SUMMARYThe aim of this study was to investigate the relationship between the etiology of the couples and risk of fertilization failure (FF) in conventional in vitro fertilization (IVF) cycles and the effect of rescue intracytoplasmic sperm injection (ICSI) technique to offspring. A total of 2542 IVF cycles were divided into four groups according to infertile etiology: Group A -primary infertility with normal semen parameters; Group B -secondary infertility with oligoasthenozoospermia; Group C -primary infertility with oligoasthenozoospermia; and Group D -secondary infertility with normal semen parameters. The results showed that there were significant differences in incidence of FF among Group A (16.8%), Group B (20.9%), Group C (48.7%), and Group D (0.9%) (p < 0.001). Logistic regression models demonstrated that primary infertility (OR: 10.898, 95% CI: 4.651-25.583, p < 0.001) and oligoasthenozoospermia (OR: 12.215, 95% CI: 5.903-25.276, p < 0.001) were independent risk factors for FF. There were no significant differences in main outcomes between conventional ICSI and rescue ICSI. In conclusion, the patients with primary infertility and oligoasthenozoospermia might be at higher risk of FF. The rescue ICSI technique is safe and helpful for IVF cycles of FF.