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Background: Y chromosome microdeletion is one of the major causes of male infertility, and obtaining mature spermatozoa in complete azoospermic factor (AZF)b deletion cases is difficult because germ cells maturation has arrested. However, there are very few reports on spermatogenesis in partial deletions of the AZFb region. We herein report a case of partial AZFb deletion in which sperm were successfully recovered by microdissection testicular sperm extraction (micro-TESE)., Case Description: A 34-year-old man with cryptozoospermia was referred to Reproduction Center, Yokohama City University Medical Center. Both testicular sizes were normal, and the seminal tract had no abnormalities. Serum testosterone and follicle-stimulating hormone levels were also normal. The karyotype was 46,XY, and the Y chromosomal microdeletion test showed no amplification of the sequence-tagged site marker sY1024, which is the proximal part of the AZFb region. We performed micro-TESE, and subsequently identified and cryopreserved many malformed immotile spermatozoa. Intracytoplasmic sperm injection was performed using frozen-thawed testicular sperm that showed slight mobility, but the embryos rarely reached the good blastocyst stage. Although two frozen-thawed embryo transfers were performed, no pregnancies resulted., Conclusions: In cases of partial AZFb deletion, spermatogenesis may be preserved, and surgical sperm retrieval should be considered even in cases of azoospermia., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-24-426/coif). The authors have no conflicts of interest to declare., (Copyright © 2025 AME Publishing Company. All rights reserved.) more...

Background: The expenses related to fertility preservation or subsequent assisted reproductive treatments are significant for adolescents and young adult patients in Japan's current healthcare system. With fertility preservation becoming more widespread in developed countries, it is expected that these costs will be covered by insurance or subsidies. It is critical for patients, healthcare providers, and the government to know the costs that patients will be responsible for. In Japan, the costs of fertility preservation and subsequent assisted reproductive technology are not covered by insurance, but patients can apply for subsidies from the local and central governments if certain conditions are met. Presently, the above-mentioned costs, as well as the amount paid by the patient, vary by facility. Therefore, it is essential to ensure patients' continued access to necessary medical care despite the associated costs., Methods: In this study, questionnaires were mailed to 186 certified fertility preservation facilities in Japan to assess patients who had undergone fertility preservation or assisted reproduction. The questionnaires were sent between October 27, 2023 and March 31, 2024, with 140 of the 186 facilities responding (response rate: 75.3%)., Results: Our findings show that approximately one-third of the costs was borne by the patients., Conclusion: Given these circumstances, sustainable pricing and insurance coverage are necessary for both patients and facilities., Competing Interests: Declarations. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: All authors have declared that no financial support was received from any organization for the submitted work. Ethical approval: Approval was obtained from the Institutional Review Board and Ethics Committee (T2023-0129). Human and Animal rights: Consent was obtained or waived by all participants in this study. All authors have confirmed that this study did not involve animal subjects or tissue., (© 2024. The Author(s).) more...

Purpose: Spermatogenesis requires a large amount of energy, which is primarily produced by the mitochondrial electron transfer chain. Mitochondrial dysfunction affects male infertility, suggesting a relationship between the electron transfer chain and male infertility. COXFA4L3 (C15ORF48) is an emerging subunit protein of cytochrome oxidase specifically expressed in germ cells during spermatogenesis, and it may be involved in male infertility. Therefore, to investigate whether COXFA4L3 could be a marker of mitochondrial dysfunction in the sperm, this study examined the protein expression and localization profile of COXFA4L3 in the sperm of male patients with infertility., Methods: Twenty-seven semen samples from a male infertility clinic at the Reproductive Center of Yokohama City University Medical Center were used to analyze sperm quality parameters and the expression and localization of energy production-related proteins. These data were compared with the outcomes of infertility treatment., Results: The expression levels of COXFA4L3 varied significantly between samples. Furthermore, COXFA4L3 was ectopically localized to the acrosome., Conclusions: Ectopic expression of COXFA4L3 and PNA-stained acrosomes may be useful parameters for fertility treatment selection. Assessing the acrosomal localization of COXFA4L3 will expedite pregnancy treatment planning., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.) more...

Introduction: 45,X/46,XY mosaicism is a rare anomaly in sexual differentiation, presenting with diverse phenotypes and often leading to infertility due to abnormal gonadal development., Aims: This report aims to present a case study of a 45,X/46,XY mosaic male patient with an ejaculatory disorder attributed to seminal vesicle dysplasia., Methods: In this case study, diagnostic procedures encompassed blood tests, semen analysis, chromosomal examination, and imaging studies to assess gonadal morphology. Treatment strategies included attempted varicocelectomy, pharmacological intervention with amoxapine, and surgical testicular sperm extraction. Additionally, the patient underwent assisted reproductive techniques, specifically intracytoplasmic sperm injection (ICSI), to facilitate pregnancy for his wife., Results: A 32-year-old man could not ejaculate, with post-orgasmic urinalysis revealing minimal sperm presence. Chromosomal analysis confirmed 45,X/46,XY mosaicism. Despite undergoing microsurgical varicocelectomy for clinical varicocele and receiving tricyclic antidepressants, no improvement in semen volume occurred. Imaging studies indicated ejaculatory disorder due to prostate and seminal vesicle aplasia. Consequently, surgical retrieval of testicular sperm was performed, leading to successful pregnancy via ICSI for his wife., Conclusion: Our approach has effectively addressed ejaculatory disorder in 45,X/46,XY mosaic men, resulting in successful pregnancy., Competing Interests: The authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Sexual Medicine.) more...

Background: Cancer survivors in the adolescent and young adult generation often experience marriage, pregnancy, and childbirth after treatment; thus, fertility preservation is very important. In male patients, testicular sperm extraction (TESE) is sometimes performed due to azoospermia. Such a procedure is called oncological TESE (onco-TESE). In the present study, we aimed to define onco-TESE as TESE for fertility preservation in cancer patients, including those receiving gonadotoxic treatment., Methods: Seventeen male patients with cancer who had undergone onco-TESE for fertility preservation at Yokohama City University Medical Center between April 2014 and March 2023 were included in the study., Results: Motile testicular sperm were acquired by TESE in 9 out of 17 cases. Among patients who had initiated chemotherapy before surgery, Motile sperm could be acquired by onco-TESE in 3 out of 9 cases. In chemotherapy-naive patients, Motile sperm were acquired by onco-TESE in 6 out of 8 cases. In the end, sperm cryopreservation was performed in 10 patients. Cryopreserved sperm were used in 2 of the 10 cases, and live birth was achieved after intracytoplasmic sperm injection in both cases., Conclusions: Before starting gonadotoxic treatment, it is important to confirm whether the patient desires to bear children. If having a baby is desired, a referral to a reproductive medicine doctor is recommended. Fertility preservation before starting gonadotoxic treatment is preferable, but fertility preservation could be considered even after such a treatment., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-24-21/coif). The authors have no conflicts of interest to declare., (2024 Translational Andrology and Urology. All rights reserved.) more...

To enhance surgical testicular sperm retrieval outcome for men with nonobstructive azoospermia, a deep-learning model was developed to identify positive seminiferous tubules by labeling 110 images with sperm-containing tubules sampled during microdissection testicular sperm extraction as training and validation data. After training, the model achieved an average precision of 0.60. more...

Introduction: Sperm immobility is a condition in which sperm are viable but not motile. We reported three patients with sperm immobility, who underwent testicular sperm extraction-intracytoplasmic sperm injection., Case Presentation: In case 1, a 32-year-old patient with sperm immobility had previously undergone intracytoplasmic sperm injection with ejaculated sperm; however, pregnancy was unsuccessful. testicular sperm extraction-intracytoplasmic sperm injection was performed at our clinic, and pregnancy was achieved. In case 2, a 23-year-old patient with clinical varicocele whose semen analysis revealed sperm immobility underwent varicocelectomy, without improvement. Using the hypo-osmotic swelling test technique, testicular sperm extraction-intracytoplasmic sperm injection was performed; however, pregnancy was not achieved. In case 3, a 44-year-old patient with sperm immobility underwent testicular sperm extraction, and motile sperm were retrieved. testicular sperm extraction-intracytoplasmic sperm injection using these sperm resulted in pregnancy., Conclusion: Although testicular sperm extraction-intracytoplasmic sperm injection is not considered a solution in patients with sperm immobility, pregnancies were achieved. testicular sperm extraction-intracytoplasmic sperm injection may be successful in some cases in which ejaculated sperm intracytoplasmic sperm injection is unsuitable., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Urological Association.) more...

Introduction: Varicocelectomy is well known to improve the pregnancy outcome of patients with clinical varicoceles in assisted reproductive technologies as well as spontaneous conception. Therefore, this study aimed to evaluate the additional effects of oral antioxidant therapy after varicocelectomy on the pregnancy outcome in the assisted reproductive technology setting., Methods: This study was a retrospective cohort study. The subjects were couples among whom the male partner had undergone varicocelectomy and was scheduled for subsequent assisted reproductive technology. Pregnancy outcomes were followed retrospectively in 62 couples with male partners who received tocopherol (antioxidant group) and 37 couples who did not (control group). The tocopherol and control groups were assigned dependent on the decision of the physician in charge and the patient's request. The clinical pregnancy rates per couple and embryo transfer, time to pregnancy, and the number of cycles during transfer to pregnancy were evaluated., Results: No significant differences were observed in the pregnancy rate per couple (antioxidant group 70.9% vs. control group 64.9%, P  = 0.55) and per embryo transfer (50.4% vs. 39.6%, P  = 0.22). Regarding the time to event analyzed by adjusted restricted mean survival time, the mean time to pregnancy was significantly shorter in the antioxidant (tocopherol) group (14.2 vs. 17.4 months, P  = 0.025). No significant difference was observed in the embryo transfer cycle to pregnancy (mean embryo transfer cycles: 2.6 vs. 3.0, P  = 0.238)., Conclusions: Additional oral tocopherol nicotinate as antioxidant therapy after varicocelectomy was shown to shorten the time to pregnancy. It is recommended that add-on effects be tested in more well-designed randomized controlled trials to examine whether it improves assisted reproductive outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Takeshima, Mihara, Tomita, Kuroda, Yumura, Ueno, Yamamoto and Murase.) more...

A 35-year-old man visited a local doctor for continuing analysis of his infertility. Semen analysis revealed azoospermia while an ultrasonography detected a right testicular tumor with a diameter of 10 mm. A blood test was negative for tumor markers. Magnetic resonance imaging showed a 1-cm tumor in the right testis and atrophy of the left testis. A testicular tumor arising from a functional unilateral testis was discovered during infertility treatment for which the patient was referred to our hospital for fertility preservation. Right and left testicular volumes were 18 mL and 3 mL, respectively, and his serum testosterone level was 2.96 ng/mL. Noting the atrophy of the contralateral testicle, we proceeded with a rapid pathology diagnosis by partial testicular resection. If no evidence of tumor malignancy was found, the surgery would have been concluded with no further dissection. Since the patient was undergoing fertility treatment, the decision was made to take sperm from the extracted testicle to preserve his fertility, followed by orchiectomy. Because a seminoma was suspected through the rapid pathological diagnosis, the man eventually underwent higher orchiectomy and testicular sperm extraction. The final diagnosis was seminoma, followed by successful retrieval of a sufficient level of sperm. Post operative serum testosterone level was found to be 0.32 ng/mL, after which testosterone replacement therapy was introduced. Through rapid diagnosis of pathology, successful management and outcome were achieved in the case of testicular cancer combined with infertility. more...

Approximately 1% of the general male population has azoospermia, and nonobstructive azoospermia accounts for the majority of cases. The causes vary widely, including chromosomal and genetic abnormalities, varicocele, drug-induced causes, and gonadotropin deficiency; however, the cause is often unknown. In azoospermia caused by hypogonadotropic hypogonadism, gonadotropin replacement therapy can be expected to produce sperm in the ejaculate. In some cases, upfront varicocelectomy for nonobstructive azoospermia with varicocele may result in the appearance of ejaculated spermatozoa; however, the appropriate indication should be selected. Each guideline recommends microdissection testicular sperm extraction for nonobstructive azoospermia in terms of successful sperm retrieval and avoidance of complications. Sperm retrieval rates generally ranged from 20% to 70% but vary depending on the causative disease. Various attempts have been made to predict sperm retrieval and improve sperm retrieval rates; however, the evidence is insufficient. Further evidence accumulation is needed for salvage treatment in cases of failed sperm retrieval. In Japan, there is inadequate provision on the right to know the origin of children born from artificial insemination of donated sperm and the rights of sperm donors, as well as information on unrelated family members, and the development of these systems is challenging. In the future, it is hoped that the pathogenesis of nonobstructive azoospermia with an unknown cause will be elucidated and that technology for omics technologies, human spermatogenesis using pluripotent cells, and organ culture methods will be developed., (© 2023 The Japanese Urological Association.) more...

Background: Late-onset hypogonadism (LOH) is a condition caused by the decline of testosterone levels with aging and is associated with various symptoms, including lower urinary tract symptoms (LUTSs). Although some reports have shown that testosterone replacement treatment for LOH improves LUTSs, no large study has revealed a correlation between LUTSs and LOH. This study investigated the correlation between the severity of LOH and LUTSs in Japanese males >40 years of age using a web-based questionnaire with the Aging Males' Symptoms (AMS) scale., Methods: We asked 2000 Japanese males to answer both the AMS and IPSS/QOL questionnaires using a web-based survey. Among these 2000 individuals, 500 individuals were assigned to each age group., Results: The IPSS total score was positively correlated with the severity of AMS (shown as median [mean ± SD]): no/little group, 2 (3.67 ± 5.36); mild group, 6 (7.98 ± 6.91); moderate group, 11 (12.49 ± 8.63); and severe group, 16 (14.83 ± 9.24) ( p < 0.0001)., Conclusions: Individuals with higher AMS values, representing cases with severe LOH symptoms, had a higher risk of experiencing nocturia and LUTSs than those with lower AMS values. more...

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Takeshima, Mimura, Aoki, Saito, Karibe, Usui, Kuroda, Komeya and Yumura.) more...

Background: Approximately 8%-12% of couples worldwide face infertility, with infertility of individuals assigned male at birth (AMAB) contributing to at least 50% of cases. Conventional semen analysis commonly used to detect sperm abnormalities is insufficient, as 30% of AMAB patients experiencing infertility show normal results in this test. From a genetic perspective, the assessment of sperm DNA fragmentation (SDF) is important as a parameter of sperm quality., Methods: In this narrative study, we review and discuss pathophysiological causes, DNA repair mechanisms, and management of high SDF. We then summarize literature exploring the association between SDF and reproductive outcomes., Main Findings: Recent systematic reviews and meta-analyses have revealed a significant association between high SDF in AMAB individuals and adverse reproductive outcomes including embryo development, natural conception, intrauterine insemination, and in vitro fertilization. However, the association with live birth rates and pregnancy rates following intracytoplasmic injection remains inconclusive. The disparities among quantitative assays, inconsistent reference range values, absent high-quality prospective clinical trials, and clinical heterogeneity in AMAB patients with elevated SDF represent the main limitations affecting SDF testing., Conclusion: The evaluation and management of SDF plays an important role in a subset of AMAB infertility, but widespread integration into clinical guidelines will require future high-quality clinical trials and assay standardization., Competing Interests: Authors declare no Conflict of Interests for this article., (© 2023 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.) more...

Background: Our web-based training program called "Educating Medical Professionals about Reproductive Issues in Cancer Healthcare" aims to help healthcare professionals communicate promptly with patients and survivors who are adolescents and young adults, with information pertinent to reproductive health issues such as the risk of infertility and fertility preservation., Methods: The study participants were professional healthcare providers, including physicians, nurses, pharmacists, social workers, midwives, psychologists, laboratory technicians, genetic counselors, and dieticians. Pre- and post- and 3-month follow-up tests consisting of 41 questions were administered to measure changes in knowledge and confidence. The participants also received a follow-up survey that covered confidence, communication techniques, and practice habits. A total of 820 healthcare providers participated in this program., Results: The mean total score from the pre-test to the post-test grew significantly (p < 0.01), and participants' self-confidence increased. In addition, there was a change in the behavior of healthcare providers, who began asking about patients' marital status and parity., Conclusion: Our web-based fertility preservation training program improved knowledge and self-confidence regarding fertility preservation issues among healthcare providers caring for adolescents and young adult cancer patients and survivors., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.) more...

Introduction: Several healthy euploid births have been reported following the transfer of mosaic embryos, including both euploid and aneuploid blastomeres. This has been attributed to a reduced number of aneuploid cells, as previously reported in mice, but remains poorly explored in humans. We hypothesized that mitochondrial function, one of the most critical factors for embryonic development, can influence human post-implantation embryonic development, including a decrease of aneuploid cells in mosaic embryos. Methods: To clarify the role of mitochondrial function, we biopsied multiple parts of each human embryo and observed the remaining embryos under in vitro culture as a model of post-implantation development ( n = 27 embryos). Karyotyping, whole mitochondrial DNA (mtDNA) sequencing, and mtDNA copy number assays were performed on all pre- and post-culture samples. Results: The ratio of euploid embryos was significantly enhanced during in vitro culture, whereas the ratio of mosaic embryos was significantly reduced. Furthermore, post-culture euploid and culturable embryos had significantly few mtDNA mutations, although mtDNA copy numbers did not differ. Discussion: Our results indicate that aneuploid cells decrease in human embryos post-implantation, and mtDNA mutations might induce low mitochondrial function and influence the development of post-implantation embryos with not only aneuploidy but also euploidy. Analyzing the whole mtDNA mutation number may be a novel method for selecting a better mosaic embryo for transfer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ijuin, Ueno, Hayama, Miyai, Miyakoshi, Hamada, Sueyoshi, Tochihara, Saito, Hamanoue, Takeshima, Yumura, Miyagi, Kurahashi, Sakakibara and Murase.) more...

Purpose: Fertility preservation (FP) is becoming increasingly common among child, adolescent, and young-adult (CAYA) patients with cancer. However, Japan has long lacked definite estimates of utilization rates for FP services among CAYA patients with cancer, and little is known about disease/FP outcomes among users. Therefore, the Japan Society for Fertility Preservation (JSFP) launched the Japan Oncofertility Registry (JOFR) in 2018 and started the online registration of information regarding primary disease, FP, and data on prognosis and pregnancy outcomes. This study reports the analytical results of FP data registered in the JOFR as of 2021. Methods: Data about patients' primary disease(s), treatment courses, cancer and pregnancy outcomes, and specific procedures were extracted from the JOFR and analyzed. Results: In 2021, 1244 patients received counseling or treatment related to FP (540 males, 704 females). While the numbers of males in each age group were approximately equal, most females were aged between 31 and 40 years. In total, 490 male and 540 female patients underwent FP procedures. Leukemia, testicular cancer, and malignant lymphoma accounted for the majority of male cases seeking treatment, whereas breast cancer was the primary disease in two-thirds of the females. Since 1999, 395 patients have accumulatively experienced subsequent pregnancy. Conclusions: As of January 2022, >7000 cases from >100 fertility facilities have been registered in the JOFR. In the future, maintaining JOFR to disseminate information on cancer prognoses, pregnancy rates, and other oncofertility outcomes is expected to drive further expansion of oncofertility services in Japan. more...

Competing Interests: The authors declare no conflicts of interest.

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

(Introduction) Beginning in April of 2022, infertility services-including assisted reproductive technologies and examinations and treatments for male infertility-were covered by health insurance in Japan. Although these changes are expected to bolster birth rates in Japan, increased numbers of patients and surgeries are anticipated, particularly following reductions in patient visits caused by COVID-19. (Materials and methods) We surveyed 13 members of the Male Infertility Special Interest Group of the Japanese Society for Reproductive Medicine using Microsoft Forms. Respondents were asked about the number of new male infertility patients and surgeries at their respective facilities before the COVID-19 pandemic, after the first wave, after the sixth wave, and after the insurance changes to cover treatments for male infertility. Respondents were also asked to describe challenges in meeting the demand created by these insurance coverage changes. (Results) Patients and surgeries (varicocelectomy and testicular sperm extraction) declined markedly after the first wave of COVID-19 but gradually recovered after the sixth wave. However, once male infertility-related services were covered by insurance in Japan, respondents observed a marked increase in new patients and surgeries compared to pre-COVID-19. The most frequently reported problem was that sperm cryopreservation was not covered by insurance. (Conclusions) This survey should be readministered after additional time has passed to capture longer-term changes following changes to insurance coverage in Japan. We anticipate the responses to the survey will reflect ongoing challenges associated with changes in insurance coverage for male infertility-related services. more...

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., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.) more...

Penile cancer is a rare cancer for which no medical guidelines have been established before in Japan. These guidelines aim to standardize, as much as possible, the therapeutic modality for penile cancer, for which empirical evidence is limited on a global scale, thereby bolstering therapeutic outcomes for patients with penile cancer. The new guidelines conform to the Minds Guide for Developing Clinical Practice Guidelines (2017) as much as possible. However, virtually no randomized comparative studies and meta-analyses based on such randomized studies have been conducted. Therefore, only the findings available at present were listed after conducting an exhaustive literature review of items with extremely low evidence levels and for which bodies of evidence and grades of recommendation were not evaluated. Clinical questions were set for items with a relatively large number of studies, including retrospective studies. However, since it is virtually impracticable to summarize bodies of evidence by systematic reviews, recommendation grades and evidence levels were discussed and determined by the consensus panel of the Preparatory Committee. The following were outlined: epidemiological, pathological, diagnostic, therapeutic, follow-up, and quality of life-related findings. Additionally, seven clinical questions were established to determine recommendation grades and evidence levels. We hope that these guidelines will prove to be useful to medical professionals engaged in clinical practice related to penile cancer in Japan and anticipate that critical reviews of the guidelines will lead to further refinement of the next edition., (© 2022 The Japanese Urological Association.) more...

Purpose: The success of vasectomy is determined by the outcome of a post-vasectomy semen analysis (PVSA). This article describes a step-by-step procedure to perform PVSA accurately, report data from patients who underwent post vasectomy semen analysis between 2015 and 2021 experience, along with results from an international online survey on clinical practice., Materials and Methods: We present a detailed step-by-step protocol for performing and interpretating PVSA testing, along with recommendations for proficiency testing, competency assessment for performing PVSA, and clinical and laboratory scenarios. Moreover, we conducted an analysis of 1,114 PVSA performed at the Cleveland Clinic's Andrology Laboratory and an online survey to understand clinician responses to the PVSA results in various countries., Results: Results from our clinical experience showed that 92.1% of patients passed PVSA, with 7.9% being further tested. A total of 78 experts from 19 countries participated in the survey, and the majority reported to use time from vasectomy rather than the number of ejaculations as criterion to request PVSA. A high percentage of responders reported permitting unprotected intercourse only if PVSA samples show azoospermia while, in the presence of few non-motile sperm, the majority of responders suggested using alternative contraception, followed by another PVSA. In the presence of motile sperm, the majority of participants asked for further PVSA testing. Repeat vasectomy was mainly recommended if motile sperm were observed after multiple PVSA's. A large percentage reported to recommend a second PVSA due to the possibility of legal actions., Conclusions: Our results highlighted varying clinical practices around the globe, with controversy over the significance of non-motile sperm in the PVSA sample. Our data suggest that less stringent AUA guidelines would help improve test compliance. A large longitudinal multi-center study would clarify various doubts related to timing and interpretation of PVSA and would also help us to understand, and perhaps predict, recanalization and the potential for future failure of a vasectomy., Competing Interests: The authors have nothing to disclose., (Copyright © 2022 Korean Society for Sexual Medicine and Andrology.) more...

Introduction: We report a case series of six patients with a chief complaint of infertility who underwent microsurgical varicocelectomy for intratesticular varicocele (ITV) after undergoing orchiopexy for undescended testis in their childhood., Case Presentation: The patients' median age was 34 years. The median age at which orchiopexy was performed was 4.5 years. All the cases of ITV were accompanied by extratesticular varicocele (ETV). All the patients underwent a microsurgical subinguinal varicocelectomy. At 3 months after operation, the ITV and ETV had disappeared in all the cases. Sperm density and motility increased in five and four patients, respectively., Conclusion: ITV occurs at a relatively high frequency after orchiopexy for undescended testis. Disorder of the valvular function of the testicular vein in peeling the testicular vessels was thought to be a primary cause and is often found on the left side. Doppler ultrasonography of the testis is considered important for diagnosis., Competing Interests: The authors declare that they have no conflicts of interest to disclose., (© 2022 The Authors. IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Urological Association.) more...

Aim: The actual status of fertility preservation treatments in the startup phase in Japan was investigated as a basis for discussing future directions., Methods: This study was conducted as "Research project to promote support of children and parenting 2016" which was supported by Ministry of Health in Japan with the approval of the institutional review board at St. Marianna University. Subjects of the survey were facilities registered with the Japan Society of Obstetrics and Gynecology as fertility preservation facilities, and facilities belonging to the Japan Association of Private Assisted Reproductive Technology Clinics and Laboratories. We provided questionnaires to survey both the medical care system and cases for which fertility preservation was implemented between 2006 and 2016., Results: Responses were obtained from 68 facilities (of the 64, 59 [92.2%] responded to the questionnaire and 9 clinics cooperated). Many facilities limited the cryopreservation of oocytes and ovaries to patients 40-41 years old and the use of eggs to patients 44-45 years old. In the patient survey, 812 cases of oocyte cryopreservation and 201 cases of ovarian tissue cryopreservation were performed during study period. Breast cancer was the most indicated disease, with oocyte cryopreservation in the late 30s and ovarian tissue cryopreservation in the early 30s. Very few babies were born from fertility preservation, and no live birth cases of ovarian tissue cryopreservation were identified., Conclusions: Even from the early days, fertility preservation was implemented according to certain standards in Japan, but was characterized by a large variety of facilities., (© 2022 Japan Society of Obstetrics and Gynecology.) more...

Purpose: In this pilot study, the authors compared the effects of antioxidant co-supplementation therapy and methylcobalamin therapy in patients with impaired semen quality., Methods: Eighty-four subjects who visited male infertility clinics and showed abnormal semen test results were randomly subjected to one of the two therapies: antioxidant co-supplementation therapy with vitamin C, vitamin E, coenzyme Q10, and flaxseed oil or methylcobalamin therapy. The oxidation-reduction potential (ORP) and 8-hydroxy-2'-deoxyguanosine levels were used as indicators of oxidative stress levels in semen. Semen analysis was also performed., Results: The authors obtained results from 67 patients who had completed 3 months of treatment. Neither antioxidant co-supplementation therapy nor methylcobalamin therapy changed the semen parameters significantly (except for the sperm concentration, which was increased by the latter therapy). When the pre-treatment ORP value in semen was higher than the cutoff value, both therapies significantly increased the sperm concentration. The 8-hydroxy-2'-deoxyguanosine level did not yield any meaningful predictive value with regard to increased sperm concentrations., Conclusions: Both antioxidant co-supplementation therapy and methylcobalamin therapy increased the sperm concentration in patients with impaired semen quality when the basal ORP levels in their semen were elevated., Competing Interests: Kazumitsu Yamasaki, Masahiro Uchida, Noriko Watanabe, Tatsuji Ihana, Yukari Ishiguro, Shinnosuke Kuroda, Teppei Takeshima, Yasushi Yumura, Makiko Mieno, Kaoru Yoshida, Teruaki Iwamoto, and Hiroyuki Nishiyama declare that they have no conflict of interest. The antioxidant co‐supplement (SO Support II) and methylcobalamin were provided by Partners. This company did not play any role in the design of the study, collection, analysis, interpretation of data, writing of the manuscript, or in the decision to publish the results., (© 2022 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.) more...

Klinefelter syndrome and monozygotic twins are both rare. The reports of monozygotic twins with Klinefelter syndrome to have undergone fertility treatment are uncommon. This case report describes a case of 30-year-old monozygotic adult twin brothers diagnosed with nonmosaic Klinefelter syndrome following the complaint of infertility. The result of semen analysis showed cryptozoospermia (very low sperm count) and azoospermia (zero sperm count) with physical findings and lifestyles being very similar. They both underwent microtesticular sperm extraction. One had successful sperm retrieval and achieved pregnancy through intracytoplasmic sperm injection, whereas the other did not. Testicular pathological findings showed Sertoli cell-only syndrome. To the best of our knowledge, this is the first report on monozygotic adult twins both of whom underwent microtesticular sperm extraction and resulted in different outcomes., (© 2021 Wiley-VCH GmbH.) more...

Objective: To evaluate the efficacy of keishibukuryogan, a traditional Kampo formula known to be an anti-Oketsu (impaired microcirculation and non-physiological blood congestion) drug, in combination with an anti-oxidant for the treatment of varicoceles., Methods: We retrospectively analyzed 119 patients with palpable and subclinical varicoceles who were treated with 7.5 g/day of keishibukuryogan and 600 mg/day of tocopherol nicotinate. Their motile sperm concentrations at the start of medication and after 3 months were compared. As a subgroup analysis, a comparison test was carried out between patients with a high-grade varicocele and those with a low-grade varicocele., Results: The mean age of the study patients was 35.6 years. Among them, 17, 41, 44 and 17 had subclinical, grade 1, grade 2 and grade 3 varicoceles, respectively. Overall, the differences in motile sperm concentration (millions/mL) before and after treatment were not significant (median 0.58, 95% confidence interval -0.12 to 1.56; P = 0.115). The results of the subgroup analysis showed that the motile sperm concentration in patients with a low-grade varicocele significantly increased (median 1.21, 95% confidence interval 0.45-2.47; P = 0.024); however, no significant improvements were seen in patients with a high-grade varicocele., Conclusions: The results of the present study showed that the combination of keishibukuryogan and an anti-oxidant had a limited effect on varicoceles, but they suggest that it is effective for the treatment of low-grade varicoceles., (© 2021 The Japanese Urological Association.) more...

Cancer therapy has priority over fertility preservation. The time available for fertility preservation in patients with cancer is often very limited and depends on the condition of the underlying disease. This case report presents the results of two rounds of controlled ovarian stimulations (COSs) performed after an induced abortion. The patient had mixed phenotype acute leukemia diagnosed during early pregnancy and underwent a surgical abortion, followed by ovarian stimulation using urinary follicle-stimulating hormone (uFSH) and gonadotropin-releasing hormone (GnRH) agonists. Oocyte retrieval was subsequently performed for oocyte cryopreservation. Despite good hormonal and ultrasonic follicular growth, no oocytes were obtained. During a second COS performed at a low human chorionic gonadotropin (hCG) level (less than 100 IU/L), several mature oocytes were obtained, suggesting that higher hCG levels during COS induce the absence of mature oocytes during normal follicular growth. It is recommended to start COS post-abortion after confirming a low hCG level while considering the timing of cancer treatment. more...

Purpose: As age increases, oxidative stress increases, sperm motility decreases, and DNA fragmentation increases. To date, reports of age-related effects on semen have focused on reactive oxygen species (ROS) or total antioxidant capacity (TAC) as indicators of oxidative stress. However, assessments of ROS and TAC must be considered within a more comprehensive context in order to correctly evaluate oxidative stress and interpret findings. In this regard, the purpose of this study was to investigate the relationship between the static oxidation reduction potential (sORP) and paternal age with the goal of using the sORP as an indicator of semen oxidative stress., Materials and Methods: Semen samples from 173 men were analyzed for the following parameters: volume, motility, and beat cross frequency (BCF). The sORP was measured by using the MiOXSYS™ system. The correlation between semen parameters and the sORP level was analyzed as a function of age. The rate of sORP positivity was compared between men <34 and ≥34 years of age, with a positive sORP defined as a level ≥1.38., Results: Volume, motility, and BCF were negatively correlated with age (p<0.001). The semen sORP level was positively correlated with age (p<0.05). The rate of sORP positivity was significantly increased in men ≥34 years of age compared with that in men <34 years of age (33% compared with 12%, respectively; p<0.01)., Conclusions: The sORP may play a role in age-related decreases in semen parameters (volume, motility, and BCF). The rate of sORP positivity increased significantly after 34 years of age., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association, 2021.) more...

Background: Between 30% and 80% of patients with male infertility produce excessive reactive oxygen species (ROS) in their ejaculate even though the cause of male infertility is unexplained in approximately half of cases. The strong connection between oxidative stress (OS) and male infertility has led recent investigators to propose the term "Male Oxidative Stress Infertility (MOSI)" to describe OS-associated male infertility., Methods: We searched the PubMed database for original and review articles to survey the effects of OS on male infertility, and then verified the effects and treatments., Main Findings: Seminal plasma contains many antioxidants that protect sperm from ROS, because low amounts of ROS are required in the physiological fertilization process. The production of excessive ROS causes OS which can lower fertility through lipid peroxidation, sperm DNA damage, and apoptosis. Several assays are available for evaluating OS, including the MiOXSYS® analyzer to measure oxidation-reduction potential. Several measures should be considered for minimizing OS and improving clinical outcomes., Conclusion: Accurately diagnosing patients with MOSI and identifying highly sensitive biomarkers through proteomics technology is vital for better clinical outcomes., Competing Interests: Conflicts of interest: The authors report no declarations of interest. Human/animal rights statements and informed consent: This article does not contain any studies with human and animal subjects performed by any of the authors. Approval by Ethics Committee: This research was supported by the Ethics Committee of Yokohama City University Medical Center., (© 2020 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.) more...

Background: Sarcopenia was initially recognized as a marker representing the nutritional condition or aging. Recently, sarcopenia has been associated with a poor prognosis and postoperative complications. We examined the importance of sarcopenia as a predictive marker of the prognosis in penile cancer., Materials and Methods: A total of 25 patients diagnosed with penile cancer who underwent penile resection from 2000 to 2010 were analyzed in this study. The psoas muscle index (PMI) was calculated based on psoas area using preoperative axial computed tomography images at the right L3 level divided by the square of the body height., Results: Nineteen (76.0%) patients underwent partial penectomy, and 6 (24.0%) underwent total penectomy. The median (mean ± standard deviation) age was 69.3 (69.0 ± 10.1) years old. Regarding the site of penile cancer, 17 (76.0%) cases were in the glans, 6 (24.0%) were in the foreskin, and 2 (8.0%) were in the shaft. Lymph node metastasis were seen in 6 cases (24.0%), and distant metastasis was seen in 1 case (4.0%). The lower PMI group (< 320.0) showed a significantly poorer progression-free survival than the higher PMI group (≥ 320.0) ( p = 0.030), although no significant difference in the overall survival was noted ( p = 0.076)., Conclusions: Sarcopenia might be a useful prognostic factor in penile cancer patients., Competing Interests: CONFLICTS OF INTEREST Authors have no conflicts of interest to declare. more...

Introduction: Post-orgasmic illness syndrome is a rare condition that occurs after ejaculation and persists for 2-7 days and is characterized by flu-like symptoms, which can significantly reduce quality of life., Case Presentation: A 21-year-old unmarried man was referred to our hospital due to flu-like symptoms that developed after ejaculation by masturbation and persisted for about 2 days. The patient's free testosterone level was slightly lower than normal. Nonsteroidal anti-inflammatory drugs were initially administered and helped relieve headache and muscle pain. Thereafter, the patient was able to ejaculate three times a week. In addition, after administering testosterone enanthate once or twice a month, his general fatigue significantly improved, and he could ejaculate every day., Conclusion: The pathophysiology of post-orgasmic illness syndrome has not been fully elucidated. The treatments for this condition must be accurately selected according to pathophysiology., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.) more...

Background: At present, one out of six couples is infertile, and in 50% of cases, infertility is attributed to male infertility factors. Genetic abnormalities are found in 10%-20% of patients showing severe spermatogenesis disorders, including non-obstructive azoospermia., Methods: Literatures covering the relationship between male infertility and genetic disorders or chromosomal abnormalities were studied and summarized., Main Findings Results: Genetic disorders, including Klinefelter syndrome, balanced reciprocal translocation, Robertsonian translocation, structural abnormalities in Y chromosome, XX male, azoospermic factor (AZF) deletions, and congenital bilateral absence of vas deferens were summarized and discussed from a practical point of view. Among them, understanding on AZF deletions significantly changed owing to advanced elucidation of their pathogenesis. Due to its technical progress, AZF deletion test can reveal their delicate variations and predict the condition of spermatogenesis. Thirty-nine candidate genes possibly responsible for azoospermia have been identified in the last 10 years owing to the advances in genome sequencing technologies., Conclusion: Genetic testing for chromosomes and AZF deletions should be examined in cases of severe oligozoospermia and azoospermia. Genetic counseling should be offered before and after genetic testing., Competing Interests: Conflict of interest: The authors report no conflicts of interest. Human/Animal rights statement: This article does not contain any studies with human or animal subjects., (© 2020 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.) more...

Although reactive oxygen species in semen are associated with unfavorable results with respect to assisted reproductive technology, their effects based on the detailed stages of embryo development are unclear. We investigated the relationship between reactive oxygen species in semen and the oocyte fertilization rate, cleavage rate, and blastulation rate of intracytoplasmic sperm injections. This retrospective study enrolled 77 couples who underwent intracytoplasmic sperm injection and analyzed 887 eggs from 141 cycles of intracytoplasmic sperm injection. The reactive oxygen species level in semen was compared between the fertilized and nonfertilized groups, between the good-cleavage-embryo and non-developed-embryo groups, and between the good-quality-blastocyst and poor-quality-blastocyst groups. The cut-off level of reactive oxygen species was calculated to predict good-cleavage-embryo and good-quality-blastocyst development. The fertilization rate was 65.4%, and the mean reactive oxygen species levels were not significantly different between the fertilized and nonfertilized groups. The reactive oxygen species level was significantly higher in the non-developed-embryo group than in the good-cleavage-embryo group (P = 0.0026) and was significantly lower in the good-quality-blastocyst group than in the poor-quality-embryo group (P = 0.015). Cleavage embryos and blastocysts were divided into high- and low-reactive-oxygen-species groups using a cut-off value of 6601 and 4926 relative light units, as calculated from the receiver operating characteristic curve. The rates of good-cleavage embryos and good-quality blastocysts were lower in the high-reactive-oxygen-species group than in the low-reactive-oxygen-species group, which were both statistically significant. To conclude, reactive oxygen species in semen is considered to have an adverse effect on both the early and late stages of embryo development in intracytoplasmic sperm injection. Abbreviations : GnRH, gonadotropin-releasing hormone; ICSI, intracytoplasmic sperm injection; IVF, in vitro fertilization; LPO, lipid peroxidation; NADPH, nicotinamide adenine dinucleotide phosphate; RLU, relative light units; ROC, receiver operating characteristic; ROS, reactive oxygen species. more...