Recently, concerns have been raised regarding possible adverse effects of gonadotrophin-releasing hormone (GnRH) antagonists on extra-pituitary reproductive cells and organs, i.e. ovarian cells, oocyte, embryo, endometrium. These concerns are based on numerous in-vitro studies suggesting decreased biosynthesis of growth factors caused by local action of GnRH antagonists. Clinically, it has been shown that the use of high doses (< or =1 mg daily) of GnRH antagonists is associated with low implantation rates in IVF. Although such direct adverse effect of GnRH antagonists cannot be ruled out at this time, so far clinical experience points to profound LH suppression as the major caveat associated with the use of high doses of GnRH antagonists. Very low LH concentrations are associated with aberrant concentrations of oestradiol during ovarian stimulation, which may in turn adversely effect implantation potential. The clinical data available thus far on the use of GnRH antagonists originate from protocols designed for clinical studies. It is predicted that as more clinical experience is gained, and with protocol modifications to suit individual patient response, GnRH antagonists will be comparable with the agonists in terms of cycle outcome.