Ovarian stimulation with follitropin delta is safe and effective: Results from the RITA randomized, double-blind, placebo-controlled trials.

Objective: To demonstrate the efficacy and safety of follitropin delta (recombinant follicle-stimulating hormone produced from the human cell line PER.C6®) for ovarian stimulation in patients aged 18-34 years and 35-42 years undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment in the United States (US).

Design: Two randomized, double-blind, placebo-controlled, parallel group, multicenter trials (RITA-1 and RITA-2).

Setting: US reproductive medicine clinics SUBJECTS: A total of 1,165 patients (578 women aged 18-34 years in RITA-1, and 587 women aged 35-42 years in RITA-2), randomized 10:1 to follitropin delta or placebo.

Intervention: Ovarian stimulation with follitropin delta at a fixed starting dose (12 μg/day for patients <35 years, 15 μg/day for patients ≥35 years) for the first four stimulation days and subsequent dose adjustments as needed, or placebo as a reference group, in a GnRH antagonist cycle.

Main outcome measure: Cumulative ongoing pregnancy rate after fresh and cryopreserved cycles initiated within 12 months from start of ovarian stimulation.

Results: Cumulative ongoing pregnancy rates with follitropin delta were 64.0% in patients aged <35 years (RITA-1) and 43.9% in patients aged ≥35 years (RITA-2) versus 0% with placebo, thus establishing superiority of follitropin delta to placebo (RITA-1: difference 64.0% [95% confidence interval (CI), 56.9% to 68.1%]; RITA-2: difference 43.9% [95% CI, 37.0% to 48.2%]). The cumulative live birth rate with follitropin delta was 62.5% in patients <35 years and 42.4% in patients ≥35 years. In the fresh transfer cycle, the ongoing pregnancy rate with follitropin delta was 49.5% in patients <35 years and 34.8% in patients ≥35 years, and the live birth rate was 48.2% and 33.9%, respectively. In cryopreserved transfer cycles, the ongoing pregnancy rate with follitropin delta was 44.2% in patients <35 years and 31.2% in patients ≥35 years, and the live birth rate was 42.8% and 29.9%, respectively. The incidence of OHSS in the fresh cycle was 3.8% in patients <35 years and 2.4% in patients ≥35 years after treatment with follitropin delta.

Conclusion: Follitropin delta, dosed based on maternal age, is an effective and safe therapeutic for ovarian stimulation in IVF/ICSI patients.

Trial registration: For RITA-1: NCT03740737 (clinicaltrials.gov), registered on 24 Oct 2018, first subject enrolled on 26 Oct 2018. For RITA-2: NCT03738618 (clinicaltrials.gov), registered on 24 Oct 2018, first subject enrolled on 29 Oct 2018.