OBJECTIVE: To determine whether electrically stimulated Ca2+ influx can "rescue" fertilization and early embryogenesis in human oocytes that fail to fertilize after intracytoplasmic sperm injection (ICSI). DESIGN: Prospective, randomized trial of a laboratory procedure. SETTING: A research laboratory at a university medical center. PATIENT(S): Discarded oocytes from ICSI-IVF cycles. INTERVENTION(S): Oocytes (n = 104) that showed no evidence of fertilization 16-24 hours after ICSI were assigned to three treatment groups: group 1 (one direct current electrical pulse at 1.36-1.50 kV/cm for 40-60 micros), group 2 (three pulses every 15-20 minutes), or group 3 (treated the same as group 2 but with no electrical stimulation). MAIN OUTCOME MEASURE(S): After stimulation, the oocytes were cultured in vitro for 3-5 days. Oocytes that displayed two pronuclei and a second polar body within 16 hours were considered to have fertilized normally. Fertilization and embryo cleavage rates were compared between groups. RESULT(S): Fertilization occurred in 26 (70%) of 37 and 38 (78%) of 49 group 1 and 2 oocytes, respectively, but in only 5 (27%) of 18 group 3 oocytes. Within 3 days, group 2 embryos routinely developed beyond the two-cell to four-cell stage (61% versus 13% in group 1); 11% of these oocytes developed to the morula or early blastocyst stage. Sex chromosome analyses indicated 10 male and 8 female embryos. CONCLUSION(S): Oocytes that fail to fertilize by 24 hours after ICSI can resume apparently normal fertilization and early embryonic development in response to electrical stimulation. Moreover, the degree of cytoplasmic activation as determined by the number of pulses applied affects fertilization efficiency and early embryonic development.