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Extracellular matrix (ECM) is characterized as widespread, abundant, and pluripotent. Among ECM members, collagen is widely accepted as one of the most prominent components for its essential structural property that can provide a scaffold for other components of ECM and the rich biological functions, which has been extensively used in tissue engineering. Emerging evidence has shown that the balance of ECM degradation and remodeling is vital to regulations of maternal–fetal interface including menstrual cycling, decidualization, embryo implantation and pregnancy maintenance. Moreover, disorders in these events may eventually lead to failure of pregnancy. Although the improvement of assisted conception and embryo culture technologies bring hope to many infertile couples, some unfavorable outcomes, such as recurrent implantation failure (RIF), recurrent pregnancy loss (RPL) or recurrent miscarriage (RM), keep troubling the clinicians and patients. Recently, in vitro three-dimensional (3D) model mimicking the microenvironment of the maternal–fetal interface is developed to investigate the physiological and pathological conditions of conception and pregnancy. The progress of this technology is based on clarifying the role of ECM in the endometrium and the interaction between endometrium and conceptus. Focusing on collagen, the present review summarized the degradation and regulation of ECM and its role in normal menstruation, endometrium receptivity and unsatisfying events occurring in infertility treatments, as well as the application in therapeutic approaches to improve pregnancy outcomes. More investigations about ECM focusing on the maternal–fetal interface interaction with mesenchymal stem cells or local immunoregulation may inspire new thoughts and advancements in the clinical application of infertility treatments. Graphical abstract

The role of extracellular matrix on unfavorable maternal–fetal interface: focusing on the function of collagen in human fertility