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Purpose: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA., Materials and Methods: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process., Results: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit., Conclusions: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Purpose: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations., Materials and Methods: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations., Results: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate., Conclusions: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Purpose: Varicoceles can be a source of elevated seminal oxidative stress (OS) and sperm DNA fragmentation (SDF). However, it remains unclear whether varicocele repair (VR) could reduce these parameters. This systematic review and meta-analysis (SRMA) aims to investigate the impact of VR on SDF and seminal malondialdehyde (MDA)., Materials and Methods: A literature search was performed in Scopus, PubMed, Ovid, Embase, and Cochrane databases. This SRMA included randomized controlled trials and observational studies reporting the pre- and postoperative levels of SDF and seminal OS in infertile men with clinical varicocele that underwent VR. Subgroup analyses included techniques of VR and SDF testing. The effect size was expressed as standardized mean difference (SMD)., Results: Out of 1,632 abstracts assessed for eligibility, 29 studies with 1,491 infertile men were included. The analysis showed a significant reduction in SDF after VR, compared to preoperative values (SMD -1.125, 95% confidence interval [CI] -1.410, -0.840; p<0.0001) with high inter-study heterogeneity (I²=90.965%). Reduction in SDF was evident with microsurgical technique and non-microsurgical inguinal approaches (SMD -1.014, 95% CI -1.263, -0.765; p<0.0001, and SMD -1.495, 95% CI -2.116, -0.873; p<0.0001), respectively. Reduction in SDF was significant irrespective of testing was done by sperm chromatin dispersion (SMD -2.197, 95% CI -3.187, -1.207; p<0.0001), sperm chromatin structure assay (SMD -0.857, 95% CI -1.156, -0.559; p<0.0001) or TUNEL (SMD -1.599, 95% CI -2.478, -0.719; p<0.0001). A significant decrease in seminal MDA levels was observed following VR (SMD -2.450, 95% CI -3.903 to -0.997, p=0.001) with high inter-study heterogeneity (I²=93.7%)., Conclusions: Using pre- and post-intervention data, this SRMA indicates a significant reduction in SDF and seminal MDA levels in infertile men with clinical varicocele treated with VR. These findings may have important implications for the future management of this selected group of infertile patients., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

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., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Like all surgeries, penile prosthesis implantation (PPI) has the potential for both postoperative complications and suboptimal patient satisfaction. In order to assess risk factors for poor satisfaction, we reviewed patients who had been prospectively recruited in a national multi-institutional registry of penile prostheses procedures (INSIST-ED) from 2014 to 20121. Patient baseline characteristics and postoperative complications were recorded. The primary endpoint of this study was unfavorable outcomes after inflatable PPI, defined as significant postoperative complications (Clavien-Dindo ≥2) and/or Sexuality with Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) scores below the 10th percentile. A total of 256 patients were included in the study. The median age was 60 years (IQR 56-67). The most common cause of erectile dysfunction (ED) was organic (42.2%), followed by pelvic surgery/radiotherapy (39.8%) and Peyronie's disease (18.0%). Postoperative complications were recorded in 9.6%. High-grade complications (Clavien ≥2) occurred in 4.7%. At 1-year follow-up, the median QoLSPP total score was 71 (IQR 65-76). In all, 14.8% of patients were classified as having experienced unfavorable outcomes because of significant postoperative complications and/or QoLSPP scores below the 10th percentile. Logistic regression analysis demonstrated patient age to be non-linearly associated with the risk of experiencing unfavorable outcomes. A U-shaped correlation showed a lower risk for younger and older patients and a higher risk for middle-aged men. ED etiology and surgical volume were not associated with PPI outcomes. Physicians should, therefore, be aware that middle-aged men may be at higher risk of being unsatisfied following PPI compared to both younger and older patients., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

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., Competing Interests: The authors have nothing to disclose., (Copyright © 2023 Korean Society for Sexual Medicine and Andrology.)

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., Competing Interests: The authors have nothing to disclose., (Copyright © 2023 Korean Society for Sexual Medicine and Andrology.)

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., Competing Interests: The authors have nothing to disclose., (Copyright © 2023 Korean Society for Sexual Medicine and Andrology.)

Microdissection testicular sperm extraction (mTESE) has been proposed as a salvage treatment option for men with a previously failed classic TESE (cTESE), but data are scarce. We aimed to assess the outcome of and potential predictors of successful salvage mTESE in a cohort of men previously submitted to unfruitful cTESE. Data from 61 men who underwent mTESE after a failed cTESE between 01/2014 and 10/2020, at 6 tertiary-referral centres in Italy were analysed. All men were investigated with semen analyses, testicular ultrasound, hormonal and genetic blood testing. Pathological diagnosis from TESE was collected in every man. Descriptive statistics and logistic regression models were used to investigate potential predictors of positive sperm retrieval (SR+) after salvage mTESE. Baseline serum Follicle-Stimulating hormone (FSH) and total testosterone levels were 17.2 (8.6-30.1) mUI/mL and 4.7 (3.5-6.4) ng/mL, respectively. Sertoli-cell-only syndrome (SCOS), maturation arrest (MA) and hypospermatogenesis were found in 24 (39.3%), 21 (34.4%) and 16 (26.2%) men after cTESE, respectively. At mTESE, SR+ was found in 30 (49.2%) men. Patients with a diagnosis of hypospermatogenesis had a higher rate of SR+ (12/16 (75%)) compared to MA (12/21 (57.1%)) and SCOS (6/24 (25%)) patients at mTESE (p < 0.01). No clinical and laboratory differences were observed between SR+ and SR- patients at mTESE. There were no significant complications after mTESE. At multivariable logistic regression analysis, only hypospermatogenesis (OR 9.5; p < 0.01) was independently associated with SR+ at mTESE, after accounting for age and FSH.In conclusion, salvage mTESE in NOA men with previous negative cTESE was safe and promoted SR+ in almost 50%. A baseline pathology of hypospermatogenesis at cTESE emerged as the only independent predictor of positive outcomes at salvage mTESE., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Penile prosthesis implantation has been associated with overall good functional outcomes. Of relevance, some patients reported higher level of satisfaction and quality of life., Aim: We investigated the profile of the patients who may benefit the most from penile prosthesis implantation., Materials and Methods: Data from a national multi-institutional registry of penile prostheses including patients treated from 2014 to 2017 in Italy (Italian Nationwide Systematic Inventarization of Surgical Treatment for Erectile Dysfunction) were analyzed. All data have been prospectively recorded by 45 surgeons on a dedicated website (www.registro.andrologiaitaliana.it) and revised by a single data manager. Patients' baseline characteristics were recorded. In order to simultaneously evaluate perceived penile prosthesis function and quality of life, all patients were re-assessed at 1-year follow-up using the validated questionnaire Quality of Life and Sexuality with Penile Prosthesis. High quality of life after surgery was defined as a score higher than the 75th percentile in each of the subdomains of the Quality of Life and Sexuality with Penile Prosthesis questionnaire. Logistic regression analysis tested the association between clinical characteristics and high quality of life after penile prosthesis implantation., Results: Follow-up data were available for 285 patients (median age 60 years; interquartile range: 56-67) who underwent penile prosthesis implantation. Erectile dysfunction etiology was organic in 40% (114), pelvic surgery/radiotherapy in 39% (111), and Peyronie's disease in 21% (60) of the cases. Patients showed good overall Quality of Life and Sexuality with Penile Prosthesis scores at 1-year follow-up for functional (22/25), personal (13/15), relational (17/20), and social (13/15) domains. Overall, 27.0% (77) of patients achieved scores consistent with the high quality of life definition. These patients did not differ in terms of median age (60 vs. 62), type of prosthesis (inflatable penile prostheses: 95% in both of the cases), and post-operative complications (10% vs. 14%) than those with lower quality of life score (all p &gt; 0.1). At logistic regression analysis, erectile dysfunction etiology was the only factor independently associated with high quality of life at 1 year after surgery (p = 0.02). Patients treated for Peyronie's disease (odds ratio: 2.62; p = 0.01; 95% confidence interval: 1.20-5.74) were more likely to report better outcomes after accounting for age, post-operative complications, and surgical volume., Conclusion: Penile prosthesis implantation is associated with an overall good quality of life. The subset of patients affected by erectile dysfunction secondary to Peyronie's disease seemed to benefit the most from penile prosthesis implantation in terms of functional outcomes, relationship with their partners and the outside world, and perceived self-image. The systematic use of validated questionnaires specifically addressed at evaluating quality of life and satisfaction after penile prosthesis implantation should be further implemented in future studies to better define the predictors of optimal satisfaction after penile prosthesis implantation., (© 2022 American Society of Andrology and European Academy of Andrology.)

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 immune 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 relationship 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 article, 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 assessment of ASA together with important measures for quality control. Additionally, laboratory and clinical scenarios are presented 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., Competing Interests: The authors have nothing to disclose., (Copyright © 2022 Korean Society for Sexual Medicine and Andrology.)