O-303 What is the ideal dose of daily FSH after corifollitropin-alfa? A multicentre-randomized control trial
Authors: Racca A , Santos-Ribeiro S , Errazuriz J , Griesinger G , Boudry L , Mackens S , Roelens C , Penning D , Delbaere A , Decleer W , Tournaye H , Blockeel C 
Published: July 2024

Abstract

Study question
Does the mean serum trigger-progesterone levels show significant variation based on the administered rFSH dose from day 8 onwards during ovarian stimulation using corifollitropin-alfa?

Summary answer
Lower rFSH doses from day 8 of ovarian stimulation onwards are linked to reduced serum progesterone (P4) levels without impact on cumulus-oocyte complexes.

What is known already
Progesterone elevation during ovulation trigger prompts a non-elective freeze-all strategy, given the lower live birth rates in fresh embryo transfers. Ongoing research explores methods to mitigate late follicular phase P4 rise to allow a fresh embryo transfer. Granulosa cells’ progesterone production is an FSH-driven and dose-dependent process, and FSH dose is furthermore pivotal for a good ovarian response. Balancing FSH dose is crucial for both optimal ovarian response and preventing undesirable P4 elevation while maintaining an adequate number of retrieved oocytes and allowing a fresh embryo transfer.

Study design, size, duration
This study is an interim-analysis of a randomized-controlled multi-center clinical-trial comparing three ovarian-stimulation-protocols: (A) corifollitropin alfa (CFA) followed by rFSH 50 IU/day; (B) CFA followed by rFSH 150 IU/day; (C) CFA followed by rFSH 250 IU/day.The primary outcome is the serum-progesterone-level on the day of hCG among the study groups, secondary outcomes included number of oocytes, clinical pregnancy rates and freeze-all cycles. 167 women (of 261) were randomized between July 2019-November 2023, with a 1:1allocation.

Participants/materials, setting, methods
Young (&lt;40 years old), normo-ovulatory cycle (25-35 days), with AFC&gt;7 and &lt;20, and a BMI&lt;29 Kg/m2 patients were recruited in the fertility clinic of three different tertiary university hospitals. On day 8 of ovarian stimulation (OS) following CFA administration, patients who needed additional rFSH were randomized into 3 groups (A-B-C). The OS was performed in a GnRH-antagonist protocol and the ovulation triggered with hCG. A fresh embryo-transfer was performed on day 5 following oocyte retrieval.

Main results and the role of chance
Overall, 167 patients were randomized, 60 in group A, 55 in group B and 52 in group C. The mean age and BMI were comparable between the groups. Mean AMH was respectively 2.2, 2.1 and 2.2 ng/mL, for group A, B and C (p = 0.95). Group A resulted in a significantly lower P4 level at trigger as compared with group B and C (respectively, 0.4ng/mL, 0.9 ng/mL and 1.4 ng/mL; p &lt; 0.001). The mean number of retrieved oocytes was 10.7, 11 and 12.1 for group A, B and C, respectively (p = 0.47), while the mean number of mature oocytes was 7.3, 6.9 and 7.8 for group A, B and C, respectively (p = 0.7). A freeze-all approach was decided for 27%, 29% and 46% for group A, B and C respectively (p = 0.057). No significant differences were found for fresh-embryo-transfer outcomes (chemical pregnancy rates: 33%, 31% and 29%, respectively for A, B and C (p = 0.12).Of interest, comparisons between serum FSH at trigger showed a mean of 12.5, 17 and 20.5 IU/L for group A, B and C, respectively (p &lt; 0.001) while the serum estradiol levels on day of trigger were comparable among the groups (1659, 2092 and 2098 ng/L for group A, B and C, respectively (p = 0.091).

Limitations, reasons for caution
This is an interim analysis planned to detect the mean difference in COC between groups. Therefore, the mean differences of the primary outcome should be interpreted as exploratory findings which warrant future investigation.

Wider implications of the findings
Administering a lower rFSH dose from day 8 onward during ovarian stimulation results in comparable numbers of COC but also leads to significantly lower serum P4 levels. Consequently, this finding has the potential to reduce the overall consumption of rFSH, thereby possibly increasing the likelihood of a fresh embryo transfer.

Trial registration number
NCT03686852