Evaluation of Safety and Efficacy of Platelet-Rich Plasma Injection for Intraovarian Growth in Patients with Low Ovarian Reserve

The primary objective of this study is to **compare ovarian reserve markers** and the results obtained in the IVF-ICSI laboratory before and after the infusion of Plasma Rich in Growth Factors (PRGF) in patients with Low Ovarian Reserve. This is clinically relevant as it aims to assess the potential of PRGF to improve ovarian function and fertility outcomes in this patient population, which could lead to enhanced treatment strategies for individuals with diminished ovarian reserve.

Secondary objectives include:

• Comparing pre- and post-treatment pregnancy rates to evaluate the impact of PRGF on fertility success.
• Collecting data on complications associated with the intraovarian injection of PRGF to ensure the safety profile of this intervention.

The clinical trial focuses on a **population** of women diagnosed with **low ovarian reserve**, specifically classified under groups 3 and 4 of the POSEIDON classification. This includes women aged below 35 years with diminished ovarian reserve, characterized by an AMH level of less than 1.2 ng/ml and an AFC of less than 5, as well as women aged 35 years and above with similar ovarian reserve parameters. Participants must have at least one ovary, have experienced infertility for at least one year, and have a forecast of safe ovarian access on the day of puncture. The study exclusively involves female subjects, with no male participants included, and does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants were selected based on their agreement to participate and provide written consent. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the **safety** and **efficacy** of plasma rich in growth factors for patients with low ovarian reserve. This is a pilot, open, non-comparative study, focusing on the infusion of platelet-rich plasma to assess changes in ovarian reserve markers and outcomes in the IVF-ICSI laboratory. The trial is set to commence recruitment on September 15, 2024, and is expected to conclude by March 31, 2026. Participants will be involved in the study for a maximum treatment period of one month, with a daily dose limit of 4 ml of the injectable product.

The trial will include several study visits, beginning with a screening visit to confirm eligibility based on criteria such as age, ovarian reserve status, and infertility duration. Participants must have at least one ovary and provide written consent. The primary endpoints include comparing ovarian reserve markers and laboratory results before and after the intervention. Secondary endpoints involve assessing pregnancy rates and related complications. Follow-up visits will monitor these parameters, with the end-of-study visit marking the completion of data collection.

Participants may be withdrawn from the study if they experience adverse reactions, fail to comply with the protocol, or withdraw consent. The trial is categorized as Phase II, indicating its exploratory nature in assessing the treatment's potential benefits and risks. The study's methodology ensures a structured approach to data collection and analysis, providing valuable insights into the treatment's impact on low ovarian reserve.

The clinical trial involves the administration of an **experimental medication** known as "Plasma rich in growth factors," which is an **injectable** formulation. The active substance in this product is **platelet concentrate**, also referred to as "Platelet Rich Plasma Human." This substance is derived from blood and is categorized as a structurally diverse substance. The product is manufactured by Biotechnology Institute I Mas D S.L. The administration route for this medication is via **injection**, with a maximum daily dose of 4 ml and a total maximum dose of 4 ml. The treatment period is limited to a single day. The study aims to evaluate the safety and efficacy of this treatment in patients with low ovarian reserve.

In this trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the experimental medication. Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol. The trial is designed to assess changes in ovarian reserve markers and outcomes in the IVF-ICSI laboratory before and after the infusion of the plasma rich in growth factors.

The efficacy of the clinical trial will be assessed by evaluating both primary and secondary endpoints. The primary endpoints focus on comparing **ovarian reserve markers** before and after the intervention with Plasma Rich in Growth Factors (PRGF). These markers include Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estradiol, Anti-Müllerian Hormone (AMH), and Antral Follicle Count (AFC). Additionally, the trial will assess the outcomes in the IVF-ICSI laboratory, such as the number of canceled cycles, oocytes recovered, MII oocytes on the day of puncture, fertilized oocytes, embryos achieved per EOC cycles, good quality embryos, and frozen embryos.

Secondary endpoints will include the comparison of pregnancy rates and the collection of pregnancy-related complications pre- and post-treatment. These will be measured by the number of pregnancies per cycle started, pregnancies per transfer, number of abortions, frequency of twin pregnancies, hemoperitoneum, and post-puncture infections. Additional endpoints will test the hypothesis by examining causes of sterility, time of sterility in years, number of embryos transferred, stage of transferred embryos, EOC days, and total dose of gonadotropins. The trial is designed to provide comprehensive data on the efficacy of PRGF in patients with low ovarian reserve, as classified by the POSEIDON criteria.