What are the analytical and clinical validity and the clinical utility of in vitro screening of embryos by whole-genome sequencing? At present there are still many limitations in terms of analytical and clinical validity and utility and many ethical questions remain. Whole-genome sequencing of IVF/ICSI embryos is technically possible. Many loss-of-function mutations exist in the general population without serious effects on the phenotype of the individual. Moreover, annotations of genes and the reference genome are still not 100 correct. We used publicly available samples from the 1000 Genomes project and Complete Genomics, together with 42 samples from in-house research samples of parents from trios to investigate the presence of loss-of-function mutations in healthy individuals. In the samples, we looked for mutations in genes that are associated with a selection of severe Mendelian disorders with a known molecular basis. We looked for mutations predicted to be damaging by PolyPhen and SIFT and for mutations annotated as disease causing in Human Genome Mutation Database (HGMD). More than 40 of individuals who can be considered healthy have mutations that are predicted to be damaging in genes associated with severe Mendelian disorders or are annotated as disease causing. The analysis relies on current knowledge and databases are continuously updated to reflect our increasing knowledge about the genome. In the process of our analysis several updates were already made. At this moment it is not advisable to use whole-genome sequencing as a tool to set up health profiles to select embryos for transfer. We also raise some ethical questions that have to be addressed before this technology can be used for embryo selection. This research was supported by: Research Council KU Leuven (Projects: GOA/10/09 MaNet, KUL PFV/10/016 SymBioSys); Flemish Government: IWT Agency for Innovation by Science and Technology (Project: OO ExaScience Life), Hercules Foundation (Project: Hercules III PacBio RS), iMinds Future Health Department (Projects: SBO 2013, ArtD Instance), Flemish tier-1 Supercomputer (Project: VSC Tier 1 Exome sequencing); K.H. was supported by the Centre for Society and Life Sciences (CSG, non-profit organization) (Project number: 70.1.074). None of the authors has any conflict of interest to declare. N/A.