title: Intra-individual stability over time of standardized anti-Mullerian hormone in FMR1 premutation carriers.
abstract: BACKGROUND
  Carriers of a premutation (CGG repeat length 55-200) in the fragile X mental retardation (FMR1) gene are at risk for primary ovarian insufficiency (FXPOI). The anti-Müllerian hormone (AMH) level acts as a useful marker of ovarian follicle reserve and, thus, may serve to predict when this ovarian reserve becomes too low to sustain ovarian function. We investigated the intra-individual variation of AMH levels over time for premutation carriers compared with non-carriers.
  
  
  METHODS
  We determined AMH levels in blood samples from 240 women ascertained through fragile X families, of which 127 were premutation carriers and 113 were non-carriers. Linear mixed models were used to assess the effect of age and premutation status on AMH levels and to determine a modeled AMH value. The stability over time of the deviation of observed AMH levels from modeled levels, referred to as standardized AMH values, was assessed through correlation coefficients of 41 longitudinal samples.
  
  
  RESULTS
  At all ages, premutation carriers exhibited lower AMH levels. For all women, AMH was found to decrease by 10% per year. The added effect of having a premutation decreased AMH levels by 54%. The deviation of an individual's AMH level from the modeled value showed a reasonable intra-individual correlation. The Pearson correlation coefficient of two samples taken at different ages was 0.36 (P = 0.05) for non-carriers and 0.69 (P = 0.01) for carriers.
  
  
  CONCLUSIONS
  We developed a unique standardized AMH value, taking FMR1 premutation status and the subject's age into account, which appears to be stable over time and may serve as a predictor for FXPOI after further longitudinal assessment.
authors.affiliation: Department of Obstetrics and Gynecology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. m.spath@obgyn.umcn.nl
authors.forename: M A
authors.initials: MA
authors.lastname: Spath
authors.forename: T B
authors.initials: TB
authors.lastname: Feuth
authors.forename: E G
authors.initials: EG
authors.lastname: Allen
authors.forename: A P T
authors.initials: AP
authors.lastname: Smits
authors.forename: H G
authors.initials: HG
authors.lastname: Yntema
authors.forename: A Geurts
authors.initials: AG
authors.lastname: van Kessel
authors.forename: D D M
authors.initials: DD
authors.lastname: Braat
authors.forename: S L
authors.initials: SL
authors.lastname: Sherman
authors.forename: C M G
authors.initials: CM
authors.lastname: Thomas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging; D054304:Anti-Mullerian Hormone / Q000097:blood*; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D016649:Primary Ovarian Insufficiency / Q000209:etiology* / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D054304:Anti-Mullerian Hormone; D051860:Fragile X Messenger Ribonucleoprotein 1