Human Growth Hormone to Enhance Ovarian Response: Does it Work?
There is an ever increasing tendency for women to delay childbearing. This has contributed to a significant rise in the number of women seeking fertility treatment. Alas, the older a woman gets, the more difficult it becomes for her to conceive – either naturally or through assisted reproductive technology (ART). This is due to an inevitable increase in egg aneuploidy (numerical chromosome irregularity) and to diminishing ovarian reserve (DOR) that accompanies advancing age. Although less significant than the increase in egg aneuploidy, advancing age and DOR are both also associated with non-chromosomal egg deterioration involving a decline in mitochondrial activity as well as a progressive reduction in the ability of the granulosa cells that line the inside of the follicle to respond to FSH stimulation.
Getting older women and those with DOR to respond optimally to ovarian stimulation often represents a serious challenge. Many will fail to respond adequately to standard ovarian stimulation regimens, and will require a very individualized and strategic approach to ovarian stimulation — one that regulates and limits exposure of ovarian follicles to LH-induced local male hormones (predominantly testosterone). This, in my opinion, is best addressed by using a modified long pituitary down regulation protocol with an agonist (e.g. Lupron/Buserelin/Superfact) coming off a birth control pill. Thereupon, as soon as the period starts, the agonist is supplanted by an antagonist (e.g. Cetrotide/Orgalutron/Ganirelix) and stimulation with recombinant FSH (Follistim/Gonal-F/Puregon) along with a small amount of menotropin (e.g. Menopur) until optimal follicle development prompts initiation of the hCG trigger.
We have reported on the finding that in some women with very severe DOR, the addition of intramuscular administration of estradiol valerate (i.e. Delestrogen) prior to and during gonadotropin stimulation (i.e. “estrogen priming”) is capable of further enhancing follicle growth.
Several researchers have shown that the administration of human growth hormone (HGH), as an adjunct to ovarian stimulation, enhances follicle response in older women and those with severe DOR. Two basic mechanisms have been proposed: a) enhanced response to gonadotropins by up-regulating the FSH receptors on follicular granulosa cells and, b) a direct effect of HGH on the egg itself whereby mitochondrial activity is enhanced. Human eggs do have HGH receptors but eggs retrieved from older women show decreased expression of such receptors (as well as a reduced amount of functional mitochondria) when compared with those derived from younger women. It was recently shown that older women treated with HGH showed a marked increase in functional mitochondria in their eggs along with improved egg quality.
There is now sufficient evidence to support the selective use of HGH treatment to enhance ovarian response to gonadotropin therapy in older women and those who have severely diminished ovarian reserve (DOR).
The description of several treatment protocols for HGH administration is beyond the scope of this blog and should be discussed with the treating physician.