{"title":"A machine learning model for predicting fertilization following short-term insemination using embryo images.","authors":"Masato Saito, Hirofumi Haraguchi, Ikumi Nakajima, Shinya Fukuda, Chenghua Zhu, Norio Masuya, Kazunori Matsumoto, Yuya Yoshikawa, Tomoki Tanaka, Satoshi Kishigami, Leona Matsumoto","doi":"10.1002/rmb2.12649","DOIUrl":"10.1002/rmb2.12649","url":null,"abstract":"<p><strong>Purpose: </strong>This study established a machine learning model (MLM) trained on embryo images to predict fertilization following short-term insemination for early rescue ICSI and compared its predictive performance with the embryologist's manual classification.</p><p><strong>Methods: </strong>Embryo images at 4.5 and 8 h post-insemination were preprocessed into vectors using ResNet50. The Light Gradient Boosting Machine (Light GBM) was employed for training vectors. Fertilization in the test dataset was assessed by MLM, with seven senior and 11 junior embryologists. Predictive metrics were analyzed using repeated measures ANOVA and paired <i>t</i>-tests.</p><p><strong>Results: </strong>Comparing MLM, senior embryologists, and junior embryologists, significant differences were observed in accuracy (0.71 ± 0.01, 0.75 ± 0.05, 0.61 ± 0.05), recall (0.84 ± 0.02, 0.84 ± 0.10, 0.61 ± 0.07), F1-score (0.78 ± 0.01, 0.81 ± 0.04, 0.66 ± 0.04), and area under the curve (0.73 ± 0.0 3, 0.73 ± 0.06, 0.61 ± 0.07), the MLM outperforming junior embryologists with <1 year of experience. No significant differences were observed between the MLM and senior embryologists with over 5 years of experience.</p><p><strong>Conclusions: </strong>MLM can effectively predict fertilization following short-term insemination by analyzing cytoplasmic changes in images. These results underscore the potential to enhance clinical decision-making and improve patient outcomes.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"24 1","pages":"e12649"},"PeriodicalIF":2.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12000234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977662","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":"Toll-like receptors in mammalian sperm.","authors":"Takashi Umehara, Takahiro Yamanaka, Masayuki Shimada","doi":"10.1002/rmb2.12651","DOIUrl":"10.1002/rmb2.12651","url":null,"abstract":"<p><strong>Background: </strong>Toll-like receptors (TLRs) are critical components of the innate immune system and are expressed in various cells, including the reproductive system. Although their roles in female reproductive tissues such as the ovaries and uterus, including their involvement in fertilization and implantation, have been extensively reviewed, their expression and function in male germ cells, particularly in sperm, remain underexplored.</p><p><strong>Methods: </strong>This review provides a comprehensive summary of research on TLRs expressed in sperm, including findings from experimental models in mice, humans, and industrial livestock.</p><p><strong>Results: </strong>The activation of TLR2 and TLR4, which detect Gram-positive and Gram-negative bacteria, has been shown to reduce sperm motility and viability, thereby impairing fertilization. Conversely, low levels of TLR2 activation have been reported to promote the fertilization of bull sperm, suggesting that TLR2/4 may act as regulators of fertilization. TLR7 and TLR8, which are exclusively expressed in X chromosome-bearing sperm (X-sperm), have attracted increasing research interest. These receptors modulate sperm metabolism, selectively reduce the motility of X sperm, and enable the separation of X and Y sperm.</p><p><strong>Conclusion: </strong>TLRs in the sperm serve as immune receptors that detect bacterial and viral infections, thereby reducing sperm functionality, preventing miscarriage, protecting maternal health, and sex selection.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"24 1","pages":"e12651"},"PeriodicalIF":2.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12000229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009012","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":"Japanese reproductive medicine under health insurance: A brief review and prospects.","authors":"Akira Iwase","doi":"10.1002/rmb2.12646","DOIUrl":"10.1002/rmb2.12646","url":null,"abstract":"","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"24 1","pages":"e12646"},"PeriodicalIF":2.7,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780602","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":"Serum copper to zinc ratio and risk of endometriosis: Insights from a case-control study in infertile patients.","authors":"Yanping Liu, Guihong Cheng, Hong Li, Qingxia Meng","doi":"10.1002/rmb2.12644","DOIUrl":"10.1002/rmb2.12644","url":null,"abstract":"<p><strong>Purpose: </strong>Endometriosis is a prevalent gynecological disorder, yet data on the role of trace metal elements in its risk remain limited. We aimed to investigate the relationship between serum copper (Cu), zinc (Zn), iron (Fe), magnesium (Mg) levels, and the Cu/Zn ratio with the risk of endometriosis.</p><p><strong>Methods: </strong>This study involved 568 infertile patients diagnosed with endometriosis, compared to 819 infertile patients without endometriosis (Control group). Basic characteristics, hormonal parameters, and essential trace elements of the patients were measured and analyzed.</p><p><strong>Results: </strong>The findings indicated a notable decrease in serum Zn levels in the endometriosis group compared to controls, alongside a significant increase in the Cu/Zn ratio (<i>p</i> < 0.001). Restricted cubic spline (RCS) analysis revealed a linear relationship between Zn levels and the Cu/Zn ratio and endometriosis risk. Moreover, Zn levels exhibited a negative correlation with endometriosis risk (<i>p</i> trend = 0.005), while the Cu/Zn ratio displayed a positive correlation with endometriosis risk, even after adjusting for age, body mass index (BMI), and baseline hormones (<i>p</i> trend < 0.001). Compared to the first quartile of Cu/Zn ratio after adjustment, the odds ratios (ORs) with 95% confidence intervals (CIs) for the second and fourth quartiles were 1.97 (1.37, 2.83) and 2.63 (1.80, 3.84), respectively.</p><p><strong>Conclusions: </strong>This study provided evidence of decreased serum Zn levels and an increased Cu/Zn ratio being associated with an elevated risk of endometriosis among infertile patients. These findings offer valuable real-world data, enriching our understanding of endometriosis.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"24 1","pages":"e12644"},"PeriodicalIF":2.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730621","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":"Impact of heparin-aspirin therapy in patients with recurrent pregnancy loss characterized by thrombophilia resistant to low-dose aspirin therapy: A retrospective study.","authors":"Tomoko Ichikawa, Takami Watanabe, Yumene Kubota, Shigeru Matsuda, Daisuke Shigemi, Sayuri Kasano, Ryoko Yokote, Mirei Yonezawa, Nozomi Ouchi, Yasuyuki Negishi, Yoshimitsu Kuwabara, Toshiyuki Takeshita, Shunji Suzuki","doi":"10.1002/rmb2.12643","DOIUrl":"10.1002/rmb2.12643","url":null,"abstract":"<p><strong>Purpose: </strong>Heparin and aspirin (HA) therapy is used for antiphospholipid syndrome (APS)-associated recurrent pregnancy loss (RPL). Low-dose aspirin (LDA) is recommended for thrombophilic predispositions, such as antiphospholipid antibodies that do not completely meet the Sydney classification criteria for APS, protein S deficiency, factor XII deficiency and increased platelet aggregation. However, no established strategy exists for cases where LDA is ineffective. Therefore, this study aimed to identify the characteristics of RPL cases unresponsive to LDA and to determine whether HA is more effective than LDA in such cases.</p><p><strong>Methods: </strong>A total of 913 LDA-treated pregnancies were categorized into live births and miscarriages, and their characteristics were retrospectively analyzed.</p><p><strong>Results: </strong>The live birth rates following one, two, or three or more LDA therapies were 78.5%, 61.5% and 16.7%, respectively. Live birth rates were significantly lower when lupus anticoagulant (LAC) aPTT was positive but did not qualify as obstetric APS following LDA therapy (birth rates: 33.3%, <i>p</i> = 0.048). Three or more LDA therapies decreased the live birth rate, whereas HA therapy significantly increased the live birth rate (<i>p</i> = 0.0019).</p><p><strong>Conclusions: </strong>HA therapy is recommended over repeated LDA treatment, particularly when LAC aPTT is positive but does not qualify as obstetric APS.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"24 1","pages":"e12643"},"PeriodicalIF":2.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721184","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}
Teresa Helene Wentges, Heba M El-Shorafa, Janine Beckmann, Michael Gabriel, Matti Poutanen, Burkhard Greve, Ludwig Kiesel, Sebastian D Schäfer, Martin Götte
{"title":"Combined targeting of TCF7L1/2, PTEN, CDK6, and BCCIP by microRNA miR-29c-3p is associated with reduced invasion and proliferation of endometriotic cells.","authors":"Teresa Helene Wentges, Heba M El-Shorafa, Janine Beckmann, Michael Gabriel, Matti Poutanen, Burkhard Greve, Ludwig Kiesel, Sebastian D Schäfer, Martin Götte","doi":"10.1002/rmb2.12645","DOIUrl":"10.1002/rmb2.12645","url":null,"abstract":"<p><strong>Purpose: </strong>Endometriosis is a chronic gynecological disorder associated with pain symptoms and infertility. The expression of microRNA miR-29c-3p is dysregulated in endometriosis. We aimed to identify novel molecular targets of miR-29c-3p functionally linked to proliferation and invasive growth in endometriosis.</p><p><strong>Methods: </strong>The epithelial endometriotic cell line 12Z and primary endometriotic stromal cells (PESC) were transfected with control miRNA or pre-miR-29c-3p, and subjected to cell cycle analysis, cell viability, wound healing, and Matrigel invasion assays. Expression of bioinformatically predicted miR-29c-3p targets was analyzed by qPCR and western blot. Target gene expression in endometriotic lesions and healthy endometrium was studied in the EndometDB endometriosis database.</p><p><strong>Results: </strong>miR-29c-3p decreased 12Z and PESC cell viability and the proportion of PESC in the S-phase. 12Z cell invasion, but not migration, was decreased after miR-29c-3p upregulation. miR-29c-3p decreased the mRNA expression of <i>CDK6</i>, <i>BCCIP</i>, <i>TCF7L1</i>, <i>TCF7L2</i>, <i>PTEN</i>, <i>COL4A1</i>, <i>E-Cadherin</i>, and <i>N-Cadherin</i>. A decrease of CDK6 and PTEN and an increase of p21 were confirmed at the protein level. EndometDB database analysis demonstrated dysregulated expression of the selected targets in both deep endometriosis and ovarian endometriosis.</p><p><strong>Conclusions: </strong>miR-29c-3p effectively curbs endometriotic cell proliferation and invasion by combined inhibition of cell cycle regulators and transcription factors, unveiling a promising therapeutic strategy.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"24 1","pages":"e12645"},"PeriodicalIF":2.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11933757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711165","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":"The effect of ionizing radiation on testicular interstitial stromal cells.","authors":"Esraa Tamam, Chen Yan, Reiko Sekiya, Tao-Sheng Li","doi":"10.1002/rmb2.12639","DOIUrl":"10.1002/rmb2.12639","url":null,"abstract":"<p><strong>Purpose: </strong>Testis is one of the most radiosensitive tissues. Interstitial stromal cells play a supportive role in male fertility, but radiation-induced damage to those cells has not yet been well understood. We aimed to investigate radiation-induced changes in interstitial stromal cells in the testis.</p><p><strong>Methods: </strong>Adult male C57BL/6N mice (8 weeks) received a single pelvic exposure to a relatively high dose (1 Gy) or a very high dose (8 Gy) X-ray. We collected the testicular tissues for evaluation at 1, 9, and 60 days after irradiation.</p><p><strong>Results: </strong>We detected a recoverable moderate degeneration of seminiferous tubules after 1 Gy exposure but an irreversible severe damage to the testis after 8 Gy exposure. Immunostaining results revealed that 1 Gy exposure induced DNA damage at day 1, upregulated intratubular GDNF at days 1 and 9, upregulated FGF at all time points, and upregulated CSF-1R at day 9. In contrast, 8 Gy exposure induced DNA damage at days 1 and 9, upregulated intratubular GDNF at days 1 and 9, downregulated CD105 at day 60, and upregulated FGF at all time points.</p><p><strong>Conclusion: </strong>Radiation-induced dynamic changes to interstitial stromal cells in the testis. Upregulated interstitial CSF-1R and FGF2 may support spermatogenesis recovery after high-dose radiation.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"24 1","pages":"e12639"},"PeriodicalIF":2.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664393","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":"Correction to \"Age, sexual abstinence duration, sperm morphology, and motility are predictors of sperm DNA fragmentation\".","authors":"","doi":"10.1002/rmb2.12642","DOIUrl":"https://doi.org/10.1002/rmb2.12642","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1002/rmb2.12585.].</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"24 1","pages":"e12642"},"PeriodicalIF":2.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658463","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":"Influence of lifestyle and the circadian clock on reproduction.","authors":"Masanori Ono, Yidan Dai, Tomoko Fujiwara, Hiroshi Fujiwara, Takiko Daikoku, Hitoshi Ando, Naoaki Kuji, Hirotaka Nishi","doi":"10.1002/rmb2.12641","DOIUrl":"10.1002/rmb2.12641","url":null,"abstract":"<p><strong>Background: </strong>The biological reproductive process requires the precise coordination of annual and daily signals to adapt to environmental shifts. Humans and animals have developed shared neuroendocrine systems that have adapted to process daily and seasonal light signals within the hypothalamic-pituitary -gonadal axis. However, the stability of circadian and seasonal biological processes is at risk due to industrialization and contemporary round-the-clock lifestyles. These threats include skipping breakfast, excessive artificial illumination during inappropriate hours because of irregular work schedules, nighttime urban lighting, and widespread environmental pollution from endocrine-disrupting chemicals. This review aimed to explore the interplay between lifestyle factors, circadian rhythms, and reproductive functions.</p><p><strong>Methods: </strong>This review examined the reciprocal influences of circadian clocks on reproductive hormones, exploring the underlying mechanisms and their implications for fertility and reproductive health. We emphasized key findings regarding molecular clock components, endocrine pathways, and the critical importance of synchronizing circadian rhythms with hormonal cycles.</p><p><strong>Main findings: </strong>The intersection of reproductive endocrinology and circadian biology reveals complex interactions between hormonal regulation and circadian rhythms. Circadian rhythm misalignments due to environmental factors, including late-night work and skipping breakfast, negatively impact endocrine and reproductive functions.</p><p><strong>Conclusions: </strong>More strategies are needed to mitigate the effects of circadian disruption on reproductive functions.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"24 1","pages":"e12641"},"PeriodicalIF":2.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617036","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}
Johan Smitz, Flor Sánchez, Sergio Romero, Heidi Van Ranst, Ellen Anckaert, Robert B Gilchrist, Tuong M Ho, Lan N Vuong, Yoshiharu Morimoto
{"title":"Human oocyte capacitation culture: Essential step toward hormone-free assisted reproductive technology.","authors":"Johan Smitz, Flor Sánchez, Sergio Romero, Heidi Van Ranst, Ellen Anckaert, Robert B Gilchrist, Tuong M Ho, Lan N Vuong, Yoshiharu Morimoto","doi":"10.1002/rmb2.12640","DOIUrl":"10.1002/rmb2.12640","url":null,"abstract":"<p><strong>Background: </strong>In vitro oocyte maturation (IVM) is not a novel concept; however, its wide-scale practice has been limited because of the lower clinical outcomes compared to conventional assisted reproductive technologies.</p><p><strong>Methods: </strong>This comprehensive review addresses the significant advances made in oocyte in vitro maturation with the biphasic capacitation (CAPA)-IVM strategy applied to small ovarian antral follicles in humans over the last 10 years. CAPA-IVM consists of a prematuration phase wherein immature oocytes are temporarily meiotically arrested to gain competence before undergoing meiotic resumption.</p><p><strong>Main findings: </strong>The integration of knowledge from basic research in animal models into clinical practice has led to a reevaluation of IVM for policystic ovary syndrome (PCOS) and onco-fertility patients. The introduction of meticulously conceived growth factors, hormonal supplements, and culture conditions led to an integrated biphasic CAPA-IVM system that promotes oocyte competence. A series of prospective randomized controlled studies validated the reproducible improvements in clinical outcomes and the safety of CAPA-IVM. So far, nearly 1000 babies have been born using this approach.</p><p><strong>Conclusion: </strong>The use of CAPA-IVM in clinical studies has set the tone for major progress in the field and is achieving a safer, less expensive, and less emotionally loaded IVF experience, currently validated for PCOS patients.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"24 1","pages":"e12640"},"PeriodicalIF":2.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617033","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}