Effectiveness of progesterone-primed ovarian stimulation in assisted reproductive technology: a systematic review and meta-analysis

PURPOSE: Progestin-primed ovarian stimulation (PPOS) is a new ovarian stimulation protocol that has been used over the last decade to enhance reproductive function. The purpose of this study is to evaluate whether PPOS is as effective as conventional protocols (without GnRHa downregulation). METHOD: Search terms included “medroxyprogesterone”, “dydrogesterone”, “progestin-primed ovarian stimulation”, “PPOS”, “oocyte retrieval”, “in vitro fertilization”, “IVF”, “ICSI”, “ART”, and “reproductive”. The selection criteria were nonrandomized studies and randomized controlled studies. For data collection and analysis, the Review Manager software, Newcastle–Ottowa Quality Assessment Scale and GRADE approach were used. RESULTS: The clinical pregnancy rates were not significantly different in either RCTs or NRCTs [RR 0.96, 95% CI (0.69–1.33), I(2) = 71%, P = 0.81]; [RR 0.99, 95% CI (0.83–1.17), I(2) = 38%, P = 0.88]. The live birth rates of RCTs and NRCTs did not differ [RCT: RR 1.08, 95% CI (0.74, 1.57), I(2) = 66%, P = 0.69; NRCT: OR 1.03 95% CI 0.84–1.26), I(2) = 50%, P = 0.79]. The PPOS protocol had a lower rate of OHSS [RR 0.52, 95% CI (0.36–0.75), I(2) = 0%, P = 0.0006]. The secondary results showed that compared to the control protocol, the endometrium was thicker [95% CI (0.00–0.78), I(2) = 0%, P = 0.05], the number of obtained embryos was higher [95% CI (0.04–0.65), I(2) = 17%, P = 0.03] and more hMG was needed [in NRCT: 95% CI (307.44, 572.73), I(2) = 0%, P < 0.00001] with the PPOS protocol. CONCLUSION: The PPOS protocol produces more obtained embryos and a thicker endometrium than the control protocol, with a lower rate of OHSS and an equal live birth rate. The PPOS protocol could be a safe option as a personalized protocol for infertile patients. TRIAL REGISTRATION: Registration at PROSPERO: CRD42020176577.