title: 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.
abstract: 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.
  
  
  METHODS
  Retrospective, controlled cohort study.
  
  
  METHODS
  Academically affiliated, private fertility center.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  Statistical correlation of higher (allele-2) triple repeat counts with patients' clinical diagnoses and with FSH and AMH levels.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, USA. ngleicher@thechr.com
authors.forename: Norbert
authors.initials: N
authors.lastname: Gleicher
authors.forename: Andrea
authors.initials: A
authors.lastname: Weghofer
authors.forename: David H
authors.initials: DH
authors.lastname: Barad
mesh_terms: D000328:Adult; D054304:Anti-Mullerian Hormone / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D006801:Humans; D010053:Ovary / Q000503:physiopathology; D010865:Pilot Projects; D016649:Primary Ovarian Insufficiency / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D012189:Retrospective Studies; D019680:Trinucleotide Repeat Expansion
chemical_list: D054304:Anti-Mullerian Hormone; D005640:Follicle Stimulating Hormone; D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human