#182 : Pharmacokinetics of Ovarian Stimulation for Projected Poor Responder Patients in IVF. A Randomised Trial Comparing a Corifollitropin Alfa Agonist Flare Protocol with a Corifollitropin Alfa Antagonist Protocol

Background & Aims: Approximately 10% of patients have a sub-optimal response to controlled ovarian stimulation. Many different protocols for superovulation have been developed for this group of patients but the optimal approach for “poor responder” patients is yet to be determined. Use of corifollitropin alfa (Elonva) in a flare (EF) protocol is a novel approach to ovarian stimulation for predicted poor responder patients. We hypothesised that the unique pharmacokinetic and pharmacodynamic profiles of corifollitropin alfa would maximise FSH exposure and follicular recruitment in the critical early follicular phase due to the initial suprathreshold release of bioactive FSH in the initial 2-3 days of exposure to Elonva, in combination with the ‘flare’ of endogenous FSH release.

Method: Twenty-one women aged 31-41 were identified as predicted poor responder patients according to the Poseidon criteria. Each participant was randomised to treatment with Elonva/Synarel flare or Elonva/Orgalutran antagonist. Serum FSH and E2 were measured daily for five days following injection of Elonva. The study was approved by the Southeastern Sydney HREC.

Results: Serum FSH concentrations were significantly higher at each time point in the EF group when compared with the antagonist group (p=0.022). Peak FSH two days after injection of Elonva, was also significantly higher 27 vs 11 IU/L. Serum E2 concentrations were also significantly higher in the EF group at each time point (p=0.039). On day seven of stimulation, E2 concentrations were 3000 vs 1850 pmol/L.

Conclusion: The corifollitropin alfa agonist flare protocol produces significantly higher FSH and E2 concentrations than a standard corifollitropin alfa antagonist protocol for projected poor responder patients, with reduced patient burden for a group who may need multiple ovarian stimulation cycles to achieve a pregnancy. A larger RCT is required to study embryology and pregnancy outcomes, costs and patient burden.