Purpose: To determine if fertilization and embryo development and pregnancy was possible following in vitro fertilization (IVF) in a couple with long-term unexplained infertility where the female partner had diminished egg reserve and where fertilization failure occurred despite conventional oocyte insemination and intracyoplasmic sperm injection (ICSI). Methods: In vitro fertilization was performed using a low-dose follicle stimulating hormone (FSH) stimulation protocol. Prior to ICSI, artificial oocyte activation with calcium ionophore was used. Results: Only one mature oocyte was retrieved but it fertilized and cleaved to a good quality 8-cell embryo on day 3. A pregnancy with fetal viability was achieved but she subsequently miscarried. A second attempt successful. Conclusions: Fertilization and pregnancy is possible even in women with diminished egg reserve with previous failed fertilization with ICSI by performing artificial oocyte activation with calcium ionophore. It is not clear if the sperm lacked oscillin or if the eggs were not responsive to oscillin.