Ovarian Stimulation: Today and Tomorrow

H.      M. Fatemi; C.      Blockeel; P.      Devroey

Abstract

In assisted reproductive technology, medications and ovarian stimulation play a crucial role. The availability of gonadotrophins and GnRH analogues has allowed the tailoring of several stimulation schemes. The two most commonly used gonadotrophin forms are urinary hMG and recombinant FSH in combination with GnRH agonists or GnRH antagonists. Cycles stimulate with recombinant FSH appear to have a higher risk of premature progesterone rise in the late follicular phase, if not triggered on time. Recently, corifollitropin alfa, a new long acting recombinant FSH was introduced which sustain multiple follicular growth for 7 days in women undergoing ovarian stimulation using GnRH antagonists. GnRH antagonist and agonist do have similar live birthrate. However, GnRH antagonists reduce significantly the risk of OHSS. Moreover, with the introduction of GnRH antagonists, it became possible to trigger ovulation with a bolus of a GnRH agonist as an alternative to hCG. The early OHSS is eliminated completely with the GnRH agonist trigger. However, due to an uncorrectable luteal phase deficiency, a poor clinical outcome is present, when GnRHa is used to trigger final oocyte maturation in IVF/ICSI antagonist protocols. Therefore, it has been suggested to cryopreserve the embryos and transfer in consecutive natural cycles. Future trials should aim to eliminate OHSS and multiple pregnancy rates by performing a single stimulation in a simplified corifolitropin alfa/GnRH antagonist cycle triggered by a GnRH agonist followed by Cryo-thawed SET in consecutive natural cycles. With this approach, the two major complications of COH for IVF could be eliminated without jeopardizing the outcome.

Keywords: Corifollitropin alfa, future of IVF, GnRH agonist, GnRH antagonist, gonadotropins, ovarian stimulation, follicular stimulation, granulosa cell, aminoacids, monoclonal antibodies, infertility therapy, gonadotrophin flare, non-peptide mimetics, gonadotrophin compounds, hypo-estrogenaemia