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Genetic associations with diminished ovarian reserve: a systematic review of the literature

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Abstract

Purpose

Diminished ovarian reserve (DOR) affects 10 % of women seeking fertility treatment. Although it is much more prevalent than premature ovarian failure, less is known about its etiology. The purpose of this article is to review the possible genetic causes of, and associations with, pathologic DOR.

Methods

A systematic review was conducted using PubMed from 1966 through November 2013.

Results

Twenty-one articles identified genes associated with DOR: one gene mutation (FMR1), three polymorphisms (GDF9, FSHR, and ESR1), and seven genes differentially expressed between women with DOR and controls (AMH, LHCGR, IGF1, IGF2, IGF1R, IGF2R and GREM1). Six candidate genes were discovered in mice, including Foxl2, Gdf9, Bmp15, Aire, Wnt4, and Gpr3. Two case reports of chromosomal translocations were also identified.

Conclusions

While the etiology of pathologic DOR is likely multifactorial, it is possible that many cases attributed to an idiopathic cause may have a genetic component. Larger studies are needed to expose the impact gene mutations, polymorphisms, and epigenetics have on pathologic DOR.

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Acknowledgments

We would like to thank Dr. Alan DeCherney and Dr. Peter McGovern for their support.

Funding

This research was supported, in part, by the Program in Reproductive and Adult Endocrinology, NICHD, NIH and ZIA HD-008737- to JHS.

Conflicts of interest

The authors have no conflicts to disclose.

Author information

Authors and Affiliations

  1. Obstetrics & Gynecology Department, St Luke’s Roosevelt Hospital Center, 1000 Tenth Ave, Suite 10 C, New York, NY, 10019, USA

    Alexis D. Greene

  2. Program in Reproductive and Adult Endocrinology, NICHD, NIH, 10 Center Drive, Bethesda, MD, 20892, USA

    George Patounakis & James H. Segars

Authors
  1. Alexis D. Greene
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  2. George Patounakis
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  3. James H. Segars
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Corresponding author

Correspondence to James H. Segars.

Additional information

Capsule Diminished ovarian reserve (DOR) can be a normal process of aging. In other cases DOR occurs at earlier ages, pathologic DOR, a multifactorial condition which may be caused by genetic or epigenetic anomalies. We review what is currently known about the contribution of genetic causes to the clinical condition of DOR.

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Greene, A.D., Patounakis, G. & Segars, J.H. Genetic associations with diminished ovarian reserve: a systematic review of the literature. J Assist Reprod Genet 31, 935–946 (2014). https://doi.org/10.1007/s10815-014-0257-5

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