The cell division cycle 20 (CDC20, HGNC:1723) is the co-activator of anaphase-promoting complex/cyclosome (APC/C) during mitosis, and plays a role in maintaining the genome by regulating spindle assembly checkpoints . In oocytes, the activation of APC/C by CDC20 is a key step in homologue disjunction and in transition from meiosis I to meiosis II. CDC20 is therefore an essential component of the mammalian cell cycle mechanism regulating both miotic and meiotic exit. Although CDC20 is an extensively studied gene, until now, no solid evidence has been provided to establish the causal relationship between CDC20 mutations and human diseases. The only report was an association study relating CDC20 mutations with idiopathic azoospermia.Here, we identified biallelic CDC20 mutations in five infertile individuals with oocyte maturation arrest, fertilization failure, and early embryonic arrest. We investigated the effects of the corresponding mutations in cell lines and mouse oocytes and explored a potential therapeutic treatment by direct CDC20 cRNA injection.