One of the most frustrating problems in assisted reproductive technology, particularly in-vitro fertilization (IVF), is the poor responder to stimulation of the ovary in order to produce a reasonable number of eggs. These ‘poor responders’ mainly, but not exclusively, are comprised of women at the older end of the fertile age group. They are often more than 40 years old, have raised FSH levels and low AMH concentrations, all of which reflect a low ovarian reserve of available eggs.
The number of strategies that have been tried in order to improve the number of eggs available for fertilization indicate the lack of success of any single one of them to date. These include the addition to the stimulation protocol of growth hormone, LH, testosterone, letrozole and aspirin and the use of very high doses of gonadotrophins and flare-up, stop and ultra-short protocols of GnRH agonists!
One of the latest suggestions is the supplementation of DHEA (dihydroepiandrosterone), usually in doses of 75mg tablets/day for periods ranging from 1-6 months before and during the treatment cycle. In the USA, DHEA may be bought over the counter and has been very widely advertised as the drug that rejuvenates and improves a vast number of bodily functions in an aging population. Little wonder that it was taken up as the solution for rejuvenating ovarian function.
DHEA is a weak androgen hormone, physiologically produced mainly by the adrenal gland. There is, therefore, some justification in thinking that it may improve the functions of the ovary as androgens are thought to encourage the growth of follicles from their primitive stage to a stage which makes them available as candidates for ovulation. Strong evidence that DHEA can solve the problem of the poor responder is sadly still lacking but despite this, as so often happens when miracle cures are claimed for previously unsolvable problems, many are administering DHEA willy-nilly.
Most of the observational evidence of improvement in ovarian response and increased pregnancy rates by DHEA has come from one group in the USA. They have also published that DHEA improves the chromosomal make up of the embryo (reduces aneuploidy and therefore miscarriage rates) and decreases AMH levels. Although they attempted to start a randomized controlled trial they reported that it was abandoned as all patients demanded to receive DHEA! Fortunately, a number of research groups, obviously with a less demanding population of poor responders, are presently performing randomized controlled trials with sufficient numbers to examine whether DHEA can really help this difficult group of patients. However, on present evidence, it is difficult to escape the conclusion that eggs that do not exist any longer cannot be stimulated!
Prof Roy Homburg