Frontiers in endocrinology · 2026
Impact of GnRH antagonist protocols versus progestin-primed ovarian stimulation on reproductive outcomes in advanced reproductive age women: a propensity score-matched retrospective cohort study.
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Qi Zhaokang, Wang Tingting, Ren Jinxin, Zhao Shuai, Song Jingyan, Lian Fang, Zhao Yuewen
Аннотация
PURPOSE: This study aims to compare the live birth rate (LBR) and reproductive outcomes between gonadotropin-releasing hormone antagonist (GnRH-ant) and progestin-primed ovarian stimulation (PPOS) protocols in infertile women of advanced reproductive age (ARA).
METHODS: A retrospective analysis was conducted on 1588 female patients with ARA who underwent in vitro fertilization or intracytoplasmic sperm injection at the Reproductive and Genetic Center of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine between January 1, 2020, and February 29, 2024, and met the inclusion and exclusion criteria. To ensure scientific rigor, propensity score matching (1:1) was applied to balance the baseline characteristics. Ultimately, reproductive outcomes were analyzed for GnRH-ant (n = 277) and PPOS (n = 277) protocol groups.
RESULTS: Non-significant differences were observed in baseline characteristics between the two groups. Regarding cycle data, the total gonadotropin dosage was significantly lower in the GnRH-ant group (P < 0.001), whereas the duration of gonadotropin stimulation was slightly longer (P = 0.004). On the trigger day, serum luteinizing hormone (P = 0.002), estradiol (P = 0.038), and progesterone (P < 0.001) levels were significantly higher in the GnRH-ant group compared to the PPOS group. Regarding oocyte retrieval and embryo outcomes, the GnRH-ant group demonstrated significantly higher numbers of oocytes retrieved (P < 0.001), 2-pronuclei fertilized oocytes (P = 0.003), cleavage-stage embryos (P < 0.001), and blastocysts (P = 0.010), indicating superior embryo development outcomes compared to the PPOS group. For pregnancy outcomes, 159 and 262 transfer cycles were performed in the GnRH-ant and PPOS groups, respectively. The GnRH-ant group exhibited significantly higher rates than the PPOS group in clinical pregnancy rate (CPR) (P = 0.024), ongoing pregnancy rate (P = 0.018), and LBR (P = 0.045), reflecting favorable cycle outcomes. Although the GnRH-ant group had a higher implantation rate (P = 0.066), these differences did not reach statistical significance. The PPOS group exhibited a lower miscarriage rate compared to the GnRH-ant group; however, this difference was also statistically non-significant (P = 0.981). Statistically non-significant difference was observed in ectopic pregnancy rates between the groups, and no cases of ovarian hyperstimulation syndrome occurred in either group. Finally, multivariate logistic regression analysis revealed that the treatment protocol was an independent factor influencing the LBR. The probability of live birth in the GnRH-ant group was significantly higher than that in the PPOS group (odds ratio = 6.085, 95% confidence interval: 2.489-14.880, P < 0.001).
CONCLUSION: This study indicates that the GnRH-ant stimulation protocol is advantageous as compared to the PPOS protocol for infertile women with ARA undergoing controlled ovarian stimulation combined with frozen embryo transfer, as evidenced by improved embryological outcomes, higher CPRs, and higher LBRs.
METHODS: A retrospective analysis was conducted on 1588 female patients with ARA who underwent in vitro fertilization or intracytoplasmic sperm injection at the Reproductive and Genetic Center of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine between January 1, 2020, and February 29, 2024, and met the inclusion and exclusion criteria. To ensure scientific rigor, propensity score matching (1:1) was applied to balance the baseline characteristics. Ultimately, reproductive outcomes were analyzed for GnRH-ant (n = 277) and PPOS (n = 277) protocol groups.
RESULTS: Non-significant differences were observed in baseline characteristics between the two groups. Regarding cycle data, the total gonadotropin dosage was significantly lower in the GnRH-ant group (P < 0.001), whereas the duration of gonadotropin stimulation was slightly longer (P = 0.004). On the trigger day, serum luteinizing hormone (P = 0.002), estradiol (P = 0.038), and progesterone (P < 0.001) levels were significantly higher in the GnRH-ant group compared to the PPOS group. Regarding oocyte retrieval and embryo outcomes, the GnRH-ant group demonstrated significantly higher numbers of oocytes retrieved (P < 0.001), 2-pronuclei fertilized oocytes (P = 0.003), cleavage-stage embryos (P < 0.001), and blastocysts (P = 0.010), indicating superior embryo development outcomes compared to the PPOS group. For pregnancy outcomes, 159 and 262 transfer cycles were performed in the GnRH-ant and PPOS groups, respectively. The GnRH-ant group exhibited significantly higher rates than the PPOS group in clinical pregnancy rate (CPR) (P = 0.024), ongoing pregnancy rate (P = 0.018), and LBR (P = 0.045), reflecting favorable cycle outcomes. Although the GnRH-ant group had a higher implantation rate (P = 0.066), these differences did not reach statistical significance. The PPOS group exhibited a lower miscarriage rate compared to the GnRH-ant group; however, this difference was also statistically non-significant (P = 0.981). Statistically non-significant difference was observed in ectopic pregnancy rates between the groups, and no cases of ovarian hyperstimulation syndrome occurred in either group. Finally, multivariate logistic regression analysis revealed that the treatment protocol was an independent factor influencing the LBR. The probability of live birth in the GnRH-ant group was significantly higher than that in the PPOS group (odds ratio = 6.085, 95% confidence interval: 2.489-14.880, P < 0.001).
CONCLUSION: This study indicates that the GnRH-ant stimulation protocol is advantageous as compared to the PPOS protocol for infertile women with ARA undergoing controlled ovarian stimulation combined with frozen embryo transfer, as evidenced by improved embryological outcomes, higher CPRs, and higher LBRs.