A pilot study of premature ovarian senescence: I. Correlation of triple CGG repeats on the FMR1 gene to ovarian reserve parameters FSH and anti-Müllerian hormone

Objective: To assess whether the number of triple CGG expansion of the FMR1 (fragile X) gene, known to correlate at premutation (55-200 repeats) and full mutation (>200 repeats) ranges with risk toward premature ovarian failure (POF), also correlates with milder forms of premature ovarian senescence. Design: Retrospective, controlled cohort study. Setting: Academically affiliated, private fertility center. Patient(s): Forty consecutive, new infertility patients, of which 11 presented with a primary diagnosis of repeated pregnancy loss (controls), 23 with prematurely elevated, age-specific baseline follicle stimulating hormone (FSH) levels (i.e., premature ovarian aging, POA) and 6 with POF. Intervention(s): Determination of number of triple CGG repeats on both alleles of FMR1 gene and of FSH and anti-Müllerian hormone (AMH) levels as a reflection of ovarian reserve. Main Outcome Measure(s): Statistical correlation of higher (allele-2) triple repeat counts with patients' clinical diagnoses and with FSH and AMH levels. Result(s): Mean triple CGG counts increased in parallel to increasing severity of premature ovarian senescence. Repeat expansion numbers at all levels correlated statistically to FSH. An AMH level of <1.0 ng/mL statistically correlated to >32 triple repeats. Conclusion(s): Over 30 triple CGG repeats denote increased risk (and severity) toward premature ovarian senescence in parallel to increasing expansions. Numbers, considered well within the normal range, therefore already denote risk, suggesting that CGG repeats may represent a new test to predict ovarian function and assess female infertility.