Abstract
Fragile X syndrome is a monogenic disorder caused by the expansion of CGG trinucleotide repeats in the fragile X mental retardation 1 (FMR1) gene and is a major cause of inherited intellectual disability and reproductive impairment. Preimplantation genetic testing for monogenic disorders (PGT-M) has become an important strategy in assisted reproduction to prevent the transmission of FMR1-related disorders. This narrative review aimed to summarize current evidence on the molecular basis, technical approaches, clinical outcomes, and challenges associated with PGT-M for FMR1 CGG repeat expansions. A literature search was performed in the PubMed database, including English-language original studies, clinical investigations, and reviews. The reviewed studies demonstrate that advances in multiplex PCR, linked-marker analysis, and next-generation sequencing have significantly improved diagnostic accuracy, overcoming earlier limitations related to CGG repeat analysis, allele dropout, and mosaicism. Although women carrying FMR1 premutations frequently present with diminished ovarian reserve and reduced response to ovarian stimulation, pregnancy and live birth rates per embryo transfer are comparable to those of non-carriers when individualized stimulation protocols are applied. The combined application of PGT-M and Preimplantation Genetic Testing for Aneuploidy may be considered in selected clinical scenarios to optimize embryo selection, although indications should be individualized. In addition to its clinical benefits, PGT-M raises ethical, psychological, and economic considerations, emphasizing the importance of genetic counseling in reproductive decision-making. Overall, PGT-M represents a safe and effective tool in assisted reproduction for couples at risk of transmitting FMR1 related disorders, with growing relevance in clinical practice and public health.