A new instrument to personalize ovarian stimulation: results of the CERES study after using a novel gonadotropin – follitropin delta

Authors: Bagócsi T. 1;  Rumpík D. 2;  Křenek O. 2;  Machač Š. 3;  Vrublovský P. 3;  Štěpán J. 4;  Černý M. 5;  Mardešićová N. 6;  Dvořák J. 7;  Višňová H. 8
Authors‘ workplace: Reprofi t International s. r. o., Brno 1;  Klinika reprodukční medicíny a gynekologie, Zlín 2;  IVF Clinic a. s., Olomouc 3;  Sanatorium Sanus, Hradec Králové 4;  GENNET, s. r. o., Praha 5;  PRONATAL Sanatorium, Praha 6;  PRONATAL Kolín 7;  IVF Cube SE, Praha 8
Published in: Ceska Gynekol 2021; 86(2): 86-92
Category: Original Article
doi: 10.48095/cccg202186


: Objective: The aim of the study CERES (CzEch REkovelle real life Study) was to gather experience with the use of a novel gonadotrophine, to evaluate the efficacy of follitropin delta in Czech clinical settings and to compare our results with the clinical trial ESTHER-1. Methods: Individualized follitropin delta daily dose in µg based on the patient’s anti-Müllerian hormone (AMH) level and body weight (AMH < 15 pmol/ L: 12 µg/ d; AMH > 15 pmol/ L: 0.10–0.19 µg/ kg/ d; max. 2 µg/ d). Results: A total of 85 women (aged 24–42 years) was included in the study. The average patient’s age was 32.9 years, the average body weight was 67.8 kg, and the mean level of AMH was 23.2 pmol/ L. There were initiated 85 controlled ovarian stimulations with follitropin delta and 84 egg collections. Forty patients (47%) had optimal number of retrieved eggs (8–14), 75 patients (88%) had embryotransfer, 10 patients (12%) had no embryo suitable for transfer, 65 patients had single embryo transfer and 10 patients had 2 embryos for transfer. There were reported 37 clinical pregnancies (43.5% cPR – clinical pregnancy rate), 30 live births (35.3% LBR – live birth rate), 3 (3.5%) early moderate ovarian hyperstimulation syndroms (OHSS) and no hospitalization due to the treatment. Conclusion: Individualized ovarian stimulation optimizes ovarian response, maintains treatment efficacy and improves safety by reducing OHSS incidence. The results of the Czech population study are fully comparable with the international, randomized, assessor-blinded trial ESTHER-1.


follitropin delta – controlled ovarian stimulation – anti-Müllerian hormone – ovarian response – ovarian hyperstimulation syndrome – personalized medicine


1. Cartland GF, Nelson JW. The preparation and purification of extracts containing the gonad-stimulating hormone of pregnant mare serum. J Biol Chem 1937; 119(1): 59–67.

2. Howles CM. Genetic engineering of human FSH (Gonal-F). Hum Reprod Update 1996; 2(2): 172–191. doi: 10.1093/ humupd/ 2.2.172.

3. Leao RB, Esteves SC. Gonadotropin therapy in assisted reproduction: an evolutionary perspective from bio­logics to bio­tech. Clinics 2014; 69(4): 279–293. doi: 10.6061/ clinics/ 2014(04)10.

4. Cottingham I, Plaksin D, White RB. Recombinant Fsh including alpha 2,3- and alpha 2,6-sialylation. World Intellectual Property Organization, Patent: WO 2009/ 127826 A1. 2009 [online]. Available from: https:/ / lens.org/ 199-058-359-047-42X.

5. Ulloa-Aguirre A, Timossi C, Damián-Matsumura P et al. Role of glycosylation in function of follicle-stimulating hormone. Endocrine 1999; 11(3): 205–215. doi: 10.1385/ ENDO:11:3:205.

6. 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 Clin Pharmacol 2014; 54(11): 1299–1307. doi: 10.1002/ jcph.328.

7. Steward RG, Lan L, Shah AA 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(4): 967–973. doi: 10.1016/ j.fertnstert. 2013.12.026.

8. Humaidan P, Alviggi C, Fischer R et al. The novel POSEIDON stratification of ‘low prognosis patients in assisted reproductive technology’ and its proposed marker of successful outcome. F1000Res 2016; 5: 2911. doi: 10.12688/ f1000research.10382.1.

9. Drakopoulos P, Blockeel C, Stoop D et al. Conventional ovarian stimulation and single embryo transfer for IVF/ ICSI. How many oocytes do we need to maximize cumulative live birth rates after utilization of all fresh and frozen embryos? Hum Reprod 2016; 31(2): 370–376. doi: 10.1093/ humrep/ dev316.

10. La Marca A, Sighinolfi G, Radi D et al. Anti-Müllerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART). Hum Reprod Update 2010; 16(2): 113–130. doi: 10.1093/ humupd/ dmp036.

11. Iliodromiti S, Anderson RA, Nelson SM. Technical and performance characteristics of anti-Müllerian hormone and antral follicle count as bio­markers of ovarian response. Hum Reprod Update 2015; 21(6): 698–710. doi: 10.1093/ humupd/ dmu062.

12. Vrublovský P. Hodnota AMH jako prediktor výsledku ovariální stimulace. Ceska Gynekol 2016; 81(1): 23–26.

13. Klein BM, Arce JC. Impact of body weight of IVF/ ICSI patients on the pharmacokinetics and pharmacodynamic responses to FE 999049, a recombinant FSH derived from a human cell-line. Hum Reprod 2014; 29(Suppl 1): i322.

14. Arce JC, Klein BM, Erichsen L. Using AMH for determining a stratified gonadotropin dosing regimen for IVF/ ICSI and optimizing outcomes. In: Seifer DB, Tal R (eds). Anti-Müllerian hormone: bio­logy, role in ovarian function and clinical significance. USA: Nova Science Publishers 2016: 83–102.

15. Nyboe Andersen A, Nelson SM, Fauser BC et al. Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial. Fertil Steril 2017; 107(2): 387–396. doi: 10.1016/ j.fertnstert.2016.10.033.

16. Arce JC, Nyboe Andersen A, Fernández-Sánchez M et al. Ovarian response to recombinant human follicle-stimulating hormone: a randomized, antimüllerian hormone-stratified, dose-response trial in women undergoing in vitro fertilization/ intracytoplasmic sperm injection. Fertil Steril 2014; 102(6): 1633–1640. doi: 10.1016/ j.fertnstert.2014.08.013.

17. Řežábek K. Asistovaná reprodukce. 2. vyd. Praha: Maxdorf 2014.

18. Diedrich K, Ludwig M, Griesinger G. Reproduktionsmedizin. Berlin: Springer Medizin 2013.

19. Brinsden PR. Textbook of in vitro fertilization and assisted reproduction: the Bourn Hall guide to clinical and laboratory practice. 3rd ed. London: Taylor & Francis 2005.

20. Gardner DK, Weissman A, Howles CM et al. Textbook of assisted reproductive techniques. 5th ed. Boca Raton: CRC Press 2018.

21. Gordon K, Levy MJ, Ledger W et al. Reducing the incidence of weekend oocyte retrievals in a rFSH/ GnRH antagonist protocol by optimizing the start day of rFSH and delaying human chorionic gonadotropin (hCG) by 1 day. Fertil Steril 2011; 95(4): S16.

22. Gleicher N, Weghofer A, Barad DH. Anti-Müllerian hormone (AMH) defines, independent of age, low versus good live-birth chances in women with severely diminished ovarian reserve. Fertil Steril 2010; 94(7): 2824–2827. doi: 10.1016/ j.fertnstert.2010.04.067.

23. Nelson SM, Yates RW, Fleming R. Serum anti-Müllerian hormone and FSH: prediction of live birth and extremes of response in stimulated cycles – implications for individualization of therapy. Hum Reprod, 2007; 22(9): 2414–2421. doi: 10.1093/ humrep/ dem204.

24. Mardešić T. Antimülleriánský hormon v moderní reprodukční medicíně. Gynekol Porod 2019; 3(4): 213–219.

25. Anderson RA, Anckaert E, Bosch E et al. Prospective study into the value of the automated Elecsys antimüllerian hormone assay for the assessment of the ovarian growing follicle pool. Fertil Steril 2015; 103(4): 1074–1080. doi: 10.1016/ j.fertnstert.2015.01.004.

26. Gassner D, Jung R. First fully automated immunoassay for anti-Müllerian hormone. Clin Chem Lab Med 2014; 52(8): 1143–1152. doi: 10.1515/ cclm-2014-0022.

27. Practice committee of the american society for reproductive medicine. Ovarian hyperstimulation syndrome. Fertil Steril 2008; 90(Suppl 5): S188–S193. doi: 10.1016/ j.fertnstert.2008.08.034

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