<p>Assisted reproductive technology (ART) is widely used to treat infertility, a global health burden. Controlled ovarian hyperstimulation (COH) is a crucial first step in ART that enables the collection of a large number of mature oocytes. Ovarian reserve (OR), namely, the number and quality of primordial follicles, indicates female reproductive potential and is an important determinant of infertility treatment outcomes. However, changes in the immune response and related regulatory mechanisms at single-cell resolution in patients with varying levels of OR during COH remain unclear. In this study, single-cell RNA sequencing (scRNA-seq) was performed on peripheral blood mononuclear cell (PBMC) samples obtained from 4 patients with a normal OR (N group), 4 with a diminished OR (D group), and 4 with a high OR (H group) before (B group) and after COH (A group). Single-cell transcriptome profiling revealed 20 cell clusters and cell distribution patterns. GDT, CD8 Teff and CD4 naïve T cells were enriched predominantly in the NA, HA and DA groups, respectively. We also identified differentially expressed genes (DEGs) with similar patterns between the NA and NB groups and between the HA and HB groups. An analysis of intercellular communication revealed variable changes in cell–cell interactions, and the candidate ligand–receptor pair HLA-B/KIR3DL2 was identified in the HA group compared with the HB group. Moreover, we detected systematic proinflammatory features in NA and HA patients accompanied by upregulated expression of proinflammatory genes, including JUN, JUNB, NFKBIA, MAP3K8 and CCL5. We also identified essential transcription factors (TFs) related to follicle development and maturation. This study provides new information on the specific regulatory role of the immune response in COH that will facilitate the identification of potential targets to improve infertility treatment outcomes in patients with varying levels of OR.</p> Graphical abstract <p></p>