P-671 Progestin primed ovarian stimulation using dydrogesterone in oocyte donation cycles: a longitudinal study
Authors: Hendrickx S , Drakopoulos P , De Munck N , Ruttens S , Tournaye H , De Vos M , Blockeel C 
Published: June 2022

Abstract

Study question
Does progestin primed ovarian stimulation (PPOS) with dydrogesterone starting from stimulation day 6 yield similar outcomes compared with a GnRH antagonist protocol in oocyte donors?

Summary answer
The number of retrieved oocytes and metaphase II oocytes was similar in both stimulation protocols.

What is known already
The use of progestins in the follicular phase to suppress a premature LH surge as an alternative to the GnRH analogue is an emerging regimen for ovarian stimulation. There is robust evidence of the safety and efficacy of PPOS compared to conventional ovarian stimulation regimens in oocyte donation cycles. Progestins and gonadotropins are typically administered simultaneously from day 2 or day 3 of the cycle onwards. Reports on initiation of progestins at a later stage, from day 6 of stimulation, are scarce.

Study design, size, duration
This is a retrospective longitudinal cohort study comparing two strategies of ovarian stimulation in the same oocyte donors. Oocyte donors who had a PPOS protocol between January 2021 and December 2021 and who had another ovarian stimulation cycle using a GnRH antagonist protocol within the same year were included in the analysis. Dydrogesterone 10 mg twice daily was started on day 6 of stimulation onwards. In total, 68 cycles from 34 oocyte donors were Included.

Participants/materials, setting, methods
All oocyte donors had the same type of gonadotropin and daily dose in both stimulation cycles. The primary outcome was the number of retrieved cumulus oocyte complexes (COC) and the number of metaphase II oocytes. Secondary outcomes were the duration of stimulation, the total dose of gonadotropins, the occurrence of premature ovulation and the difference in total cost between the two stimulation protocols.

Main results and the role of chance
The average female age was 28.3 years (SD 4.3), BMI 24.0 kg/m2 (SD 2.9) and AMH 2.9 µg/l (SD 1.5). When comparing the PPOS cycle with the GnRH antagonist cycle, the mean number of retrieved COCs was 20.0 ± 9.9 and 20.2 ± 9.3, respectively (p = 0.33) and the number of metaphase II oocytes was also similar (15.6 ± 7.9 and 16.9 ± 8.0, respectively; p = 0.35). The duration of stimulation (10.6 ± 1.7 days versus 10.9 ± 1.7 days; p = 0.26) and cumulative dose of gonadotropins (2284.6 ± 494.9 IU versus 2338.2 ± 462.1 IU; p = 0.25) were comparable in the PPOS and the GnRH antagonist group. No events of premature ovulation were observed in both groups. There was a significant difference in total medication cost per cycle between both protocols, 903.3 ± 195.7 € for PPOS versus 1205.3 ± 243.9 € (p &lt; 0.001) for the GnRH antagonist protocol. This means a cost reduction of 25% for the PPOS group compared to the GnRH antagonist group. GEE multivariate regression analysis allowing adjustment for relevant confounders (age, BMI, AMH) showed that the type of protocol was not significantly associated with the number of MII oocytes retrieved (coefficient 1.23, p = 0.33).

Limitations, reasons for caution
The small sample and the retrospective design are limitations of this study.

Wider implications of the findings
PPOS is a patient friendly and well-tolerated protocol. A simplified protocol of ovarian stimulation with the advantage of cost reduction. The protocol can easily be applied in oocyte donation and cycles with elective freeze all. Adequately powered RCTs should be performed to confirm our results.

Trial registration number
not applicable