New approaches to ovarian stimulation.

Suppression of endogenous hormone production by gonadotrophin-releasing hormone (GnRH) agonists followed by controlled ovarian hyperstimulation (COH) with human gonadotrophins, especially the so-called 'long protocol' has developed from second-line into first-line therapy. Due to this attitude premature luteinization can be safely avoided, enhancing therapeutic efficacy. Recombinant preparations of human follicle stimulating hormone (FSH) have been proven to be effective within COH according to the long protocol. The high purity of these compounds may have clinical advantages. GnRH antagonists could be successfully introduced in COH protocols. Also, daily injections in the midcycle phase according to the 'Lübeck protocol', as single or only dual administrations around day 9 seem to abolish any premature LH rises. Due to their different pharmacological mode of action, based on a classic competitive receptor blockage GnRH antagonists avoid any flare-up period and allow ovarian stimulation to start within the spontaneous cycle. Pregnancy rates are comparable to those after long protocol stimulation. Combination of softer stimulation regimes like clomiphene citrate and low dose HMG with midcycle administration of GnRH antagonists may be the way to a cheap, safe and efficient ovarian stimulation. It seems to be high time for modest forms of ovarian stimulation, lowering burden and risk for our patients.