The Case For DHEA Supplementation In Patients With Diminished Ovarian Reserve!
Can medications improve egg quality? The conventional wisdom over the years has been that women are born with all of the eggs that they will ever have and that the quality of eggs diminishes as women age. As the quality of eggs diminishes, a greater number of eggs become chromosomally abnormal, fewer embryos will implant, and miscarriage rates increase. The progressive deterioration of egg quality has largely been perceived as progressive and irreversible. The concept that the aging single cell (the egg) is responsible for the decrease in implantation rates, and increase in miscarriage rates has been supported by our observations of the outcomes of egg donation treatment. With the substitution of an egg matured within the follicle environment of a younger woman (the egg donor), the pregnancy rate dramatically increases while miscarriage rates plummet. When studies using a supplement such as DHEA clearly demonstrate a significant reduction in miscarriage rates, what is happening? Could the conventional wisdom that eggs are incapable of being rejuvenated be incorrect? It may not be logical to presume that a damaged aged egg is capable of being repaired rendering it more likely to become fertilized and implant, while becoming less likely to result in miscarriage. However, we are left trying to explain how it could be that DHEA supplementation increases implantation rates and reduces miscarriage rates. One theory, expressed by Dr. Norbert Gleicher in “Defining ovarian reserve to better understand ovarian aging”, Reproductive Biology and Endocrinology 2011, 9:23, is that DHEA is working through its effect on eggs that are not engaged in the maturation process, but rather are contained in non-growing immature follicles. The theory is that the beneficial effects of DHEA that have been observed are the result of improvements in the follicular environment, and hence improved egg quality. Theoretically, once follicles are recruited and begin the process of maturation, the eggs within these follicles may be adversely affected by a poor quality ovarian environment.
It is well known that DHEA levels decline with advancing age. Recent animal studies have clearly demonstrated the importance of androgens (male hormones) to normal follicle development. Until very recently our attempts to improve fertility have focused on stimulation of the ovarian follicles that have been recruited and begun the process of maturation. Medications such as DHEA that most likely work at the level of the intra-ovarian environment may be the wave of the future with respect to improving egg quality especially in patients with diminished ovarian reserve. Studies are in progress with other supplements that work at the intracellular level such as CoenzymeQ10, testosterone, and growth hormone.
Since the safety profile of supplemental DHEA has been good thus far, it may be reasonable to introduce supplementation 2-3 months before planned treatment in patients with diminished ovarian reserve. Since the goal is to influence the follicular environment before maturation is underway, it is logical to begin early rather than later, theoretically before eggs have undergone damage. We are only beginning to gain an understanding of egg aging, and DHEA supplementation may lead to a greater understanding of this phenomena as well as cell aging in more general terms.
