Ovarian reserve determinations suggest new function of FMR1 (fragile X gene) in regulating ovarian ageing

Norbert Gleicher, Andrea Weghofer, David H. Barad

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


With regard to ovarian reserve, 26-34 triple CGG repeats on the FMR1 gene denote 'normal'. This study explores whether two-allele analyses reflects risk towards diminished ovarian reserve based on age in consecutive patients (34 oocyte donors and 305 infertility patients), longitudinally and cross-sectionally. Box and whisker plots confirmed the normal range of CGG counts. Patients were then defined as normal with both alleles in range, as heterozygous with one allele outside and as homozygous with both alleles outside of range. Ovarian reserve was assessed by anti-Müllerian hormone (AMH). Normals at young ages exhibited significantly higher AMH concentrations than either heterozygous or homozygous females (P = 0.009). By approximately age 35, heterozygous women have higher AMH concentrations than normal women, while homozygous women exceed normal women shortly before age 50 years. These data support a control function of the FMR1 gene over ovarian reserve, thus defining life-long ovarian reserve patterns. Heterozygous and homozygous abnormal CGG counts reduce ovarian reserve at younger ages and improve ovarian reserve at older ages. They, thus, at expense of reduced fertility in the young, preserve fertility into older age. This function of potential evolutionary importance may explain the preservation of the FMR1 gene despite its, at times, severe neuropsychiatric risks.

Original languageEnglish
Pages (from-to)768-775
Number of pages8
JournalReproductive BioMedicine Online
Issue number6
StatePublished - Jun 2010
Externally publishedYes


  • Anti-Müllerian hormone (AMH)
  • FMR1 (fragile X) gene
  • Infertility
  • Ovarian reserve


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