Follitropin delta in repeated ovarian stimulation for IVF: a controlled, assessor-blind Phase 3 safety trial

Reprod Biomed Online. 2019 Feb;38(2):195-205. doi: 10.1016/j.rbmo.2018.10.012. Epub 2018 Dec 14.


Research question: To evaluate the immunogenicity of follitropin delta in repeated ovarian stimulation.

Design: Controlled, assessor-blind trial in IVF/intracytoplasmic sperm injection patients undergoing repeated cycles of ovarian stimulation (cycles 2 and 3), following initial stimulation with follitropin delta or follitropin alfa (cycle 1) in a preceding randomized trial. In cycles 2 and 3, 513 and 188 women, respectively, were treated as randomized in cycle 1, with dosing based on ovarian response in the previous cycle.

Results: The incidence of treatment-induced anti-FSH antibodies with follitropin delta was 0.8% and 1.1% in cycles 2 and 3, respectively, which was similar to the incidence in cycle 1 (1.1%). No antibodies were of neutralizing capacity. Women with pre-existing anti-FSH antibodies were safely treated with follitropin delta without boosting an immune response. Treatment with follitropin delta and follitropin alfa gave similar outcomes for mean number of oocytes retrieved (9.2 versus 8.6 [cycle 2]; 8.3 versus 8.9 [cycle 3]), ongoing pregnancy (27.8% versus 25.7%; 27.4% versus 28.0%) and live birth rates (27.4% versus 25.3%; 26.3% versus 26.9%). The presence of anti-FSH antibodies did not affect the ovarian response.

Conclusions: The trial demonstrated the low immunogenicity potential of follitropin delta in repeated ovarian stimulation, and confirmed the appropriateness of the follitropin delta dosing regimen in repeated cycles, with documented efficacy and safety.

Keywords: Follitropin delta; Immunogenicity; Ovarian response; Pregnancy; Safety.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Neutralizing
  • Drug Administration Schedule
  • Female
  • Follicle Stimulating Hormone / immunology
  • Follicle Stimulating Hormone, Human / administration & dosage
  • Follicle Stimulating Hormone, Human / adverse effects*
  • Humans
  • Ovarian Follicle / drug effects*
  • Ovulation Induction / methods*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Treatment Outcome
  • Young Adult


  • Antibodies, Neutralizing
  • Follicle Stimulating Hormone, Human
  • Recombinant Proteins
  • follitropin alfa
  • follitropin delta
  • Follicle Stimulating Hormone