JBRA Assisted Reproduction 2025;29(Suppl.2 SBRA 2025):96
Poster Presentation

29th Annual Congress of the SBRA. São Paulo/SP - Brazil, 2025
doi: 10.5935/1518-0557.20263683

P-84. Evaluating ovarian stimulation outcomes using the Fisher Protocol versus luteal and follicular phase stimulation with delta-follitropin plus hMG: A real-world observational multicenter study

Giovana De-Nardo Maffazioli1, Oscar Duarte2, João A Dias-Jr1, Carlos Roberto Izzo1, Georges Fassolas1, Luiz Fernando Henrique1, Eduardo Hideki Miyadahira2, Marcelo Welker Sapojkin Rossine2, Vanessa Heinrich2, Carolina Rebello Da Costa2, Roberto de Azevedo Antunes3, Maria do Carmo Borges de Souza3, Layna Almeida3, Verônica de Almeida Raupp3, Brunna Stumpo Vaz3, Edson Borges-Jr4, Daniela Braga4, Maite Del Collado4, Caio Parente5, Emerson Barchi Cordts5, Renato Oliveira5.

1 Clinica Originare - Medicina Reprodutiva - São Paulo - SP - Brasil
2 Vida Bem Vinda Medicina Reprodutiva - São Paulo - SP - Brasil
3 Fertipraxis – Centro de Reprodução Humana - Rio de Janeiro - RJ – Brasil
4 Fertility Medical Group - São Paulo - SP - Brasil 5 Ideia Fertil - São Paulo - SP - Brasil

Objective: To assess whether luteal phase stimulation (LPS) or synthetic progesterone pretreatment (FPP) improve oocyte yield and clinical outcomes in GnRH antagonist ovarian stimulation protocols.
Methods: Retrospective multicenter study that included data from five assisted reproduction clinics in Brazil. Women aged 18– 42 undergoing their first controlled ovarian stimulation cycle (2018–2025) for IVF, ICSI, oocyte donation, or cryopreservation were eligible. All participants received delta-follitropin plus menotropin (hMG). Groups were divided according to stimulation starting: early follicular phase (FPS) versus LPS versus FPP. FPP was administered according to the Fisher protocol for IVI/ ICSI cycle programming. AMH was assessed within 12 months prior. The primary outcome was follicular output rate (FORT). Appropriated statistical tests were used to analyze the data.
Results: Among 700 patients, 403 belonged to the FPS group, 27 to the LPS and 340 to the FPP. The groups were similar in age (36.7±3.9 vs. 36.7±5.8 vs. 37.0±3.5 years, p=0.55), BMI (24.0±4.2 vs 22.5±2.6±23.1±3.0 kg/m2, p=0.08), AMH levels [1.33 (0.67–2.51) vs. 1.63 (0.94–2.89) vs 1.47 (0.75-2.41) ng/mL, p=0.67], and baseline antral follicle count [10 (7-14) vs 8 (5-10) vs 10 (7-14) follicles, p=0.32]. FORT was higher in FPP group compared to FPS, but did not differ from the LPS group (53.2±30.1% vs. 50.3±15.0% vs 59.9±32.2%, p=0.03), even after adjustment for duration of stimulation (p=0.04). Oocyte yield was similar [9 (5–16) vs. 9 (6–13) vs. 10 (6-16), p=0.32], but MII count was higher in the FPP group compared to FPS [7 (4–11) vs.7 (4–11) vs 8 (5-12), p=0.003, duration of stimulation -adjusted p=0.001]. Total delta-follitropin dose was higher [93.2±24.1 vs. 84.9±20.7 vs 80.6± 14.1 mcg, p<0.0001], while the hMG dose was lower [1057.1±400.0 vs. 1280.6±533.6 vs 1347.3±326.1 IU, p<0.0001] in FPS group compared to FPP. Stimulation was shorter in the FPS compared to the other groups [9 (9–10) vs. 10 (9–11) vs 10 (9-11) days, p<0.0001]. Only one OHSS case occurred (0.3%) in the FPP group. No cycle was cancelled for low response. Maturity rate was higher in the FPP group (73.6±23.1% vs. 76.1±22.0 % vs 78.1± 18.9, p=0.02, duration of stimulation -ajusted, p=0.01). Fertilization (80.0±20.3% vs. 70.0±28.5% vs 81.2±19.3, p=0.17) and blastulation rates (49.4±30.4% vs. 55.3±34.5 vs 48.9±28.5 %, p=0.75) were similar among groups.
Conclusion: Late luteal synthetic progesterone pretreatment improved oocyte yield efficiency in GnRH antagonist cycles using delta-follitropin plus hMG, without significantly increasing gonadotropin use or stimulation duration. Moreover, luteal phase stimulation showed comparable effectiveness in stimulation outcomes and oocyte maturity, although group small sample size was a limitation. Synthetic progestogens pretreatments in the late luteal phase may improve stimulation efficiency and enable more flexible gonadotropin scheduling in assisted reproduction. Protocol choice should be individualized based on clinical context and individual needs.