The effect of the assisted zona hatching (AZH) procedure was investigated on 135 cycles with a poor prognosis of pregnancy due to: (i) maternal age > or = 38 years (45 cycles); (ii) three or more failed in-vitro fertilization (IVF) attempts (70 cycles), and (iii) patients possessing both inclusion criteria (20 cycles). The control groups (113 cycles) included patients possessing the same characteristics (42, 53 and 18 cycles respectively) and who did not undergo the AZH procedure. A total of 505 embryos was treated with AZH before transfer, resulting in: 14, 25 and 6 clinical pregnancies. The percentage of clinical pregnancies per cycle was significantly higher than controls for the first (31 vs 10% in control 1, P < 0.05) and second groups (36 vs 17% in control 2, P < 0.05). No significant difference in percentage of clinical pregnancies was found for the third group (30 vs 6%). Similarly, higher rates of implantation were obtained (11.5, 15 and 11%) compared to the respective controls (4%, P < 0.02; 6.3%, P < 0.01; and 1.5%). The rate of miscarriage in the AZH groups was similar to that obtained in the controls (22 vs 21%). Finally, the morphological analysis of the embryos transferred revealed that the poor prognosis condition is associated to a significantly slower rate of development and a higher rate of fragmentation. The present results indicate that AZH procedure improves pregnancy and implantation rates in patients with a poor prognosis of pregnancy by facilitating the hatching process in embryos which would otherwise be trapped inside the zona pellucida.