Comparative Study of Corifollitropin Alfa and Progestin-Primed Ovarian Stimulation Versus Recombinant FSH and GnRH Antagonist in Subfertility Patients

The primary objective of this study is to compare **Corifollitropin alfa** (CFA) and **Progestin primed ovarian stimulation** (PPOS) stimulation versus conventional **recombinant Follicle Stimulating Hormone** (rFSH) and **Gonadotropin-Releasing Hormone** (GnRH) antagonist ovarian stimulation cycles. The comparison focuses on the mean treatment-related quality of life and patient satisfaction in subjects undergoing elective fertility preservation and those undergoing preimplantation genetic testing (PGT). This objective is clinically relevant as it aims to determine the most effective ovarian stimulation protocol that enhances patient quality of life and satisfaction, which are critical factors in fertility treatments.

Secondary objectives include evaluating whether the effect of the treatment regimen on mean treatment-related quality of life and patient satisfaction differs between subjects undergoing elective fertility preservation and those undergoing PGT treatment. This involves testing for effect modification of the treatment by indication, distinguishing between preventive and therapeutic approaches.

The clinical trial focuses on **subfertility** and involves a study population exclusively composed of female participants. The age range for participants is between 18 and 40 years, with a **Body Mass Index (BMI)** requirement of 18 kg/m² to less than 32 kg/m². The trial does not include a vulnerable population. Participants were selected based on specific indications for oocyte cryopreservation or in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) and preimplantation genetic testing for aneuploidy (PGT-A). The trial is designed for individuals undergoing their first ovarian stimulation cycle. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy and patient satisfaction of two ovarian stimulation protocols in women with **subfertility**. This is a prospective, randomized, double-blind, controlled trial with a cross-over design. The trial will compare the use of **corifollitropin alfa** in progestin-primed ovarian stimulation (PPOS) cycles against conventional recombinant follicle-stimulating hormone (rFSH) with a gonadotropin-releasing hormone (GnRH) antagonist. The primary objective is to assess treatment-related quality of life and patient satisfaction, with secondary endpoints including patient feedback post-treatment. The trial is expected to conclude by May 2025, with recruitment starting in October 2023.

Participants will undergo a series of study visits, beginning with an inclusion visit to confirm eligibility based on criteria such as age (18-40 years), body mass index (18-32 kg/m²), and indication for oocyte cryopreservation or in vitro fertilization (IVF) with preimplantation genetic testing (PGT-A). The trial will include two stimulation cycles, each followed by a questionnaire to assess the primary endpoint. The end-of-study visit will occur after the completion of the second cycle and the final questionnaire. The total duration of participant involvement is anticipated to be approximately 14 weeks, depending on individual response to treatment cycles.

Participants may be withdrawn from the study if they experience adverse events that compromise safety, fail to comply with the study protocol, or withdraw consent. The trial will ensure that all procedures adhere to ethical standards and regulatory requirements, with data collected and analyzed to provide robust evidence on the comparative effectiveness of the two stimulation protocols. The study will utilize **subcutaneous injection** as the route of administration for the investigational products, ensuring consistency in delivery and dosing across the trial population.

The clinical trial involves the administration of several experimental medications, each with specific pharmaceutical forms, dosages, and administration routes. **Orgalutran**, containing the active substance **ganirelix**, is provided as a 0.25 mg/0.5 mL solution for injection. It is administered via subcutaneous injection with a maximum daily dose of 0.25 micrograms and a total dose not exceeding 2.25 micrograms over a treatment period of up to 9 days. This medication is biosynthetic in origin and is not a pediatric formulation.

**Gonapeptyl Daily**, with the active substance **triptorelin acetate**, is available as a 0.1 mg/1 mL solution for injection. It is administered subcutaneously with a maximum daily and total dose of 0.2 micrograms, limited to a single day of treatment. This biosynthetic product is also not formulated for pediatric use.

**Elonva**, containing **corifollitropin alfa**, is provided as a 150 micrograms solution for injection. It is administered via subcutaneous injection with a maximum daily and total dose of 150 micrograms, restricted to a single day of treatment. This product is biosynthetic and not intended for pediatric use.

**Puregon**, with the active substance **follitropin beta**, is available in multiple formulations: 300 IU/0.36 mL, 600 IU/0.72 mL, and 900 IU/1.08 mL solutions for injection. Each formulation is administered subcutaneously with a maximum daily dose of 225 IU and a total dose not exceeding 3150 IU over a treatment period of up to 14 days. These biosynthetic products are not pediatric formulations.

**Cerazette**, containing **desogestrel**, is provided as 75 microgram film-coated tablets. It is administered orally with a maximum daily dose of 75 micrograms and a total dose not exceeding 1050 micrograms over a treatment period of up to 14 days. This chemical-based product is not formulated for pediatric use.

Participant compliance with the dosing schedules is monitored throughout the trial to ensure adherence to the prescribed treatment regimens. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments. All medications are administered according to the specified routes and dosages to evaluate their efficacy and safety in the context of the study's objectives.

Efficacy in the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint focuses on treatment-related quality of life and patient satisfaction, which will be evaluated through a second questionnaire (Q2). This questionnaire is completed at the end of each stimulation cycle, specifically after the agonist trigger and before the oocyte retrieval. The secondary endpoint involves patient feedback, which will be collected from a third questionnaire (Q3) completed within three weeks after the completion of the second stimulation cycle.

The trial aims to compare two ovarian stimulation protocols: CFA/PPOS stimulation versus conventional recombinant follicle-stimulating hormone (rFSH) and **GnRH antagonist** ovarian stimulation cycles. The assessment of efficacy will be based on the mean treatment-related quality of life and patient satisfaction in subjects undergoing elective fertility preservation and those undergoing preimplantation genetic testing (PGT).