Repeated implantation failure (RIF) is one of the most prominent problems in the field of assisted reproduction. Neu5Gc on the surface of decidual macrophages (dMΦ) leads to different activation patterns of dMΦ, which affects embryo implantation and development. Cmah -/- (Neu5Gc-deficient) mice induced to produce anti-Neu5Gc antibodies in vivo were given a special diet rich in Neu5Gc and their fertility was monitored. The long-term diet rich in Neu5Gc induced the decrease of endometrial receptivity of female mice. The pregnancy rate of female mice fed the normal diet was 63.6% (n = 11) and the average number of embryos was 9.571 ± 1.272, while the pregnancy rate of female mice fed the diet rich in Neu5Gc was 36.4% (n = 11) and the average number of embryos in pregnant mice was 5.750 ± 3.304. The intake of Neu5Gc and the production of anti-Neu5Gc antibody led to M1 polarization of endometrial dMΦ and abnormal embryo implantation.