Association of skewed X-chromosome inactivation with FMR1 CGG repeat length and anti-Mullerian hormone levels: A cohort study

David H. Barad, Sarah Darmon, Andrea Weghofer, Gary J. Latham, Qi Wang, Vitaly A. Kushnir, David F. Albertini, Norbert Gleicher

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Background: Premutation range CGGn rep5/3/2017 5:00:21 PMward primary ovarian insufficiency (POI), also called premature ovarian failure (POF). This prospective cohort study was undertaken to determine if X-chromosome inactivation skew (sXCI) is associated with variations in FMR1 CGG repeat length and, if so, is also associated with age adjusted antimüllerian hormone (AMH) levels as an indicator of functional ovarian reserve (FOR). Methods: DNA samples of 58 women were analyzed for methylation status and confirmation of CGGn repeat length. Based on previously described FMR1 genotypes, there were 18 women with norm FMR1 (both alleles in range of CGG n=26-34), and 40 women who had at least one allele at CGGn<26 or CGG>34 ( not-norm FMR1). As part of a routine evaluation of ovarian reserve, patients at our fertility center have their serum AMH assessed at first visit. Regression models were used to test the association of ovarian reserve, as indicated by serum AMH, with sXCI. Results: sXCI was significantly lower among infertility patients with norm FMR1 (6.5±11.1, median and IQR) compared to those with not-norm FMR1 (12.0±14.6, P=0.005), though among young oocyte donors the opposite effect was observed. Women age >30 to 38years old demonstrated greater ovarian reserve in the presence of lower sXCI as evidenced by significantly higher AMH levels (GLM sXCI_10%, f=11.27; P=0.004). Conclusions: Together these findings suggest that FMR1 CGG repeat length may have a role in determining X-chromosome inactivation which could represent a possible mechanism for previously observed association of low age adjusted ovarian reserve with FMR1 variations in repeat length. Further, larger, investigations will be required to test this hypothesis.

Original languageEnglish
Article number34
JournalReproductive Biology and Endocrinology
Issue number1
StatePublished - 28 Apr 2017
Externally publishedYes


  • AMH
  • FMR1
  • Methylation
  • Ovarian reserve
  • POF
  • Primary Ovarian Insufficiency
  • Skewed X-chromosome inactivation


Dive into the research topics of 'Association of skewed X-chromosome inactivation with FMR1 CGG repeat length and anti-Mullerian hormone levels: A cohort study'. Together they form a unique fingerprint.

Cite this