Comparison of a progestin-primed ovarian stimulation protocol with a flexible GnRH antagonist protocol in patients with polycystic ovary syndrome who are participating in an IVF programme: study protocol for a randomised controlled trial

Abstract

IntroductionWomen with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF) protocols are typically characterised by an increased number of oocytes retrieved. The oocytes are often of poor quality, leading to lower pregnancy rates, higher miscarriage rates and an increased risk of developing ovarian hyperstimulation syndrome (OHSS). Since our previous preliminary study showed that a novel progestin-primed ovarian stimulation (PPOS) protocol blocked the luteinising hormone (LH) surge during IVF and achieved a higher pregnancy rate with a lower incidence of OHSS, we designed a prospective randomised controlled trial to compare the efficacy and safety of this PPOS protocol with the flexible gonadotropin-releasing hormone (GnRH) antagonist protocol in patients with PCOS who are undergoing IVF procedures.Methods and analysisPatients with PCOS will be randomised to one of two controlled ovarian stimulation regimens—GnRH antagonist or PPOS—using a computer-generated random number. A freeze-all strategy using embryo vitrification techniques and frozen embryo transfer will be performed in both groups. The primary outcome is the live-birth rate per transfer. Secondary outcomes include the incidence of premature LH surges, the duration and total dose of human menopausal gonadotropin stimulation, the number of oocytes retrieved, the incidence of moderate or severe OHSS, the number of embryos available for transfer, implantation rates, clinical pregnancy rates, pregnancy loss rates, ectopic pregnancy rates, pregnancy and neonatal complications, and congenital anomalies. The necessary sample size for this trial was estimated as 392 participants, with 196 participants in each group. Intention-to-treat analysis was used in processing our experimental data.Ethics and disseminationThis study was approved by the Institutional Review Board of the hospital (2016-133-T82). The trial will be conducted according to the principles of the World Medical Association’s Declaration of Helsinki and in accordance with Good Clinical Practice standards. The findings of this trial will be published in a peer-reviewed journal.Trial registration numberChiCTRIPR16009580.

Does the cell number of 0PN embryos on day 3 affect pregnancy and neonatal outcomes following single blastocyst transfer?

“…Previous studies reported that the IVF outcomes of patients with endometriosis were improved by pretreatment with DNG, and myo-inositol is of proven utility in those with PCOS [ 45 , 46 ]. Our centre also published some work in this field on the basis of a novel ovarian stimulation strategy named progestin primed ovarian stimulation (PPOS) [ 15 , 47 , 48 ].…”

Comparison of the Cumulative Live Birth Rates of Progestin-Primed Ovarian Stimulation and Flexible GnRH Antagonist Protocols in Patients With Low Prognosis

“…To our knowledge, regarding the comparison of PPOS protocols and GnRH antagonist protocols, there are 11 studies, including four RCTs (20,22,26,27), two prospective studies (28,29) and five retrospective cohort studies (19,21,(30)(31)(32). The populations in these studies had different characteristics, including PCOS, POR, normal ovarian response and donor oocyte cycles.…”

“…There are a large number of randomized controlled, prospective and retrospective studies on GnRH antagonist regimens that fully prove the effectiveness and safety of these regimens (10)(11)(12)(13). Regarding the PPOS protocols, although it has not been applied for a long time, studies have shown that it can achieve exact effectiveness and safety in different populations (19)(20)(21)(22). However, due to the short application time of the protocols and the limited amount of data, the long-term safety of offspring deserves further study.…”

“…In 2015, Kuang et al (18) proposed a new COS protocol named progestin-primed ovarian stimulation (PPOS), which has advantages in terms of its effectiveness for suppressing the LH surge as well as its oral administration. Additionally, clinical effectiveness and safety have been demonstrated in women with polycystic ovary syndrome (PCOS), normal ovarian response and POR (19)(20)(21)(22). To our knowledge, there have been no studies comparing PPOS and GnRH antagonist protocols according to the POSEIDON criteria, which would be meaningful for the formulation of individualized clinical programs.…”

Comparison of Cumulative Live Birth Rates Per Aspiration IVF/ICSI Cycle Between GnRH Antagonist Protocol and Progesterone-Primed Ovarian Stimulation Protocol for Infertility With Normal Ovarian Reserve: A Randomised Controlled Trial

“…Studies have demonstrated that PPOS is effective for suppressing premature LH surge and decreasing OHSS incidence when used in combination with a freeze-all strategy and a GnRH-agonist trigger [8]. Several randomised controlled trials (RCTs) have compared the number of oocytes retrieved and pregnancy outcomes, including clinical pregnancy and live birth rate, between progestin-mediated and GnRH antagonist protocols in patients with PCOS [9,10] and poor responders [11]. Although these trials have reported no signi cant differences between the protocols, RCT data regarding the use of PPOS in patients with infertility who have normal ovarian reserve are limited.…”