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An intrauterine device (IUD) is one of the most effective reversible contraceptive methods currently available. Women who use IUDs may become pregnant, albeit rarely, and many such women continue to use IUDs. Because it is difficult to remove or it may cause miscarriage. This study measured the changes in human leucocyte antigen-G (HLA-G) and insulin-like growth factor II (IGF-II) levels in the decidua and villi to explore the effect of a copper IUD on embryonic development. A total of 54 samples of decidual and villus tissue were collected from pregnant women with IUDs (27 samples) or without IUDs (27 samples). Hematoxylin-eosin staining was used to identify morphological characteristics. Immunohistochemistry was used to detect HLA-G and IGF-II; the protein expression levels were measured via Western blotting. HLA-G was expressed on the membranes of trophoblasts of villus tissues and the glandular epithelium, and in stromal cells of decidual tissues, in both the IUD and control groups. IGF-II was expressed in the glandular epithelium and cytoplasm of trophoblasts and decidual cells in both groups. Compared to the control group, IGF-II expression was significantly reduced in villus tissues of the IUD group (p < 0.05). The mean sac diameter was significantly positively correlated with IGF-II expression in the villi (p < 0.05). A copper IUD may affect embryonic development by regulating the expression of villus IGF-II. • Women who use IUDs may become pregnant, and may continue to use IUDs • IGF-II is involved in the regulation of several stages of early pregnancy • The copper IUD may affect the development of the embryo by affecting villus IGF-II. [ABSTRACT FROM AUTHOR]