O-131 Progesterone Primed Ovarian Stimulation (PPOS) Vs Clomiphene Primed Ovarian Stimulation (CPOS) in high responder (HR) patients undergoing controlled ovarian stimulation - A Randomized Control Trial
Authors: Gambhir I , Gedela D.R , Mantravadi K.C 
Published: June 2022

Abstract

Study question
In high responder individuals, stimulation with PPOS or CPOS would offer better outcomes?

Summary answer
Data from this trial concludes that stimulation with CPOS or PPOS seem to offer comparable outcomes in high responders individuals.

What is known already
Progesterone and Clomiphene Citrate have been used to suppress premature LH surge in patients undergoing controlled ovarian stimulation (COS) for In Vitro Fertilization. Their use will negate the need of using additional injections and thereby would improve the patient acceptability and reduce pain and drop out rates. This Randomized Control Trial (RCT) intends to look at the efficiency of these protocols.

Study design, size, duration
This is a Prospective RCT conducted between September 2020-December 2021 with prior approval from Institutional Ethical committee (ECR/1312/INST/TG/2019). HR patients as defined by Antral Follicular Count (AFC), Anti-Mullerian hormone (AMH) or previous response were randomized into PPOS (n = 50) & CPOS (n = 50) arm at start of stimulation based on a computer generated randomization sheet.
Exclusion criteria
Age &gt; 35 yrs, history of Total Fertilization Failure, Inadequate post-trigger hormonal values, incomplete retrieval of oocytes.

Participants/materials, setting, methods
After randomization, all patients were started on Inj rFSH & Inj HP-HMG (dosage depending upon BMI).
PPOS arm- Tab.Medroxy Progesterone Acetate10 mg/day started from day 2 of the cycle along with gonadotropins and continued until trigger.
CPOS arm- Clomiphene citrate 150 mg/day (divided doses) starting from the 8thday of stimulation or when lead follicle reached 12 mm diameter and continued until trigger.
All the subjects underwent Frozen Embryo replacement cycle with two good grade blastocysts.

Main results and the role of chance
Baseline variables of patients were comparable between both arms. There were 6-dropouts in PPOS arm and 8 dropouts in CPOS arm due to Covid -19 infection. Hence a total of 44 patients in PPOS arm and 42 patients in CPOS arm were available for analysis.
Premature LH surge rates, cycle cancellation rate, blastocyst rate (BR), Implantation Rate (IR) per initiated FET cycle were the primary outcomes.
Dose and duration of gonadotropins, number of oocytes, maturation rate, fertilization rate (FR), and OHSS rate were the secondary outcomes
Outcomes between PPOS Vs CPOS were as follows: LH Surge – 2.3% vs 2.5% (p = 1)
Cycle cancellation rate – 9.1% Vs 10% (p = 1)
BR – 57% vs 56% (p = 0.547)
IR – 44% Vs 49% (p = 0.687)
Secondary outcomes - Dose and duration of gonadotropins, number of oocytes retrieved, fertilization rate, maturation rate & OHSS rate were comparable in both groups.
All the outcomes compared between the two arms seemed to be similar with no statistical significance. Progesterone or Clomiphene priming seems to offer optimal outcomes with no superiority of one protocol over the other.

Limitations, reasons for caution
The RCT was performed on a small sample size and should be confirmed on a larger cohort. Moreover, this is the first study comparing both the drugs in high responders and confirms the efficacy of both drugs as LH suppressants without compromising outcomes.

Wider implications of the findings
This study provides assuring data on using the two oral agents, progesterone and clomiphene citrate with equal efficacy and without affecting the outcomes. These agents can help in reducing the dosage of gonadotropins and this in turn can help in minimizing the complications like OHSS during controlled ovarian stimulation.

Trial registration number
Not applicable