Ovarian hyperstimulation syndrome prevention by gonadotropin-releasing hormone agonist triggering of final oocyte maturation in a gonadotropin- releasing hormone antagonist protocol in combination with a "freeze- all" strategy: A prospective multicentric study

Objective: To prospectively study ovarian hyperstimulation syndrome (OHSS) incidence and cumulative live birth rate in a cohort of patients at risk of OHSS undergoing ovarian stimulation in a GnRH antagonist protocol and receiving a GnRH agonist triggering followed by cryopreservation of all two pronuclei (2PN)-stage zygotes by two methods, vitrification or slow-cooling, for later ET. Design: Prospective, clinical cohort study. Setting: Five IVF centers in Germany; time frame: June 2008 to June 2010. Patient(s): Fifty-one female patients undergoing IVF considered at risk of developing severe OHSS (≥20 follicles ≥11 mm and/or E₂ level ≥4,000 pg/mL) after ovarian stimulation in a GnRH antagonist protocol. Intervention(s): Triptorelin (0.2 mg SC) for triggering final oocyte maturation. All 2PN-stage zygotes were cryopreserved by vitrification or slow-cooling for later repetitive frozen-thawed ET. Main Outcome Measure(s): Severe OHSS incidence and cumulative live birth rate per patient. Result(s): Of 51 patients, 1 patient (2%, 95% confidence [CI] 0.3%-10.3%) had zero oocyte retrieved, 1 patient did not undergo frozen-thawed ET, and 1 patient had no surviving oocyte after thawing. Thus, 48 patients underwent at least one frozen-thawed ET. The cumulative live birth rate was 37.3% (19/51, 95% CI 25.3%-51.0%). The live birth rate per first frozen-thawed ET was 5.9% (1/17, 95% CI 10.0%-27.0%) and 19.4% (6/31, 95% CI 9.2%-36.3%) in the slow-cooling and vitrification group, respectively (difference: 13.5%, 95% CI of the difference: -9.9%-31.1%). Three cases of OHSS II (3/51, 5.9%, 95% CI 2.0%-15.9%) and one early-onset case of OHSS III (1/51, 2%, 95% CI 0.3%-10.3%) occurred. Conclusion(s): Agonist triggering with cryopreservation is efficacious and safe, although a single case of a severe early-onset OHSS occurred.