“…Data regarding Ca 2+ ionophore use with ICSI and its relationship to human oocyte competence, embryo development, and neurodevelopmental outcomes in children appear reassuring [17,37,38], but immature oocytes or mature oocytes failing to fertilize may harbor inherent defects that potentially harm the embryo [39]. Also relevant is the potential impact of Ca 2+ ionophore use with ICSI on the rates of miscarriage, genetic abnormalities, and minor as well as major congenital malformations [15,40]. Theoretically, nonphysiological patterns of calcium oscillation in artificially activated oocytes might perturb calcium-mediated signal transduction, mitochondrial respiration, developmental programming, or epigenetic events in ways that alter postimplantation embryo development [41,42].…”