Biotechnological drugs for reproductive disorders: a review of developments

Recombinant gonadotrophins, in particular recombinant follitropin (follicle-stimulating hormone; FSH), are now available for ovarian hyperstimulation for assisted reproduction. In contrast with urinary FSH (urofollitropin), follitropin is available in virtually unlimited quantities. Follitropin is as potent as urofollitropin in all protocols of ovarian stimulation. Furthermore, it shows an improved purity without contamination by urinary proteins not related to FSH, and can be injected subcutaneously by the patients themselves. In patients with complete luteinising hormone (LH) deficiency, follitropin stimulates follicular development, although serum levels of estradiol remain low. For this group of patients the addition of LH is necessary. Ongoing phase III studies on the use of recombinant LH in this indication will provide an answer to how much LH is needed in order to guarantee sufficient follicular growth and hormonal response. Gonadorelin (gonadotrophin releasing hormone; GnRH) analogues are used to avoid the surge of endogenous LH in ovarian stimulation protocols. Gonadorelin antagonists are now in clinical testing for the same indication. Gonadorelin antagonists allow sufficient suppression of endogenous LH levels. In contrast with gonadorelin analogues, they avoid any flare-up effect, i.e. an initial release of gonadotrophins from pituitary reservoirs. Recombinant gonadotrophins and gonadorelin antagonists are new tools towards a more individual approach to ovarian stimulation.