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Evidence of an age-related correlation of ovarian reserve and FMR1 repeat number among women with “normal” CGG repeat status

  • Genetics
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

An Erratum to this article was published on 16 November 2015

Abstract

Purpose

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.

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Authors and Affiliations

  1. 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

    Stephanie L. F. Gustin & Valerie L. Baker

  2. Quantitative Sciences Unit, Center for Biomedical Informatics Research, Stanford University School of Medicine, 1070 Arastradero Road, Palo Alto, CA, 94304, USA

    Victoria Y. Ding & Manisha Desai

  3. Clinical Research Division, ReproSource, Inc, 300 Tradecenter, Suite 6540, Woburn, MA, 01801, USA

    Benjamin Leader

Authors
  1. Stephanie L. F. Gustin
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  2. Victoria Y. Ding
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  3. Manisha Desai
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  4. Benjamin Leader
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  5. Valerie L. Baker
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Corresponding author

Correspondence to Stephanie L. F. Gustin.

Additional information

Capsule Using novel multivariate regression models, we observed a statistically significant correlation ofovarian reserve and FMR1 CGG repeat number in women with <55 CGG repeats. Our data suggests that increasing CGG repeat number within the normal rage is associated with a more rapid decline in ovarianreserve.

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Supplemental Figure 1

Comparing the association of summary measures Sum, Max, Gap, and Min with log(AMH). Fitting interaction terms in a linear model reveals a “trumpet” phenomenon for “Sum,” “Max,” and “Min”. The slope of each individual gray line varies based on age, such that the younger women have a positive association, and the older women have a negative association as the CGG repeat length increases. Gap does not exhibit this similar pattern, as it is not significantly associated with AMH at any CGG repeat length. The red line is the overall effect, without controlling for age. Gray lines darken with each increasing age category (<=30, 30–35, >35) (DOC 57 kb)

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Gustin, S.L.F., Ding, V.Y., Desai, M. et al. Evidence of an age-related correlation of ovarian reserve and FMR1 repeat number among women with “normal” CGG repeat status. J Assist Reprod Genet 32, 1669–1676 (2015). https://doi.org/10.1007/s10815-015-0577-0

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  • DOI: https://doi.org/10.1007/s10815-015-0577-0

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