Comparison of Progestin-Primed Ovarian Stimulation Versus GnRH Antagonists in Female Infertility Undergoing DUOSTIM for Embryo Accumulation and PGT-A

The primary objective of this study is to evaluate the difference in the number of **euploid embryos** obtained in two groups of patients undergoing embryo accumulation for preimplantation genetic testing for aneuploidy (PGT-A) through double ovarian stimulation. The study compares two methods of pituitary suppression: the use of **gestagens** from the beginning of stimulation and the use of **GnRH antagonists**. This is clinically relevant as it may influence the success rates of in vitro fertilization (IVF) treatments in patients with **female infertility**, potentially optimizing protocols for better outcomes in terms of embryo quality and genetic normalcy.

The clinical trial focuses on **female infertility** and involves a study population exclusively composed of female participants. The age range for participants is less than 43 years, and they must have regular menstrual cycles between 21 and 35 days. Participants are required to have both ovaries present and must be indicated for in vitro fertilization (IVF) with preimplantation genetic testing for aneuploidy (PGT-A). The trial does not include a vulnerable population. Participants were selected based on their ability to participate and complete the study, as well as their consent to participate. 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 efficacy of two different methods of pituitary suppression in patients undergoing double ovarian stimulation for preimplantation genetic testing for aneuploidy (PGT-A) in the context of **female infertility**. This study employs a randomized, double-blind, controlled trial design to ensure the reliability and validity of the results. Participants will be randomly assigned to one of two groups: one receiving **medroxyprogesterone acetate** from the start of stimulation and the other receiving **ganirelix** as a pituitary suppressor. The primary endpoint is the number of euploid embryos obtained, with the trial expected to conclude by June 2025.

The trial will commence with an inclusion (screening) visit, where participants will be assessed against the inclusion criteria, which include being under 43 years of age, having regular menstrual cycles, and the presence of both ovaries. Following successful screening, participants will be enrolled and randomized into one of the two treatment arms. The study will involve multiple follow-up visits to monitor the ovarian response and collect data on embryo development. The end-of-study visit will occur after the final embryo transfer or upon completion of the embryo accumulation process.

Participant involvement is anticipated to last up to 14 days, corresponding to the maximum treatment period for both **medroxyprogesterone acetate** and **ganirelix**. Conditions that may lead to early termination from the study include adverse reactions to the medications, withdrawal of consent, or failure to adhere to the study protocol. The trial is categorized as a low-intervention clinical trial, reflecting its phase IV status and the established safety profile of the medications involved.

The clinical trial involves the administration of **Progevera 10 mg comprimidos**, which contains the active substance **medroxyprogesterone acetate**. This medication is provided in the form of a **tablet** and is administered orally. The maximum daily dose is 10 mg, with a total maximum dose of 140 mg over a treatment period of 14 days. The pharmaceutical product is manufactured by Pfizer, S.L., and is classified under the ATC code G03DA02, indicating its role as a progestin. The medication is used as part of a protocol to study its effects on ovarian stimulation and pituitary suppression in patients undergoing embryo accumulation for preimplantation genetic testing for aneuploidy (PGT-A).

In addition to Progevera, the trial also includes the use of **GANIRELIX**, which is a **solution for injection in a pre-filled syringe**. The active substance in this medication is **ganirelix**, and it is administered via **subcutaneous injection**. The maximum daily dose is 0.25 mg, with a total maximum dose of 2.75 mg over a 14-day treatment period. GANIRELIX serves as a comparator in the study, functioning as a **GnRH antagonist** to suppress pituitary activity. This medication is utilized to compare its efficacy in obtaining euploid embryos against the progestin-primed ovarian stimulation protocol. Compliance with the dosing schedule is monitored throughout the trial to ensure accurate assessment of the treatment outcomes.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the number of **euploid embryos** obtained. This endpoint will be used to determine the effectiveness of two different methods of pituitary suppression in patients undergoing double ovarian stimulation for preimplantation genetic testing for aneuploidy (PGT-A). The trial will compare the use of gestagens from the beginning of stimulation with the use of GnRH antagonists. The collection and analysis of the number of euploid embryos will be conducted at specified timepoints throughout the trial, although specific timepoints are not detailed in the provided data. The trial aims to establish whether there is a significant difference in the number of euploid embryos between the two groups, thereby assessing the efficacy of the respective pituitary suppression methods.