Comparison of Random Start Ovarian Stimulation Versus Conventional Early Follicular Phase Stimulation in Elective Oocyte Cryopreservation Using Dydrogesterone, Follitropin Alfa, and Triptorelin Acetate

The primary objective of this randomized controlled trial is to compare the **efficacy** of Random Start Ovarian Stimulation (RSOS) with conventional early follicular phase stimulation in elective oocyte cryopreservation cycles. This comparison is clinically relevant as it aims to optimize the process of oocyte cryopreservation, which is a critical component in the prevention of female infertility. By evaluating the effectiveness of RSOS, the study seeks to provide insights that could enhance fertility preservation strategies, potentially offering more flexible and efficient options for women seeking to preserve their reproductive potential.

The clinical trial focuses on the **prevention of female infertility** and involves a study population exclusively composed of female participants. The age range for eligible participants is between 25 and 39 years, with a **Body Mass Index (BMI)** requirement of 18 to less than 30 kg/m². Participants are required to have a regular menstrual cycle length of 24-35 days and must not be using hormonal contraception or should have discontinued its use at least two months prior to the trial. The trial does not include a vulnerable population, and the participants must have normally accessible ovaries. The sponsor has not provided information regarding the total number of participants. The selection criteria ensure that participants are in general good health, with specific lifestyle considerations such as the absence of hormonal contraceptive use. The trial aims to compare the efficacy of Random Start Ovarian Stimulation to conventional early follicular phase stimulation in Elective Oocyte Cryopreservation cycles.

The clinical trial is designed as a **randomized controlled trial** to evaluate the efficacy of Random Start Ovarian Stimulation compared to conventional early follicular phase stimulation in elective oocyte cryopreservation cycles. The trial aims to prevent female infertility by assessing the total number of mature cryopreserved oocytes per ovarian stimulation cycle. The study will involve participants aged 25 to 39 years with a body mass index between 18 and 30 kg/m², who have a regular menstrual cycle and are not currently using hormonal contraception. The trial is expected to commence recruitment on October 1, 2024, and conclude by October 1, 2027.

Participants will be involved in the study for a maximum treatment period of 21 days. The trial will include several study visits, beginning with an inclusion (screening) visit to assess eligibility based on the inclusion criteria. Follow-up visits will be scheduled to monitor the ovarian stimulation process, including the administration of medications such as **dydrogesterone**, **follitropin alfa**, and **triptorelin acetate**. The end-of-study visit will evaluate the primary and secondary endpoints, including the total number of oocytes retrieved and the total consumption of gonadotropins.

Participant involvement may be terminated early if they do not adhere to the study protocol, experience adverse effects, or withdraw consent. The trial will maintain a double-blind design to ensure unbiased results, with neither participants nor investigators aware of the treatment allocation. The study's low interventional nature is justified by its focus on established medical practices and minimal risk to participants. The trial's findings will contribute to optimizing ovarian stimulation protocols for elective oocyte cryopreservation, potentially enhancing fertility preservation strategies.

The clinical trial involves the administration of several experimental medications. **Dydrogesterone**, marketed under the name Duphaston, is provided in the form of a **film-coated tablet**. Each tablet contains 10 mg of dydrogesterone, a chemical substance. The medication is administered orally with a maximum daily dose of 30 mg and a total maximum dose of 630 mg over a treatment period of up to 21 days. The product is manufactured by Theramex Ireland Limited and is not a paediatric formulation.

**Follitropin alfa**, marketed as Bemfola, is supplied as a **solution for injection** in a pre-filled pen. Each pen contains 300 IU/0.50 mL of follitropin alfa, a protein-based substance. The medication is administered via subcutaneous injection, with a maximum daily dose of 300 IU and a total maximum dose of 6300 IU over a treatment period of up to 21 days. This product is manufactured by Gedeon Richter PLC and is not intended for paediatric use.

**Triptorelin acetate**, marketed as Gonapeptyl Daily, is provided as a **solution for injection**. Each vial contains 0.1 mg/mL of triptorelin acetate, a chemical substance. The medication is administered through subcutaneous injection, with a maximum daily dose of 0.2 mg/mL and a total maximum dose of 0.2 mg/mL over a treatment period of 1 day. The product is manufactured by Ferring N.V. and is not a paediatric formulation.

In this clinical trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the prescribed treatment regimen. The trial aims to evaluate the efficacy of these medications in the context of Random Start Ovarian Stimulation for Elective Oocyte Cryopreservation cycles.

Efficacy in the clinical trial titled "RAndom sTArT Ovarian stimUlatIon (RSOS) in eLective oocyte cryopreservation cycLEs (RATATOUILLE)" will be assessed by evaluating both primary and secondary endpoints. The primary endpoint is the total number of mature cryopreserved oocytes per ovarian stimulation cycle in elective oocyte cryopreservation. Secondary endpoints include the total number of oocytes retrieved, the total consumption of gonadotropins (measured in international units, IU) used during ovarian stimulation, and the duration of ovarian stimulation, which is defined as the time from the first day of stimulation until the application of the trigger for the final oocyte maturation.