Premature Ovarian Aging
CHR investigators have been conducting extensive genetic research on ovarian reserve in order to better understand how ovarian aging occurs, and to develop a method of early diagnosis and prediction of POA development.
Thanks to research at CHR, a young woman’s future fertility can be predicted based on her FMR1 genotype.
Significant evidence from animal studies suggests that ovarian reserve is genetically controlled. How this genetic control works in humans has, however, so far not been determined. Over the last few years, CHR investigators have extensively researched and published on effects of the FMR1 (fragile X mental retardation 1) gene on ovarian reserve. Our research has revealed that this gene, which is well known for its neuro-psychiatric consequences, also plays a crucial role in ovarian aging.
CHR research has identified that, for ovarian function, the “normal” range of CGG repeats on the FMR1 gene is 26 to 34, with the median at 30, as shown in the figure below [modified from Gleicher et al. Reprod Biomed Online 2010;20(6):768-75.]. This “normal” range is specific to ovarian function, and separate from the well known “normal” range for the neuro-psychiatric risks.
Probably most importantly, CHR investigators defined new FMR1 genotypes and sub-genotypes, each associated with specific ovarian aging patterns. Because each woman has two alleles (copies) of the FMR1 gene, there are various genotypes and sub-genotypes, based on whether neither, one or both of the alleles are in the normal range, and if abnormal, high abnormal or low abnormal.
For example, a CHR publication in the prestigious online medical journal PLoS ONE identified the FMR1 sub-genotype "het-norm/low" to be associated with almost 50% lower pregnancy rates after IVF. [Gleicher et al, PLoS ONE 2010:16;5(12):e15303]. Implications of these findings go beyond fertility treatment and IVF because, based on a young girl's FMR1 genotype, one can now predict reasonably well how she, likely, will age her ovaries.
We are only at the beginning of a better understanding of the ovarian aging process. One can foresee that this new knowledge about genetic regulation of ovarian aging via the FMR1 gene will lead to better diagnostic tools and, therefore, chances for early intervention. For example, if a young woman knows that her ovarian function may prematurely decline, exposing her to the risk of early menopause, she can take proactive steps to preserve her fertility.
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Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned specialist in reproductive endocrinology, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.