Pallav Sengupta, Germar-M Pinggera, Aldo E Calogero, Ashok Agarwal
{"title":"Oxidative stress affects sperm health and fertility-Time to apply facts learned at the bench to help the patient: Lessons for busy clinicians.","authors":"Pallav Sengupta, Germar-M Pinggera, Aldo E Calogero, Ashok Agarwal","doi":"10.1002/rmb2.12598","DOIUrl":"10.1002/rmb2.12598","url":null,"abstract":"<p><strong>Background: </strong>Increased oxidative stress (OS), resulting from the delicate balance between reactive oxygen species (ROS) production and antioxidant defense, is closely linked to sperm abnormalities and male subfertility. Elevated ROS levels particularly affect sperm quality. The vulnerability of spermatozoa to ROS is due to the absence of DNA repair mechanisms and the high presence of polyunsaturated fatty acids in their membranes.</p><p><strong>Methods: </strong>This article updates and advances our understanding of the molecular damage caused by OS in spermatozoa, including lipid peroxidation, DNA damage, motility, and functionality. Additionally, the review discusses the challenges in diagnosing OS in semen and recommends accurate and sensitive testing methods. Case studies are utilized to demonstrate the effective management of male infertility caused by OS.</p><p><strong>Main findings: </strong>Highlighting the need to bridge the gap between research and clinical practice, this review suggests strategies for clinicians, such as lifestyle and dietary changes and antioxidant therapies. The review emphasizes lifestyle modifications and personalized care as effective strategies in managing male infertility caused by OS.</p><p><strong>Conclusion: </strong>This review calls for early detection and intervention and interdisciplinary collaboration to improve patient care in male infertility cases related to increased OS.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"23 1","pages":"e12598"},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11366688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of immune cells in the establishment of implantation and maintenance of pregnancy and immunomodulatory therapies for patients with repeated implantation failure and recurrent pregnancy loss.","authors":"Shigeru Saito","doi":"10.1002/rmb2.12600","DOIUrl":"10.1002/rmb2.12600","url":null,"abstract":"<p><strong>Background: </strong>Immune cells play an important role in the establishment of pregnancy, and abnormalities in the immune system can cause implantation failure and miscarriage.</p><p><strong>Methods: </strong>Previous papers have been summarized and the role of immune cells in reproduction is reviewed.</p><p><strong>Results: </strong>The immune environment in the uterus changes drastically from before implantation to after pregnancy to maintain pregnancy. In allogeneic pregnancies, immature dendritic cells (DCs) that induce immune tolerance from outside the uterus flow into the uterus, and mature DCs that remain in the uterus express programmed cell death ligand 2, which suppresses the immune response. Macrophages are classified into M1-macrophages, which induce inflammation, and M2-macrophages, which suppress inflammation; M1-macrophages are required for luteinization, and M2-macrophages induce the differentiation of endometrial epithelial cells to enable implantation. Regulatory T cells, which suppress rejection, are essential for the implantation and maintenance of allogeneic pregnancies. Implantation failure and fetal loss are associated with decreased numbers or qualitative abnormalities of DCs, macrophages, and regulatory T cells. The clinical usefulness of immunomodulatory therapies in patients with repeated implantation failure and recurrent pregnancy loss has been reported.</p><p><strong>Conclusion: </strong>The provision of individualized medical care in cases of implantation failure or miscarriage may improve clinical outcomes.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"23 1","pages":"e12600"},"PeriodicalIF":2.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11292669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Risk factors for non-previa placenta accreta spectrum in pregnancies conceived through frozen embryo transfer during a hormone replacement cycle in Japan.","authors":"Seiko Matsuo, Tomomi Kotani, Sho Tano, Takafumi Ushida, Kenji Imai, Tomoko Nakamura, Satoko Osuka, Maki Goto, Masami Osawa, Yoshimasa Asada, Hiroaki Kajiyama","doi":"10.1002/rmb2.12592","DOIUrl":"https://doi.org/10.1002/rmb2.12592","url":null,"abstract":"<p><strong>Purpose: </strong>Non-previa placenta accreta spectrum (PAS) is associated with assisted reproductive technology (ART), particularly frozen embryo transfer during hormone replacement therapy (HRC-FET). We especially aimed to evaluate the prevalence and risk factors for non-previa PAS in HRC-FET pregnancies.</p><p><strong>Methods: </strong>Overall, 279 women who conceived through ART at three ART facilities and delivered at a single center were included in this retrospective study. Data regarding endometrial thickness at embryo transfer, previous histories, and type of embryo transfer-HRC-FET, frozen embryo transfer during a natural ovulatory cycle (NC-FET), and fresh embryo transfer (Fresh-ET)-were collected. Univariable logistic regression analyses were conducted.</p><p><strong>Results: </strong>The prevalence of non-previa PAS was 27/192 (14.1%) in the HRC-FET group and 0 (0.0%) in both the NC-FET and Fresh-ET groups. Significantly high odds ratio [95% confidence interval] of non-previa PAS was associated with a history of artificial abortion (6.45 [1.98-21.02]), endometrial thickness <8.0 mm (6.11 [1.06-35.12]), resolved low-lying placenta (5.73 [2.13-15.41]), multiparity (2.90 [1.26-6.69]), polycystic ovarian syndrome (2.62 [1.02-6.71]), and subchorionic hematoma (2.49 [1.03-6.04]).</p><p><strong>Conclusions: </strong>A history of artificial abortion, endometrial thickness <8.0 mm, and resolved low-lying placenta may help in antenatal detection of a high-risk population of non-previa PAS in HRC-FET pregnancies.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"23 1","pages":"e12592"},"PeriodicalIF":2.7,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Roles of lipid mediators in early pregnancy events.","authors":"Shizu Aikawa, Yasushi Hirota","doi":"10.1002/rmb2.12597","DOIUrl":"10.1002/rmb2.12597","url":null,"abstract":"<p><strong>Background: </strong>Early pregnancy events, including embryo implantation, are critical for maintaining a healthy pregnancy and facilitating childbirth. Despite numerous signaling pathways implicated in establishing early pregnancy, a comprehensive understanding of implantation remains elusive.</p><p><strong>Methods: </strong>This paper provides a comprehensive review of the current research on lipids in the context of early pregnancy, with a particular focus on feto-maternal communications.</p><p><strong>Main findings: </strong>Embryo implantation entails direct interaction between uterine tissues and embryos. Introducing embryos triggers significant changes in uterine epithelial morphology and stromal differentiation, facilitating embryo implantation through communication with uterine tissue. Studies employing genetic models and chemical compounds targeting enzymes and receptors have elucidated the crucial roles of lipid mediators-prostaglandins, lysophosphatidic acid, sphingosine-1-phosphate, and cannabinoids-in early pregnancy events.</p><p><strong>Conclusion: </strong>Given the high conservation of lipid synthases and receptors across species, lipid mediators likely play pivotal roles in rodents and humans. Further investigations into lipids hold promise for developing novel diagnostic and therapeutic approaches for infertility in humans.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"23 1","pages":"e12597"},"PeriodicalIF":2.7,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11247399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Very severe oligozoospermia with AZFc microdeletion patients may affect intracytoplasmic sperm injection clinical outcomes: A propensity score matching analysis.","authors":"Huan Zhang, Huanzhu Li, Shujuan Ma, Shuoping Zhang, Wen Li, Yifan Gu, Erchen Zhang, Liang Hu","doi":"10.1002/rmb2.12596","DOIUrl":"10.1002/rmb2.12596","url":null,"abstract":"<p><strong>Purpose: </strong>To explore whether spermatozoa from AZFc microdeletion patients affect their outcomes of intracytoplasmic sperm injection (ICSI).</p><p><strong>Methods: </strong>Eighty-five patients with AZFc microdeletion were recruited. A control group of one hundred and forty patients with severe oligozoospermia but without AZF microdeletion was selected using propensity score matching analysis with a 1:2 nearest neighbor algorithm ratio. The ICSI outcomes of the two groups were compared.</p><p><strong>Results: </strong>AZFc microdeletion had lower rates of normal fertilization (73% vs. 80%, <i>p</i> = 0.17) and high-quality embryos (44% vs. 58%, <i>p</i> = 0.07) than the control group. There was no significant difference in the clinical pregnancy rate, miscarriage rate, and live birth rate between the two groups. When the sperm concentration was <1 million/mL, the AZFc microdeletion group exhibited lower rates of fertilization (71% vs. 80%, <i>p</i> = 0.03), high-quality embryo (44% vs. 58%, <i>p</i> = 0.02), clinical pregnancy (57% vs. 76%, <i>p</i> = 0.02), and live birth (49% vs. 72%, <i>p</i> = 0.01) than the control group. However, if sperm concentration was ≥1 million/mL, no significant differences were found.</p><p><strong>Conclusion: </strong>If the sperm concentration is <1 million/mL, AZFc microdeletion do have a detrimental effect on most outcomes of ICSI.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"23 1","pages":"e12596"},"PeriodicalIF":2.7,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11232045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141564221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Developmental perturbation in human embryos: Clinical and biological significance learned from time-lapse images.","authors":"Kenji Ezoe, Tsubasa Takahashi, Tetsuya Miki, Keiichi Kato","doi":"10.1002/rmb2.12593","DOIUrl":"10.1002/rmb2.12593","url":null,"abstract":"<p><strong>Background: </strong>Time-lapse technology (TLT) has gained widespread adoption worldwide. In addition to facilitating the undisturbed culture of embryos, TLT offers the unique capability of continuously monitoring embryos to detect spatiotemporal changes. Although these observed phenomena play a role in optimal embryo selection/deselection, the clinical advantages of introducing TLT remain unclear. However, manual annotation of embryo perturbation could facilitate a comprehensive assessment of developmental competence. This process requires a thorough understanding of embryo observation and the biological significance associated with developmental dogma and variation. This review elucidates the typical behavior and variation of each phenomenon, exploring their clinical significance and research perspectives.</p><p><strong>Methods: </strong>The MEDLINE database was searched using PubMed for peer-reviewed English-language original articles concerning human embryo development.</p><p><strong>Main findings: </strong>TLT allows the observation of consecutive changes in embryo morphology, serving as potential biomarkers for embryo assessment. In assisted reproductive technology laboratories, several phenomena have not revealed their mechanism, posing difficulties such as fertilization deficiency and morula arrest.</p><p><strong>Conclusion: </strong>A profound understanding of the biological mechanisms and significance of each phenomenon is crucial. Further collaborative efforts between the clinical and molecular fields following translational studies are required to advance embryonic outcomes and assessment.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"23 1","pages":"e12593"},"PeriodicalIF":2.7,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11232294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141564220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Potential for artificial intelligence in medicine and its application to male infertility.","authors":"Hideyuki Kobayashi","doi":"10.1002/rmb2.12590","DOIUrl":"10.1002/rmb2.12590","url":null,"abstract":"<p><strong>Background: </strong>The third AI boom, which began in 2010, has been characterized by the rapid evolution and diversification of AI and marked by the development of key technologies such as machine learning and deep learning. AI is revolutionizing the medical field, enhancing diagnostic accuracy, surgical outcomes, and drug production.</p><p><strong>Methods: </strong>This review includes explanations of digital transformation (DX), the history of AI, the difference between machine learning and deep learning, recent AI topics, medical AI, and AI research in male infertility.</p><p><strong>Main findings results: </strong>In research on male infertility, I established an AI-based prediction model for Johnsen scores and an AI predictive model for sperm retrieval in non-obstructive azoospermia, both by no-code AI.</p><p><strong>Conclusions: </strong>AI is making constant progress. It would be ideal for physicians to acquire a knowledge of AI and even create AI models. No-code AI tools have revolutionized model creation, allowing individuals to independently handle data preparation and model development. Previously a team effort, this shift empowers users to craft customized AI models solo, offering greater flexibility and control in the model creation process.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"23 1","pages":"e12590"},"PeriodicalIF":2.7,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of varicocele repair in the era of assisted reproductive technologies: Lessons from 2000 cases of microsurgical varicocele repair.","authors":"Koji Shiraishi","doi":"10.1002/rmb2.12589","DOIUrl":"10.1002/rmb2.12589","url":null,"abstract":"<p><strong>Backgrounds: </strong>In an era of advanced maternal age, there is less conclusive evidence regarding the treatment outcomes of varicocele repair for assisted reproductive technology (ART). Progress in basic research on varicocele is notable whereas there are many clinically relevant points to discuss.</p><p><strong>Methods: </strong>Based on our experience with more than 2000 cases of microsurgical varicocele repair, we focused on the effectiveness of varicocele repair, pathophysiology, surgical approaches, contributions to ART, sperm DNA fragmentation, and varicocele-associated azoospermia in this review with the aim of identifying clearer directions for basic and clinical research on varicocele.</p><p><strong>Results: </strong>Microsurgical low ligation for varicocele repair is expected to remain the gold standard for surgical therapy. Based on the findings from a number of systematic reviews and meta-analyses, negative opinions regarding the efficacy of microsurgical varicocele repair in male infertility treatment have become virtually nonexistent. However, the majority of evidence regarding surgical indications and effectiveness pertains to improvements in semen parameters or non-ART pregnancy rates.</p><p><strong>Conclusions: </strong>Further understandings regarding to pathophysiology of varicocele will likely be gained through comprehensive genetic, transcriptomic, and epigenetic analyses using blood and testicular samples from humans and we hope to develop new diagnostic methods and pharmacotherapy.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"23 1","pages":"e12589"},"PeriodicalIF":2.7,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"KEAP1-NRF2 system regulates age-related spermatogenesis dysfunction.","authors":"Sohei Kuribayashi, Shinichiro Fukuhara, Hiroaki Kitakaze, Go Tsujimura, Takahiro Imanaka, Koichi Okada, Norichika Ueda, Kentaro Takezawa, Kotoe Katayama, Rui Yamaguchi, Koichi Matsuda, Norio Nonomura","doi":"10.1002/rmb2.12595","DOIUrl":"10.1002/rmb2.12595","url":null,"abstract":"<p><strong>Purpose: </strong>The average fatherhood age has been consistently increasing in developed countries. Aging has been identified as a risk factor for male infertility. However, its impact on various mechanisms remains unclear. This study focused on the KEAP1-NRF2 oxidative stress response system, by investigating the relationship between the KEAP1-NRF2 system and age-related changes in spermatogenesis.</p><p><strong>Methods: </strong>For examination of age-related changes, we used 10-, 30-, 60-, and 90-week-old mice to compare sperm count, sperm motility, and protein expression. For assessment of Keap1 inhibition, 85-week-old C57BL/6J mice were randomly assigned to the following groups: control and bardoxolone methyl (KEAP1 inhibitor). Whole-exome sequencing of a Japanese cohort of patients with non-obstructive azoospermia was performed for evaluating.</p><p><strong>Results: </strong>Sperm count decreased significantly with aging. Oxidative stress and KEAP1 expression in the testes were elevated. Inhibition of KEAP1 in aging mice significantly increased sperm count compared with that in the control group. In the human study, the frequency of a missense-type SNP (rs181294188) causing changes in NFE2L2 (NRF2) activity was significantly higher in patients with non-obstructive azoospermia than in healthy control group.</p><p><strong>Conclusions: </strong>The KEAP1-NRF2 system, an oxidative stress response system, is associated with age-related spermatogenesis dysfunction.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"23 1","pages":"e12595"},"PeriodicalIF":2.7,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11194679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sperm morphology: Evaluating its clinical relevance in contemporary fertility practice.","authors":"Daniel L Pelzman, Jay I Sandlow","doi":"10.1002/rmb2.12594","DOIUrl":"10.1002/rmb2.12594","url":null,"abstract":"<p><strong>Background: </strong>The World Health Organization (WHO) recommends reporting sperm morphology in a standard semen analysis. However, the clinical utility and prognostic value of morphology is often debated.</p><p><strong>Methods: </strong>We reviewed and summarized studies that assessed both the benefits and limitations of sperm morphology in the context of natural fertility, assisted reproductive technologies, and recurrent pregnancy loss. We additionally describe possible environmental and anatomical etiologies of teratozoospermia.</p><p><strong>Results: </strong>Sperm morphology evaluation has continuously evolved since the release of the first WHO manual in 1980. Initially, several large studies reported significant inverse associations between fertility outcomes and teratozoospermia. Most recent studies, however, fail to show an association between sperm morphology and natural or assisted fertility outcomes.</p><p><strong>Conclusion: </strong>Sperm morphology analysis may have limited diagnostic and prognostic value. Providers should be aware of these limitations when counseling or managing infertile patients.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"23 1","pages":"e12594"},"PeriodicalIF":2.7,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11194684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}