Evaluation of cpFT Trifluoroacetate in Enhancing Live Birth Rates Post-ICSI in Women Under 37 with Infertility: A Multicenter, Randomized Study

The primary objective of this study is to demonstrate the improvement in the rate of **live births** after Intracytoplasmic Sperm Injection (ICSI) by supplementing the pre-ICSI incubation medium of oocytes and that of preimplantation embryos with cpFT (1µM) during the first embryo transfer in women under 37 years of age. This is clinically relevant as it aims to enhance the success rates of assisted reproductive technologies, potentially offering a more effective treatment for **infertility**.

Secondary objectives include evaluating various factors that may influence the success of ICSI and subsequent pregnancy outcomes. These are: - Level of **Metaphase II oocytes** - Quality of the embryonic culture - Evaluation of the kinetics of embryonic development when possible - Evaluation of the embryo quality at the blastocyst stage - Quality of the embryos after vitrification - Implantation rate with positive Beta hCG after transfer - Clinical pregnancy rates with cardiac activity - The rate of miscarriages per pregnancy - Evaluation of the health of the baby during pregnancy and at birth - Assessment of the baby health and development at one year old - Evaluation of the placental weight and epigenetic markers when delivery in Cochin only.

The clinical trial focuses on **infertility** and involves both male and female participants. The study population includes women aged 18 to 36 years and men aged 18 to 58 years, all of whom are part of couples requiring Medically Assisted Reproduction (AMP) and are eligible for Intracytoplasmic Sperm Injection (ICSI). Participants must be affiliated with a Social Security system and exclusively use the CSCM-C culture medium from Biocare/Irvine. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. The selection criteria emphasize the need for specific reproductive assistance and age range, ensuring a targeted approach to addressing infertility through the trial's objectives.

The clinical trial is designed to evaluate the efficacy of **cpFT trifluoroacetate** in improving live birth rates following intracytoplasmic sperm injection (ICSI) in women under 37 years of age. This is a multicenter, prospective, randomized, double-blind, controlled study. The trial will span approximately six years, with an estimated recruitment start date of July 29, 2021, and an estimated end date of July 29, 2027. Participants will be randomly assigned to receive either the investigational product or a control, with neither the participants nor the investigators aware of the group assignments, ensuring the double-blind nature of the study.

Study visits will follow a structured sequence, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, need for medically assisted reproduction, and use of specific culture media. Eligible participants will then proceed to the baseline visit, where initial assessments and randomization will occur. Follow-up visits will be scheduled to monitor the progress of oocyte maturation, embryo development, and pregnancy outcomes. The end-of-study visit will conclude the participant's involvement, with final assessments conducted to evaluate the primary endpoint of live birth rate and secondary endpoints such as oocyte and embryo quality, pregnancy rates, and neonatal outcomes.

Participant involvement is expected to last until the completion of the first embryo transfer and subsequent pregnancy monitoring, with the possibility of extending to pediatric assessments until the child reaches one year of age. Conditions that may lead to early termination from the study include withdrawal of consent, protocol non-compliance, or adverse events that compromise participant safety. The trial aims to provide comprehensive data on the potential benefits of **cpFT trifluoroacetate** in enhancing reproductive outcomes in the context of ICSI.

The clinical trial involves the use of an **experimental medication** known as cpFT, which is a **solution** containing the active substance **cpFT trifluoroacetate**. This compound is classified as a **protein - other** and is not administered directly to patients. Instead, cpFT is used to supplement the culture medium for oocytes and preimplantation embryos during the in vitro fertilization process. The solution is applied at a concentration of 1 µM, with a maximum treatment period of 6 days. The **route of administration** is not applicable as the peptide is not administered to the patient directly. The purpose of this supplementation is to enhance the maturation and ploidy of human oocytes and improve preimplantation embryonic development.

In this study, no **non-experimental treatments** such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the application of cpFT in the culture medium. The trial does not involve any direct administration of the peptide to the participants, and therefore, there is no need for participant compliance monitoring related to drug administration. The study aims to demonstrate the improvement in live birth rates following intracytoplasmic sperm injection (ICSI) by using cpFT during the first embryo transfer in women under 37 years of age.

Efficacy in this clinical trial will be assessed primarily through the **Live Baby birth rate** after the first embryo transfer for women under 37 years of age. This primary endpoint is designed to evaluate the effectiveness of supplementing the pre-ICSI incubation medium of oocytes and preimplantation embryos with cpFT (1 µM) during the first embryo transfer. Secondary endpoints will provide additional insights into the trial's efficacy, including the number of Metaphase 2 oocytes at decoronization and before ICSI, blastoformation rate, and the number of embryo culture failures. The kinetics of embryonic development will be analyzed using videos from incubators equipped with recording cameras. The quality of blastocysts will be assessed according to the Gardner classification, both before and after thawing, to determine survival rates. Further secondary endpoints include the **hCG level** greater than 1000 over the number of embryos transferred, the number of pregnancies with cardiac activity on the 12th-week ultrasound, and the number of miscarriages over the number of pregnancies with positive cardiac activity. Additional parameters such as pregnancy and ectopic pregnancy rates, rate of pregnancy therapeutic termination, and rate of anomaly on morphological ultrasounds at 6 months and malformation at birth will be recorded. The term of delivery, weight, height, and head circumference of the baby at birth will also be documented. Pediatric consultations will analyze examinations until the child is 1 year old, including status-weight curve and developmental scales such as Denver and Brunet Lezine. The weight of the placenta and studies involving DNA, RNA, Western-Blot, methylation, and histological analysis will be conducted to further assess efficacy.