Objective: To explore the effects of progestin-primed ovarian stimulation (PPOS) using fixed versus degressive doses of medroxyprogesterone acetate (MPA) in conjunction with letrozole (LE) in infertile women. Design: Retrospective cohort study. Setting: Tertiary-care academic medical center. Population: We studied 3173 infertile women undergoing their first IVF/ICSI treatment from 2017 to 2020. Methods: Propensity score matching (PSM) analysis was performed with 1:1 in 1068 and 783 patients who underwent a fixed dose of MPA combined with LE and a degressive dose of MPA combined with LE protocols, respectively. Main outcome measures: Incidence of premature luteinizing hormone (LH) surges and number of oocytes retrieved. Results: We created a perfect match of 581 patients in each group. The dosage of MPA, premature LH surge, progesterone (P) level and LH level on the hCG trigger day and LH level on the day after hCG trigger were significantly higher in the LE + fixed MPA group than in the LE + degressive MPA group. The E 2 level on the hCG trigger day, the duration of Gn, the number of oocytes retrieved were lower in the LE + fixed MPA group than in the LE + degressive MPA group. Conclusions: Using degressive MPA dose combined with LE could reduce the total MPA dosage and premature LH surge and increase the number of oocytes retrieved in women undergoing the PPOS protocol. Funding: National Natural Science Foundation of China (82101726) and Innovation and Entrepreneurship Training Program for students of Hubei University of Medicine (X202110929037 and S202110929032). Keywords: progestin primed ovarian stimulation, medroxyprogesterone acetate, letrozole, controlled ovarian stimulation.