Can Treatment Choice Affect Cost of Therapy in Patients Predicted to Be High-Responders? Results of an Economic Analysis of the Menopur in GnRH Antagonist Single Embryo Transfer - High Responder (MEGASET-HR) Trial

To determine difference in treatment cost associated with cumulative live birth between highly purified-human menotropin (HP-hMG; Menopur®) and recombinant follicle stimulating hormone (rFSH; Gonal-F®) in predicted high responder women undergoing assisted reproductive technology. Cost analysis of a multicenter, randomized, open label, assessor blind, non-inferiority trial. Ovulatory women aged 21-35y with BMI 18-30 kg/m2 and serum anti-Müllerian hormone (AMH) ≥5 ng/mL (N=620) were randomized 1:1 to a 150 IU start dose of HP-hMG or rFSH in a GnRH antagonist cycle with dose adjustments allowed on day 6 of stimulation . All embryos were fertilized by intracytoplasmic sperm injection and underwent Day 5 trophectoderm biopsy for preimplantation genetic screening (PGS). Whereas morphology guided single, fresh blastocyst transfer, PGS results were only available to guide frozen blastocyst transfers. Live birth outcomes resulting from all fresh and any frozen transfers occurring within 6 months of randomization were collected. A decision tree of all per protocol trial outcomes and their associated probabilities was constructed. The resultant model was then used to perform a cost analysis using real-world trial site procedural costs and wholesale acquisition cost (WAC) of medication from when the trial began (September 2015) inflation-adjusted to 2019 cost. Demographics for the HP-hMG and rFSH arms were similar. The primary non-inferiority end-point was met, and the cumulative live birth rate was 50.6% (157/310) for HP-hMG and 51.5% (159/309) for rFSH (difference; -0.8%; 95% CI -8.7, 7.1). Mean total dose of HP-hMG was 616 IU greater, while patients with rFSH underwent 43 more transfers, had a higher cumulative early pregnancy loss rate (-11.0%; 95%CI: -18.8, -3.1) and higher adverse event rate of ovarian hyperstimulation syndrome (-11.7%; 95% CI: -17.3, -6.1). Results of the cost analysis showed that per patient treatment cost of HP-hMG was lower at $14,744 compared to $15,759 with rFSH. Cost analysis of data from the MEGASET-HR trial shows that treatment of predicted high-responders with HP-hMG may be associated with lower treatment costs compared to rFSH, despite potentially higher initial medication cost. The savings were driven by fewer embryo transfers needed and lower rate of adverse events associated with HP-hMG therapy.