Objective <p>Poor responders pose a significant challenge in fertility treatment, leading to decreased oocyte quality and fertilization rates. Assisted oocyte activation (AOA) has emerged as a method to improve fertilization rates. This study aims to evaluate the effect of AOA on fertilization, pregnancy, and live birth rates in patients with diminished ovarian reserve.</p> Materials and methods <p>This prospective non-randomized comparative study included a cohort of infertility patients with diminished ovarian reserve, divided into three groups: the control group receiving standard treatment (Group I/Conventional ICSI), the electrical activation group undergoing piezoelectric stimulation (Group II/ICSI + Piezoelectric), and the chemical activation group treated with calcium ionophore (Group III/ICSI + Calcium Ionophore). Each group consisted of 50 patients. The effects of electrical and chemical activation applied after ICSI on fertilization, pregnancy, and live birth rates were evaluated.</p> Results <p>There were no statistically significant differences among the groups in hormone levels (FSH, LH, E2, PRL, and AMH), number of oocytes, or number of MII oocytes. Fertilization rates were significantly higher in the piezoelectric group compared to the control group (<i>p</i> = 0.007). Although the fertilization rate in the calcium ionophore group was higher than that in the control group, this difference did not reach statistical significance (<i>p</i> = 1.000). There was no statistically significant difference in fertilization rates between the piezoelectric and calcium ionophore groups (<i>p</i> = 0.071). Regarding pregnancy rates, the highest implantation rate was observed in the calcium ionophore group (37%), but this difference does not reach statistical significance (<i>p</i> = 0.224). No significant differences were observed among the groups in embryo quality, clinical pregnancy, ongoing pregnancy, and live birth rates.</p> Conclusion <p>In patients classified as diminished ovarian reserve, artificial oocyte activation (AOA) was associated with higher fertilization rates for increasing fertilization rates, potentially resulting in a greater number of fertilized oocytes and transferable embryos. However, this apparent benefit does not translate into improved biochemical pregnancy outcomes. Moreover, no significant differences were observed between groups in terms of embryo quality, clinical pregnancy, ongoing pregnancy, and live birth rates. These findings suggest that while AOA may enhance early laboratory outcomes, its impact on clinically meaningful reproductive endpoints remains limited. Therefore, further adequately powered randomized studies are required to clarify the efficacy and safety of AOA.</p>