Evaluation of Fixed-Dose Follitropin Delta for Ovarian Stimulation in Infertility: A Study on Ovarian Response During Intrauterine Insemination

The primary objective of this study is to observe the effect of a fixed dose of **follitropin delta** (3.66 mcg) on the ovarian response during ovarian stimulation for intrauterine insemination (IUI). This is clinically relevant as it aims to optimize the ovarian stimulation process, potentially improving outcomes for women experiencing **infertility**. Understanding the ovarian response to a fixed dosage can lead to more standardized and effective treatment protocols, reducing variability and enhancing the success rates of IUI procedures.

Secondary objectives include the description of the clinical efficacy, efficiency, and safety of **follitropin delta** for women undergoing IUI cycles. These objectives are crucial for evaluating the overall benefit-risk profile of the treatment, ensuring that it not only enhances fertility outcomes but also maintains a favorable safety profile for patients.

The clinical trial focuses on **infertility** and involves a study population of normo-ovulatory female patients aged 18 to 38 years. Participants are required to have a body mass index (BMI) between 18 and 29 kg/m², regular menstrual cycles, at least one healthy Fallopian tube, and a normal uterine cavity. This is the first treatment for intrauterine insemination (IUI) for all participants, and they must be affiliated with social security. The trial does not include male subjects or vulnerable populations. The sponsor has not provided information regarding the total number of participants. The selection criteria ensure that participants are generally in good health, with specific lifestyle considerations such as regular menstrual cycles and a healthy reproductive system being key factors for inclusion.

The clinical trial is designed to evaluate the effect of a fixed dose of **follitropin delta** on ovarian response during ovarian stimulation for intrauterine insemination (IUI) in patients with **infertility**. This is a Phase IV, randomized, double-blind, controlled trial. The trial is expected to commence recruitment on June 2, 2025, and conclude by September 2, 2027. Participants will be involved in the study for a maximum treatment period of 13 weeks, depending on their response to the treatment and the number of cycles they undergo.

The study will include several visits, starting with an inclusion (screening) visit to assess eligibility based on criteria such as age (18-38 years), body mass index (BMI) between 18 and 29 kg/m², regular menstrual cycles, and at least one healthy Fallopian tube. Following the screening, participants will undergo a series of follow-up visits corresponding to each treatment cycle. These visits will monitor the ovarian response, including the number of follicles and hormone levels, and assess the need for any dose adjustments. The primary endpoint is the percentage of cycles with two mature follicles at the stage of triggering ovulation, with secondary endpoints including the number of follicles, hormone levels, and pregnancy outcomes.

The end-of-study visit will occur after the completion of the treatment cycles or upon early termination. Conditions that may lead to early termination include the development of more than two follicles ≥14 mm, four follicles ≥10 mm, or no response to treatment. Participants will be monitored for any unexpected and related events, such as ovarian hyperstimulation syndrome (OHSS), ectopic pregnancy, or thromboembolic events. The trial aims to provide comprehensive data on the efficacy and safety of follitropin delta in the context of IUI, contributing to the optimization of treatment protocols for infertility.

The clinical trial involves the administration of several treatments, including both experimental and non-experimental medications. **Dydrogesterone**, marketed as DUPHASTON 10 mg, is provided in the form of a **film-coated tablet**. The route of administration is oral, with a maximum daily dose of 30 mg and a total maximum dose of 1.2 grams over a treatment period of up to 6 months. This medication is produced by Theramex Ireland Limited and is classified under the ATC code G03DB01.

**Follitropin delta** is administered as part of the experimental treatment in two different dosages: REKOVELLE 36 micrograms/1.08 mL and REKOVELLE 12 micrograms/0.36 mL, both provided as a solution for injection in a pre-filled pen. The administration route is subcutaneous injection. The maximum daily dose for both formulations is 4.32 micrograms, with a total maximum dose of 56.16 micrograms over a 13-day treatment period. This product is manufactured by Ferring Pharmaceuticals A/S and is used off-label for the indication in this trial.

**Progesterone**, marketed as UTROGESTAN 200 mg, is available as a soft capsule for oral or vaginal use. The maximum daily dose is 400 mg, with a total maximum dose of 16.8 grams over a 6-month treatment period. This medication is produced by Besins Healthcare France and is classified under the ATC code G03DA04.

**Choriogonadotropin alfa**, marketed as Ovitrelle 250 micrograms, is provided as a solution for injection in a pre-filled pen. The route of administration is injection, with a single maximum dose of 250 micrograms. The treatment period is limited to one day. This product is manufactured by Merck Europe B.V. and is classified under the ATC code G03GA08.

Participant compliance with the dosing schedules is monitored throughout the trial to ensure adherence to the prescribed treatment regimens. The trial aims to evaluate the effect of a fixed dose of follitropin delta on ovarian response during ovarian stimulation for intrauterine insemination.

The efficacy of the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the percentage of cycles with two mature follicles, with a diameter of at least 14 mm, at the stage of triggering ovulation, and no follicles between 10 and 13 mm. This will be measured to evaluate the ovarian response to the fixed dose of **follitropin delta** during ovarian stimulation for intrauterine insemination (IUI).

Secondary endpoints include a comprehensive set of parameters to further assess efficacy. These include the number of follicles with a diameter of at least 14 mm and those between 10 and 13 mm on the day of trigger, the presence or absence of dose adjustment in subsequent cycles, and hormone levels such as E2, PG, and LH on the day of trigger. Additional measures include the frequency of spontaneous LH surge, cycle cancellation rate, pregnancy rates (biochemical, clinical, ongoing), multiple pregnancy rate, time to pregnancy, and the number of stimulation days. Other parameters include endometrial thickness, pregnancy outcomes according to cycle rank, cumulative pregnancy outcomes up to three cycles, and the incidence of adverse events such as ovarian hyperstimulation syndrome (OHSS), ectopic pregnancy, ovarian torsion, and thromboembolic events.

Data collection will occur at specified timepoints throughout the trial, with particular attention to the day of trigger and the end of stimulation. The analysis will involve comparing these parameters across cycles and evaluating the impact of any dose adjustments. The trial is designed to provide a comprehensive evaluation of the efficacy of the fixed dose of **follitropin delta** in achieving successful ovarian stimulation for IUI.