Role of Myeloid-Derived Suppressor Cells as a Potential Biomarker in Implanation Failure: A Systematic Review

Pregnancy requires maternal immune tolerance of the semi-allogeneic fetus without compromising host defense. Myeloid-derived suppressor cells (MDSCs) have emerged as key regulators of maternal fetal tolerance, but their role in early miscarriage (EM), recurrent pregnancy loss (RPL), and recurrent implantation failure (RIF) remains incompletely defined.

To systematically evaluate the role of MDSCs in EM, RPL, and RIF and assess their potential as biomarkers and therapeutic targets in implantation failure and pregnancy loss.

A systematic review in accordance with PRISMA guidelines. Searches were conducted in Google Scholar up to April 13, 2025, using the terms "Myeloid Derived Suppressor Cells," "in vitro fertilization," "early miscarriage," "pregnancy loss," and "implantation failure." Studies were eligible if they quantified MDSCs in peripheral blood or endometrial samples of women with EM, RPL, or RIF and animal-only studies. Reviews, abstracts, and inaccessible full texts were excluded.

Of 70 records identified, 11 met inclusion criteria (seven human, five murine, one has included human samples and murine models). In human studies, reduced granulocytic MDSCs (G-MDSCs) were strongly associated with EM and RPL, correlating with low estradiol/progesterone, impaired STAT3 signaling, and a Th1-dominant cytokine milieu. Findings in RIF were heterogeneous: some reported decreased polymorphonuclear MDSCs with functional impairment, while others observed elevated monocytic MDSCs (M-MDSCs) with diminished suppressive capacity, suggesting dysfunctional or compensatory expansion. Placental enrichment of G-MDSCs demonstrated their tolerogenic role in situ, promoting Treg induction and macrophage polarization. Murine models confirmed it as the cause since MDSC depletion abolished pregnancy, while progesterone-STAT3-ROS signaling supported their expansion and suppressive function. Adoptive MDSC transfer partially rescued fetal resorption in abortion-prone models.

MDSCs are central to maternal fetal tolerance, and their dysregulation contributes to EM, RPL, and RIF. Human and animal data support their potential as predictive biomarkers and therapeutic targets in implantation failure. Standardization of MDSC phenotyping and mechanistic studies of subset-specific functions are warranted to advance clinical translation.