Received March 09, 2025
Accepted September 02, 2025

Objective: The objective of this study was to evaluate the effect of a stop gonadotropin-releasing hormone (GnRH) agonist with letrozole protocol in improving in vitro fertilization (IVF) cycles in poor ovarian responders (PORs) and to suggest a suitable new ovulation stimulation protocol for this group of infertile women. Methods: This randomized controlled trial was conducted at the Infertility Center of Taleghani Hospital, Tehran, Iran, from August 2024 to December 2024. The participants were 60 women who fulfilled the POSEIDON Group 4 criteria and had poor ovarian response in their previous IVF cycles. Participants were randomly assigned to the study and control groups and underwent a new IVF cycle. The study group underwent a new cycle with a stop agonist using the letrozole protocol, and the control group underwent the conventional stimulation protocol, which was the same as the previous cycle. Results: Compared with the conventional protocol, the stop-GnRH agonist and letrozole protocols resulted in a significantly greater number of follicles >13 mm on the day of human chorionic gonadotropin (hCG) administration and a greater number of mature oocytes retrieved, with a significantly greater number of total embryos obtained at days 3 and 5 and a greater number of top-quality embryos. The mean biochemical and clinical pregnancy rates were similar between groups. Conclusions: The stop-GnRH agonist and letrozole protocol is a short and original protocol that seems to yield better outcomes for patients and may offer promising results for treating POSEIDON Group 4 patients with previous failed IVF.