{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T15:36:11Z","timestamp":1793028971636,"version":"4.5.0"},"reference-count":78,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Early pregnancy loss(EPL) remains a major obstacle to successful\n                      <jats:italic>in vitro<\/jats:italic>\n                      fertilization\/intracytoplasmic sperm injection-embryo transfer(IVF\/ICSI-ET). Immune dysregulation at the maternal-fetal interface has been increasingly implicated in implantation failure and early miscarriage, while inflammasome-mediated pyroptosis has emerged as a potential contributor to inflammatory tissue injury. However, the direct evidence linking pyroptosis to IVF\/ICSI-ET-related EPL remains limited.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To critically appraise direct and indirect evidence regarding immune dysregulation and the potential role of pyroptosis in IVF\/ICSI-ET-related EPL, and to define current translational limitations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A structured review of epidemiological, clinical, and mechanistic studies published between 2020 and 2025 was conducted using literature relevant to EPL, IVF\/ICSI-ET, maternal-fetal immune regulation, inflammasome activation, and pyroptosis. Evidence was considered according to its direct relevance to IVF\/ICSI-ET-related EPL and interpreted with attention to study design, methodological limitations, and translational applicability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Established clinical predictors of EPL after IVF\/ICSI-ET include maternal age, body mass index, endometrial characteristics, and embryonic or sperm-related factors. Immune abnormalities involving uterine natural killer cells, macrophage polarization, and regulatory T-cell imbalance may contribute to impaired maternal-fetal tolerance. Pyroptosis-related pathways, particularly those involving the NLRP3\/ASC\/Caspase-1 axis, gasdermin D cleavage, and IL-1\u03b2\/IL-18 release, provide a biologically plausible framework for both physiological epithelial remodeling during implantation and inflammatory injury when dysregulated. Nevertheless, most pyroptosis-related evidence is indirect and derived from pregnancy-related complications or non-reproductive inflammatory diseases rather than from IVF\/ICSI-ET-specific EPL studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Immune dysregulation is likely contributes to in IVF\/ICSI-ET-related EPL, whereas pyroptosis should currently be regarded as a promising but insufficiently validated mechanistic candidate. Future studies should prioritize cell-specific, temporally resolved, and clinically relevant investigations to clarify whether immune-pyroptosis interactions have diagnostic or therapeutic value in this setting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1844319","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T04:56:21Z","timestamp":1779425781000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Direct and indirect evidence for pyroptosis and immune dysregulation in IVF\/ICSI-ET-related early pregnancy loss"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiao","family":"Wang","sequence":"first","affiliation":[{"name":"Jinan University","place":["Guangzhou, Guangdong, China"]},{"name":"Affiliated Hospital of Guangdong Medical University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangmou","family":"Chen","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Guangdong Medical University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenghua","family":"Liu","sequence":"additional","affiliation":[{"name":"Jinan University","place":["Guangzhou, Guangdong, China"]},{"name":"Department of Reproductive Health and Infertility, Guangdong Province Maternity and Child Care Hospital","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deaf049","article-title":"International Committee for Monitoring Assisted Reproductive Technologies (ICMART): world report for cycles conducted in 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