Intensified ovarian stimulation in a GnRH antagonist protocol with agonist triggering: A prospective, clinical feasibility study

The threat of severe ovarian hyperstimulation syndrome (OHSS) and the increase in discomfort for the patient has limited the feasibility of maximizing the oocyte yield per treatment cycle. A gonadotrophin-releasing hormone (GnRH) antagonist protocol with agonist triggering and vitrification of all 2PN oocytes can eliminate the risk of OHSS. This prospective, single-centre, cohort study in 30 good-responder IVF patients ≤36 years reports the feasibility of arbitrarily intensifying stimulation in a GnRH antagonist protocol in terms of tolerability, safety and efficacy. Ovarian stimulation was performed with 225-375 IU FSH, induction of final oocyte maturation with 0.2 mg GnRH agonist followed by vitrification of all 2 pronuclear (2PN) oocytes and repetitive vitrified-warmed embryo transfer cycles. Main outcomes were severe OHSS incidence, tolerability, assessed by a questionnaire, and cumulative live birth rate. On average, 17 oocytes were retrieved (range 4-42) and 8.4 oocytes at the 2PN stage were cryopreserved (range 3-22). No case of severe OHSS was observed (0%, 95 CI 0-11.4%). Tolerability was good. The cumulative live birth rate per patient undergoing at least one vitrified-warmed embryo transfer was 26.9% (7/26, 95% CI 13.7-46.1%). This approach can be explored in future larger-sized controlled studies. The more oocytes that are available after ovarian stimulation, the more often a patient can undergo an embryo transfer when frozen-thawed cycles using cryopreserved embryos are taken into account. However, the feasibility of retrieving a large number of oocytes has so far been hampered by the risk of ovarian hyperstimulation syndrome (OHSS). An approach combining a gonadotrophin-releasing hormone (GnRH) antagonist protocol stimulation with agonist triggering of final oocyte maturation and vitrification of all 2 pronuclear oocytes eliminates the risk of OHSS. Herein we report the feasibility of arbitrarily intensifying stimulation in a GnRH antagonist protocol in terms of tolerability, safety and efficacy. It was found in a small study on young patients that harvesting a large number of oocytes (on average 17) is not associated with poor tolerability or an increased risk of OHSS. The live birth rate after vitrified-thawed embryo transfers was 26.9%. Thus, this approach can be studied in larger-sized controlled trials.