Human oocytes have the aggregated chromosome phase (AC phase) during the first and second meiosis. This needs to be better understood, as the timing of ICSI significantly influences ART outcomes. In fact, performing ICSI after the completion of MII spindle formation is known to improve successful fertilization and embryo development. This human AC phase should also be taken into consideration in the application of nuclear transfer/mitochondrial replacement for patients suffering from severe mitochondrial diseases, to prevent the transmission of these diseases to their offspring, with the aim of limiting the risk of mitochondrial carryover. The possible risks and benefits of AC transfer and other procedures for mitochondrial replacement are reviewed and discussed in this paper.