Evaluation of Intraovarian Platelet Concentrate and Sodium Chloride Injection on IVF Outcomes in Women with Low Ovarian Reserve: A Randomized Controlled Trial

The primary objective of this randomized controlled trial is to **quantify** the mean difference in oocytes obtained with the use of PRFG-Endoret® compared to a placebo injection in patients with low ovarian reserve. This study is clinically relevant as it aims to evaluate the potential efficacy of **platelet-rich plasma** and growth factors in improving in vitro fertilization (IVF) outcomes for women experiencing **female infertility** due to diminished ovarian reserve. The intervention involves the intraovarian injection of a **platelet concentrate** solution, which is hypothesized to enhance ovarian function and increase the number of retrievable oocytes, thereby potentially improving the success rates of IVF procedures.

The clinical trial focuses on **female infertility**, specifically targeting women diagnosed with low ovarian response according to POSEIDON III/IV criteria. The study population comprises females exclusively, with an age range of 18 to 42 years. Participants are required to have regular menstrual cycles, with intervals ranging from 24 to 35 days. The trial does not include a vulnerable population. Participants must have normal karyotypes in both partners and a body mass index (BMI) greater than 18 kg/m². Additionally, they must have a complete preoperative blood workup valid for six months, with a minimum platelet count of over 160,000/mcL, and negative serologies for HIV, HCV, HBV, and RPR within the last three months. The trial excludes male subjects and does not involve any oocyte or embryo accumulation treatments. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the efficacy of **platelet concentrate** in improving in vitro fertilization (IVF) outcomes for patients diagnosed with low ovarian reserve, a condition contributing to **female infertility**. This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the researchers know which treatment the participants are receiving, thereby minimizing bias. The trial will compare the effects of intraovarian injection of platelet-rich plasma and growth factors against a placebo, specifically **sodium chloride** solution. The primary endpoint is the number of oocytes retrieved following the administration of the study treatment. The trial is expected to commence recruitment on September 1, 2025, and conclude by April 30, 2027.

Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility is confirmed based on criteria such as age, ovarian response, and health status. This visit will include a comprehensive screening process to ensure participants meet all inclusion criteria, such as having a normal karyotype and negative serologies for specific infections. Following the inclusion visit, participants will receive the study treatment and attend follow-up visits to monitor their response and any potential side effects. The end-of-study visit will assess the primary endpoint and gather final data on the participants' outcomes.

The expected duration of participant involvement is approximately one month, corresponding to a single IVF cycle. Participants may be withdrawn from the study early if they experience adverse effects, fail to comply with study procedures, or if the investigator deems it necessary for their safety. The trial is conducted under strict ethical guidelines, ensuring the safety and well-being of all participants throughout the study period.

The clinical trial involves the administration of **PLATELET CONCENTRATE**, a **solution for injection**. This experimental medication is derived from a structurally diverse blood-derived substance, specifically platelet-rich plasma with growth factors. The **PLATELET CONCENTRATE** is administered via injection, with a maximum daily dose of 6 ml and a total dose not exceeding 6 ml over the treatment period. The administration is conducted once, as the maximum treatment period is limited to one day. The trial aims to assess the impact of this treatment on in vitro fertilization (IVF) outcomes in patients with low ovarian reserve.

In addition to the experimental treatment, the study utilizes a non-experimental treatment, **Suero Fisiológico Braun 0.9%**, which serves as a placebo. This product is a **solution for injection** containing **sodium chloride** as the active substance. It is classified under the ATC code V07AB, which includes solvents and diluting agents, including irrigating solutions. The placebo is also administered via injection, with the same dosing schedule as the experimental treatment, allowing for a maximum daily and total dose of 6 ml over a single day. The placebo is provided by B.BRAUN MEDICAL, S.A., and is used to compare the effects of the **PLATELET CONCENTRATE** on the primary outcome of the trial.

The efficacy of the clinical trial titled "Impact of Intraovarian Injection of Platelet-Rich Plasma and Growth Factors on IVF Outcomes in Patients with Low Ovarian Reserve: A Randomized Controlled Trial" will be assessed by evaluating the primary endpoint, which is the number of oocytes retrieved after intraovarian administration of the study treatment, **PRGF Endoret®**, compared to a placebo. This endpoint is designed to quantify the mean difference in oocytes obtained between the treatment and control groups.