P-611 Progestin-Primed Ovarian Stimulation is a non-inferior alternative to the GnRH Antagonist Protocol in patients undergoing ovarian stimulation: a propensity score weighting analysis
Authors: Le Duc T , Long H B , Do T T T , Phan N Q , Giap T M P , Nguyen T L H , Le H 
Published: June 2023

Abstract

Study question
To evaluate the effectiveness of the progestin-primed ovarian stimulation (PPOS) protocol versus the gonadotropin-releasing hormone antagonist (GnRH-ant) protocol in ovarian stimulation.

Summary answer
The PPOS protocol with dydrogesterone provided similar embryo outcomes to the GnRH-ant protocol. The serum LH concentration during ovarian stimulation using PPOS was well-controlled.

What is known already
Since Yanping Kuang's proposal PPOS in 2015, several studies on the effectiveness of this treatment regimen have been published. Although it has been suggested that outcomes of the PPOS regimen were comparable to those of GnRH-ant regimen, the findings were limited due to differences in study design, patient characteristics, dosage and type of progestins. While medroxyprogesterone acetate is often used in PPOS studies, dydrogesterone has seen far less popularity. Additionally, dydrogesterone is a relatively weak LH inhibitor compared to MPA, leading to concern about the increased incidence of unexpected LH surge

Study design, size, duration
We conducted a retrospective study among women who underwent In Vitro Fertilization at the Assisted Reproduction Center, Tam Anh General Hospital, Vietnam from January 1st, 2022 to October 10th, 2022.

Participants/materials, setting, methods
We included 804 patients who underwent ovarian stimulation, among which 208 used the PPOS protocol with dydrogesterone (30 mg dydrogesteron per day from the beginning of stimulation until the trigger-day) and 598 women used the GnRH-ant protocol (cetrorelix 0.25 daily, from day 6 of ovarian stimulation until the trigger-day). In addition to unadjusted analysis, we used propensity score weighting to account for confounding that might possibly remain.

Main results and the role of chance
Baseline characteristics were comparable in both groups. In both unadjusted and adjusted analysis, the mean number of good cleavage embryos in PPOS (6.33) was non-inferior to GnRH-ant (6.44; unadjusted ratio of two means 1.02, 95%CI 0.92, 1.13). The trigger-day estradiol level in patients with PPOS was higher (4,420 vs 3,830 pmol/L in GnRH-ant) despite similar total follicle stimulating hormone dose and fewer days of ovarian stimulation. The overall number of oocytes retrieved, the number of MII oocytes, the number of cleavage embryos, the number of blastocysts, and the number of good blastocysts were comparable between the two protocols. None of the PPOS patients had an unexpected LH surge, and serum LH levels decreased slightly during ovarian stimulation.

Limitations, reasons for caution
Due to the nature of the retrospective study design, we did not record the progesterone level on the trigger-day in the PPOS regimen; therefore, identifying LH surge based on LH and progesterone levels is not feasible. Furthermore, we did not study the outcomes of embryo transfer.

Wider implications of the findings
These results supported the use of PPOS with dydrogesterone as a cheap and effective alternative for clinicians in clinical practice. In patients with an indication for freeze-all embryo, the PPOS protocol could be recommended.

Trial registration number
Not Applicable