Journal of Assisted Reproduction and Genetics最新文献

{"title":"The potential of large language models in the field of infertility: a systematic review.","authors":"Wei Li, Attiq Ur-Rehman, Meng-Wei Ge, Lu-Ting Shen, Xi-Yuan Peng, Kang Zhong, Rui Feng, SiQi Gao, Fei-Hong Hu, Yi-Jie Jia, Hong-Lin Chen","doi":"10.1007/s10815-025-03679-z","DOIUrl":"https://doi.org/10.1007/s10815-025-03679-z","url":null,"abstract":"<p><strong>Purpose: </strong>Large language models have demonstrated significant potential across a wide range of medical fields and may potentially induce a transformation in the field of infertility and sterility. This systematic review aims to synthesize existing research and explore the current strengths and limitations of large language models in the field of infertility and sterility.</p><p><strong>Methods: </strong>Researchers conducted a comprehensive search across three databases and employed a thematic synthesis approach for data analysis.</p><p><strong>Results: </strong>The analysis included a total of 13 studies. Large language models exhibited advantages in the accuracy and reproducibility of information output and consultation, demonstrated robust learning capabilities, and were able to provide satisfactory recommendations to patients. However, there were significant variations in the performance of different large language models, and the readability of the output information was poor, making it difficult to provide comprehensive answers.</p><p><strong>Conclusion: </strong>In the domain of infertility, large language models have not yet achieved full reliability and should be regarded solely as information sources whose outputs require careful verification; they are presently incapable of substituting for clinical diagnosis. Their development requires increased investment in relevant technologies and the use of authoritative, accurate information to unlock their potential in this field and other medical areas.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of environmental knowledge and needs among infertile couples undergoing assisted reproductive technology (ART): insights from a pilot survey.","authors":"Sarah Marcelle, Stephanie Johnson, Thierry Gustin, Annick Delvigne","doi":"10.1007/s10815-025-03667-3","DOIUrl":"https://doi.org/10.1007/s10815-025-03667-3","url":null,"abstract":"<p><p>This pilot survey aims to evaluate the interest, knowledge, and exposure of infertile couples undergoing assisted reproductive technology (ART) regarding environmental toxins. Ultimately, we will seek to identify the most appropriate means of information delivery according to the patients in order to optimize environmental health education. This was a cross-sectional, single-center pilot survey based on an anonymous and voluntary survey, conducted among infertile couples undergoing ART. Among the 257 respondents, 93% were convinced of the impact of environmental toxins on fertility, pregnancy, and the health of future children, while 84% expressed a desire to receive additional information, primarily (56%) in the form of brochures and dedicated pages on the ART center's website. Patients gave 49.7% correct answers regarding the effects of environmental toxins, with significant variability depending on the sources of exposure. The most concerning exposures involved food plastics and volatile organic compounds released by ambient fragrances. This study confirms infertile patients' strong interest in environmental health and identifies key areas of knowledge gaps and preferred formats for educational tools. These findings support the integration of accessible and targeted environmental health information during ART care, particularly in the preconception period.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of a machine learning-based predictive model for live birth outcomes following fresh embryo transfer in patients with endometriosis.","authors":"Suqin Zhu, Huiling Xu, Rongshan Li, Xiaojing Chen, Wenwen Jiang, Beihong Zheng, Yan Sun","doi":"10.1007/s10815-025-03677-1","DOIUrl":"https://doi.org/10.1007/s10815-025-03677-1","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aims to develop a machine learning-based predictive model for patients with endometriosis, with the goal of precisely identifying key factors and reliable predictive markers that influence live birth outcomes following fresh embryo transfer. Through systematic evaluation of multiple algorithms, efforts will be made to identify the optimal model for elucidating high-risk factors affecting live birth, thereby providing a basis for formulating targeted interventions to enhance the live birth rate in this population undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This study adopted a retrospective cohort design and included 1836 patients with endometriosis who underwent fresh embryo transfer via in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) at Fujian Provincial Maternity and Children's Hospital between 2018 and 2023. Participants were randomly allocated to either the training set or the validation set, with a 70:30 split (1285 in the training set and 551 in the validation set), making this an internal validation study. Independent variables were screened using the least absolute shrinkage and selection operator (LASSO) and recursive feature elimination (RFE) algorithms. For eight machine learning models, namely decision tree (DT), K-nearest neighbor (KNN), logistic regression (LR), light gradient boosting machine (LightGBM), naive Bayes model (NBM), random forest (RF), support vector machine (SVM), and extreme gradient boosting (XGBoost), we determined the optimal hyperparameter configurations using the grid search strategy. All models were trained, and their performances were evaluated through receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and Brier score (BS). The results showed that the XGBoost model exhibited the best predictive performance and was thus selected as the final modeling solution. In addition, the feature importance analysis combined with the SHapley Additive exPlanations (SHAP) value dependency plots systematically revealed the relative contributions and influence mechanisms of key features on the model predictions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Lasso and RFE analyses identified eight predictive variables for model development. The AUC values for DT, KNN, LightGBM, LR, naive Bayes, RF, SVM, and XGBoost in the training set were 0.784, 0.987, 0.841, 0.800, 0.803, 0.988, 0.799, and 0.920, while those in the test set were 0.765, 0.748, 0.801, 0.805, 0.810, 0.820, 0.807, and 0.852, respectively. XGBoost demonstrated the highest predictive performance among all models. SHAP analysis identified anti-Mullerian hormone (AMH), female age, antral follicle count (AFC), infertility duration, GnRH agonist protocol, revised American Fertility Society (rAFS) stage, normal fertilization number, and number of transferred embryos as key predictors for live birth following fr","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence in primary ovarian insufficiency management: opportunities and challenges.","authors":"RunTang Zhou, YanHong Wei, Yingguan Xiong, BingBing Su, JunHao Xie, Linlin Hu, XiaoCan Lei","doi":"10.1007/s10815-025-03660-w","DOIUrl":"https://doi.org/10.1007/s10815-025-03660-w","url":null,"abstract":"<p><p>Primary ovarian insufficiency (POI) is also known as premature ovarian failure (POF), defined as loss of normal, predictable ovarian activity before the age of 40 years. In addition, POI patients suffer from long-term complications such as osteoporosis, cardiovascular disease, and depression. The impact on women caused by POI and its complications make it become a major health challenge worldwide. The recent advances in digital health technology (DHT), especially artificial intelligence (AI), provide an important opportunity to improve the efficiency of the management of POI. Clinical work has improved the efficiency of healthcare with the assistance of AI, enabling clinicians to improve clinical treatment efficiency, and mitigate the differences in healthcare level caused by suboptimal resource allocation. This article reviews the application progress of AI in the treatment of POI in recent years, and discusses the opportunities and challenges of AI in clinical application. In addition, we explored the integration of existing digital health technology resources to discuss an AI-assisted eco-smart healthcare system for the treatment of POI.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of mouse oocyte vitrification through microencapsulation in sodium alginate hydrogel.","authors":"Jing Shen, Na Ye, Yuqi Zhang, Chenxi Liu, Weijie Li, Xinli Zhou","doi":"10.1007/s10815-025-03673-5","DOIUrl":"https://doi.org/10.1007/s10815-025-03673-5","url":null,"abstract":"<p><strong>Purpose: </strong>Vitrification (ice-free) is considered more effective than slow freezing for oocyte cryopreservation. However, high concentrations of toxic cryoprotective agents (CPAs) are typically required, followed by multi-step washing to remove CPAs, risking osmotic shock and impairing oocytes development. This study aimed to establish a hydrogel encapsulation strategy using a microfluidic system to improve vitrification outcomes.</p><p><strong>Methods: </strong>Three different sizes of oocyte-loaded sodium alginate hydrogel microspheres (OHMs) (~ 262 µm, ~ 193 µm, and ~ 156 µm) were prepared using an optimized three-channel microfluidic system. The effects of particle size, vitrification solutions (VS1, VS2, VS3, and VS4), CPA loading durations (4, 8, and 12 min), and warming/dilution procedures (one-step, two-step, and three-step) on oocyte vitrification were systematically evaluated.</p><p><strong>Results: </strong>OHMs with a particle size of 262 µm, loaded with VS3 (containing 10% DMSO) for 8 min and subjected to the two-step warming and dilution procedure, achieved excellent post-thaw survival (91.98%), cleavage (75.84%), and blastocyst rates (23.86%). The survival rate was comparable to that of the Cryotop group vitrified with 15% DMSO (91.81%), while the cleavage and blastocyst rates were significantly higher than those of the Cryotop group (67.42% and 20.03%, respectively). Besides, OHMs resulted in minimal oocyte volume changes upon CPA loading (minimum normalized volume of 0.8739) compared to the Cryotop multi-step method (0.4396).</p><p><strong>Conclusions: </strong>Compared with the Cryotop carrier method, the microfluidic hydrogel microcapsule technique reduces CPA concentration, shortens loading time, and minimizes osmotic injury. This approach provides a promising strategy for fertility preservation and may be extended to other biological samples.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of re-biopsy and re-vitrification on clinical outcomes in preimplantation genetic testing for aneuploidy.","authors":"Huijiao Wu, Hui Wang, Yunhao Liang, Yu Deng, Yu Jiang, Li Yang, Shuai Liu, Zhiheng Chen","doi":"10.1007/s10815-025-03675-3","DOIUrl":"https://doi.org/10.1007/s10815-025-03675-3","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate whether re-biopsy and re-vitrification affect embryo developmental potential and clinical outcomes.</p><p><strong>Methods: </strong>Embryos that underwent preimplantation genetic testing for aneuploidy (PGT-A) and single embryo transfer between December 2017 and April 2024 were studied. All embryos were categorized into three groups: fresh biopsy and vitrification (BV group; n = 346); thawed, biopsied, and subsequently vitrified (VBV group; n = 12); fresh biopsied, vitrified, further thawed and biopsied again due to inconclusive results from the previous biopsy (BVBV group; n = 19). The live birth rate and miscarriage rate will be evaluated after embryo transfer in each group.</p><p><strong>Results: </strong>Live birth rate (LBR) was not statistically significant among the BV group (50.00%), VBV group [41.67%; adjusted relative risks (aRR) 0.96; 95% confidence interval (95% CI): 0.81-1.14], and BVBV group (42.11%; aRR 0.97, 95% CI: 0.83-1.13). The miscarriage rate was not statistically significant: BV group (11.27%); VBV group (25%; aRR 1.09, 95% CI: 0.95-1.25), and BVBV group (5.26%; aRR 0.97, 95% CI: 0.91-1.02).</p><p><strong>Conclusions: </strong>The differences in LBR and miscarriage rates among the groups were not statistically significant. However, the limited sample sizes of the VBV and BVBV groups cannot rule out the possibility of moderate differences. Some embryos can be successfully salvaged, leading to live births. To minimize inconclusive results, the laboratory should refine the procedural details.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the plasma proteome linked to corpus luteum presence and conception mode across pregnancy stages and postpartum.","authors":"Dhanya Ramachandran, Robin Tarek Dewender, Bianca Schröder-Heurich, Wiebke Froböse, Florian Avdulahu, Katja Richter, Valerie L Baker, Virginia D Winn, Andreas Pich, Frauke von Versen-Höynck","doi":"10.1007/s10815-025-03632-0","DOIUrl":"https://doi.org/10.1007/s10815-025-03632-0","url":null,"abstract":"<p><strong>Purpose: </strong>Observational data suggest that women conceiving without a corpus luteum are at higher risk of developing preeclampsia. While the underlying mechanisms remain unclear, the absence of corpus luteum-derived secretory products may be a contributing factor. This study investigates whether the plasma proteome differs between women who conceive with or without a corpus luteum and examines the relationship with mode of conception.</p><p><strong>Methods: </strong>Plasma samples from 12 participants were collected at three time points: first trimester, third trimester, and postpartum. The cohort included women who conceived unassisted (UC) after infertility, via artificial cycle frozen embryo transfer (AC FET), or natural cycle frozen embryo transfer (NC FET). A total of 36 plasma protein samples were analyzed using mass spectrometry-based proteomics to compare the proteome of women who conceived with and without a corpus luteum, across different conception methods and pregnancy stages.</p><p><strong>Results: </strong>In total, 528 proteins were quantified. No differentially expressed plasma proteins were identified between women with and without a corpus luteum. However, 15 proteins showed differential expression between UC and FET at all time points, with Bonferroni-corrected p < 9.47 × 10^-5 and FC ≥ |2|. Several altered proteins, including PAPPA and ANG, were linked to preeclampsia. SERPINA7 was differentially detected when comparing time points within the unassisted conception method. No significant differences were detected between AC FET and NC FET.</p><p><strong>Conclusion: </strong>This pilot study revealed a unique proteomic signature associated with the mode of conception. The findings suggest biologically plausible candidate proteins for further testing. Validation in larger cohorts or with alternative proteome analysis technologies is needed.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discrepancies between application and genetic consultation during routine ovum donor screening in large fertility network.","authors":"Camelia Varriale, Laurel Anderson, Emily Daugherty, Jacqueline Pierre-Louis, Katie Caesar, Daragh Castaneda, Lauri Black","doi":"10.1007/s10815-025-03672-6","DOIUrl":"https://doi.org/10.1007/s10815-025-03672-6","url":null,"abstract":"<p><strong>Purpose: </strong>To compare the personal and family medical history information obtained from a written application to a formal genetic risk assessment performed in consultation with a certified genetic counselor, as well as categorize and qualify any discrepant information.</p><p><strong>Methods: </strong>This was a retrospective cohort study of female subjects applying to become deidentified ovum donors, between ages 21 and 31 and who were determined to be eligible candidates with initial application and interview. Information provided by prospective ovum donors in their self-reported written application was compared to their genetic risk assessment performed in consultation with a certified genetic counselor, which documents family demographics and health history for a minimum of three generations. Discrepancies were categorized as relating to a health change or no health change (demographic) and then grouped by number of changes. Demographic changes included ages, number of family members, and age at time of death. Health changes were any new information relating to a health condition in prospective ovum donors and/or any family members.</p><p><strong>Result(s): </strong>A total of 600 randomly selected ovum donor applications and the associated genetic risk assessments were compared; 84% of these applicants reported novel health information during the genetic risk assessment. Of the total 600, 19% no longer met American Society of Reproductive Medicine (ASRM) or internal program guidelines for eligibility.</p><p><strong>Conclusions: </strong>Genetic risk assessment performed by a certified genetic counselor provides a more comprehensive representation of personal and family medical history and accurate assessment of the eligibility of an ovum donor compared to self-reported information alone.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A signature serum biomarker for non-invasive diagnosis of preeclampsia patients.","authors":"Teeba Ammar Rashid, Shahd Rajab Farhan, Aysar Ashour Khalaf, Gaurav Sanghvi, Subasini Uthirapathy, Renuka Jyothi, Mayank Kundlas, Kamal Kant Joshi, Anna Rudova, Yasser Fakri Mustafa","doi":"10.1007/s10815-025-03671-7","DOIUrl":"https://doi.org/10.1007/s10815-025-03671-7","url":null,"abstract":"<p><strong>Purpose: </strong>This study seeks to identify a non-invasive biomarker for preeclampsia (PE), given its considerable influence on both maternal and fetal health.</p><p><strong>Methods: </strong>The identification of differentially expressed genes (DEGs) in PE serum was conducted utilizing GSE192902. Weighted gene co-expression network analysis (WGCNA) was employed to identify functional modules, which were subsequently evaluated for their biological functions. Binary logistic regression was employed to evaluate genes derived from the intersection of DEGs and the most correlated module, with the aim of developing a biomarker model. The analysis of placental gene expression profiles was conducted utilizing GSE234729, and the model underwent validation in GSE149437.</p><p><strong>Results: </strong>Over 1500 DEGs were identified in the serum of PE patients, with 63% exhibiting downregulation. Co-expression analysis revealed that the expression patterns of PE are structured into 13 distinct modules, with the dark-red module, comprising 55 genes, demonstrating the most significant correlation to the onset of PE. Following this, eight genes from the 26 differentially expressed genes (ADRB1, ARX, C2orf72, FOXB2, HIC1, IRX4, MEX3D, and MIR6724-4) were employed to construct a biomarker model, which attained an area under the curve of 76% (95% CI: 69-83%) in the training cohort and 74% (95% CI: 61-87%) in the validation cohort. Six DEGs were identified from the intersection of results pertaining to serum, placenta, and the dark-red module. However, only two, C2orf72 and RASGEF1C, exhibited consistent downregulation in both placenta and blood.</p><p><strong>Conclusion: </strong>This comprehensive analysis reveals a promising biomarker model that may facilitate early detection of PE.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of integrated stress response by ISRIB promotes mouse and human primordial follicle activation via the mTOR pathway.","authors":"Tiantian Hao, Weiyong Wang, Ziyong Zhao, Zhenyu Zhou, Wenbo Zhang, Yashuang Weng, Longwei Gao, Hongwei Wei, Wenjun Zhou, Shuang Liu, Meijia Zhang, Yuezhou Chen","doi":"10.1007/s10815-025-03669-1","DOIUrl":"https://doi.org/10.1007/s10815-025-03669-1","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study is to investigate the effect of integrated stress response (ISR) inhibitor (ISRIB) on primordial follicle activation.</p><p><strong>Methods: </strong>We identified drugs promoting primordial follicle activation and investigated their mechanisms through culturing newborn mouse ovaries in vitro. Validation was performed in vivo through intraperitoneal injection in newborn mice. Additionally, we analyzed its potential mechanisms through transcriptome sequencing. Finally, the function and mechanisms of ISRIB were further validated through culturing human ovarian tissues in vitro.</p><p><strong>Results: </strong>ISR activity was present in neonatal mouse ovaries. ISRIB in vitro culture and in vivo intraperitoneal injection significantly decreased the protein levels of phosphorylated eukaryotic translation initiation factor 2 subunit alpha (p-eIF2α) and activating transcription factor 4 (ATF4). ISRIB also significantly increased the growing follicle number and the protein levels of phosphorylated mammalian target of rapamycin (p-mTOR), KIT ligand (KITL), phosphorylated protein kinase B (p-Akt), and phosphorylated forkhead Box O3a (p-FOXO3a) in neonatal mouse ovaries and/or cultured human ovarian fragments. ISRIB significantly increased the relative fluorescence intensities of p-mTOR in the pre-granulosa cells of primordial follicles, and ISRIB-induced increase of p-Akt and p-FOXO3a was completely reversed by KIT inhibitor ISCK03. In the excessive ISR mouse model induced by corticosterone, ISRIB could partially reverse the apoptosis of primordial and growing follicles.</p><p><strong>Conclusion: </strong>ISRIB promoted mouse and human primordial follicle activation via the mTOR pathway and partly reversed corticosterone-induced decrease of growing follicles. These results suggest that ISRIB may be a potential drug for rescuing infertility in POI patients.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}