Follitropin Delta Achieves Ongoing Pregnancy in 64% Under Age 35

Follitropin delta (Rekovelle; Ferring), a recombinant follicle-stimulating hormone produced in a human cell line, achieved cumulative ongoing pregnancy rates of 64.0% in patients younger than 35 years and 43.9% in those aged 35 to 42 years.¹ No patient receiving a placebo achieved an ongoing pregnancy, according to 2 phase 3 trials published in Fertility and Sterility.

Trial Design and Dosing

The RITA-1 (NCT03740737) and RITA-2 (NCT03738618) trials were randomized, double-blind, placebo-controlled studies at 23 and 24 US sites, respectively, between October 2018 and November 2020. They enrolled 1165 patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI): 578 women aged 18 to 34 years in RITA-1 and 587 aged 35 to 42 years in RITA-2, randomized 10:1 to follitropin delta or placebo.

Dosing was age-based instead of the algorithm using anti-Müllerian hormone and body weight that the drug follows globally. Patients younger than 35 years started at 12 μg per day and those 35 or older at 15 μg per day for 4 days, then adjusted in 3-μg steps by ovarian response in a gonadotropin-releasing hormone antagonist protocol.

The primary end point was cumulative ongoing pregnancy, defined as at least 1 viable intrauterine fetus at 8 to 9 weeks after transfer on ultrasound, across fresh and cryopreserved transfer cycles initiated within 12 months of starting stimulation. Follitropin delta was superior to placebo in both trials (P < .001). The cumulative live birth rate was 62.5% in the younger group and 42.4% in the older group.

Per transfer cycle, fresh cycles produced ongoing pregnancy rates of 49.5% in the younger group and 34.8% in the older group, with live birth rates of 48.2% and 33.9%. Cryopreserved cycles produced ongoing pregnancy rates of 44.2% and 31.2%, with live birth rates of 42.8% and 29.9%.

Nearly All Transfers Used a Single Blastocyst

According to the investigators, single blastocyst transfer was used in all transfers in patients younger than 35 years and 94.5% of transfers in older patients. They said outcomes compared favorably with earlier trials that used follitropin beta as a comparator, citing cumulative ongoing pregnancy rates of 51.9% in North American women aged 36 years or younger and 30.1% in US women aged 35 to 42 years.^2,3 They also cited a Society for Assisted Reproductive Technology cumulative live birth rate of about 55% for women younger than 35 years from 2017 to 2021.⁴ These comparisons are indirect.¹

Ovarian hyperstimulation syndrome (OHSS) in the fresh cycle occurred in 3.8% of patients younger than 35 years and 2.4% of those 35 years or older. Moderate or severe OHSS occurred early in 1.9% of younger and 0.8% of older patients and late in 0.8% of each group. Adverse drug reactions were reported in 12.0% of patients receiving follitropin delta and 3.7% of those receiving placebo, with pelvic discomfort the most common at 4.7%. Injection site reactions were similar, at 4.2% of follitropin delta assessments and 4.9% of placebo assessments.

Why the Trials Used Placebo

Follitropin delta is a new molecular entity, meaning a new drug rather than a biosimilar, and US recombinant FSH products come in proprietary pen devices, which the authors said ruled out a double-blind comparison with an approved gonadotropin. A placebo comparator was selected after discussions with the FDA. Patients with poor ovarian response were offered medication and financial support for treatment outside the trial.

The authors acknowledged that demonstrating superiority over placebo “is not as clinically relevant as showing efficacy relative to FDA-approved gonadotropins,” and findings may not apply to women with a body mass index above 38 kg/m², who were excluded. Ferring designed the trials with the academic investigators and collected the data. Three of the 5 authors are or were affiliated with the company, and Ferring funded medical writing support.

The investigators concluded that follitropin delta, dosed on the basis of maternal age, is an effective and safe option for ovarian stimulation in patients undergoing IVF or ICSI.

“The RITA trials are also the first to use a cumulative pregnancy end point, including fresh and frozen cycle outcomes, with standardized criteria for trial procedures and assessments that allow a full understanding of the contribution of controlled ovarian stimulation with follitropin delta on clinical end points,” the authors wrote.

References

1. Scheiber MD, Doody KJ, Foster ED, Grover SA, Heiser PW; RITA-1 and RITA-2 trial groups. Ovarian stimulation with follitropin delta is safe and effective: results from the RITA randomized, double-blind, placebo-controlled trials. Fertil Steril. 2026;125(1):54-63. doi:10.1016/j.fertnstert.2025.07.032
2. Boostanfar R, Mannaerts B, Pang S, et al. A comparison of live birth rates and cumulative ongoing pregnancy rates between Europe and North America after ovarian stimulation with corifollitropin alfa or recombinant follicle-stimulating hormone. Fertil Steril. 2012;97(6):1351-1358. doi:10.1016/j.fertnstert.2012.02.038
3. Boostanfar R, Gates D, Guan Y, Gordon K, McCrary Sisk C, Stegmann BJ. Efficacy and safety of frozen-thawed embryo transfer in women aged 35 to 42 years from the PURSUE randomized clinical trial. Fertil Steril. 2016;106(2):300-305.e5. doi:10.1016/j.fertnstert.2016.03.041
4. Society for Assisted Reproductive Technology. SART final national summary report. Accessed October 13, 2026. https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx