{"title":"The Effect of Oral Cyclosporine A on Immune Indicators and Pregnancy Outcomes in Patients With Adverse Pregnancies: A Retrospective Study","authors":"Maojiao Wang, Zhongchao Fu, Rangeng Shi, Peng Zhang, Shiqi Lin, Jiang Liu, Chenli Ye, Weiling Cao, Xiaogui Cheng","doi":"10.1111/aji.70210","DOIUrl":"10.1111/aji.70210","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The use of low-dose cyclosporine A (CsA) has been shown to increase live birth rates in cases of unexplained recurrent spontaneous abortions, without causing significant side effects for the pregnant woman or fetus. The primary aim of this study was to evaluate the effect of CsA on immune system indicators and pregnancy success in adverse pregnancies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data were collected from patients diagnosed with adverse pregnancies caused by immune-related abnormalities at the Department of Rheumatology and Immunology in a tertiary hospital in Shenzhen, China, between September 2023 and October 2024. Information collected included patient details, cytokine levels, lymphocyte subpopulations, blocking antibody changes, and CsA blood concentration during medication. This helped determine the effective blood concentration range of CsA for these patients, aimed at enhancing the drug's safety and effectiveness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Outcome</h3>\u0000 \u0000 <p>The study included a total of 661 participants, among whom 279 achieved successful pregnancies after CsA treatment (A clinically confirmed pregnancy is considered a successful pregnancy). The CD3+, CD4+, and CD8+ blocking antibody efficiency levels were significantly increased after CsA administration (<i>P</i> < 0.001, <i>p</i> = 0.003, <i>p</i> = 0.017), and the former two changes were strongly correlated with pregnancy success (<i>p</i> = 0.002, <i>P</i> < 0.001). The receiver operating characteristic (ROC) curve revealed that increases in CD3+, CD4+ blocking antibodies were strong predictors of successful pregnancy outcomes. Cytokine levels, including IL-2, IL-4, IL-6, IL-10, IL-17, IFN-<i>γ</i>, and TNF-<i>α</i>, decreased significantly after treatment (<i>P</i> < 0.01). Ratios such as IL-2/IL-10 and IFN-<i>γ</i>/IL-10 also showed significant reductions (<i>P</i> < 0.001), while the IFN-<i>γ</i>/IL-4 and TNF-<i>α</i>/IL-4 ratios increased significantly (<i>P</i> < 0.001). The majority of patients had blood CsA concentrations between 10–70 ng/mL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that CsA can effectively regulate immune markers and restore immune balance, reducing the impact of immune-related adverse pregnancy outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997052","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":"Comment on: “Study on the Effects of Doxycycline Treatment on Endometrial Microbiota and Pregnancy Outcomes in Chronic Endometritis”: Beyond Composition: The Potential Role of Microbial Load in CE Pathophysiology","authors":"Yinglan Ma, Qun Zhou, Huilin Yang","doi":"10.1111/aji.70204","DOIUrl":"10.1111/aji.70204","url":null,"abstract":"","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964984","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}
Abigail C. Fischer, Hanah M. Georges, Deidre M. Jones, Lawrence W. Chamley, Vikki M. Abrahams
{"title":"Nicotinamide Riboside Mitigates Antiphospholipid Antibody-Induced Dysfunction in Human Trophoblast Cells","authors":"Abigail C. Fischer, Hanah M. Georges, Deidre M. Jones, Lawrence W. Chamley, Vikki M. Abrahams","doi":"10.1111/aji.70205","DOIUrl":"10.1111/aji.70205","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Obstetric antiphospholipid syndrome (APS) is characterized by the presence of circulating anti-phospholipid antibodies (aPL), which disrupt early placentation and contribute to adverse pregnancy outcomes including pregnancy loss and preterm birth. aPL, specifically those targeting beta 2 glycoprotein 1 (β<sub>2</sub>GPI), interact with placental trophoblast cells and induce inflammation, disrupt angiogenic factor production, and reduce cell migration. In addition, aPL have been shown to promote a state of oxidative stress in trophoblast cells and in APS patients. This study aimed to investigate if the antioxidant, nicotinamide riboside (NR), could mitigate the negative effects of aPL on trophoblast cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>The human first-trimester trophoblast cell line, Sw.71, was treated with or without aPL in the presence or absence of NR. Trophoblast supernatants were measured by ELISA for pro-inflammatory cytokines/chemokines and angiogenic factors. Cell migration was measured using a two-chamber colorimetric assay. ROS production was measured using a fluorescence assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>NR blocked aPL-induced trophoblast inflammation and ROS production, and reversed the effects of aPL on trophoblast angiogenic factor production. However, NR was unable to rescue aPL-induced trophoblast migratory dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>NR mitigated some, but not all, aPL-induced trophoblast dysfunction. This provides new insight into the role of antioxidant therapies on aPL-induced pregnancy complications, and a possible new avenue of managing obstetric APS to explore further.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958375","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}
Xiaoxuan Yang, Yan Su, Yaping Guo, Mianqiu Zhang, Juan Zhang, Xiaojing Hou, Shuangshuang Zhao, Huiqing An, Xiufeng Ling, Rong Shen
{"title":"Impact of Anti-Endometrial Antibodies on IVF Implantation and Pregnancy Outcomes: A Retrospective Study","authors":"Xiaoxuan Yang, Yan Su, Yaping Guo, Mianqiu Zhang, Juan Zhang, Xiaojing Hou, Shuangshuang Zhao, Huiqing An, Xiufeng Ling, Rong Shen","doi":"10.1111/aji.70202","DOIUrl":"10.1111/aji.70202","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problems</h3>\u0000 \u0000 <p>To investigate the impact of anti-endometrial antibodies (EMAb) on pregnancy outcomes in infertile patients undergoing in vitro fertilization (IVF) and to assess the potential value of personalized treatment strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>A total of 47 EMAb-positive and 166 EMAb-negative oocyte retrieval cycles were retrospectively included following propensity score matching (PSM) to control for basic clinical characteristics influencing pregnancy outcomes. The two groups were compared in terms of various aspects closely associated with IVF outcomes. Pregnancy outcomes were assessed based on implantation, clinical pregnancy, miscarriage, and ongoing pregnancy rates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No significant differences were found between the two groups regarding infertility-related clinical characteristics, oocyte- and embryo-related indicators, endometriosis incidence, and so forth. Compared with the EMAb-negative group, the implantation rate in the EMAb-positive group was lower by 10.3 percentage points (<i>p</i> = 0.047), whereas the 8.2-point lower clinical pregnancy rate did not reach statistical significance (<i>p</i> = 0.234). There were no significant differences in ongoing pregnancy and miscarriage rates between the two groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study observed that the presence of EMAb was associated with less favorable IVF outcomes, primarily reflected in lower implantation and clinical pregnancy rates. However, once the implantation was successful, the risk of miscarriage did not increase. These findings suggest a potential role for EMAb screening in guiding personalized treatment strategies, such as increasing the number of embryos transferred or using immunosuppressive agents, to improve IVF outcomes. Future research should involve more extensive and diverse populations to explore the mechanisms of action of EMAb and their impact on IVF treatment outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145931425","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}
Mojtaba Aghaei, Mehdi Torabizadeh, Mohammad Amin Vahid, Najmaldin Saki
{"title":"Indications for Performing the APCA Test in Female Infertility","authors":"Mojtaba Aghaei, Mehdi Torabizadeh, Mohammad Amin Vahid, Najmaldin Saki","doi":"10.1111/aji.70206","DOIUrl":"10.1111/aji.70206","url":null,"abstract":"","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909878","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}
Yingyi Guo, Yue Hou, Jinshuang Wu, Ning Lou, Dongxia Yang
{"title":"Identification and Subtype Analysis of Lipid Metabolism-Related Diagnostic Biomarkers for Endometriosis Based on WGCNA and Machine Learning","authors":"Yingyi Guo, Yue Hou, Jinshuang Wu, Ning Lou, Dongxia Yang","doi":"10.1111/aji.70201","DOIUrl":"10.1111/aji.70201","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Endometriosis (EM), a disorder driven by persistent systemic inflammation, impacts around 10% of women in their reproductive period, often diagnosed only via surgery. Metabolic alterations, particularly in lipid metabolism, may uncover novel biomarkers. We aimed to identify diagnostic markers and molecular subtypes by integrating lipid metabolism gene expression and machine learning.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We downloaded gene expression datasets (GSE51981 and GSE7305) from the Gene Expression Omnibus (GEO) database. Differential expression was analyzed using limma (|log<sub>2</sub>FC| > 1, <i>p</i>.adj < 0.05); intersected with lipid genes to yield candidate genes. Weighted gene co-expression network analysis (WGCNA) demonstrated endometriosis-connected gene modules. Integrating lipid metabolism-related differentially expressed genes with WGCNA hub genes, followed by least absolute shrinkage and selection operator (LASSO) and XGBoost machine learning, identified diagnostic biomarkers. Their performance was validated using receiver operating characteristic (ROC) curves in an independent dataset. Immune infiltration, including CIBERSORT and single-sample GSEA (ssGSEA), gene set enrichment analysis (GSEA), and non-negative matrix factorization (NMF)-based subtype analyses were performed. MicroRNA (miRNA) and transcription factor (TF) regulatory networks were constructed using online databases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 106 lipid metabolism-related differential genes. WGCNA revealed the turquoise module strongly correlated with endometriosis. ELOVL6 and MED20 were identified as key genes through machine learning algorithms. The two key genes emerged as robust diagnostic biomarkers, showing high area under the ROC curves (AUCs) across both training and validation sets. Immune infiltration analysis revealed distinct immune cell patterns in endometriosis, with ELOVL6 and MED20 correlating with specific immune cells. Subtype analysis, based on lipid metabolism scores, stratified patients into high and low score groups with differential gene expression and immune cell infiltration. Regulatory networks identified miRNAs and TFs targeting ELOVL6 and MED20.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study identified ELOVL6 and MED20 as promising lipid metabolism-related diagnostic biomarkers for endometriosis. We also uncovered distinct molecular subtypes linked to lipid metabolism, providing novel insights into endometriosis heterogeneity and potential therapeutic targets.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809213","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}
Xue Wei, Cai Liu, Weijing Wang, Lu Jiang, Fang Wang
{"title":"Immunological and Coagulation Predictors of Subchorionic Hematoma in Recurrent Pregnancy Loss: A Predictive Modeling Approach","authors":"Xue Wei, Cai Liu, Weijing Wang, Lu Jiang, Fang Wang","doi":"10.1111/aji.70200","DOIUrl":"10.1111/aji.70200","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Subchorionic hematoma (SCH) is a common complication in early pregnancy, particularly in women with recurrent pregnancy loss (RPL), and is associated with adverse pregnancy outcomes. However, reliable predictive tools for SCH in this high-risk group are lacking. The aim of this study was to identify coagulation and immune-related predictors associated with SCH in women with RPL and to construct a predictive model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>A retrospective analysis was performed on 1002 patients with RPL in the Reproductive Medicine Center of the Second Hospital of Lanzhou University. Clinical data, coagulation indicators, thromboelastography (TEG), and immunity indicators were collected. Predictors were selected via LASSO and logistic regression, and a LightGBM model was developed and validated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eleven predictors were included in the final model: age, BMI, previous pregnancy losses, TEG-lysis index at 30 min, TEG- maximum amplitude, serum immunoglobulins IgG, complement C3, antiβ2 glycoprotein 1 antibody, rheumatoid factor IgM and interleukin-2/interleukin-6, interferon-γ/interleukin-6. The model demonstrated moderate and stable discrimination with AUCs of 0.745, 0.653, and 0.647 in the training, internal, and external validation sets, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The model effectively identifies SCH risk in RPL patients and informs individualized monitoring and early intervention strategies in clinical practice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793068","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}
Jessica Weng, Jennifer L. Wayland, Indira U. Mysorekar, Elizabeth A. Bonney
{"title":"Abandoning Reproductive Science Betrays Us All","authors":"Jessica Weng, Jennifer L. Wayland, Indira U. Mysorekar, Elizabeth A. Bonney","doi":"10.1111/aji.70199","DOIUrl":"10.1111/aji.70199","url":null,"abstract":"","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793082","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}
Monika M. Kowatsch, Kenneth Omollo, Frideborg Bradley, Anna Månberg, Peter Nilsson, Sofia Bergström, Julius Oyugi, Joshua Kimani, Kristina Broliden, Keith R. Fowke, Julie Lajoie
{"title":"HIV-Exposed Seronegative Female Sex Workers Show Different Cellular Immune Profiles Across the Menstrual Cycle","authors":"Monika M. Kowatsch, Kenneth Omollo, Frideborg Bradley, Anna Månberg, Peter Nilsson, Sofia Bergström, Julius Oyugi, Joshua Kimani, Kristina Broliden, Keith R. Fowke, Julie Lajoie","doi":"10.1111/aji.70198","DOIUrl":"10.1111/aji.70198","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Female sex workers (FSWs) are at higher risk of acquiring HIV. Interestingly, some FSWs who are highly exposed remain seronegative for HIV (HESN). This natural resistance to HIV infection has been attributed to an immune quiescence (IQ) phenotype. Our study investigates how the menstrual cycle phases (follicular and luteal) impact the immune responses in Kenyan FSWs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This is a part of the Longitudinal Assessment of Mucosal Immune Quiescence study (LAMIQ), 48 FSWs not living with HIV and not using hormonal contraception were followed for a menstrual cycle and divided into two groups based on duration of sex work: New Negative (NN) with 3 years or less and HESN with at least 7 years of involvement in sex work. We obtained blood and cervicovaginal samples and measured sex hormone, cytokine, and chemokine levels, and blood and endocervical T-cell and NK-cell phenotypes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We observed differences in how the immune response of NN and HESN responds to sex hormones. Indeed, the level of mucosal Annexin A3 measured was higher during the luteal phase in HESN, which was not observed in NN. HESN exhibited a higher CD39 expression on their Treg during the luteal phase, while maintaining CTLA-4 expression compared to NN. Furthermore, in HESN, NK cell activation varied across the menstrual cycle phases. They had a higher expression of NKG2D and an increase in the cluster of CD95+ HLA-DR+ NK cells during the follicular phase. This suggests stronger innate immune activation in HESN during the follicular phase of the menstrual cycle.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our data indicate that, in HESN, there is a modulation of the immune response based on the menstrual cycle, which potentially limits the availability of HIV target cells at the female genital tract during the luteal phase of the menstrual cycle (window of susceptibility).</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12716113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793035","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}
Marcelo Garrido, Francisco Monico Moreira, Luis Antonio Gilberti Panucci, Graziela Garrido Mori
{"title":"Extracellular Vesicles for the Maintenance of Pregnancies in Situations of Recurrent Spontaneous Abortion: Scoping Review","authors":"Marcelo Garrido, Francisco Monico Moreira, Luis Antonio Gilberti Panucci, Graziela Garrido Mori","doi":"10.1111/aji.70197","DOIUrl":"10.1111/aji.70197","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Given the immune system's role in pregnancy, the immunomodulation generated by the use of extracellular vesicles (EVs) has been considered a possible treatment in situations of recurrent spontaneous abortion (RSA). Thus, this study evaluated, through a scoping review, the applicability of extracellular vesicle therapies for immunomodulation in maintaining pregnancies in situations of RSA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study was based on the Guidance for Conducting Systematic Scoping Reviews and was registered on the OSF Home platform. A systematic search was performed in the PubMed/MEDLINE, Scopus, and Cochrane Library databases up to June 2025 by two independent reviewers to answer the question addressed in the present review.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 440 articles were analyzed, and after applying the eligibility criteria and excluding duplicate studies, three studies were selected. All three studies showed reduced embryonic absorption, promoting pregnancy maintenance. The EVs were extracted from trophoblasts, decidual stromal cells, or bone marrow stem cells, and administered intravenously, primarily, in dose of 100 or 200 µg. All EVs have immunomodulatory relevance in pregnancy, modifying the lymphocyte and cytokine patterns, and contributing to angiogenesis and trophoblast growth.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We conclude that EVs represent a potential area for the development of future therapies for pregnancies with RSA, and new studies are necessary to confirm these findings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145766954","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}