Comparing pregnancy rates following ovarian stimulation with follitropin-Δ to follitropin -α in routine IVF: A retrospective analysis

  • Peter Kovacs
    Corresponding author.
    Dunamenti REK, IVF Center, Budapest, Hungary

    Dunamenti REK, IVF Center, Istenhegyi ut 54/a, Budapest, Hungary
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  • Jayapriya Jayakumaran
    University of Central Florida College of Medicine, Department of Obstetrics and Gynecology, Orlando, FL 32827, United States
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  • Yao Lu
    Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, PR China

    Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, PR China
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  • Steven R Lindheim
    University of Central Florida College of Medicine, Department of Obstetrics and Gynecology, Orlando, FL 32827, United States

    Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, PR China

    Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, PR China

    Wright State University Boonshoft School of Medicine, Dayton, OH, 45409 USA
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Published:November 08, 2022DOI:


      • Follitropin—Δ is associated with increased FSH exposure due to unique glycosylation.
      • RCTs reported reduced gonadotropin need and more optimal response with follitropin- Δ.
      • RCTs included selected, better prognosis patients.
      • Retrospective analyses of REI practice’s experience with follitropin- Δ.
      • Less than “ideal” patients suggest similar findings to RCTs.


      Study objectives

      Follitropin-Δ, a new recombinant follicle stimulation hormone, uses a fixed daily dose producing a predictable ovarian response while using less gonadotropins compared to follitropin-α. We report clinical outcomes comparing each in the routine IVF setting and further compare qualified to disqualified subjects based on previous randomized controlled trial (RCT) inclusion criteria.

      Study design

      Retrospective analysis of all cycles performed by a single provider between January 2020 to January 2021. All IVF cycles without patient inclusion–exclusion criteria were considered for the analysis. Clinical outcomes in two groups (follitropin-Δ vs follitropin-α ± 75 IU human menopausal gonadotropin (hMG) in expected poor responders) were compared. In addition, comparisons were made between qualified versus disqualified subgroups.


      No differences in baseline demographics, number of MII oocytes, fertilization/MII oocyte, percent of good quality embryos were noted. Compared to those using follitropin-α, follitropin-Δ resulted in lower daily (170 vs 211 IU/d, p = 0.002) and total Gn used (1739 vs 2194 IU, p = 0.003). Optimal range response (8–14 oocytes) (22/44 [50 %] vs 78/203 [38.6 %]; p = 0.10) and fresh (fCP) and cumulative clinical pregnancy (cCP) rates per transfer (29.5 % vs 24.1 % and 35 % vs 25.1 %, p = 0.08) were similar between groups. Based on previous RCTs, those who would have qualified compared to those who would have disqualified, patients using follitropin-Δ were just as likely to have an optimal oocyte response (qualified: 48 % vs disqualified: 57.1 %) and resulted in similar cCP (41.4 % vs 25 %, p-0.23).


      While follitropin-Δ requires less daily and total dosing compared to follitropin-α, optimal range of retrieved oocytes and clinical outcomes appear to be comparable. Using RCT inclusion criteria, similar findings were noted in those who would have qualified compared to disqualified patients.


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        • Templeton A.
        • Morris J.K.
        • Parslow W.
        Factors that affect outcome of in-vitro fertilisation treatment.
        Lancet. 1996; 348: 1402-1406
      1. Bosch E, Broer S, Griesinger G, Grynberg M, Humaidan P, Kolibianakis E, Kunicki M, La Marca A, Lainas G, Le Clef N, Massin N, Mastenbroek S, Polyzos N, Sunkara SK, Timeva T, Töyli M, Urbancsek J, Vermeulen N, Broekmans F. ESHRE guideline: ovarian stimulation for IVF/ICSI. Ovarian Stimulation TEGGO. Hum Reprod Open. 2020 May 1;2020(2):hoaa009. 10.1093/hropen/hoaa009.

        • Steward R.G.
        • Lan L.
        • Shah A.A.
        • Yeh J.S.
        • Price T.M.
        • Goldfarb J.M.
        • et al.
        Oocyte number as a predictor for ovarian hyperstimulation syndrome and live birth: an analysis of 256,381 in vitro fertilization cycles.
        Fertil Steril. 2014; 101: 967-973
        • Sunkara S.K.
        • Rittenberg V.
        • Raine-Fenning N.
        • Bhattacharya S.
        • Zamora J.
        • Coomarasamy A.
        Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles.
        Hum Reprod. 2011; 26: 1768-1774
      2. Polyzos NP, Drakopoulos P, Parra J, Pellicer A, Santos-Ribeiro S, Tournaye H, Bosch E, Garcia-Velasco J. Cumulative live birth rates according to the number of oocytes retrieved after the first ovarian stimulation for in vitro fertilization/intracytoplasmic sperm injection: a multicenter multinational analysis including 15,000 women. Fertil Steril. 2018 ;110(4):661-70.e1. 10.1016/j.fertnstert.2018.04.039.

        • Andersen A.N.
        • Nelson S.M.
        • Fauser B.C.
        • García-Velasco J.A.
        • Klein B.M.
        • Arce J.C.
        ESTHER-1 study group. Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial.
        Fertil Steril. 2017; 107: 387-396
        • Lunenfeld B.
        Historical perspectives in gonadotrophin therapy.
        Hum Reprod Update. 2004; 10: 453-467
      3. van Wely M, Kwan I, Burt AL, Thomas J, Vail A, Van der Veen F, Al-Inany HG. Recombinant versus urinary gonadotrophin for ovarian stimulation in assisted reproductive technology cycles. Cochrane Database Syst Rev 2011 Feb 16;2011(2):CD005354. 10.1002/14651858.CD005354.pub2.

        • Olsson H.
        • Sandström R.
        • Grundemar L.
        Different pharmacokinetic and pharmacodynamic properties of recombinant follicle-stimulating hormone (rFSH) derived from a human cell line compared with rFSH From a non-human cell line.
        J Pharmacol. 2014; 54: 1299-1307
        • Koechling W.
        • Plaksin D.
        • Croston G.E.
        • Jeppesen J.V.
        • Macklon K.T.
        • Andersen C.Y.
        Comparative pharmacology of a new recombinant FSH expressed by human cell line.
        Endocr Connect. 2017; 6: 297-305
        • Arce J.C.
        • Klein B.M.
        • Erichesn L.
        Using AMH for determining a stratified gonadotropin dosing regimen for IVF/ICSI and optimizing outcomes.
        in: Seifer D.B. Tal R. Anti-Müllerian hormone: biology, role in ovarian function and clinical significance. Nova Science Publishers, Hauppauge, New York2016: 83-112
        • Ishihara O.
        • Klein B.M.
        • Arce J.C.
        Japanese Follitropin Delta Phase 2 Trial Group. Individualized follitropin delta dosing reduces OHSS risk in Japanese IVF/ICSI patients: a randomized controlled trial.
        RBMO. 2021; 42: 909-918
        • Qiao J.
        • Zhang Y.
        • Lian X.
        • Ho T.
        • Huang H.-Y.
        • Kim S.-H.
        • et al.
        A randomised controlled trial to clinically validate follitropin delta in its individualised dosing regimen for ovarian stimulation in Asian IVF/ICSI patients.
        Hum Reprod. 2021; 36: 2452-2462
      4. Bosch E, Havelock J, Martin FS, Rasmussen BB, Klein BM, Mannaerts B, Arce JC; ESTHER-2 Study Group. Follitropin delta in repeated ovarian stimulation for IVF: a controlled, assessor-blind Phase 3 safety trial. RBMO 2019;38:195-205. 10.1016/j.rbmo.2018.10.012.

        • Viraj S.
        Phase IV drug development.
        Perspect Clin Res. 2010; 1: 57-60
        • Maheshwari A.
        • McLernon D.
        • Bhattacharya S.
        Cumulative live birth rate: time for a consensus?.
        Hum Reprod. 2015; 30: 2703-2707
        • Arce J.C.
        • Larsson P.
        • García-Velasco J.A.
        Establishing the follitropin delta dose that provides a comparable ovarian response to 150 IU/day follitropin alfa.
        RBMO. 2020; 41: 616-622
      5. Wyns C, Bergh C, Calhaz-Jorge C, De Geyter Ch, Kupka MS, Motrenko T, Rugescu I, Smeenk J, Tandler.Schneider A, Vidakovic S, Gossens V. The European IVF-monitoring Consortium for the European Society of Human Reproduction and Embryology (ESHRE). ART in Europe, 2016: results generated from European registries by ESHRE. Hum Reprod Open 2020;0:1-17. 10.1093/hropen/hoaa032.

      6. Hershkop E, Segal L, Fainaru O, Kol S. ‘Model’ versus ‘everyday’ patients: can randomized controlled trial data really be applied to the clinic? RBMO 2017;34:274-79. 10.1016/j.rbmo.2016.11.010.

        • Rothwell P.M.
        External validity of randomised controlled trials: “to whom do the results of this trial apply?”.
        Lancet. 2005; 365: 82-93
        • Glasgow R.E.
        • Green L.W.
        • Klesges L.M.
        • Abrams D.B.
        • Fisher E.B.
        • Goldstein M.G.
        • et al.
        External validity: we need to do more.
        Ann Behav Med. 2006; 31: 105-108
        • Dekkers O.M.
        • von Elm E.
        • Algra A.
        • Romijn J.A.
        • Vandenbroucke J.P.
        How to assess the external validity of therapeutic trials: a conceptual approach.
        Int J Epidemiol. 2010; 39: 89-94