The recent development of the CRISPR/Cas9 technology as a versatile and efficient tool has enabled human germline gene editing and can be applied to correct abnormal DNA sequences during fertilization. However, its future implementation for therapeutic approaches is still heavily debated, not only from an ethical perspective, but also because many uncertainties regarding the safety and efficiency of the technique still exist. More specifically, two recent studies described that, after application of classical CRISPR/Cas9 in human embryos, chromosomal constitution was severely affected, leading to loss of heterozygosity, which is the (partial) loss of the chromosomal contribution of both parents to the cell. The origin of this loss of heterozygosity is however still under investigation, but it has already been hypothesized that DNA breaks generated by the CRISPR/Cas9 technology catalyze this phenomenon. For these reasons, alternative CRISPR/Cas9 methods for DNA mutational repair that function without the generation of DNA breaks (base and prime editing), which are currently almost unexplored in human embryos, are of interest. In this proposal, both the classical and alternative CRISPR/Cas9 methods will be directly compared in terms of efficiency and safety, next to attempts to deliver the CRISPR/Cas9 tools directly in the sperm, aiming for the correction of infertility-related PLCZ1 mutations, as a proof-of principle.