Objective To investigate the effect of total dose of medroxyprogesterone acetate (MPA) in progestin⁃primed ovarian stimulation (PPOS) regimen on ovarian responsiveness. Methods A retrospective analysis was conducted on 2855 patients who received PPOS regimen and underwent in vitro fertilization/intracytoplasmic sperm injection. Patients were assigned to low⁃ or high⁃dose MPA group (with total dose of MPA ≤63 mg per cycle, 1401 cases, or total dose of MPA >63 mg per cycle, 1454 cases) according to total dose of MPA. After propensity score matching (PSM) at a ratio of 1:1, the ovarian sensitivity index (OSI), clinical pregnancy rate, live birth rate, ovulation induction status, laboratory embryo outcomes, and frozen⁃thawed embryo transfer status were compared between patients of the two groups. Linear regression model was adopted to analyze the relation of total dose of MPA with OSI. Smooth curve fitting and threshold effect analysis were employed to evaluate the dose⁃effect relation of total dose of MPA with OSI. Results After PSM, there was no statistically significant difference in general status between patients of the two groups (P>0.05). Compared with the high⁃dose MPA group, the low⁃dose MPA group exhibited higher OSI, less total doses of MPA and gonadotropin (Gn), and less usage days of Gn, whereas higher luteinizing hormone level on human chorionic gonadotropin trigger day, as well as more number of available blastocysts (P<0.05). However, there was no statistically significant difference in clinical pregnancy rate and live birth rate between patients of the two groups (P>0.05). The results of linear regression analysis revealed that the total dose of MPA negatively correlated with OSI (P<0.05). Compared with the low⁃dose MPA group, the OSI of patients in the high⁃dose MPA group decreased by 0.451 units (after adjusting for confounding factors). The results of threshold effect analysis indicated that there was a non⁃linear relation between the total dose of MPA and OSI. When the total dose of MPA ≥50 mg/per cycle, for every 1 mg increased in the total dose of MPA, the OSI decreased by 0.029 units (β=⁃0.029, P<0.05). Conclusion In PPOS regimen, the dose⁃effect relation of MPA with OSI is significant, especially within the range where the total dose of MPA is ≥50 mg/per cycle, an increase in the total dose of MPA can lead to a decrease in OSI. However, low⁃dose MPA not only can maintain similar pregnancy outcomes as high⁃dose MPA, but also can enhance ovarian responsiveness, while reducing the total dosage and duration of Gn administration.

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