P-666 Comparison of IVF outcomes in women undergoing IVF stimulation using progestin primed ovarian stimulation (PPOS) Vs GnRH antagonist (GnRH-Antag) protocol
Authors: Salkar J , Hegde V , Agarwal A , Vytla D , Mogili I , Bommakanti L , Sindu K 
Published: July 2024

Abstract

Study question
Can PPOS achieve improved patient & provider satisfaction while simultaneously blocking LH-surge, maintaining similar IVF outcomes like oocyte/embryo yield/clinical pregnancy rates(CPR) when compared to GnRH-Antag?

Summary answer
PPOS can achieve similar IVF outcomes as compared to GnRH-Antag protocol and is a patient friendly, cost-effective choice for ovarian stimulation without affecting oocyte/embryo yield/CPR.

What is known already
GnRH-Antag protocol is among the most widely used methods, as it blocks LH surge & significantly lowers the risk of OHSS [Lambalk CB,2017]. However, this protocol has disadvantages like frequent monitoring, dose adjustment, high therapeutic cost and multiple injections[Ata B,2015]. PPOS successfully prevents ovulation and provides comparable IVFoutcomes (oocyte yield, blastocyst/euploid embryo rates, CPR) along with patient cost savings and increased convenience across all infertility diagnoses [Annalyn M.Welp, 2023].
It should be noted that most studies are non-randomized and comprise low to moderate-quality evidence. However, the consistency of the findings across different studies from different centres provides assurance in effect estimates.

Study design, size, duration
A retrospective cohort study conducted at a tertiary care fertility unit. Data for 449 women aged 21 to 40 years undergoing IVF stimulation using PPOS (n = 226) and GnRH-Antag (n = 223) protocol was retrieved from the hospital’s electronic database and analysed for a period between September 2022 to October 2023.
Study population consisted of women undergoing freeze-all strategy either for lowering the risk of OHSS (hyper-responders) or for embryo pooling in view of very low ovarian reserve.

Participants/materials, setting, methods
For both groups either rFSH/rLH/HMG were used & doses were indivisualised based on patient’s age, BMI & ovarian reserve.
PPOS group received twice daily dose of medroxyprogesterone acetate tablet(10 mg)/dydrogesterone(10 mg) from Day2 of cycle. GnRH-Antag group received Inj.Cetrorelix acetate (0.25 mg) daily as flexible protocol. Final oocyte maturation was induced with Triptorelin(0.2mg)/Choriogonadotropin alfa(250mcg)/both, once 2-3follicles reached 18-20mm. Transvaginal oocyte pick-up was performed 35-36h later. Women in PPOS group underwent freeze-all strategy followed by Frozen-Thawed Embryo-transfer.

Main results and the role of chance
Normally distributed continuous variables were compared using independent t-test, and categorical variables were compared by χ2 and Fisher’s exact test, where appropriate.
Patient demographics, clinical/ovarian stimulation characteristics, embryological and IVF outcomes were compared for two groups.
Patient demographics {Age(p-value:0.08), BMI(p-value:0.06), duration(p-value:0.09)/type(p-value:0.76) of infertlity}, total gonadotropin dose (p-value: 0.39) and duration of ovarian stimulation (p-value: 0.81) were comparable between the two groups. Though the mean LH level on trigger day was slightly higher in PPOS group (5.53 IU/L) than GnRH-Antag group (3.24 IU/L) (p-value: 0.02), statistically significant difference was not seen in the oocyte yield (p-value: 0.18), M-II oocytes (p-value: 0.17) & fertilization rate (p-value: 0.23) in the two groups. The number of Day3 (p-value: 0.65), Day5 (p-value: 0.07) & Day6 (p-value: 0.08) embryos available in the two groups were also comparable.
IVF outcomes in terms of positive B-HCG result (p-value: 0.68), clinical pregnancy rate (p-value: 0.61) & miscarriage rate (p-value: 0.27) showed no statistically significant difference in the two groups.
Thus, we conclude that PPOS can achieve similar IVF outcomes as compared to the GnRH-Antag protocol, while at the same time proving to be patient friendly by reducing the need of multiple injection pricks, injection cost and the frequency of hospital visits.

Limitations, reasons for caution
This is a retrospective study and hence randomized comparison was not possible. PPOS can be used only when freeze-all strategy is planned, fresh embryo-transfer cannot be considered if need arises depending upon embryo quality. IVF service providers have to depend on patient compliance for using oral progestins to block LH-surge.

Wider implications of the findings
Study findings suggest that PPOS is a patient friendly and equally effective and safe IVF stimulation protocol when compared to GnRH-Antagonist. More RCT will be useful for investigating different aspects of PPOS (it’s utility for women with different ovarian reserve functions, conventional versus flexible approach, optimal dose of each progestin).

Trial registration number
Not applicable