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 3394 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 with overt POI. Compared with controls, FMR1 gene premutation is significantly associated with overt POI (OR = 8.13; 95% CI: 4.35-15.19; p < .00001), whereas there was no significant correlation between intermediate repeat length and overt POI (OR = 0.86; 95% CI: 0.62-1.18; p = .34). Seven studies, representing 1347 patients and 1948 controls, were eligible for evaluation of the premutation and intermediate repeat length in occult POI. The association between premutation and occult POI was significant (p < .00001), with a pooled fixed effects OR of 11.32 (4.45-28.80), and no significant correlation of intermediate size to occult POI was found in the case-control comparison (OR = 1.00; 95% CI: 0.68-1.47; p = .98). 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.