Comparison of Cumulative Live Birth Rates and Cost-Effectiveness Between GnRH Antagonist and Progestin-Primed Ovarian Stimulation Protocols Running title: Cost-effectiveness of GnRH-ant vs PPOS

Objective: This study compared the cumulative live birth rates (CLBRs) and cost-effectiveness of the GnRH antagonist (GnRH-ant) versus progestin-primed ovarian stimulation (PPOS) protocols in controlled ovarian stimulation (COS). Methods: In this retrospective study, women who underwent COS with GnRH-ant or PPOS at Taichung Veterans General Hospital, from 2018 through 2022, were analyzed. After applying exclusion criteria, eligible participants were matched in a 3:1 ratio using propensity score matching based on age and anti-Müllerian hormone levels. Clinical outcomes and cost-effectiveness were evaluated, with incremental cost-effectiveness ratio (ICER) and probabilistic sensitivity analysis (PSA) conducted based on various willingness-to-pay (WTP) thresholds. Results: A total of 225 patients who underwent COS with GnRH-ant and 85 patients with PPOS were included. GnRH-ant required significantly lower gonadotropin doses, a shorter stimulation duration, and yielded a higher MII oocyte rate. Pregnancy and live birth rates after the first embryo transfer were similar between the two protocols, while the GnRH-ant group had a numerically higher CLBR (56.08% vs 54.12%) and a significantly shorter time from stimulation to live birth (351.28 ± 138.59 vs. 394.42 ± 105.90 days, p < 0.001) per aspirated cycle compared to PPOS. Medical costs by procedure and in total were comparable, with an ICER of $2,067.14 per additional live birth for GnRH-ant. PSA indicated a 40% probability of cost-effectiveness at a $2,000 WTP threshold, with the probability increasing to 58.0% at $10,000 and 61.3% at $30,000. Conclusion: Both protocols yielded similar pregnancy and live birth outcomes, with GnRH-ant being a cost-effective option under more lenient WTP settings. Moreover, GnRH-ant was associated with a shorter time from stimulation to live birth, potentially benefiting women who seek to conceive sooner.