O-011 A prospective multicentre, non-interventional, real-world study to assess the pattern of use, effectiveness and safety of follitropin delta in routine clinical practice (the PROFILE study)
Authors: Blockeel C , Griesinger G , Rago R , Rivière S , Larsson P , Yip Sonderegger Y L , Laven J S E 
Published: June 2022

Study question

To observe real-world utilization of algorithm-based dosing of follitropin delta in women naïve to ovarian stimulation (OS) and undergoing either in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI).

Summary answer

Individualized dosing of follitropin delta in real-world clinical practice results in predictable ovarian response while minimizing risk of ovarian hyperstimulation syndrome (OHSS).

What is known already

Follitropin delta (REKOVELLE, Ferring Pharmaceuticals, Switzerland), is the first recombinant human follicle-stimulating hormone (FSH) to be produced in a human cell line. The algorithm-based individualized dosing regimen for follitropin delta was developed to target an ovarian response of 8–14 oocytes while reducing the risk of extreme ovarian hypo- and hyper-response as compared with conventional dosing strategies. The efficacy and safety of follitropin delta has been demonstrated in randomized controlled trials (RCTs) compared with a standard daily starting dose of 150 IU recombinant FSH. Real-world implementation of individualized follitropin delta dosing using the algorithm in OS cycles is currently unknown.

Study design, size, duration

PROFILE was a prospective, open-label, non-interventional, multinational study conducted between March 2018 and October 2020 in which 1258 women were screened, 1013 met the inclusion/exclusion criteria and 944 women initiated their first OS cycle. No study drugs were reimbursed or provided by the study sponsor. All IVF/ICSI treatment protocols were conducted according to routine clinical practice, including how to prescribe follitropin delta and undertaking fresh/frozen transfers. Participants were followed for up to three OS cycles.

Participants/materials, setting, methods

All participants met inclusion criteria: ≥18 years, were naïve to IVF/ICSI treatment and the decision had made before enrolment to use follitropin delta for OS. Main exclusion criteria were any contraindication(s) preventing prescription of follitropin delta, and undergoing OS for oocyte donation or fertility preservation. The main outcomes were use of dosing algorithm, follitropin delta dosing patterns, ovarian response and pregnancy for first OS cycle, and adverse drug reactions (ADRs) for up to three cycles.

Main results and the role of chance

Baseline demographics for 944 women who initiated Cycle 1 were: age, 33.5±4.7 years; bodyweight, 67.1±13.6 kg; anti-Müllerian hormone, 20.3±16.1 pmol/L (2.84 ng/mL) (mean±standard deviation). Cycles 2 and 3 were initiated by 156 and 29 women, respectively. In Cycle 1, clinicians used the dosing algorithm to calculate the follitropin delta starting dose for 893/944 women (94.5%), although some clinicians adjusted the prescribed daily starting dose. The difference between the calculated and prescribed daily dose was small (0.2±1.40 µg); most women (822/944, 87.1%) were prescribed a daily dose of follitropin delta within 0.33 µg (1 click of pen) of the algorithm-calculated dose. The mean daily starting dose was 10.4 µg and mean total dose administered was 104 µg over 10.1 days. A mean of 10.1±7.03 oocytes were retrieved per woman. A fresh transfer was performed for 592/944 women (62.7%) and subsequent positive β-human chorionic gonadotropin (βhCG) reported for 352/944 women (37.3%). Ongoing pregnancy rate after fresh transfer was 27.0% (n = 255) and cumulative ongoing pregnancy rate after fresh/frozen transfer was 36.4% (n = 344). Four women discontinued follitropin delta due to ADRs. OHSS was reported for 37 women (3.9%); 12 (1.3%) OHSS events were reported as serious ADRs. No new safety signals were reported.

Limitations, reasons for caution

There may be bias towards IVF/ICSI treatment protocols used in countries with highest enrolment. Reasons for prescribing follitropin delta as part of a mixed FSH regimen in 33/944 women (3.5%) were not reported.

Wider implications of the findings

In real-world clinical practice, nearly all clinicians use the dosing algorithm to calculate individualized daily follitropin delta dose. Despite some women being prescribed dose deviations, first cycle ovarian response was predictable with good ongoing pregnancy rates. OHSS incidence was within expected range. PROFILE confirms efficacy and safety from pivotal RCTs.

Trial registration number

NCT03393780