A comparison of the effects of progestin-primed ovarian stimulation protocol and gonadotropin-releasing hormone antagonist protocol in assisted reproductive technology: a systematic review and meta-analysis

OBJECTIVE: We aimed to compare the effects of the progestin-primed ovarian stimulation (PPOS) protocol and gonadotropin-releasing hormone antagonist (GnRH-A) protocol in women with different ovarian reserves who underwent assisted reproductive technology (ART). METHODS: We searched published studies in the Cochrane Library, Web of Science, Embase, PubMed, CNKI, and CBM databases. Patients in the experimental group underwent the PPOS protocol, and those in the control group underwent the GnRH-A protocol. Randomised controlled trials (RCTs) and non-randomised controlled trials (N-RCTs) of PPOS and GnRH-A protocols were collected. We searched the literature published until November 1, 2024. A subgroup analysis was performed for patients with different ovarian reserves. RESULTS: This study included 36 studies. The primary outcome showed that the live birth rate was similar between the PPOS and GnRH-A groups. In the high ovarian response (HOR) patients, the incidence of ovarian hyperstimulation syndrome (OHSS) was significantly lower in the PPOS protocol group than in the GnRH-A group [OR = 0.24, 95% confidence interval (CI) = 0.12-0.48, p < 0.0001]. In the secondary outcomes, the endometrial thickness in the PPOS protocol group decreased compared with the GnRH-A group (mean difference (MD) =  - 1.13, 95% CI =  - 1.76 to - 0.51, p = 0.0004). In the HOR subgroup, gonadotropin (Gn) dose (MD = 222.88, 95% CI = 59.30-386.46, p = 0.008) and duration (MD = 0.70, 95% CI = 0.48-0.92, p < 0.00001) were increased in the PPOS protocol group compared with the GnRH-A protocol group. In the normal ovarian response (NOR) subgroup, the number of viable embryos in the PPOS protocol group was greater than that in the GnRH-A group (MD = 2.00, 95% CI = 0.10-3.90, p = 0.04). CONCLUSION: The PPOS protocol had similar clinical effects to the GnRH-A protocol. In HOR patients, the Gn duration and dose in the PPOS protocol group increased, whereas OHSS incidence was reduced. Meanwhile, in NOR patients, the number of viable embryos in the PPOS protocol group increased. The PPOS protocol can be widely promoted in clinical practice when patients do not choose to proceed with fresh embryo transfer due to their own circumstances.