Cheung S, Xie P, Parrella A, et al. - Via this prospective cohort study, researchers sought to determine the gamete responsible for complete fertilization failure with intracytoplasmic sperm injection (ICSI) and to treat it with using a newly proposed assisted gamete treatment (AGT). Among 114 included couples with an adequate number of spermatozoa for ICSI and a fertilization rate of ≤ 10%, after controlling for maternal age, the phospholipase Cζ (PLCζ) assay indicated that 52 couples were confirmed negative for sperm-related oocyte activation deficiency (OAD), indicating oocyte-related factors in their failed fertilization cycles. Treatment was provided with one of two AGT protocols, AGT-initial or AGT-revised, to couples in a subsequent attempt that was compared with their historical cycle. In couples with an oocyte-related OAD, successful fertilization, term pregnancies, and deliveries were observed in correlation with tailoring the superovulation protocol. In couples with a sperm-related OAD as evaluated by PLCζ assay, mouse oocyte activation test, and the evaluation of gene mutations and function, AGT was successful. An even higher fertilization rate was obtained with the AGT-revised protocol than the AGT-initial protocol, leading to the birth of healthy offspring in all couples who attained a clinical pregnancy.