With advances in cancer treatment, such as cytotoxic chemotherapy and radiotherapy, grave new sequelae of treatment have emerged for young cancer survivors. One sequela that cannot be overlooked is male infertility, with reportedly 15% to 30% of cancer survivors losing their fertility potential. Cytotoxic therapy influences spermatogenesis at least temporarily, and in some cases, permanently. The degree of spermatogenesis impairment depends on the combination of drugs used, their cumulative dose, and the level of radiation. The American Society of Clinical Oncology has created an index to classify the risks to fertility based on treatment. Medical professionals currently use this risk classification in fertility preservation (FP) programs. FP programs are currently being promoted to prevent spermatogenesis failure resulting from cancer treatment. For patients who are able to ejaculate and whose semen contains sperm, the semen (sperm) is cryopreserved. Moreover, for patients who lack the ability to ejaculate, those with azoospermia or severe oligozoospermia, and those who have not attained puberty (i.e., spermatogenesis has not begun), testicular biopsy is performed to collect the sperm or germ cells and cryopreserve them. This method of culturing germ cells to differentiate the sperm has been successful in some animal models, but not in humans. FP has recently gained popularity; however, some oncologists and medical professionals involved in cancer treatment still lack adequate knowledge of these procedures. This hinders the dissemination of information to patients and the execution of FP. Information sharing and collaboration between reproductive medicine specialists and oncologists is extremely important for the development of FP. In Japan, the network of clinics and hospitals that support FP is expanding across prefectures.

We report the case of a 46-year-old Chinese male patient who visited our clinic complaining of infertility. Semen analysis revealed azoospermia, and azoospermia factor c region partial deletion (b1/b3) was detected using Y chromosome microdeletion analysis. Testicular sperm extraction was performed after genetic counseling. The bilateral ductus deferens and a portion of the epididymis were absent, whereas the remaining epididymis was expanded. Motile intratesticular spermatozoa were successfully extracted from the seminiferous tubule. On histopathology, nearly complete spermatogenesis was confirmed in almost every seminiferous tubule. To our knowledge, this is the first case report of b1/b3 deletion with a congenital bilateral absence of the vas deferens and almost normal spermatogenesis.
Asian Continental Ancestry Group ; Azoospermia ; Epididymis ; Genetic Counseling ; Humans ; Infertility ; Infertility, Male ; Male ; Middle Aged ; Semen Analysis ; Seminiferous Tubules ; Spermatogenesis* ; Spermatozoa ; Vas Deferens* ; Y Chromosome*

Onco-testicular sperm extraction is used to preserve fertility in patients with bilateral testicular tumors and azoospermia. We report the case of a testicular tumor in the solitary testis of a patient who had previously undergone successful contralateral orchiectomy and whose sperm was preserved by onco-testicular sperm extraction. A 35-year-old patient presented with swelling of his right scrotum that had lasted for 1 month. His medical history included a contralateral orchiectomy during childhood. Ultrasonography revealed a mosaic echoic area in his scrotum, suggesting a testicular tumor. The lesion was palpated within the normal testicular tissue along its edge and semen analysis showed azoospermia. Radical inguinal orchiectomy and onco-testicular sperm extraction were performed simultaneously. Motile spermatozoa were extracted from normal seminiferous tubules under microscopy and were frozen. Eventual intracytoplasmic sperm injection using the frozen spermatozoa is planned. Onco-testicular sperm extraction is an important fertility preservation method in patients with bilateral testicular tumors or a history of a previous contralateral orchiectomy.
Adult ; Azoospermia* ; Fertility ; Fertility Preservation ; Humans ; Infertility, Male ; Male ; Methods ; Microscopy ; Orchiectomy ; Scrotum ; Semen Analysis ; Seminiferous Tubules ; Sperm Injections, Intracytoplasmic ; Sperm Retrieval ; Spermatozoa* ; Testicular Neoplasms* ; Testis* ; Ultrasonography

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.

Purpose: Despite the significant role of varicocele in the pathogenesis of male infertility, the impact of varicocele repair (VR) on conventional semen parameters remains controversial. Only a few systematic reviews and meta-analyses (SRMAs) have evaluated the impact of VR on sperm concentration, total motility, and progressive motility, mostly using a before-after analytic approach. No SRMA to date has evaluated the change in conventional semen parameters after VR compared to untreated controls. This study aimed to evaluate the effect of VR on conventional semen parameters in infertile patients with clinical varicocele compared to untreated controls. Materials and Methods: A literature search was performed using Scopus, PubMed, Embase, and Cochrane databases following the Population Intervention Comparison Outcome (PICOS) model (Population: infertile patients with clinical varicocele; Intervention: VR [any technique]; Comparison: infertile patients with clinical varicocele that were untreated; Outcome: sperm concentration, sperm total count, progressive sperm motility, total sperm motility, sperm morphology, and semen volume; Study type: randomized controlled trials and observational studies). Results: A total of 1,632 abstracts were initially assessed for eligibility. Sixteen studies were finally included with a total of 2,420 infertile men with clinical varicocele (1,424 patients treated with VR vs. 996 untreated controls). The analysis showed significantly improved post-operative semen parameters in patients compared to controls with regards to sperm concentration (standardized mean difference [SMD] 1.739; 95% CI 1.129 to 2.349; p<0.001; I2=97.6%), total sperm count (SMD 1.894; 95% CI 0.566 to 3.222; p<0.05; I2=97.8%), progressive sperm motility (SMD 3.301; 95% CI 2.164 to 4.437; p<0.01; I2=98.5%), total sperm motility (SMD 0.887; 95% CI 0.036 to 1.738; p=0.04; I2=97.3%) and normal sperm morphology (SMD 1.673; 95% CI 0.876 to 2.470; p<0.05; I2=98.5%). All the outcomes showed a high inter-study heterogeneity, but the sensitivity analysis showed that no study was sensitive enough to change these results. Publication bias was present only in the analysis of the sperm concentration and progressive motility. No significant difference was found for the semen volume (SMD 0.313; 95% CI -0.242 to 0.868; I2=89.7%). Conclusions This study provides a high level of evidence in favor of a positive effect of VR to improve conventional semen parameters in infertile men with clinical varicocele. To the best of our knowledge, this is the first SRMA to compare changes in conventional semen parameters after VR with changes in parameters of a control group over the same period. This is in contrast to other SRMAs which have compared semen parameters before and after VR, without reference to a control group. Our findings strengthen the available evidence and have a potential to upgrade professional societies’ practice recommendations favoring VR to improve conventional semen parameters in infertile men.

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.

Artificial intelligence (AI) in medicine has gained a lot of momentum in the last decades and has been applied to various fields of medicine. Advances in computer science, medical informatics, robotics, and the need for personalized medicine have facilitated the role of AI in modern healthcare. Similarly, as in other fields, AI applications, such as machine learning, artificial neural networks, and deep learning, have shown great potential in andrology and reproductive medicine. AI-based tools are poised to become valuable assets with abilities to support and aid in diagnosing and treating male infertility, and in improving the accuracy of patient care. These automated, AI-based predictions may offer consistency and efficiency in terms of time and cost in infertility research and clinical management. In andrology and reproductive medicine, AI has been used for objective sperm, oocyte, and embryo selection, prediction of surgical outcomes, cost-effective assessment, development of robotic surgery, and clinical decision-making systems. In the future, better integration and implementation of AI into medicine will undoubtedly lead to pioneering evidence-based breakthroughs and the reshaping of andrology and reproductive medicine.

Azoospermia ; Cysts ; Humans ; Male ; Prostate ; Prostatic Diseases ; Saccule and Utricle ; Urethra

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.