Androgens: Improving Response to Ovarian Stimulation prior to IVF
Ovarian stimulation is the most significant improvement in IVF. Response to stimulation together with age are the most important determinants of successful outcome. Women with prior low response to stimulation and women with expected low response (diminished ovarian reserve) are at higher risk for cycle cancellation and produce a smaller number of mature eggs and embryos. Many approaches were suggested to improve response in low responders including
Increasing the dose of gonadotropins (injection medications)
Use of antagonist protocol
Use of flare lupron protocol
Use of oral medications e.g clomid or letrozole
Synchronization of follicles prior to stimulation using estrogens
Minimal stimulation IVF
Adjutant use of growth hormone
Use of androgens.
Androgen may Improve Ovarian response to stimulation
Testosterone is known to increase the sensitivity of the ovary to FSH (the hormone that stimulate recruitment and development of follicles in the ovary). Testosterone increases the number of FSH receptors in the follicle and thus its response to stimulation. Women that naturally have high androgens e.g polycystic ovary syndrome (PCOS) show an strong response to FSH. Androgen stimulation increase growth of early follicles and expand the number of follicles available for stimulation. Agonists (lupron) and antagonists (ganirelex) used in ovarian stimulation suppresses testosterone levels in some women.
Two major preparations are available to deliver androgens prior to starting stimulation
Testosterone gel 10 to 12.5 mg applied to skin per day for 21 days or
DHEA oral tablets 75 mg for variable period 4 weeks to 4 months
There were three randomized clinical trials (generally the best type of studies in biological sciences) investigating the use of transdermal testosterone prior to IVF. Of the 221 patients included in these studies. Women receiving testosterone required less fertility medications, had significantly more eggs retrieved and less cycles were cancelled due to low response. There were no side effects in all studies. There was a two fold increase in pregnancy and live birth rates in women that used transdermal testosterone. There is evidence that transdermal testosterone prior to stimulation improves IVF outcomes.
The mechanism of action of DHEA is not well understood. There were many studies on DHEA but only one was randomized clinical trial. When all the studies with control group were considered, they demonstrated a significantly lower number of oocytes retrieved in DHEA treated women when compared to the controls. There was no significant difference in the clinical pregnancy rate between women pre-treated with DHEA compared to those without DHEA pre-treatment. It is possible that DHEA can improve embryo quality, but this dud not translate into higher pregnancy rate. It is suggested that DHEA should be used for 2-4 months prior to IVF which delays treatment start.
The conclusions related to the use of androgens prior to IVF require more confirmation in larger studies. However, if andregens are used, transdermal testosterone is the preferred androgen pre-treatment prior to ovarian stimulation and IVF.Androgens: Improving Response to Ovarian Stimulation prior to IVF by Dr. Amr Azim