Oral GnRH Antagonist (Linzagolix) Versus Injectable GnRH Antagonist in Controlled Ovarian Stimulation for In Vitro Fertilization: A Randomized Controlled Non-Inferiority Trial With a Concurrent Comparator Cohort Undergoing Progestin-Primed Ovarian Stimulation (PPOS)
Women undergoing IVF/ICSI who are candidates for a GnRH-antagonist protocol are randomly assigned 1:1 to oral linzagolix or the standard injectable GnRH antagonist (ganirelix or cetrorelix). A third, non-randomized group of women with a clinical indication for progestin-primed ovarian stimulation (PPOS) - for example, a need for a freeze-all strategy - is enrolled concurrently as a comparator cohort. The randomized comparison (linzagolix vs. injectable antagonist) is the primary, non-inferiority analysis; the PPOS cohort provides an exploratory, non-randomized comparison, analyzed with adjustment for baseline differences.
Aperçu de l'étude
Statut
Les conditions
Description détaillée
This is a single-center, prospective, randomized, controlled non-inferiority trial with a concurrent non-randomized comparator cohort, conducted at CENTRO AMBRA. Women eligible for a GnRH-antagonist protocol are randomized 1:1 to oral linzagolix or the injectable GnRH antagonist using a computer-generated permuted-block randomization sequence (block size of 4, no stratification); allocation is concealed until treatment initiation. A separate, concurrent cohort of women with a clinical indication for PPOS is enrolled as a non-randomized comparator; because assignment to this cohort reflects clinical criteria, it may differ systematically from the randomized arms - confounding by indication limited to the PPOS comparison. This is addressed through pre-specified multivariable adjustment and, where sample size permits, propensity-score methods; the PPOS comparison is interpreted as an association, the randomized comparison as supporting non-inferiority. As treatment is known to investigators and patients, there is no masking (open-label); oocyte and embryo assessment follows standardized, predefined procedures. A target of 40 participants per group (120 total) was defined based on the pre-specified non-inferiority margin of 2.0 MII oocytes. All participants undergo a routine clinical follow-up visit 5 days after oocyte pick-up."
Type d'étude
Inscription (Estimé)
Phase
- N'est pas applicable
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: A - Linzagolix
|
Description: Linzagolix Type: Drug Group: A Description: Linzagolix 200 mg administered orally once daily, started per center protocol (fixed stimulation day or upon appearance of the dominant follicle) and continued through the day of trigger. Investigational off-label use for suppression of the premature LH surge during controlled ovarian stimulation. |
|
Comparateur actif: B - Injectable GnRH Antagonist (Ganirelix/Cetrorelix)
|
Ganirelix Type: Drug Group: B Description: Ganirelix acetate 0.25 mg administered by daily subcutaneous injection, per fixed or flexible protocol according to center practice, to suppress the premature LH surge during controlled ovarian stimulation. Cetrorelix Type: Drug Arm: B Description: Cetrorelix acetate 0.25 mg administered by daily subcutaneous injection, per fixed or flexible protocol according to center practice, to suppress the premature LH surge during controlled ovarian stimulation. |
|
Comparateur actif: C - PPOS (Progestin-Primed Ovarian Stimulation) Cohort
|
This is a non-randomized, concurrently enrolled comparator cohort (not part of the 1:1 randomization). Medroxyprogesterone Acetate - Type: Drug - Arm: C - Description: Medroxyprogesterone acetate 10 mg/day administered orally from stimulation day 1-2 through the day of trigger, as part of a progestin-primed ovarian stimulation (PPOS) protocol with mandatory freeze-all strategy. Micronized Progesterone - Type: Drug - Arm: C - Description: Micronized progesterone 100-200 mg/day administered orally from stimulation day 1-2 through the day of trigger, as part of a progestin-primed ovarian stimulation (PPOS) protocol with mandatory freeze-all strategy. |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Number of Mature (MII) Oocytes Retrieved
Délai: At oocyte retrieval, approximately 36 hours after trigger (first study cycle)
|
Number of metaphase II (mature) oocytes collected at oocyte retrieval. Non-inferiority of linzagolix versus the injectable GnRH antagonist will be concluded if the lower bound of the 95% confidence interval for the adjusted mean difference in MII oocytes (adjusted for ovarian reserve, age, BMI, gonadotropin type and dose, and trigger type) excludes a loss greater than the pre-specified non-inferiority margin of 2.0 MII oocytes. An exploratory comparison with the PPOS cohort is also performed, adjusted for baseline confounders. |
At oocyte retrieval, approximately 36 hours after trigger (first study cycle)
|
Mesures de résultats secondaires
Mesure des résultats |
Délai |
|---|---|
|
Incidence of Premature LH Rise
Délai: From initiation of LH-suppressive treatment to the day of trigger (up to approximately 12 days)
|
From initiation of LH-suppressive treatment to the day of trigger (up to approximately 12 days)
|
Collaborateurs et enquêteurs
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Estimé)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Maladies urogénitales
- Maladies génitales
- Maladies urogénitales féminines
- Maladies urogénitales féminines et complications de la grossesse
- Maladies génitales, femme
- Infertilité
- Infertilité féminine
- Hormones
- Hormones, substituts hormonaux et antagonistes hormonaux
- Composés polycycliques
- Grossesse
- Stéroïdes
- Composés à anneau fusionné
- Hormones stéroïdes gonadiques
- Hormones gonadiques
- Grossenones
- Présceau
- Médroxyprogestérone
- Hydroxyprogestérones
- Hormones du corpus luteum
- Congée de progestérone
- Acétate de médroxyprogestérone
- Progestérone
- ganirelix
- cetrorelix
- linzagolix
Autres numéros d'identification d'étude
- LINZA-COS
Informations sur les médicaments et les dispositifs, documents d'étude
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