Three cases of sperm immobility for intracytoplasmic sperm injection using testicular sperm.

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.

Clinical management of nonobstructive azoospermia: An update.

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.

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.

Correlation between Higher Aging Males' Symptoms Scores and a Higher Risk of Lower Urinary Tract Symptoms.

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.

Sperm DNA fragmentation testing in clinical management of reproductive medicine.

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.

Mitochondrial DNA mutations can influence the post-implantation development of human mosaic embryos.

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.

Effect of a web-based fertility preservation training program for medical professionals in Japan.

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.

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.

Current Status and Issues of the Japan Oncofertility Registry.

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.

Add-on effects of oral tocopherol supplementation to surgical varicocelectomy on the outcome of assisted reproductive technology: a single-center pilot study report.

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.

Microsurgical varicocelectomy for intratesticular varicocele with a history of orchiopexy for undescended testis.

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.

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.

Summary of the Clinical Practice Guidelines for Penile Cancer 2021 by the Japanese Urological Association.

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.

Effects of antioxidant co-supplementation therapy on spermatogenesis dysfunction in relation to the basal oxidation-reduction potential levels in spermatozoa: A pilot study.

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.

A practical survey of fertility-preservation treatments in the startup phase in Japan.

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.

Monozygotic adult twins with nonmosaic Klinefelter syndrome with different results of sperm retrieval.

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.