Randomized, assessor-blinded trial comparing highly purified human menotropin and recombinant follicle-stimulating hormone in high responders undergoing intracytoplasmic sperm injection

Fertil Steril. 2020 Aug;114(2):321-330. doi: 10.1016/j.fertnstert.2020.03.029. Epub 2020 May 13.

Abstract

Objective: To evaluate the efficacy and safety of highly purified human menotropin (HP-hMG) and recombinant follicle-stimulating hormone (rFSH) for controlled ovarian stimulation in a population of patients predicted to be high responders.

Design: Randomized, open-label, assessor-blinded, parallel-group, noninferiority trial.

Setting: Fertility centers.

Patient(s): A total of 620 women with serum antimüllerian hormone (AMH) ≥5 ng/mL.

Intervention(s): Controlled ovarian stimulation with HP-hMG or rFSH in a GnRH antagonist assisted reproductive technology (ART) cycle. Fresh transfer of a single blastocyst was performed unless ovarian response was excessive, in which all embryos were cryopreserved. Subjects could undergo subsequent frozen blastocyst transfer within 6 months of randomization.

Main outcome measure(s): Ongoing pregnancy rate (OPR) after fresh transfer (primary endpoint), as well as cumulative live birth, ovarian hyperstimulation syndrome (OHSS), and pregnancy loss rates.

Results: OPR/cycle start after fresh transfer was 35.5% with HP-hMG and 30.7% with rFSH (difference: 4.7%, 95% CI -2.7%, 12.1%); noninferiority was established. Compared to rFSH, HP-hMG was associated with significantly lower OHSS (21.4% vs. 9.7% respectively; difference: -11.7%, 95% CI -17.3%, -6.1%) and cumulative early pregnancy loss rates (25.5% vs. 14.5% respectively; difference: -11.0%, 95% CI -18.8%, -3.14%). Despite 43 more transfers in the rFSH group, cumulative live birth rates were similar with HP-hMG and rFSH at 50.6% and 51.5% respectively (difference: -0.8%, 95% CI -8.7%, 7.1%).

Conclusion(s): In high responders, HP-hMG provided comparable efficacy to rFSH with fewer adverse events, including pregnancy loss, suggesting its optimized risk/benefit profile in this population.

Clinical trial registration number: NCT02554279 (clinicaltrials.gov).

Keywords: GnRH antagonist; Highly purified menotropin; Menopur; high responders; recombinant FSH.

Publication types

  • Comparative Study
  • Equivalence Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Spontaneous / etiology
  • Adult
  • Anti-Mullerian Hormone / blood
  • Biomarkers / blood
  • Female
  • Fertility
  • Fertility Agents, Female / adverse effects
  • Fertility Agents, Female / therapeutic use*
  • Follicle Stimulating Hormone, Human / adverse effects
  • Follicle Stimulating Hormone, Human / therapeutic use*
  • Humans
  • Infertility / diagnosis
  • Infertility / physiopathology
  • Infertility / therapy*
  • Live Birth
  • Male
  • Menotropins / adverse effects
  • Menotropins / therapeutic use*
  • Ovarian Hyperstimulation Syndrome / chemically induced
  • Ovary / drug effects*
  • Ovary / physiopathology
  • Ovulation / drug effects*
  • Ovulation Induction* / adverse effects
  • Pregnancy
  • Pregnancy Rate
  • Prospective Studies
  • Recombinant Proteins / therapeutic use
  • Single Embryo Transfer
  • Sperm Injections, Intracytoplasmic* / adverse effects
  • Treatment Outcome
  • United States
  • Young Adult

Substances

  • Biomarkers
  • Fertility Agents, Female
  • Follicle Stimulating Hormone, Human
  • Recombinant Proteins
  • Menotropins
  • Anti-Mullerian Hormone

Associated data

  • ClinicalTrials.gov/NCT02554279