Oral GnRH Antagonist (Linzagolix) Versus Injectable GnRH Antagonist for Ovarian Stimulation in IVF/ICSI

This study compares two medications used to prevent a premature hormone surge (LH surge) during controlled ovarian stimulation for in vitro fertilization (IVF). The standard approach uses an injectable GnRH antagonist (ganirelix or cetrorelix), given as a daily injection under the skin. This study evaluates linzagolix, an oral GnRH antagonist already approved for uterine fibroids and endometriosis, used here for the first time in ovarian stimulation (off-label use). Women undergoing IVF/ICSI at CENTRO AMBRA will be randomly assigned (1:1) to receive either oral linzagolix (200 mg/day) or the standard injectable antagonist. The study's hypothesis is that linzagolix is not inferior to the injectable antagonist in the number of mature (MII) eggs retrieved, within a pre-specified margin of 2.0 oocytes, while offering the advantage of oral rather than injectable administration. A separate, non-randomized group of women who are clinically indicated for a progestin-based stimulation protocol (PPOS) with a freeze-all strategy will be enrolled at the same time for descriptive comparison. Secondary objectives include how effectively each treatment suppresses the LH surge, whether a GnRH agonist can be used to safely trigger final egg maturation under linzagolix, the occurrence of ovarian hyperstimulation syndrome (OHSS) and other safety outcomes, the length of stimulation and amount of hormone medication needed, and embryology outcomes such as fertilization and blastocyst formation rates. The study plans to enroll approximately 189 women in total.

Inclusion Criteria: * Female, aged 18 to 42 years * Indication for IVF/ICSI with controlled ovarian stimulation at CENTRO AMBRA * Population unselected for ovarian reserve (normal, poor, and high responders are eligible) * Written informed consent, including consent for off-label use of linzagolix and for data processing * For the two antagonist arms (Linzagolix and Injectable GnRH Antagonist): acceptance of randomization Exclusion Criteria: * Known contraindications or hypersensitivity to the study drugs * Uterine pathology relevant to the study outcome (e.g., uterine malformations, significant submucosal fibroids) * Contraindications to pregnancy or to ovarian stimulation * Concurrent participation in another interfering interventional study