Structured review on immune dysregulation and pyroptosis in IVF/ICSI-ET early pregnancy loss

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Frontiers in Medicine Published May 23, 2026 Medically reviewed May 23, 2026 Study authors: Xiao Wang, Guangmou Chen, Fenghua Liu DOI ↗ By Dr. Lars van Dijk, PhD · Surgical, Procedural & Diagnostic

Key Takeaway

Consider immune dysregulation as a likely contributor in IVF/ICSI-ET early pregnancy loss, but view pyroptosis as an unvalidated candidate.

This is a structured review examining the role of immune dysregulation and pyroptosis in early pregnancy loss related to IVF/ICSI-ET. The authors synthesize existing evidence, noting that immune dysregulation is likely a contributor to this condition. In contrast, pyroptosis is described as a promising but insufficiently validated mechanistic candidate.

The review indicates that most pyroptosis-related evidence is indirect, derived from pregnancy-related complications or non-reproductive inflammatory diseases rather than from IVF/ICSI-ET-specific early pregnancy loss studies. Direct evidence linking pyroptosis to IVF/ICSI-ET-related early pregnancy loss remains limited.

Key limitations acknowledged by the authors include the indirect nature of the current evidence base and the lack of direct studies in the specific IVF/ICSI-ET population. The authors note that pyroptosis should currently be regarded as a promising but insufficiently validated mechanistic candidate.

Practice relevance is restrained; the authors suggest 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.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedMay 2026

View Original Abstract ↓

Early pregnancy loss(EPL) remains a major obstacle to successful in vitro 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. 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. 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. 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-1β/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. 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.