O-302 Feasibility and efficacy of a flexible and simplified ovarian stimulation protocol for oocyte donors, combining random-start corifollitropin alpha and progestin primed ovarian stimulation protocol (PPOS)
Authors: Mathieu D’Argent E , Guivarc’h Leveque A , Catteau-Jonard S , Cedrin I , Peigné M , Jung C , Goro S , Massin N 
Published: July 2024

Abstract

Study question
Is the total number of retrieved oocytes in donors equivalent, according to the onset phase of stimulation with corifollitropin alpha in a random-start PPOS protocol?

Summary answer
The total number of retrieved and mature oocytes were not different after starting stimulation in the early, mid or late follicular or luteal phases.

What is known already
Recent studies have shown the ability to obtain oocytes of equivalent quality after follicular or luteal phase ovarian stimulation and have also demonstrated the efficacy and safety of the PPOS protocol in oocytes donors.
In order to provide a more friendly, simplified and flexible ovarian stimulation protocol reducing the burden for donors, we studied the impact on oocyte yield of combining a random start corifollitropin alpha stimulation with the concomitant prevention of premature LH surge by progestin administration.

Study design, size, duration
This multicenter open-labelled RCT was performed in 4 oocytes donation centers from July 2020 to September 2023 to assess the equivalence in terms of number of retrieved oocytes of a delayed onset of corifollitropin alpha stimulation with concomitant administration of desogestrel in Mid Follicular Phase (MFP/D4-D7 of the natural cycle), Late Follicular Phase (LFP/D8-D11), Ovulatory Phase (OP/D12-D15) or Luteal Phase (LP/D16-D30) compared to the standard start in Early Follicular Phase (EFP/D1-D3).

Participants/materials, setting, methods
From 110 randomized oocyte donors,102 reached triggering of ovulation with triptoreline acetate and OPU : EFP n = 22, MFP n = 20, LFP n = 19, OP n = 18 and LP n = 23. The sample size was calculated to show an equivalence between groups in total number of retrieved oocytes. Secondary endpoints were the number of mature oocytes, premature LH surge and Ovarian Hyperstimulation Syndrome rates. Differences were tested using a ANOVA test or a Pearson’s Chi2 test, as appropriate.

Main results and the role of chance
Donors were 33 [29.2-35.0] years old [95% Confidence interval] with a mean BMI of 23.4 [21.1-26.3] kg/m2. The mean number (SD) of retrieved oocytes was 14.2 (9.1). In intention to treat analysis, there was no significant difference between the 5 groups, regarding the total number of retrieved oocytes. The mean numbers of retrieved oocytes from the 5 groups were 12.5 (7.7), 13.2 (8.0), 15.7(9.8), 17.8 (11.4), and 12.8(8.3), respectively in the EPF group, the MPF group, the LPF group, the OP group and the FP group, with no significant differences between the groups (p = 0.30). The mean (SD) number of mature oocytes was 11.8 (7.6) with no significant differences between the 5 groups. Only one premature LH surge was reported in the MFP group (0.98%). Four minor to moderate OHSS were reported (3.9%).

Limitations, reasons for caution
The main limitation of our study is the small sample size responsible for a lack of power. But to our knowledge, this is the first RCT to compare the number of oocytes retrieved, according to the onset phase of ovarian stimulation in a random-start PPOS protocol, for oocyte donors.

Wider implications of the findings
The proportion of ovarian stimulation cycles with freeze-all is constantly increasing worldwide. Therefore simplified, ultra-flexible ovarian stimulation protocols could be proposed to maintain the spread of the workload along the working days without programming, with fewer injections and reduced burden for patients, with the same efficacy.

Trial registration number
NCT03895099