Does the Timing of Antagonist Treatment Influence Cycle Outcomes in Unexpected Low Responders of POSEIDON Class 1 and 2?

: Unexpected low responders are patients with normal ovarian reserve tests who exhibit suboptimal responses to stimulation but have promising treatment potential due to adequate follicle availability. This study aimed to compare the live birth rates (LBRs) between fixed and flexible gonadotropin-releasing hormone antagonist (GnRH-ant) protocols in low-prognosis patients from Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) groups 1 and 2. : This retrospective cohort study included 117 women classified as POSEIDON groups 1 and 2 who underwent GnRH-ant protocols for in vitro fertilization (IVF)/Intracytoplasmic Sperm Injection (ICSI) at the Petrova Maternity Hospital in Zagreb (2019-2020). The primary outcome analyzed was the live birth rate (LBR). The secondary outcomes were the GnRH start day, duration of gonadotropin therapy, number of oocytes, number of embryos, number of blastocysts, number of third-day embryos, number of vitrified embryos, positive pregnancy test, clinical pregnancy, and miscarriage rate. Group comparisons were conducted using Mann-Whitney and chi-squared tests. : In POSEIDON group 1, the fixed protocol significantly improved outcomes, with higher rates of clinical pregnancy, 12-week ongoing pregnancy, and LBRs (58.8% vs. 8.3%). More fresh transferable embryos were also noted ( < 0.05). In POSEIDON group 2, no significant differences were observed between protocols for any outcomes. : The fixed GnRH-ant protocol improved pregnancy outcomes for POSEIDON group 1 but showed no advantage over the flexible protocol in POSEIDON group 2.