0335), as well as Health Research Authority approval. Results will be published in open-access peer-reviewed journals. Findings will also be translated into patient information resources (leaflets, online information sheets). TRIAL REGISTRATION NUMBER: ISRCTN11634296; Pre-results.

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.

Early-Medium-Term Outcomes of Primary Focal Cryotherapy to Treat Nonmetastatic Clinically Significant Prostate Cancer from a Prospective Multicentre Registry.

BACKGROUND: Focal cryotherapy can be used to treat patients with clinically significant nonmetastatic prostate cancer to reduce side effects. OBJECTIVE: Early-medium-term cancer control and functional outcomes. DESIGN, SETTING, AND PARTICIPANTS: A prospective registry-based case series of 122 consecutive patients undergoing focal cryotherapy between October 1, 2013, and November 30, 2016, in five UK centres. Median follow-up was 27.8mo [interquartile range (IQR) 19.5-36.7]. A total of 35 patients (28.7%) had National Comprehensive Cancer Network (NCCN) high risk and 87 (71.3%) had intermediate risk disease. Risk and zonal stratification included multiparametric magnetic resonance imaging (mpMRI) with targeted and systematic biopsies, or transperineal mapping biopsies. INTERVENTION: Focal cryoablation of MR-visible tumours. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Follow-up involved prostate-specific antigen (PSA) monitoring, mpMRI, and for-cause biopsies. Primary outcome was failure-free survival (FFS), defined as transition to radical, whole-gland, or systemic therapy, or metastases/death. Secondary outcomes included adverse events and functional outcomes. RESULTS AND LIMITATIONS: A total of 80 (65.6%) had anterior ablation, 23 (19.7%) combined posterior and anterior ablation, and two (1.6%) posterior ablation alone (SeedNet or Visual-ICE, BTG plc). Median age was 68.7yr (IQR 64.9-73.8) and preoperative PSA 10.8ng/ml (IQR 7.8-15.6). Overall FFS at 3yr was 90.5% [95% confidence interval (CI) 84.2-97.3]. When stratified for the NCCN risk group, 3-yr outcomes were 84.7% (95% CI 71.4-100) in high risk and 93.3% (95% CI 86.8-100) in intermediate risk. At last follow-up, incontinence defined as any pad use was 0/69 (0%) and erectile dysfunction (defined as erections insufficient for penetration) was 5/31 (16.1%). Limitations include lack of long-term outcomes. CONCLUSIONS: Focal cryotherapy primarily for anterior intermediate and high-risk prostate cancer results in good rates of cancer control and low rates of treatment-related side effects. PATIENT SUMMARY: In this multicentre study of 122 patients undergoing focal cryotherapy for medium- to high-risk prostate cancer, at 3yr, no patient died from their cancer whilst failure-free survival, was approximately 90%. None of the patients needed pads for managing urine leakage, although 16% had erection problems.

Reporting on longitudinal live birth rates and cumulative delivery rates are more realistic outcome measures than sperm retrieval rates in couples undergoing mTESE-ICSI.

The live birth rates (LBRs) in men with non-obstructive azoospermia (NOA) undergoing microdissection TESE (mTESE) are under reported, with surgical sperm retrieval rate often used as the primary outcome measure. We analysed longitudinal and cumulative delivery rates following mTESE- intracytoplasmic sperm injection (ICSI) in NOA. Sperm was retrieved in 45% of patients undergoing mTESE. Median male and female age were 42 years (IQR 37-47) and 35 years (IQR 31-38) respectively. A total of 141 ICSI cycles and 23 frozen embryo transfers resulted in 62 pregnancies and 37 LBRs. The longitudinal LBR, crude and expected cumulative delivery rates after five cycles were 15.5%, 48.7% and 71.1%, respectively. Reassuringly, there was no significant difference in pregnancy rate (PR) (p = 0.37) or LBR (p = 0.68) using fresh or frozen sperm or embryo (p = 0.74). Sperm retrieval was significantly correlated with Johnsen score (JS) (p = 0.006) and hypospermatogenesis (HS) (p = 0.04), whilst LBR only significantly correlated with female age (p = 0.04). The longitudinal LBR for a couple embarking on mTESE for azoospermia is only 15.5%, although the cumulative delivery rates are promising. Reassuringly, the outcomes using fresh versus frozen embryos or sperm are comparable. Reporting on delivery rates from a single mTESE procedure are more objective and realistic measures of treatment success in men with NOA.