Oral GnRH antagonists in controlled ovarian stimulation: many questions still unanswered

After the so-called long protocol using gonadotropin-releasing hormone (GnRH) agonists had been the gold standard in controlled ovarian stimulation until the turn of the millennium, the market launch of peptide GnRH antagonists heralded a new era in the treatment of involuntarily childless couples. The fact that GnRH antagonists are only used when there is a risk of a premature luteinizing hormone (LH) surge, i.e., premature ovulation, led to a significant shortening of the stimulation time and the necessary amount of gonadotropins to be administered. Additionally, this treatment modality reduced the risk of higher-grade ovarian hyperstimulation syndrome (OHSS). Since the 1920s over 80% of all treatments worldwide have been carried out according to the multiple dose antagonist protocol developed in Bonn and L & uuml;beck. The introduction of the peptide GnRH antagonists was a real game changer. Since the introduction of elagolix on the US market, and of relugolix and linzagolix on the US and European markets, substances have become available that can be administered orally as non-peptide GnRH antagonists. These preparations have become established in the treatment of uterine leiomyoma and endometriosis. Consequently, controlled ovarian stimulation appears to be the next possible area of application; however, published experiences to date are still sparse. The question arises as to whether these new small molecules can have the same effectiveness in preventing premature luteinization or the same efficiency in the treatment with methods of assisted reproduction as the peptidic representatives of this group of substances.