Empty follicle syndrome (EFS) is characterized by a lack of retrieved oocytes in the presence of multiple follicle development, in both natural and stimulated cycles. The aim of the present case report is to point out the possibility of genetic factors that could be responsible for some occurrences of EFS. Two sisters with moderate deafness underwent controlled ovarian hyperstimulation and IVF/ICSI cycles at the same centre. During all three cycles there were normal follicular development, estradiol levels and bio-available hCG plasma levels, but no oocytes and cumulus-corona complexes were retrieved, despite second hCG injections. These cases may represent an inherited condition of EFS with hearing loss with genetic factors affecting both the aetiology of EFS and the hearing loss.