P-618 Impact of ovarian stimulation on outcome of oocyte in-vitro maturation (IVM) in women with polycystic ovaries: corifollitropin alfa (CFA) versus follitropin beta (FSH-B)
Authors: De Vos M , Mostinckx L , Smitz J , Blockeel C , Segers I 
Published: July 2024

Abstract

Study question
Do corifollitropin alfa and follitropin beta have different effects on oocyte yield and live birth rates after IVM in women with polycystic ovaries?

Summary answer
In patients who underwent IVM, one injection of CFA resulted in lower oocyte retrieval rates, but similar birth rates compared to three injections of FSH-B.

What is known already
IVM involves the maturation of cumulus oocyte complexes (COCs) from antral follicles and has been offered to women with polycystic ovaries as an alternative for conventional ovarian stimulation (OS). Exogenous FSH is typically administered for two to five days in IVM cycles to enhance meiotic and developmental competence of immature oocytes in vivo. Previous studies have shown that the number of COCs is associated with ongoing pregnancy after IVM. Because one injection of CFA yields more oocytes compared to daily FSH-B injections in conventional OS protocols, CFA has the potential to combine patient-friendliness and maximised COC yield in IVM cycles.

Study design, size, duration
We conducted a randomised controlled superiority trial from 12/2017 to 12/2023. The primary endpoint was the number of COCs at collection. We randomised 145 patients to either one CFA 100μg injection or three daily injections of FSH-B 150IU. Laboratory and safety parameters, and pregnancy outcomes after frozen embryo transfer (FET) were analysed on an intention-to-treat basis. All cycles were scheduled using oral contraceptive pretreatment.

Participants/materials, setting, methods
Eligible patients were &lt;37 years, had ≥24 antral follicles, and BMI 18-30 kg/m2. We analysed serum estradiol, progesterone, LH, and FSH on stimulation day 1 and 3, at oocyte retrieval (OR), and at OR + 6d. Oocyte retrieval (OR) was performed five days after the start of OS. No ovulation trigger was given. Monophasic IVM for 30h, ICSI and elective freeze-all were done in a tertiary fertility clinic. Data were analysed using STATA 13.0.

Main results and the role of chance
After randomisation, 70 patients underwent OR after FSH-B and 72 had OR after CFA. Hormone levels at OR were significantly different between FSH-B-treated (FSH 6.8 ± 2.8IU/L, LH 3.3 ± 2.7IU/L, E2 106.7 ± 147.0ng/L, Prog 0.19 ± 0.16μg/L) and CFA-treated patients (FSH 24.3 ± 7.9IU/L, LH 1.8 ± 1.6IU/L, E2 575.6 ± 516.2ng/L, Prog 0.29 ± 0.21 μg/L, p ≤ 0.001). On average, 43.1 ± 21.7(FSH-B) vs. 50.8 ± 29.2(CFA) follicles, all &lt;10mm, were punctured during OR (p = 0.06). More COCs per follicle were retrieved after FSH-B (68.3 ± 31.5% vs. 51.0 ± 24.7%, p = 0.001), resulting in a tendency towards more COCs after FSH-B (31.4 ± 23.3), compared to CFA (23.4 ± 11.7, p = 0.07). Maturation rates after IVM were similar (49 ± 19% vs. 50 ± 15%, p = 0.79). In spite of a tendency towards more mature oocytes after FSH-B (16.0 ± 14.6 vs. 11.7 ± 7.9, p = 0.09), the number of good-quality cryopreserved embryos was similar (3.9 ± 2.9(FSH-B) vs. 3.5 ± 2.7(CFA), p = 0.36). Live birth rate (LBR) after the first FET (25.7%(FSH-B) vs. 34.7%(CFA), p = 0.24) and cumulative LBR six months after OR (40.0%(FSH-B) vs. 45.8%(CFA), p = 0.48) were comparable. None of the patients developed ovarian hyperstimulation syndrome (OHSS).

Limitations, reasons for caution
Outcomes are only applicable for patients with high antral follicle count (AFC) who are treated using a monophasic IVM culture system. The sample size was too small to draw significant conclusions for live birth rate.

Wider implications of the findings
In subfertile patients with high AFC who have IVM treatment, follicle priming with one injection of CFA is safe, convenient, and as efficacious as priming with FSH-B. The observation of lower oocyte retrieval rates after CFA compared to FSH-B in the specific setting of an IVM cycle merits further scrutiny.

Trial registration number
EudraCT 2017-002571-25