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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.)

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

Objective: To evaluate the efficacy of the second micro-testicular sperm extraction (TESE)in men with nonobstructive azoospermia in whom the first micro-TESE failed., Design: Retrospective., Setting: Private clinic., Patient(s): One hundred twenty-five men with nonobstructive azoospermia with failed previous micro-TESE. The patients were divided into 2 groups according to their surgical sperm retrieval status during the second micro-TESE. If sperm could not be found, these patients were classified as Group 1, and, if sperm was found, the patients were classified as Group 2. The 2 groups were compared for clinical parameters and pathologic findings., Intervention(s): Micro-TESE., Main Outcome Measure(s): Surgical sperm retrieval status., Result(s): Sperm was recovered successfully in 23 of 125 (18.4%) men with the second micro-TESE. Testicular volume was significantly lower in Group 2 (8.2 ± 5.4 mL) than Group 1 (11.3 ± 5.3 mL). Seven of 14 (50%) patients with Klinefelter's Syndrome had sperm recovery with repeat micro-TESE. The sperm retrieval rate was significantly higher in the Leydig cell hyperplasia and tubular sclerosis groups than in the Sertoli cell only and maturation arrest groups (54.5%, 10.1%, and 18.6%, respectively)., Conclusion(s): On the basis of our results, 18.4% of men with failed first micro-TESE had a probability of sperm retrieval with the second micro-TESE. Patients with successful sperm recovery had smaller testicular volumes than those with a failed second attempt. Severe testicular atrophy was not a contraindication for the second micro-TESE in such patients., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the frequency of parental consanguineous marriages (PCMs) in men with diagnosed idiopathic nonobstructive azoospermia (INOA) and to compare clinical and pathological parameters between azoospermic men with and without PCM., Design: Retrospective., Setting: A private clinic., Patients: Two hundred forty-six men with INOA. Patients were divided into two groups: group 1 with PCM and group 2 without PCM. Clinical parameters, surgical sperm retrieval rates, and pathological findings were compared between the groups., Interventions: Surgical sperm retrieval., Main Outcome Measures: PCM and clinical parameters., Results: Among the 246 patients with INOA, 81 had PCM. Men with PCM had lower follicle-stimulating hormone (13.7 vs. 21.9 mIU/mL), higher testosterone (3.8 vs. 3.4 ng/mL), and larger testes (14.1 vs. 11.8 mL). In parallel with the clinical findings, the most common pathological pattern in men with PCM was maturation arrest. However, there was no difference in surgical sperm retrieval rate between men with (23.4%) and without (32.1%) PCM., Conclusions: Our data showed that PCM was present for 33% of men with INOA. The clinical parameters of men with PCM and INOA were significantly different than those without PCM, primarily demonstrating maturation arrest in testicular pathology. Further genetic research in families who have infertile male siblings may elucidate underlying rare genetic abnormalities in spermatogenesis., (© 2020 The Authors.)

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause., Competing Interests: None of the authors declares competing financial interests. The authors do not have any potential interest in promoting MiOXSYS., (Copyright © 2019 Korean Society for Sexual Medicine and Andrology.)

Objective: To investigate the genetic cause of nonobstructive azoospermia (NOA) in a consanguineous Turkish family through homozygosity mapping followed by targeted exon/whole-exome sequencing to identify genetic variations., Design: Whole-exome sequencing (WES)., Setting: Research laboratory., Patient(s): Two siblings in a consanguineous family with NOA., Intervention(s): Validating all variants passing filter criteria with Sanger sequencing to confirm familial segregation and absence in the control population., Main Outcome Measure(s): Discovery of a mutation that could potentially cause NOA., Result(s): A novel nonsynonymous mutation in the neuronal PAS-2 domain (NPAS2) was identified in a consanguineous family from Turkey. This mutation in exon 14 (chr2: 101592000 C>G) of NPAS2 is likely a disease-causing mutation as it is predicted to be damaging, it is a novel variant, and it segregates with the disease. Family segregation of the variants showed the presence of the homozygous mutation in the three brothers with NOA and a heterozygous mutation in the mother as well as one brother and one sister who were both fertile. The mutation is not found in the single-nucleotide polymorphism database, the 1000 Genomes Project, the Baylor College of Medicine cohort of 500 Turkish patients (not a population-specific polymorphism), or the matching 50 fertile controls., Conclusion(s): With the use of WES we identified a novel homozygous mutation in NPAS2 as a likely disease-causing variant in a Turkish family diagnosed with NOA. Our data reinforce the clinical role of WES in the molecular diagnosis of highly heterogeneous genetic diseases for which conventional genetic approaches have previously failed to find a molecular diagnosis., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)