Clinical and endocrinological effects of letrozole during the luteal phase after controlled ovarian stimulation in oocyte donors: a low interventional, randomized, controlled trial

The primary objective of this study is to determine whether the use of **letrozole** during the luteal phase in oocyte donors diminishes the ovarian volume. This is clinically relevant as it may impact the management of **female infertility** by potentially reducing the risk of ovarian hyperstimulation syndrome, a common complication in oocyte donation and assisted reproductive technologies.

Secondary objectives include: - To determine the differences in the levels of **VEGF**, VEGF/sFlt-1 ratio, **LH**, **FSH**, **oestradiol**, **progesterone**, and **testosterone** in the plasma of oocyte donors depending on whether or not they receive letrozole during the luteal phase after ovarian stimulation. - To determine the differences in the duration of the luteal phase in oocyte donors depending on whether or not they receive letrozole during the luteal phase after ovarian stimulation. These secondary objectives aim to provide insights into the endocrinological effects of letrozole, which could further inform its use in clinical practice.

The clinical trial focuses on **female infertility** and involves participants who are exclusively female, aged between 18 and 34 years. The study population comprises women who have been accepted into an oocyte donation program and exhibit hyperresponsiveness to stimulation, characterized by the presence of 18 or more follicles of size 11 mm or greater on the day of the last ultrasound control visit prior to ovarian puncture. Participants are required to provide dated and signed informed consent. The trial does not include a vulnerable population, and the sponsor has not provided information regarding the total number of participants. The selection criteria ensure that the participants are in a specific reproductive health status, and no significant lifestyle considerations such as diet or physical activity are highlighted in the trial details.

The clinical trial is designed to evaluate the **clinical** and endocrinological effects of **letrozole** during the luteal phase in oocyte donors, specifically focusing on its impact on ovarian volume. This study is a low interventional, randomized, controlled trial, aiming to assess the efficacy of letrozole, a non-steroidal aromatase inhibitor, administered orally. The trial is expected to run from February 1, 2023, to August 31, 2025, with a maximum treatment period of 10 days for each participant. The primary endpoint is the measurement of ovarian volume, while secondary endpoints include plasma values of VEGF, sFlt-1, oestradiol, progesterone, FSH, LH, and testosterone.

Participants will be women aged 18 to 34 who are part of an oocyte donation program and exhibit hyperresponsiveness to stimulation, defined by the presence of 18 or more follicles of size 11 mm or greater on the day of the last ultrasound control visit before ovarian puncture. The study will begin with a screening visit to confirm eligibility based on the inclusion criteria, including obtaining informed consent. Following the screening, participants will be randomized to receive either letrozole or a control treatment during the luteal phase.

Study visits will be scheduled to monitor the participants' response to the treatment, with follow-up visits to assess the primary and secondary endpoints. The end-of-study visit will conclude the trial for each participant, ensuring all necessary data is collected and any adverse events are documented. Participants are expected to be involved in the study for the duration of the treatment period and follow-up visits, with conditions for early termination including withdrawal of consent or any adverse events that may compromise participant safety.

The clinical trial involves the administration of **letrozole**, a non-steroidal aromatase inhibitor, as the experimental medication. Letrozole is provided in an oral pharmaceutical form, identified by the code PHF00082MIG. The active substance, letrozole, is of chemical origin and is classified under the ATC code L02BG04. The maximum daily dose of letrozole is 5 mg, with a total maximum dose of 5 mg per day. The treatment period is limited to a maximum of 10 days. The primary route of administration is oral, ensuring ease of use and compliance. Letrozole is not formulated for pediatric use and is not classified as an orphan drug.

In this study, no additional non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus remains solely on the effects of letrozole during the luteal phase in oocyte donors. Participant compliance with the dosing schedule is monitored to ensure adherence to the prescribed regimen. The trial aims to evaluate the clinical and endocrinological effects of letrozole, specifically its impact on ovarian volume during the luteal phase following controlled ovarian stimulation.

The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary endpoint is the measurement of **ovarian volume** in oocyte donors. This parameter will be used to determine whether the use of Letrozole during the luteal phase diminishes ovarian volume. Secondary endpoints include the plasma values of various biomarkers: VEGF, sFlt-1, oestradiol, progesterone, FSH, LH, and testosterone. These biomarkers will provide additional insights into the endocrinological effects of Letrozole.

The trial is designed as a low interventional, randomized, controlled study. The schedule for measuring and collecting these efficacy parameters will be aligned with the trial's protocol, ensuring systematic data collection at specified timepoints. The analysis of these parameters will be conducted using validated laboratory tests and methodologies to ensure accuracy and reliability of the results. The trial aims to provide comprehensive data on the clinical and endocrinological effects of Letrozole, contributing to the understanding of its efficacy in the specified context.