Antioxidants for male infertility: therapeutic scheme and indications. A retrospective single-center real-life study.

BACKGROUND: This single-center real-life study was conducted to evaluate the most effective combination of nutraceuticals and the most appropriate indications for the treatment of male infertile patients. METHODS: Infertile patients aged 20-55 years were treated with a combination of antioxidants (Androlen®; Enfarma, Misterbianco, Catania, Italy) (group A), with Androlen® (Enfarma) and a mixture of fibrinolytic molecules (Lenidase®, Enfarma) (group B), or Androlen® (Enfarma) and other molecules different from those used for the patients of the group B (group C). Patients were also subdivided according to the presence of varicocele, mild testicular hypotrophy, idiopathic infertility, and chronic male accessory gland infection. RESULTS: Forty-three patients were enrolled. In the overall analysis, only progressive motility significantly improved after therapy. Subgroup analysis showed a significant increase in progressive motility, total motile sperm count (TMSC), and in the percentage of alive spermatozoa after treatment in the group A. Progressive motility improved significantly in patients with varicocele, while the TMSC in patients with varicocele and those with idiopathic infertility. The percentage of alive spermatozoa increased in patients with testicular hypotrophy. CONCLUSIONS: Treatment with antioxidants increased progressive sperm motility, especially in patients with varicocele or idiopathic infertility.

Artificial Intelligence in Andrology: From Semen Analysis to Image Diagnostics.

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.

Pre- and post-chemotherapy spermatogenesis in male patients with malignant bone and soft tissue tumors.

Introduction: Malignant bone and soft tissue tumors, commonly called sarcomas, predominantly originate in bone and soft tissues and typically affect individuals at a younger age. Following the resection of the primary tumor, treatment often necessitates radiation therapy and gonadotoxic chemotherapy, the specifics of which depend on the disease's stage Conversely, there is a notable concern regarding the potential loss of fertility due to these treatments. Consequently, it is recommended that men consider sperm cryopreservation before initiating treatment. This study aims to assess spermatogenesis in male patients diagnosed with malignant bone and soft tissue tumors before and after chemotherapy. Methods: This study involved 34 male patients diagnosed with malignant bone and soft tissue tumors and subsequently underwent sperm cryopreservation before initiating treatment. Medical records included details about the primary disease, age, marital status at presentation, semen analysis results, treatment regimen and number of courses, post-treatment semen analysis, renewal status and outcomes. Results: The mean age at the time of sperm cryopreservation was 22.8 years. The median semen volume was 2.5 mL, sperm concentration was 32.6 million/ml, and sperm motility was 38.5%. Following chemotherapy, semen analysis was conducted on 12 patients, with ifosfamide being the predominant drug used in all cases. Among these 12 patients, eight retained viable spermatozoa, and two successfully achieved spontaneous pregnancies resulting in live births. In one of the remaining four cases where no sperm were detected in ejaculate, a live birth was achieved through intracytoplasmic sperm injection using cryopreserved sperm. Discussion: While ifosfamide, the primary chemotherapy drug for patients with malignant bone and soft tissue tumors, was associated with severe impairments in spermatogenesis, recovery of spermatogenesis was observed in many cases. However, there were instances of prolonged azoospermia. Even in such cases, assisted reproduction using cryopreserved sperm remained viable for achieving parenthood. In light of these findings, offering patients the opportunity for fertility preservation is advisable.

Controversy and Consensus on Indications for Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations.

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.

Long-Term Fertility Function Sequelae in Young Male Cancer Survivors.

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.

Fertility and sexual dysfunction in young male cancer survivors.

Background: Newly emerging serious post-treatment complications among young male cancer survivors involve fertility and sexual function, preventing them from pursuing a normal family life. Methods: We studied and summarized published studies that assess the relationship between cancer treatments and reduced spermatogenesis or sexual dysfunction. Main findings: Infertility often occurs because of anticancer therapies that impair spermatogenesis. While some patients postremission functionally recover fertility, others experience a decreased sperm count and azoospermia. Fertility-preserving modalities are currently being promoted worldwide to preserve spermatogenesis following cancer therapy. Patients who can ejaculate and have sperm in their semen should cryopreserve semen. However, for patients who have never ejaculated before puberty or in whom spermatogenesis has not been established, testis biopsy is performed to collect and preserve sperm or germ cells. Fertility preservation is gaining popularity and requires continuous information dissemination to oncologists and cancer treatment professionals. Furthermore, male sexual dysfunction predominantly involves erectile dysfunction and ejaculation disorder. Conclusion: Although preventive and therapeutic methods for these disorders have been established within urology, patients and medical professionals in other fields remain uninformed of these advances. Therefore, dissemination of information regarding fertility preservation techniques should be accelerated.

Skin Metastasis of Renal Cell Carcinoma.

Renal cell carcinoma (RCC) accounts for around 3% of all cases of skin metastasis. In these patients, solitary metastasis from RCC shows a favorable prognosis. A 68-year-old woman was found to have a right renal tumor in 2009, and the pathological diagnosis was pathological T3 and grade 3 right clear cell RCC. Left-sided RCC developed and was resected in 2018. She subsequently noticed a cutaneous nodule on her abdomen. We performed surgical resection, and the pathological diagnosis was skin metastasis of RCC. We herein report a case of skin metastasis of RCC that developed 11 years after the initial diagnosis that was successfully treated by surgical resection.

Bilateral Encrusted Metallic Stent Successfully Removed by Ureteroscopic Lithotripsy Using a Ho:YAG Laser in a Patient with Malignant Myeloma.

Ureteral stent encrustation is sometimes encountered, especially in cases in which a ureteral stent has been forgotten. An 84-year-old female patient with malignant myeloma underwent metallic ureteral stent insertion to treat malignant ureteral obstruction. At the time of scheduled ureteral stent exchange, the stent was heavily encrusted and could not be removed on either side. We performed endoscopic lithotripsy to remove the encrusted ureteral stents. The bilaterally encrusted metallic ureteral stents were successfully removed using Ho:YAG laser lithotripsy after inserting another ureteral stent placement besides the encrusted metallic ureteral stents.

Cancer Chemotherapy and Chemiluminescence Detection of Reactive Oxygen Species in Human Semen.

Advanced treatments have improved the prognosis of cancer survivors. Anticancer drugs generate large amounts of cellular reactive oxygen species (ROS), but their direct effects on sperm ROS production are unclear. We examined 64 semen samples of men who had received cancer chemotherapy, 467 semen samples of men consulting for idiopathic infertility, and 402 semen samples of partners of female patients as a control group. ROS production was calculated as the integrated chemiluminescence between 0 and 200 seconds after the addition of luminol to unwashed semen. We found that their ROS-positive rate of semen samples in the chemotherapy group was significantly higher than that in the control group. We compared the sperm parameters (concentration and motility) and the ROS production levels between chemotherapy subgroups and one of the remaining subgroups with positive ROS, and we found that only sperm motility was significantly lower in the samples in the postchemotherapy subgroup than in the idiopathic infertility subgroup, and that both sperm parameters were significantly lower in those from postchemotherapy subgroup than in the control subgroup. The ROS production level per million spermatozoa in the postchemotherapy subgroup was significantly higher than that in the control subgroup. Additionally, we compared variables, such as age, sperm features, and the duration from the end of the treatment to the first consultation between ROS-positive and ROS-negative subgroups in samples from men in the postchemotherapy group, but we found no significant differences. Of the men in the postchemotherapy group, three underwent a long-term antioxidant therapy, and all of them had low ROS semen levels after that. In conclusion, the production of ROS in semen detected by chemiluminescence from men who undergo cancer chemotherapy is similar to that of men with idiopathic infertility, and long-term oral antioxidant therapy may reduce the amount of ROS in the semen.

Granulocyte Colony-Stimulating Factor-Producing Bladder Cancer.

Granulocyte colony-stimulating factor (G-CSF)-producing bladder cancer is rare, with only 75 cases reported in Japan. A 67-year-old woman was referred to our institution for the further examination of gross hematuria. Cystoscopy revealed a 7-cm bladder tumor. The initial white blood cell count was 17,100/µL, and a transurethral resected specimen showed G-CSF expression. CT revealed that the tumor had invaded the colon. As the patient had uncontrollable schizophrenia, radical cystectomy was abandoned. We herein report a case of G-CSF-producing bladder tumor.

A case of allograft ureteral stone successfully treated with antegrade ureteroscopic lithotripsy: use of a 3D-printed model to determine the ideal approach.

We present the case of a 46-year-old man who underwent successful antegrade ureteroscopy for lithiasis in his allograft ureter. At a scheduled follow-up 15 years after transplantation, computed tomography (CT) detected a 12-mm renal stone in the renal pelvis of the transplanted kidney. During his follow-up, gross hematuria was seen; the stone moved to the ureter, causing hydronephrosis. Ultrasound and non-contrast CT revealed hydronephrosis and a 15-mm stone in the transplanted ureter. Considering the stone size, location, and the difficulty of the access to the anastomosed ureteral orifice, percutaneous ureteroscopic approach was planned. Due to the anatomical difficulty regarding his allograft kidney, we planned to prepare a 3D image and model for selecting the best percutaneous approach. The procedure was performed and a stone-free status was acquired without complication. Under precise simulation, we performed successful antegrade ureteroscopy for lithiasis in the allograft ureter supported by 3D imaging. Use of a 3D printed model may aid in a safe and effective procedure for lithiasis in the allograft kidney and ureter.

Successful Resection of Cisplatin-Resistant Renal Pelvic Cancer after the Administration of Pembrolizumab as Second-Line Therapy.

Pembrolizumab has been used as a second-line systemic therapy for urothelial carcinoma. We herein report a case of cisplatin-resistant renal-pelvic urothelial carcinoma that was successfully resected after pembrolizumab treatment. A 74-year-old woman was referred to our hospital for further examination for gross hematuria and a renal-pelvis tumor. Retrograde pyelography showed a defect lesion in her renal pelvis and urinary cytology of the renal pelvis showed class V. Because staging CT could not deny lung metastasis, we planned to perform nephro-ureterectomy after evaluating the response to neoadjuvant chemotherapy. After three courses of gemcitabine and cisplatin chemotherapy, the original site showed progression; thus, nephro-ureterectomy was cancelled. We introduced pembrolizumab as a second-line therapy. After four courses of pembrolizumab treatment, the size of the original lesion was significantly decreased. During these therapies the lung tumor size was unchanged; thus, we determined that the lung tumor was not metastatic and performed nephro-ureterectomy. A pathological examination demonstrated that the tumor was completely resected with a negative surgical margin. We described the first case in which cisplatin-resistant renal pelvic tumor was successfully resected after pembrolizumab treatment.

High orchiectomy and ipsilateral testicular sperm extraction in a man with a testicular tumor and Klinefelter syndrome: A case report.

INTRODUCTION: Testicular epidermal cysts in Klinefelter syndrome are very rare. We report a case of Klinefelter syndrome associated with a testicular epidermal cyst. To our knowledge, this is the first report showing successful spermatozoa retrieval from the affected testis. CASE PRESENTATION: A 25-year-old married man was referred to our hospital with right scrotal induration, which was in lower pole of the right testis. Testicular cancer tumor markers were normal; endocrinological findings indicated hypergonadotropic hypogonadism. Semen analyses revealed azoospermia. Preoperative chromosome test result: 47, XXY karyotype; ultrasonography report: 1.9-cm internal heterogeneous echoic mass in the right testis (malignancy not discarded). Because the patient hoped for children, he underwent high orchiectomy with ipsilateral testicular sperm extraction (200 spermatozoa from normal testicular tissue) for future fertilization procedures. Tumor pathology was an epidermal cyst. CONCLUSION: While performing orchiectomy for testicular tumors, sperm retrieval should be attempted from normal tissues in patients planning for children.

Successful treatment of ureteral stricture after total hysterectomy: An antegrade ureteroscopic approach facilitates the insertion of a guidewire for endoscopic dilation.

INTRODUCTION: Iatrogenic ureteral injury is sometimes seen in daily clinical practice, and gynecological surgery carries the highest risk of ureteral injury among iatrogenic surgical ureteral injury. CASE PRESENTATION: A 61-year-old woman was referred to our department for right ureteral stricture and hydronephrosis after total hysterectomy. We initially attempted ureteral stenting, but hydronephrosis redeveloped 1 month after ureteral stent removal. We performed ureteroscopy via an antegrade approach and successfully incised and dilated the ureter. CONCLUSION: We encountered a case of severe ureteral stenosis after total hysterectomy that was successfully treated endoscopically using ureteroscopy via an antegrade approach.

Oxidative stress marker 8-hydroxyguanosine is more highly expressed in prostate cancer than in benign prostatic hyperplasia.

Oxidative stress is a primary cause of vascular endothelial damage. In the prostate, ischemia increases the levels of reactive oxygen species, growth factors and cytokines, and induces the development of angiogenesis, which results in cancer progression. The expression levels of an oxidative stress marker, 8-hydroxyguanosine (8-OHdG), were compared between prostate cancer and non-neoplastic prostate tissues. A prostate tissue microarray composed of 10 cases of prostatic adenocarcinoma and 70 cases of benign prostatic hyperplasia was immunohistochemically stained for 8-OHdG. All cases expressed 8-OHdG. The levels of 8-OHdG expression in prostatic cancer (30.0% moderate and 70.0% strong) were significantly higher than those in benign prostatic hyperplasia (71.4% moderate and 28.6% strong; (p<0.01). Notably, 8-OHdG is expressed more highly in prostate cancer tissues in comparison to benign prostate tissues.

The Use of a Metal Stent in the Treatment of Ureteral Stricture in a Patient Who Had Undergone Radical Cystectomy with the Creation of an Ileal Conduit.

Approximately 9.2% of patients who undergo radical cystectomy are reported to develop ureteral stricture as a result of both benign and malignant conditions. A metallic stent is a continuous, unfenestrated all-metal double-pigtail ureteric stent with no end or side holes. The patient was a 74-year-old man who underwent radial cystectomy with the creation of an ileal conduit due to advanced bladder cancer 7 years previously. Although he had no radiographic recurrence, he developed bilateral hydronephrosis. We herein report the first case of a patient with ureteral stricture after radial cystectomy with the creation of an ileal conduit who was successfully treated by the insertion of a metal stent by a combined antegrade and retrograde approach.

Fluorescent Light-Guided Cystoscopy with 5-ALA Aids in Accurate Surgical Margin Detection for TURBO: A Case Report.

Recent studies have revealed that transurethral resection in one piece (TURBO) has several benefits over standard transurethral resection of bladder tumor (TUR-Bt), including a higher rate of containing the bladder muscle tissue and single-block resection. Five-aminolevulinic acid (5-ALA) was approved for the detection of bladder tumor treated with TUR-Bt. A 71-year-old male patient who received right nephroureterectomy developed bladder tumor recurrence on routine cystoscopy follow-up. We planned TURBO using fluorescent light-guided cystoscopy with 5-ALA. We herein report a case of bladder tumor successfully treated with TURBO using fluorescent light-guided cystoscopy with 5-ALA to detect the tumor surgical margin.