Unexplained recurrent spontaneous abortion (URSA) involves aberrant trophoblast cell death. Cuproptosis, a newly identified form of metabolic cell death, is not clearly associated with URSA. This study clarifies the association between URSA and trophoblast cell cuproptosis. This study analyzed cuproptosis- related gene expression in the trophoblast cells of patients with URSA using RNA sequencing (RNA-Seq). Copper ion levels in trophoblast cells were quantified using inductively coupled plasma mass spectrometry (ICP-MS). The regulation of trophoblast cell activity by cuproptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and the mouse embryo assay (MEA). The activation mechanism of trophoblast cell cuproptosis was delineated using RNA immunoprecipitation (RIP), RNA pull-down assay and RNA half-life assay. A mouse model of immune spontaneous abortion was used to evaluate the effect of L-Glutathione reduced (GSH) on abortion rates. The SLC31A1 protein, a copper ion transporter, is overexpressed in trophoblast cells of patients with URSA and activates trophoblast cell cuproptosis. The N6-adenosine-methyltransferase 70 kDa subunit (METTL3) protein binds to SLC31A1 mRNA, promoting N6-methyladenosine (m6A) modification. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an m6A-binding protein, binds to the m6A site of SLC31A1 mRNA, reducing mRNA degradation. GSH inhibits trophoblast cell cuproptosis, reducing the abortion rate in the mouse model of immune spontaneous abortion. In conclusion, in trophoblast cells of patients with URSA, the METTL3 protein promotes m6A modification of SLC31A1 mRNA, and IGF2BP3 enhances SLC31A1 mRNA stability, inducing intracellular copper accumulation, activating cuproptosis and ultimately leading to URSA.