OBJECTIVE: To evaluate the developmental potential of zygotes without pronucleus (0PN) and to examine the pregnancy outcomes of euploid blastocysts derived from these zygotes. METHODS: A total of 4580 fresh autologous preimplantation genetic testing for aneuploidy (PGT-A) cycles from 2634 patients at a single academic center from April 2016 to December 2022 with at least one 0PN at the time of fertilization check (16-19 hours post insemination) were included in the study. RESULTS: Of all 0PNs (n = 9345), 70.4% reached the cleavage stage, while only 5.3% of the cleaved embryos reached blastocyst stage and met biopsy criteria. These rates were significantly lower than those from the 2PNs (n = 32086, 98.7% cleavage, and 43.6% biopsied blastocyst rates, p <
0.05). Logistic regression model showed that 2PNs were 19.6 times more likely to result in biopsied blastocysts than 0PNs (p <
0.05). Of the biopsied blastocysts, 39% and 45% were euploid from the 0PN (n = 349) and 2PN (n = 13,975) group, respectively (p <
0.05). After single euploid frozen blastocyst transfers (n = 27 and 1695 in the 0PN and 2PN groups, respectively), no statistical significance was observed in live birth, clinical pregnancy, biochemical pregnancy, and spontaneous pregnancy loss rates between these two groups. CONCLUSION: Compared to 2PN zygotes, the 0PNs showed lower developmental potential, including lower blastocyst formation and euploidy rates. However, euploid blastocysts from either cohort resulted in similar live birth rates, indicating a small percentage of 0PN zygotes can result in normal blastocysts and live births presenting additional reproductive opportunities for patients lacking alternatives.