title: Evidence of an age-related correlation of ovarian reserve and FMR1 repeat number among women with "normal" CGG repeat status.
abstract: OBJECTIVE
  The objective of this analysis is to examine the relationship between Fragile X Mental Retardation 1 gene (FMR1) cytosine-guanine-guanine (CGG) repeat number and ovarian reserve, with a particular focus exclusively on the range of CGG repeat number below the premutation (PM) range (<55 CGG repeats).
  
  
  METHODS
  Our study included female patients who underwent assessment of FMR1 CGG repeat number and serum anti-Mullerian hormone (AMH) in 2009-2014. To examine the association between FMR1 repeat number and serum AMH, we created three summary measures of CGG repeat number for the two alleles-"Sum," "Max," and "Gap" (absolute difference). Using multivariable regression models, controlling for age, we then analyzed the impact of these summary measures on AMH.
  
  
  RESULTS
  A total of 566 patients were included in our study. Using multivariable regression models, we found that the relationship between CGG repeat number and AMH differed depending on age. Specifically, in younger women, AMH increased by 7-8 % (Sum p < 0.01, Max p = 0.04) for every 1 unit increase in CGG repeat number. In contrast, starting at age 40, there was a 3 to 5 % decline in AMH for every 1 unit increase in CGG repeat number (Sum p < 0.01, Max p = 0.04).
  
  
  CONCLUSIONS
  This is the first study to report a statistically significant correlation of ovarian reserve and CGG repeat number in women with <55 CGG repeats. Although these women are generally considered to have a normal phenotype, our data suggest that increasing CGG repeat number within this normal range is associated with a more rapid decline in ovarian reserve.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Stanford University School of Medicine, 900 Welch Road, Suite 20, Palo Alto, CA, 94034, USA. sfisher@stanford.edu.
authors.forename: Stephanie L F
authors.initials: SL
authors.lastname: Gustin
authors.affiliation: Quantitative Sciences Unit, Center for Biomedical Informatics Research, Stanford University School of Medicine, 1070 Arastradero Road, Palo Alto, CA, 94304, USA.
authors.forename: Victoria Y
authors.initials: VY
authors.lastname: Ding
authors.affiliation: Quantitative Sciences Unit, Center for Biomedical Informatics Research, Stanford University School of Medicine, 1070 Arastradero Road, Palo Alto, CA, 94304, USA.
authors.forename: Manisha
authors.initials: M
authors.lastname: Desai
authors.affiliation: Clinical Research Division, ReproSource, Inc, 300 Tradecenter, Suite 6540, Woburn, MA, 01801, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Leader
authors.affiliation: Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Stanford University School of Medicine, 900 Welch Road, Suite 20, Palo Alto, CA, 94034, USA.
authors.forename: Valerie L
authors.initials: VL
authors.lastname: Baker
mesh_terms: D000293:Adolescent; D000328:Adult; D054304:Anti-Mullerian Hormone / Q000097:blood* / Q000235:genetics; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D006801:Humans; D008423:Maternal Age; D008875:Middle Aged; D015999:Multivariate Analysis; D065851:Ovarian Reserve / Q000235:genetics*; D018911:Trinucleotide Repeats; D055815:Young Adult
chemical_list: D054304:Anti-Mullerian Hormone; D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human
keywords: AMH; CGG repeat; FMR1; Ovarian reserve