Evaluation of Exogenous Progesterone Administration Routes and Dosages on Endometrial Function in Female Infertility

The primary objective of this study is to compare the **endometrial function**, specifically endometrial gene expression, in response to different types of exogenous **progesterone**. The study evaluates the impact of varying doses and routes of administration, including vaginal, subcutaneous, and intramuscular, on endometrial structure and function. This is clinically relevant as it aims to optimize artificial endometrial preparation cycles, which are crucial in the management of **female infertility**. Understanding the differential effects of progesterone administration can lead to improved therapeutic strategies and outcomes in assisted reproductive technologies.

The clinical trial focuses on **female infertility** and involves a study population exclusively composed of women. The participants are aged between 18 and 35 years, all of whom have regular menstrual cycles ranging from 22 to 35 days. The trial population is in good health, with no mental or medical conditions that would impede their participation. The selection criteria include women with no history of infertility who have provided informed consent. The trial does not include any vulnerable populations, and the sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the impact of different doses and routes of administration of **progesterone** on endometrial structure and function in women with **female infertility**. This study is a randomized, double-blind, controlled trial, conducted over an estimated duration from November 2021 to December 2024. Participants will be randomly assigned to receive one of the three forms of progesterone: intramuscular injection, subcutaneous injection, or vaginal use. The primary objective is to compare endometrial function by assessing gene expression related to progesterone treatment response during the window of implantation.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (18-35 years), regular menstrual cycles, and overall health status. Following successful screening, participants will be enrolled in the study and will attend regular follow-up visits to monitor treatment effects and ensure adherence to the protocol. The end-of-study visit will involve a comprehensive evaluation of the participant's response to the treatment, including the primary endpoint of gene expression analysis.

The expected length of participant involvement is up to six months, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include adverse reactions to the treatment, non-compliance with study procedures, or withdrawal of consent by the participant. The trial aims to provide valuable insights into the optimal use of progesterone in artificial endometrial preparation cycles, potentially improving treatment outcomes for women experiencing infertility.

The clinical trial involves the administration of three different formulations of **progesterone** to evaluate their impact on endometrial structure and function. The first experimental medication is **PRONTOGEST 100 mg/ml soluzione iniettabile**, a solution for injection containing the active substance **progesterone**. This formulation is administered via **intramuscular injection**. The maximum daily dose is 50 mg, with a total maximum dose of 300 mg over a treatment period of up to 6 weeks. The pharmaceutical form is a solution for injection, and the product is manufactured by IBSA Farmaceutici Italia.

The second experimental medication is **Prolutex 25 mg solución inyectable en jeringa precargada**, also a solution for injection containing **progesterone**. This formulation is administered via **subcutaneous injection**. Similar to the first medication, the maximum daily dose is 50 mg, with a total maximum dose of 300 mg over a treatment period of up to 6 weeks. The product is provided in a pre-filled syringe for ease of administration and is also manufactured by IBSA Farmaceutici Italia.

The third experimental medication is **Seidigestan 200 mg cápsulas blandas**, a soft capsule formulation containing **progesterone**. This medication is administered via **vaginal use**. The maximum daily dose for this formulation is 800 mg, with a total maximum dose of 4800 mg over a treatment period of up to 6 weeks. The product is manufactured by SEID, S.A. and is designed for vaginal administration to provide a localized effect on the endometrium.

All formulations are chemically derived and are not pediatric formulations. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed regimen.

Efficacy in this clinical trial will be assessed by evaluating the **endometrial function** through gene expression analysis. The primary endpoint involves measuring gene expression for the whole transcriptome, encompassing 22,000 genes, to assess the response to progesterone treatments during the window of implantation. Additionally, the number of differentially expressed genes between progesterone treatment groups will be compared to their natural cycle counterparts. These assessments will provide insights into the impact of different doses and routes of administration of exogenous progesterone on endometrial structure and function.