Use of a single bolus of GnRH agonist triptorelin to trigger ovulation after GnRH antagonist ganirelix treatment in women undergoing ovarian stimulation for assisted reproduction, with special reference to the prevention of ovarian hyperstimulation syndrome: preliminary report

longer half-life [ 24 h versus 60 min for LH (Yen et al., A new treatment option for patients undergoing ovarian 1968; Damewood et al., 1989)], HCG administration results stimulation is the gonadotrophin-releasing hormone in a prolonged luteotrophic effect, characterized by the develop(GnRH) antagonist protocol, with the possibility to trigger ment of multiple corpora lutea and supraphysiological levels a mid-cycle LH surge using a single bolus of GnRH agonist, of oestradiol and progesterone. This sustained luteotrophic reducing the risk of developing ovarian hyperstimulation effect may result in the development of ovarian hyperstimulasyndrome (OHSS) in high responders and the chance of tion syndrome (OHSS), the most frequent and severe complicacycle cancellation. This report describes the use of 0.2 mg tion of HMG treatment (Golan et al., 1989). The threat of triptorelin (Decapeptyl®) to trigger ovulation in eight OHSS often leads to cycle cancellation. patients who underwent controlled ovarian hyperstimulaAn alternative to HCG-induced ovulation triggering, is the tion with recombinant FSH (rFSH, Puregon®) and concomuse of gonadotrophin releasing hormone (GnRH) agonists. itant treatment with the GnRH antagonist ganirelix These compounds induce a sustained ( 24 h) release of LH (Orgalutran®) for the prevention of premature LH surges. (and FSH) from the pituitary, that effectively induces oocyte All patients were considered to have an increased risk for maturation and ovulation. Importantly, they also provide a developing OHSS (at least 20 follicles ≥11 mm and/or means by which OHSS is effectively prevented (Itskovitz serum oestradiol at least 3000 pg/ml). On the day of et al., 1988, 1991; Gonen et al., 1990; Emperaire et al., 1991; triggering the LH surge, the mean number of follicles Imoedemhe et al., 1991; Segal et al., 1992; Lanzone et al., ≥11 mm was 25.1 4.5 and the median serum oestradiol 1994; Lewit et al., 1995, 1996). concentration was 3675 (range 2980–7670) pg/ml. After The major limitation of the use of GnRH agonist to trigger GnRH agonist injection, endogenous serum LH and FSH ovulation is that GnRH agonists are ineffective in women with surges were observed with median peak values of 219 and a low gonadotrophin reserve or after pituitary down-regulation 19 IU/l respectively, measured 4 h after injection. The with a GnRH agonist. In these situations, the pituitary is mean number of oocytes obtained was 23.4 15.4, of unresponsive for inducing an endogenous LH surge. Since which 83% were mature (metaphase II). None of the GnRH agonist-based protocols are routinely used in most IVF patients developed any signs or symptoms of OHSS. So programmes, the application of GnRH agonist for induction far, four clinical pregnancies have been achieved from the of ovulation has been limited. embryos obtained during these cycles, including the first The recent introduction of GnRH antagonist protocols birth following this approach. It is concluded that GnRH (Albano et al., 1997; Ganirelix Dose Finding Group, 1998; agonist effectively triggers an endogenous LH surge for final Itskovitz-Eldor et al.; 1998) has offered new opportunities of oocyte maturation after ganirelix treatment in stimulated using GnRH agonist to trigger ovulation and preventing OHSS cycles. Our preliminary results suggest that this regimen due to the mechanism of action of GnRH antagonists, i.e. may prove effective in triggering ovulation and could be competitive inhibition and relatively short duration of action. said to prevent OHSS in high responders. The efficacy Studies in monkeys (Chillik et al., 1987) have clearly demonand safety of such new treatment regimen needs to be strated that although tonic gonadotrophins remain suppressed