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Purpose: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles. Materials and Methods: The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intraperson before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies). Results: Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129–0.278; p

Purpose: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. Materials and Methods: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. Results: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). Conclusions: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial.

Purpose: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition. Materials and Methods: An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method.Results: A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4–6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated. Conclusions: This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians.

Abstract Background The purpose of this study was to assess the usefulness of fluorodeoxyglucose positron emission tomography (18F-FDG PET)-computed tomography (CT) scan for staging urinary bladder cancer. The study also sought to determine the effect of 18F-FDG PET/CT on management decisions and its implications for patient care. Methods A total of 133 patients with bladder cancer who had both conventional imaging and 18F-FDG PET/CT for initial staging were identified. All 18F-FDG-PET/CT findings were classified as true positive, true negative, false positive, or false negative based on their potential to impact the intent of treatment. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated using the standard definition. Furthermore, the rate of change in therapy intent was determined for the entire sample and for subgroups with non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) patients. Results The overall concordance rate between PET/CT and conventional imaging was around 54%. On conventional images, 18% of patients had localized disease, which was upstaged in 6.8% of cases using 18F-FDG PET/CT. Pelvic lymph node involvement was detected in 18.8% of cases using conventional imaging, which was downstaged to localized disease in 4.5% of cases using 18F-FDG PET/CT. While 63.2% of patients had systemic disease on a CT scan, 24.7% of cases were downstaged using PET/CT. Overall, the rate of change in therapy intent was 26.3% for the entire sample, 24.5% for NMIBC subgroup, and 27.3% for MIBC patients. Conclusions The study found that 18F-FDG PET/CT is an effective and accurate tool for staging bladder cancer in newly diagnosed patients. Approximately one quarter of patients had a change in management intent based on 18F-FDG PET/CT results. The study suggests that PET/CT should be used as a standard for newly diagnosed patients, but more research is needed to confirm this.

Purpose: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations. Materials and Methods: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus. Results: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing. Conclusions: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians.

BackgroundMost studies investigating the relationship between preoperative frailty and postoperative outcomes among bladder cancer patients only assess frailty retrospectively in patients who have undergone radical cystectomy. Transurethral resection of bladder tumor (TURBT) is a commonly performed procedure in outpatient settings for a large number of bladder cancer patients. The prevalence of frailty among bladder cancer patients and its impact on postoperative complications and mortality are not well studied. MethodsTo assess the prevalence of frailty among bladder cancer patients planned for TURBT at a tertiary cancer center using the modified frailty index (mFI) and Risk Analysis Index (RAI) and further assess the impact of these indices on 30-day postoperative complications and mortality rates. ResultsBetween May 2020 and March 2021, 343 consecutive patients were enrolled. The mean age of the cohort was 64.8 ± 13.1 years, 86.6% were male, and 82% had non–muscle-invasive bladder cancer (NMIBC). The majority of the cohort (92%) was found to have low American Society of Anesthesiologists (ASA) score class (I + II), while 35.3% were labeled as frail using mFI 2+, and 32.1% based on RAI (III, IV). The 30-day readmission, postoperative complications, and mortality rates in this cohort were 3.8%, 2.3%, and 6.6%, respectively. RAI was a better indicator of mortality compared to mFI. As such, patients with low RAI score (I, II) had 0.054 odds for 30-day mortality compared to the patients with high RAI score (III, IV) (OR 0.054; CI 95%, 0.004 to 0.784; P = 0.033). ConclusionFrailty, as measured by Risk Analysis Index, is an independent predictor of early mortality in patients undergoing TURBT. Preoperative frailty assessment may improve risk stratification and patient counseling prior to su rger y.

IntroductionThe American Urological Association (AUA) and the European Association of Urology (EAU) currently recommend partial nephrectomy (PN) over ablation for cT1b lesions. However, recent series have shown comparable outcomes for cryoablation (CA) when compared to PN, making it an appealing alternative for a select group of patients. The objective of this manuscript is to assess treatment outcomes and complications of CA for cT1b lesions. MethodsUsing Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search was done on MEDLINE and Cochrane Library electronic databases identifying studies that reported on outcomes and complications of CA for kidney tumors. Inclusion criteria included cT1b lesions between 4 cm and 7 cm, excluding treatment of other sizes. ResultsA total of 347 patients with cT1b lesions identified on imaging underwent percutaneous or laparoscopic CA. The average age was > 65 years, the median size of lesions and RENAL score ranged between 4.3–4.8 cm and 8–9, respectively. The majority of patients had a Charlson comorbidity index (CCI) of 2, and median follow-up ranged between 13 months and 95 months. Across all the series, primary and secondary success rates were between 84%–98% and 92%–98%, respectively. The local recurrence ranged from 2.8% to 27%. For patients with documented RCC on biopsy, the 5-year overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and metastasis-free survival (MFS) ranged from 56%–91%, 85%–100%, 70%–96.4%, and 90%–96%, respectively. The major complication rate (Clavien-Dindo III-V) was low, at 6.2%. ConclusionWith promising survival outcomes and low complication rates perioperatively, CA is acceptable in a select group of patients with T1b renal tumors, including those who are older, have multiple comorbidities, or have relative or absolute contraindication to surgery.

Objectives: The incidence of bladder cancer in the Middle East is increasing. Nevertheless, data on the young population with urothelial carcinoma (UC) of the urinary bladder in this region is scarce. Therefore, we evaluated clinical and tumor characteristics, in addition to treatment details in patients younger than 45 years old. Methodology: We reviewed all patients presenting with UC of the urinary bladder from July 2006 to December 2019. Clinical characteristics including demographics, stage at presentation, and treatment outcomes were extracted. Results: Out of 1272 new cases of bladder cancer, a total of 112 (8.8%) patients were ≤45 years old. Seven patients (6%) had nonurothelial histology and were excluded from the study. The remaining 105 eligible patients with UC had a median age at presentation of 41 years (35–43). Ninety-three patients (88.6%) were males. Tumor stage at presentation: nonmuscle invasive disease (Ta-T1), locally advanced muscle-invasive bladder cancer (MIBC) (T2-3), and metastatic disease were 84.7%, 2.8%, and 12.5%, respectively. All patients with MIBC received neoadjuvant cisplatin-based chemotherapy. Radical cystectomy was performed in 8 (7.6%) cases; three patients with MIBC and five with high-volume non-MIBC. Neobladder reconstruction was done in six patients. A total of 13 patients with metastatic disease (93%) received palliative chemotherapy (gemcitabine/cisplatin), and one (7%) was a candidate for best supportive care only. Conclusion: Bladder cancer is relatively rare in the young population, although the incidence at our region is higher than other reports in the literature. Most patients present with early disease. Early diagnosis and multidisciplinary approach are paramount for the management of these patients.

Purpose: Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varicocele in the context of male infertility. Materials and Methods: Sixty practicing urologists/andrologists from 23 countries contributed 382 multiple-choice-questions pertaining to varicocele management. These were condensed into an online questionnaire that was forwarded to clinicians involved in male infertility management through direct invitation. The results were analyzed for disagreement and agreement in practice patterns and, compared with the latest guidelines of international professional societies (American Urological Association [AUA], American Society for Reproductive Medicine [ASRM], and European Association of Urology [EAU]), and with evidence emerging from recent systematic reviews and meta-analyses. Additionally, an expert opinion on each topic was provided based on the consensus of 16 experts in the field. Results: The questionnaire was answered by 574 clinicians from 59 countries. The majority of respondents were urologists/ uro-andrologists. A wide diversity of opinion was seen in every aspect of varicocele diagnosis, indications for repair, choice of technique, management of sub-clinical varicocele and the role of VR in azoospermia. A significant proportion of the responses were at odds with the recommendations of AUA, ASRM, and EAU. A large number of clinical situations were identified where no guidelines are available. Conclusions: This study is the largest global survey performed to date on the clinical management of varicocele for male infertility. It demonstrates: 1) a wide disagreement in the approach to varicocele management, 2) large gaps in the clinical practice guidelines from professional societies, and 3) the need for further studies on several aspects of varicocele management in infertile men.

Purpose: Seminal oxidative stress (OS) is a recognized factor potentially associated with male infertility, but the efficacy of antioxidant (AOX) therapy is controversial and there is no consensus on its utility. Primary outcomes of this study were to investigate the effect of AOX on spontaneous clinical pregnancy, live birth and miscarriage rates in male infertile patients. Secondary outcomes were conventional semen parameters, sperm DNA fragmentation (SDF) and seminal OS. Materials and Methods: Literature search was performed using Scopus, PubMed, Ovid, Embase, and Cochrane databases. Only randomized controlled trials (RCTs) were included and the meta-analysis was conducted according to PRISMA guidelines. Results: We assessed for eligibility 1,307 abstracts, and 45 RCTs were finally included, for a total of 4,332 infertile patients. We found a significantly higher pregnancy rate in patients treated with AOX compared to placebo-treated or untreated controls, without significant inter-study heterogeneity. No effects on live-birth or miscarriage rates were observed in four studies. A significantly higher sperm concentration, sperm progressive motility, sperm total motility, and normal sperm morphology was found in patients compared to controls. We found no effect on SDF in analysis of three eligible studies. Seminal levels of total antioxidant capacity were significantly higher, while seminal malondialdehyde acid was significantly lower in patients than controls. These results did not change after exclusion of studies performed following varicocele repair. Conclusions: The present analysis upgrades the level of evidence favoring a recommendation for using AOX in male infertility to improve the spontaneous pregnancy rate and the conventional sperm parameters. The failure to demonstrate an increase in live-birth rate, despite an increase in pregnancy rates, is due to the very few RCTs specifically assessing the impact of AOX on live-birth rate. Therefore, further RCTs assessing the impact of AOX on live-birth rate and miscarriage rate, and SDF will be helpful.

Background and Aims: Sperm DNA fragmentation (SDF) is caused by apoptosis, oxidative stress or incomplete chromatin maturation and can result in male infertility and poor reproductive outcomes. Despite growing trends, there are no specific recommendations on specific diagnostic tests used, assay cut-offs or abstinence periods prior to SDF testing. Therefore, we conducted a global survey to evaluate the approaches used to diagnose SDF, towards a consensus in the field of SDF research and clinical management. Method: The survey collected cross-sectional global data from 55 countries following the CHERRIES protocol. 436 respondents included clinicians, researchers and reproductive biologists from academic, public and private health sectors, all of whom utilize SDF testing in their routine patient care and practice (Fig. 1). Results: Survey results showed that TUNEL (28.6%), SCSA (24.1%), SCD (19.1%) and Comet (5.3%) were most frequently used to diagnose SD (Fig. 2A). Assays were chosen primarily due to their availability (70.0%), cost (44.05%) and accuracy (35.48%). Published evidence on assays (25.71%), training of staff (25.48%), cost to patients (21.67%), assay time (18.81%), ease of interpretation (18.33%) and performance (17.38%) were taken lesser into consideration when selecting SDF diagnostic tests (Fig. 2B). Assay cut-offs of “30% or higher” (33.7%) were most frequently used to diagnose SDF (Fig. 2C). Finally, an abstinence period of 3-5 days was mostly recommended (53.6%; Fig. 2D). The results of this survey provide valuable data on SDF assays used in clinical practice as well as factors affecting assay choices such as availability of resources, personnel and complexity in assay processing. As decreased abstinence period is associated with lower SDF, testing is recommended with an abstinence period of less than five days. We observed that there was a lack of standard cut-off values, and every laboratory should establish its own reference values based on predictive values for fertility outcomes. Conclusion: We present new data associated with SDF testing in real-world practice, on a global scale. The trends and conclusions derived from the study are recommended for inclusion into the 6[Formula: see text] Edition WHO Manual, towards optimized patient care.

Purpose: Azoospermia is defined as the absence of spermatozoa in the pellet of a centrifuged semen sample. In fact, when a basic semen analysis fails to detect sperm in the ejaculate, there is still the possibility of detecting rare sperm after centrifugation of the sample and examination of the pellet. In this study, we assessed the role of Cytospin centrifugation in combination with the nuclear fast picroindigocarmine (NF-PIC) staining in identifying sperm in azoospermic samples. Materials and Methods: Semen samples of 251 men diagnosed as having azoospermia after standard examination were further analyzed by Cytospin centrifugation in combination with NF-PIC staining. Results: Sperm were detected in 60 men (23.9%), thus changing their diagnosis to cryptozoospermia. Conclusions: By identifying sperm in the semen of men who were thought to have total azoospermia, the Cytospin NF-PIC test can alter the diagnosis and further treatment of these men.

Antisperm antibodies (ASA), as a cause of male infertility, have been detected in infertile males as early as 1954. Multiple causes of ASA production have been identified, and they are due to an abnormal exposure of mature germ cells to the im-mune system. ASA testing (with mixed anti-globulin reaction, and immunobead binding test) was described in the WHO manual 5th edition and is most recently listed among the extended semen tests in the WHO manual 6th edition. The relation-ship between ASA and infertility is somewhat complex. The presence of sperm agglutination, while insufficient to diagnose immunological infertility, may indicate the presence of ASA. However, ASA can also be present in the absence of any sperm agglutination. The andrological management of ASA depends on the etiology and individual practices of clinicians. In this ar-ticle, we provide a comprehensive review of the causes of ASA production, its role in immunological male infertility, clinical indications of ASA testing, and the available therapeutic options. We also provide the details of laboratory procedures for as-sessment of ASA together with important measures for quality control. Additionally, laboratory and clinical scenarios are pre-sented to guide the reader in the management of ASA and immunological male infertility. Furthermore, we report the results of a recent worldwide survey, conducted to gather information about clinical practices in the management of immunological male infertility.

Locally advanced prostate cancer poses a clinical challenge for physicians. Despite the established role of radiotherapy and androgen-deprivation therapy in these cases, some patients with locally advanced disease experience recurrent disease or persistent disease with debilitating local symptoms, such as intractable pain and urinary symptoms. In this narrative review, we sought to evaluate the role of exenterative surgery in the management of locally advanced prostate cancer. From our search, we found that total pelvic exenteration or cystoprostatectomy represents a viable therapeutic modality to manage prostate cancer directly invading the bladder, lower urinary tract symptoms, debilitating pain caused by locally advanced disease, and as salvage treatment after failure of primary treatment among other applications. Reports on minimally invasive pelvic exenteration for prostate cancer were also retrieved, as this represents a feasible and effective treatment option for experienced clinicians. Pelvic exenteration may be an effective tool for the treatment of locally advanced prostate cancer in the surgeon’s armamentarium; however, further studies are needed to establish its role in improving survival and overall patient outcomes.

Sperm vitality testing is a basic semen examination that has been described in the World Health Organization (WHO) Laboratory Manual for the Examination and Processing of Human Semen from its primary edition, 40 years ago. Several methods can be used to test sperm vitality, such as the eosin-nigrosin (E-N) stain or the hypoosmotic swelling (HOS) test. In the 6th (2021) edition of the WHO Laboratory Manual, sperm vitality assessment is mainly recommended if the total motility is less than 40%. Hence, a motile spermatozoon is considered alive, however, in certain conditions an immotile spermatozoon can also be alive. Therefore, the differentiation between asthenozoospermia (pathological decrease in sperm motility) and necrozoospermia (pathological decrease in sperm vitality) is important in directing further investigation and management of infertile patients. The causes leading to necrozoospermia are diverse and can either be local or general, testicular or extra-testicular. The andrological management of necrozoospermia depends on its etiology. However, there is no standardized treatment available presently and practice varies among clinicians. In this study, we report the results of a global survey to understand current practices regarding the physician order of sperm vitality tests as well as the management practices for necrozoospermia. Laboratory and clinical scenarios are presented to guide the reader in the management of necrozoospermia with the overall objective of establishing a benchmark ranging from the diagnosis of necrozoospermia by sperm vitality testing to its clinical management.

Sperm DNA fragmentation (SDF) is implicated in male infertility and adverse reproductive outcomes. With the publication of many studies regarding the etiologies and contributors to SDF, as well as the effects of SDF, guidelines are necessary to aid clinicians in the application of SDF for male fertility evaluation. Two recent clinical practice guidelines were published by Agarwal et al and Esteves et al. In this article, we have evaluated and compared both guidelines. We have found fairly similar recommendations between the two guidelines and have also highlighted the differences between them. Finally, we have summarized and combined the best practice recommendations from both guidelines.

Background and Aim. The chronicity of type 1 diabetes (T1D) and the demanding nature of care needed to maintain adequate glycemic control expose adolescents with T1D to various psychosocial disorders including depression. We aimed to study the frequency and risk factors of depressive symptoms in adolescents with T1D in Jordan. Methods. The study was conducted by distributing the Center for Epidemiological Studies Depression Scale for Children (CES-DC) to adolescents with T1D seen at Jordan University Hospital between February 2019 and February 2020. Demographic, clinical, and socioeconomic data were collected using electronic clinical charts. Possible predictors of depression were assessed using logistic regression analysis. Results. A total of 108 children were enrolled in the study with mean age of 13.7±2.3 years. Fifty-eight children (53.7%) had a CES depression score less than 15, and 50 children (46.3%) had a depression score of 15 or more. The number of diabetes-related hospital admissions and the frequency of self-monitoring of blood glucose (SMBG) were significantly different between the two groups. In the multivariable analysis, both gender and SMBG frequency were statistically significant. Girls were more likely to have a depression score≥15 (OR=3.41, p=0.025) than boys. Patients who were rarely testing blood glucose levels were more likely to have a depression score≥15 compared to those who were testing regularly (OR=36.57, p=0.002). Conclusion. The prevalence of depressive symptoms is relatively high in adolescents with T1D, especially in those living in developing countries. Longer diabetes duration, higher glycated hemoglobin level, and less frequent blood glucose monitoring are associated with higher depression scores.

None available.