Fertilization failure is one of the causes of infertility that becomes evident only after in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) have been attempted. Although the frequency of incidence of fertilization failure is low, if fertilization failure is encountered, medical treatment is usually stopped and serious psychological damage may occur to the patient. While fertilization failure in IVF can be dealt with using ICSI, there is no treatment for fertilization failure in ICSI. At present, clinical investigations are being conducted to evaluate oocyte activation in combination with ICSI to cope with fertilization failure of ICSI.