Does the presence of AGG interruptions within the CGG repeat tract have a protective effect on the fertility phenotype of female FMR1 premutation carriers?

Purpose: While FMR1 premutation carriers (CGG 55–200) were shown to have reduced success with IVF treatment (lower oocyte yield), studies reporting on the association between the number of CGG repeats and patients’ response to controlled ovarian hyperstimulation (COH) are inconsistent. In the present study, we aim to explore whether the number of CGG repeats in women with premutation in FMR1 gene, undergoing COH for IVF, correlates with COH variables and whether the number of AGG interruptions may function as a “protective factor” by improving the ovarian response to COH. Methods: Retrospective study, in an academic IVF-PGD unit. Fifty-seven consecutive FMR1 premutation carriers who underwent 285 IVF treatment cycles were included. The numbers of CGG repeats and AGG interruptions were retrieved and correlated to the demographics and COH variables. Results: There were no significant association between the numbers of CGG or the AGG interruptions and the number of oocyte retrieved or the peak estradiol levels. The lack of association was also observed when including all the IVF treatment cycles or only the first or last IVF treatment cycle. Moreover, no associations were found between the number of CGG repeats or AGG interruptions and other COH variables, i.e., duration of stimulation, the total dose of gonadotropin used, or the number of top-quality embryos. Conclusions: No associations were observed between the number of CGG repeats or AGG interruptions and any of the COH variables. Further studies are required to identify early biomarkers of POI to empower FMR1 premutation carriers with risk assessment tools to consider procedures such as fertility preservation.