<p>Patient statistics.</p>

Although immune tolerance is critical for pregnancy success, the specific immune dysregulations contributing to RPL, particularly in euploid pregnancies, have been difficult to characterize. To address this, we performed single-cell RNA sequencing of decidual tissues from RPL patients and first-trimester controls.

Our analysis initially revealed elevated expression of a transcriptional module of immune activation genes in RPL decidual tissues. To dissect the cellular drivers of this complex landscape, we employed genotype-based origin analysis coupled with a supervised machine learning model and a transformer-based foundation model (scGPT). This hierarchical approach prioritized maternal T cells over other immune subsets as the population carrying the most distinct and generalizable RPL-associated signatures.