AbstractProblemRecurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) represent distinct clinical conditions with established definitions, both of which have been linked to an underlying pro‐inflammatory state. This study aimed to explore the levels of monocytic‐myeloid‐derived suppressor cells (M‐MDSCs) and regulatory T cells (TReg) in a cohort of RPL and RIF women and their potential contribution to RPL and RIF.Method of studyOne hundred and eight non‐pregnant women were evaluated: 40 RPL, 41 RIF, and 27 fertile healthy controls (HC). A multiparametric flow cytometry approach was utilized to measure and quantify the frequency of M‐MDSCs and TReg cells. Cytokine levels in plasma samples were evaluated through a multiplex assay. M‐MDSCs levels were significantly higher in RPL and RIF patients compared to HC.ResultsM‐MDSCs levels were significantly higher in RPL (9.4% [7–11.6]) and RIF (8.1% [5.9–11.6]) patients compared to HC (6% [4.2–7.6]). An optimal cut‐off of 6.1% for M‐MDSCs disclosed a sensitivity of 75.6% and 89.7% and a specificity of 57.7% and 57.7% in RIF and RPL groups, respectively. A significant negative correlation was observed between M‐MDSCs and TReg (p = .002, r = −.51).ConclusionsOur preliminary data allowed us to build a predictive model that may aid as a potential diagnostic tool in the clinic. These findings could provide a better understanding of these pathologies and a better definition of patients that could benefit from personalized treatments to promote pregnancy. Additional exploration and confirmation in distinct study groups are needed to fully assess the diagnostic capabilities of this biomarker.