Genetic associations with diminished ovarian reserve: a systematic review of the literature.
OBJECTIVE
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.
Obstetrics & Gynecology Department, St Luke's Roosevelt Hospital Center, 1000 Tenth Ave, Suite 10 C, New York, NY, 10019, USA.
Alexis D
AD
Greene
George
G
Patounakis
James H
JH
Segars
D000818:Animals; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D051379:Mice; D065851:Ovarian Reserve / Q000235:genetics*; D016649:Primary Ovarian Insufficiency / Q000235:genetics*