Media Blog
Blog topic: Unwinding the Biological Clock
A recent article, written by Scottish colleagues, caused quite a stir in the media when they reported that by age 30, women carried only approximately 12% of their maximal prebirth follicle (egg) population in their ovaries (Hamish et al., PLoS ONE, 2/2/2010). What is most surprising about this article is, however, how surprised the media appear to be about these findings because they, of course, are anything but surprising.
We have known for a long time that follicle/egg numbers in human ovaries decline quite rapidly. Indeed, the story could be extended to the female embryo prior to birth because it is actually during that intrauterine time that most follicles/eggs are lost. Follicel/egg loss is, thus, a permanent feature from the time when follicle/eggs are created in embryonic life. The younger the female (including intrauterine life) the quicker and the larger the loss; the older she gets, the smaller and slower the deterioration.
CHR Research into Biological issue
Investigators at CHR have in recent years done extensive work on the concept of ovarian reserve (OR). OR is an acronym, widely used to describe the remaining fertility capacity of a woman’s ovaries. It, of course, mostly depends on how many follicles/eggs are left. It, therefore, has been known for many years that a woman’s OR declines as she ages because her follicle/egg numbers decline.
OR is, however, not only defined by smaller follicle/egg numbers; as women age their follicle/egg quality also deteriorates. Women, thus, face a double insult on their reproductive integrity as they age.
Investigators at CHR recently discovered that the decline in follicle/egg numbers is not the same in all women. It appears to differ, depending on how many triple nucleotide (CGG) repeats a woman carrier on her FMR1 (fragile X) gene. The normal number of such repeats in regards to OR appears to lie in the 26-32 range. Counts below or above negatively affect OR especially at younger ages, though, paradoxically, may actually improve OR at more advanced ages (Gleicher et al, RBMOnline; In press).
Issue is about Quality, not Quantity
It, therefore, would be a mistake to assume that all women age their ovaries in exactly the same way. There can be distinct differences and, indeed, approximately 10% of all women are believed to age their ovaries earlier that most other women.
In summary, there is nothing new in the paper by Hamish et al. All their data reiterate is that women, in contrast to males, age their ovaries and, therefore, face a relatively young age limit for reproduction.
All is, however, not bad news! CHR investigators recently also discovered that, while it does not appear possible to affect the decline in follicle/egg numbers with advancing female age, it may be possible to beneficially affect follicle/egg quality. They reached this conclusion after observing unusually low miscarriage rates in women with extremely poor OR who conceived after dehydroepiandrosterone (DHEA) supplementation.
Such low miscarriage rates suggest a positive effect of DHEA on ploidy (chromosomal abnormalities) and, therefore on follicle/egg quality. They argued that, since it appears unlikely that an already bad egg can be “‘rejuvenated,” current thinking about how eggs age within the ovary may have to be reconsidered: Instead, as is currently believed, aging eggs with advancing female age, aging ovarian environments appear the culprits that cause egg damage and increasing chromosomal abnormalities.
Under this new concept, the egg within unrecruited follicles does NOT age as women grow older. Once this egg is recruited into so-called folliculogenesis (a ca. 4.5 month long journey of follicular/egg maturation), this egg, however, enters at different female ages different quality of ovarian environments: the older the woman, the poorer. It is then this poor environment that negatively influences folliculogenesis and egg maturation, leading to poorer quality eggs (and embryos).
If confirmed, this CHR-developed concept would be revolutionary because it would suggest that, even though older women, of course, have much fewer follicles/eggs than younger women, those few they have could be matured through pharmacologically improved ovarian environments. Their maturing eggs would, therefore, be fewer but would lack the second insult of poor quality. As a consequence, older women would greatly improve their reproductive chances, even with fewer follicles and eggs available for folliculogenesis.
Conclusions from all of this are that numbers are important but quality always exceeds quantity in importance. If CHR investigators are correct in the interpretation of their DHEA data, then DHEA represents a first medication that improves ovarian environments in women with abnormal OR. Many other such medications can be expected in the future, giving older women with diminished OR a very promising future of expanded reproductive life spans.
To learn more about issues related to aging ovaries or the biological clock, please contact us.
Media contact: 212-994-4400 x.4491
CHR's Media Blog is a compilation of potential story ideas gathered from infertility-related news, our research, and our opinion to facilitate open communication with the public on this increasingly relevant field of medicine.
Editors, reporters and producers are invited to contact CHR for background or clarification on any content posted here. Also, our team of fertility experts has considerable experience providing comments for publication on infertility-related subjects and participating on broadcast panels to share our expertise.
