Association between the FMR1 CGG repeat lengths and the severity of idiopathic primary ovarian insufficiency: a meta analysis

Aim Reports on the association of the CGG repeat length in the FMR1 gene with the severity of idiopathic POI are inconclusive. Therefore, a meta analysis was performed to investigate the relationship between the expansion of repeat CGG and idiopathic POI risk.Methods Up to January 2019, 18 case-control or cohort studies involving 3022 idiopathic POI patients and 8461 controls were included for meta analysis.Results Thirteen studies, including 2047 cases and 6912 controls, met our criteria for the assessment of the premutation and intermediate repeat length in patients patients with POI. Compared with controls, FMR1 gene premutation is significantly associated with POI (OR = 8.13; 95% CI: 4.35–15.19; p < .00001), whereas there was no significant correlation between intermediate repeat length and POI (OR = 0.86; 95% CI: 0.62–1.18; p = .34). Six studies, representing 975 patients and 1749 controls, were eligible for evaluation of the premutation and intermediate repeat length in diminished ovarian reserve (DOR). The association between premutation and DOR was significant (OR=14.87; 95% CI:5.20-42.52; p < 0.00001), while no significant correlation of intermediate size to DOR was found in the case-control comparison (OR = 0.98; 95% CI: 0.65–1.47; p = 0.93).Conclusion There is a close association between premutation of the FMR1 gene and increased susceptibility to idiopathic POI of each stage and no correlation between intermediate repeat length of the FMR1 gene and the severity of idiopathic POI.