AMH in women with diminished ovarian reserve: potential differences by FMR1 CGG repeat level

Purpose: We explored whether AMH, as a surrogate for oocyte supply, varies by FMR1 genotype in women diagnosed with diminished ovarian reserve (DOR), a subset of the Primary Ovarian Insufficiency phenotype. Research is inconsistent on the relationship between AMH and FMR1 repeat length, controlling for age.

Method: Seventy-nine cycling women diagnosed with DOR, and without a family history of fragile X syndrome, provided blood for FMR1 and AMH testing. DOR was defined as elevated FSH and/or low AMH and/or low antral follicle count, with regular menses. FMR1 CGG repeats were stratified by the larger allele <35 repeats (n = 70) v. ≥35 repeats (n = 9). Quadratic and linear models were fit to predict log (AMH) controlling for age. The AMH sample used as the outcome variable was drawn at a later date than the diagnostic AMH.

Results: Serum AMH concentration median was 0.30 ng/mL; Ages ranged from 26–43 years. A quadratic model (including age²) did not show a relationship with FMR1 CGG level (p-value = 0.25). A linear model of log (AMH), corresponding to an exponential decline of AMH with increasing age, was significantly different, and had a steeper slope, for women with ≥ 35 CGG repeats than women with < 35 repeats (p = 0.035).

Conclusion: Findings suggest a greater rate of follicular loss that starts at later ages in women with DOR and ≥ 35 CGG repeats.