Objective: To determine to what degree the number of triple Cytosine/Guanine/Guanine (CGG) repeats on the FMR1 (fragile X) gene correlate with specific ovarian reserve parameters, and potentially facilitate infertility diagnosis.
Design: Retrospective cohort study.
Setting: Academically affiliated, private infertility center in New York City.
Population: One hundred fifty-eight consecutive women, presenting to an infertility center.
Methods: Triple CGG repeat counts on the FMR1 gene were correlated with baseline follicle stimulating hormone (FSH) and anti-Mullerian hormone (AMH), and compared to the distribution reported in the literature for general populations.
Main outcome measures: Distribution of CGG counts in infertile vs. general populations and correlation between CGG counts and ovarian reserve parameters.
Results: Infertile women demonstrated in both FMR1 alleles a mild shift toward higher CGG counts. In the investigated range up to 55 CGG repeats, counts inversely correlated with AMH (R (2)=0.21; p<0.001), though not with FSH, attributable to women <38 years (R (2)=0.26; p<0.001). Up to age 40, women with <35 triple repeats demonstrated higher AMH levels than those with 35-50 repeats [F (1, 87) = 5.3, p=0.025]. Counts between 35 and 50 repeats correlated inversely to AMH (R (2)=0.41; p<0.013).
Conclusions: Premature ovarian senescence and infertility in ranges up to 55 triple CGG repeats are associated with increasing triple CGG numbers on the FMR1 gene. The number of CGG repeats on the FMR1 gene appears to represent a potentially useful new test in diagnosing risk toward diminished ovarian reserve and female infertility.