Progestin-Primed Ovarian Stimulation Protocol for Patients in Assisted Reproductive Technology: A Meta-Analysis of Randomized Controlled Trials

Abstract

ObjectivesProgestin-primed ovarian stimulation (PPOS) is a new ovarian stimulation protocol that can block the luteinizing hormone (LH) surge through progesterone instead of traditional down regulating or gonadotropin-releasing hormone (GnRH) antagonist, and in order to achieve multi-follicle recruitment. This paper aims to investigate the effectiveness of PPOS and its suitability for infertile patients with different ovarian reserve functions.MethodsWe searched published randomized controlled trials (RCTs) about PPOS on Cochrane Library, PubMed, Embase, and Web of Science. The search period spanned from January 1, 2015 to November 16, 2020. The data were extracted, and the meta-analysis was performed on ovarian stimulation as well as embryological and clinical outcomes. The outcomes were pooled by a random effects model, and the risk of heterogeneity was evaluated. Subgroup analysis was performed for different ovarian reserve patients.ResultsThe clinical pregnancy rates and live birth or ongoing pregnancy rates with the PPOS protocol were not different from those with the control group. In the diminished ovarian reserve (DOR) subgroup, the PPOS protocol had a lower rate of premature LH surge [RR = 0.03, 95% CI = 0.01 to 0.13, p < 0.001]. The PPOS protocol had a lower rate of ovarian hyperstimulation syndrome (OHSS) [RR = 0.52, 95% CI = 0.36 to 0.76, p < 0.001, I2 = 0.00%]. The secondary outcomes showed that the number of oocytes retrieved, MII oocytes, and viable embryos was higher than that of the control protocol in DOR patients [(MD = 0.33, 95% CI = 0.30 to 0.36, p < 0.001), (MD = 0.30, 95% CI = 0.27 to 0.33, p < 0.001), (MD = 0.21, 95% CI = 0.18 to 0.24, p < 0.001)] and normal ovarian reserve (NOR) patients [(MD = 1.41, 95% CI = 0.03 to 2.78, p < 0.001), (MD = 1.19, 95% CI = 0.04 to 2.35, p < 0.001), (MD = 1.01, 95% CI = 0.21 to 1.81, p = 0.01)].ConclusionThe findings suggest that PPOS is an effective ovarian stimulation protocol and is beneficial for patients with different ovarian reserve functions, which needs to be validated in more RCTs with larger samples.

Optimization of assisted reproductive technology outcomes in patients with polycystic ovarian syndrome: updates and unanswered questions

“…This is in contrast to the findings of a randomized controlled trial (RCT) in women with PCOS comparing PPOS with dydrogesterone 20 mg beginning on CD2 to Cetrotide starting with follicle size of 12-13 mm [27 ]. Eftekhar et al [28] similarly report suppressed LH levels on the day of trigger in both the PPOS and antagonist groups, however the LH level was significantly higher in the PPOS group. They also found lower implantation (7.32% vs. 15.69%) and clinical pregnancy rates (14.6% vs. 29.4%) among the PPOS group compared to the GnRH antagonist group in the subsequent frozen embryo transfer cycles, though these were not statistically significant.…”

Neonatal outcomes and congenital malformations in children born after progestin-primed ovarian stimulation protocol

“…Moreover, advanced vitrification techniques and the freeze-all embryo strategy made the protocol widely used. In some prospective and retrospective cohort studies, comparable embryological and clinical outcomes were observed between the PPOS protocol and the conventional ovarian stimulation protocol, which implied that the embryo development potential could not be impaired ( 35 , 36 ). A previous study has demonstrated no significantly elevated rate of congenital anomalies for infants after the treatment with LPS compared with the conventional ovarian stimulation protocol ( 37 ).…”

Infertility treatment for Chinese women with P450 oxidoreductase deficiency: Prospect on clinical management from IVF to FET

“…P4 secreted by the corpus luteum strongly inhibited pulsatile GnRH and LH secretion ( 21 ). Progestin-primed ovarian stimulation (PPOS) is an ovarian stimulation protocol that can block the LH surge through oral progesterone instead of the traditional down-regulating or GnRH antagonist ( 22 ). In patient 1 without glucocorticoid pretreatment, we presumed that endogenous LH secretions could be suppressed in a PORD female patient with elevated P4, which is the “natural PPOS” protocol.…”