Embryo implantation: the Rubicon for GnRH antagonists

When gonadotrophin-releasing hormone (GnRH) was discovered, the agonist and antagonist of GnRH were developed to control the release of FSH and LH by the gonadotrophs. More than 10 years of research were needed to develop a G nRH antagonist free of histamine release. Recent studies have shown that th ese GnRH antagonists are effective in preventing a rise in LH during ovaria n stimulation in IVF, However, a decrease in ongoing pregnancies seems to s uggest that implantation rates per transferred embryo are reduced in GnRH a ntagonist-stimulated cycles. In my opinion, these data highlight an area le ss well known to clinicians: the role of the GnRH antagonist at the cellula r level in extrapituitary tissues. There are sufficient data in the literat ure suggesting that GnRH antagonist is an inhibitor of the cell cycle by de creasing the synthesis of growth factors. Given that, for folliculogenesis, blastomere formation and endometriun development, mitosis is everything; t he interaction between the GnRH antagonist and the GnRH receptor (present i n all these cells and tissues) may compromise the mitotic programme of thes e cells. This is the Rubicon for the GnRH antagonist: to demonstrate irrevo cably that, at the minimal doses necessary to suppress LH release, it does not affect processes such as implantation, embryo development and folliculo genesis.