Capalbo A, Fabiani M, Caroselli S, et al. - Studies have described that nearly 2–4% of couples are at risk of conceiving a child with an autosomal recessive or X-linked genetic disorder. In recent years, the creation of Expanded Carrier Screening (ECS) panels for the simultaneous detection of multiple recessive disorders has been enabled by the increasing cost-effectiveness of genetic diagnostic techniques. Herein , researchers aimed at determining the clinical validity and utility of preconception ECS application on the management of prospective parents. Of 3,877 analyzed individuals without a family history of genetic conditions, 1,212 were gamete donors and 2,665 were patients planning on conceiving from both the IVF and the natural conception group. American College of Obstetrics and Gynecology ACOG-recommended criteria (prevalence, carrier rate, severity) were followed to develop a focused ECS panel, including highly penetrant severe childhood conditions. When both partners carried an autosomal recessive pathogenic/likely pathogenic variant (PLP) on the same gene or when the woman was a carrier of an X-linked PLP variant, couples were defined at-risk. PLP for at least one of the genes tested was identified in a total of 402 individuals (10.4%). Among 766 tested couples, 173 exhibited one carrier partner (22.6%), whereas 20 couples (2.6%) were noted to be at raised risk. In this study, the clinical utility of ECS in the preconception space in IVF and general population was demonstrated by the high detection rate of at-risk couples and the high proportion opting for IVF/preimplantation genetic testing treatment.