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

NCT07732348 | Not Yet Recruiting Early Phase 1

• 1 other identifier: LINZA-COS
• Study Type: interventional
• Target: 189
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Infertility, Female; Ovulation Induction

Keywords

Oral GnRH Antagonist; Linzagolix; Controlled Ovarian Stimulation; In Vitro Fertilization; ICSI; Progestin-Primed Ovarian Stimulation; Oocyte Maturation; OHSS Prevention

Outcome Measures

Primary Outcomes (1)

• Number of Mature (MII) Oocytes Retrieved

  At oocyte retrieval, approximately 36 hours after trigger (first study cycle)

Secondary Outcomes (1)

• Incidence of Premature LH Rise

  From initiation of LH-suppressive treatment to the day of trigger (up to approximately 12 days)

Study Arms (3)

A - Linzagolix

EXPERIMENTAL

Drug: Linzagolix

B - Injectable GnRH Antagonist (Ganirelix/Cetrorelix)

ACTIVE COMPARATOR

Drug: Ganirelix ; Cetrorelix

C - PPOS (Progestin-Primed Ovarian Stimulation) Cohort

ACTIVE COMPARATOR

Drug: Medroxyprogesterone Acetate ; Dienogest ; Micronized Progesterone

Interventions

Linzagolix DRUG

Linzagolix Type: Drug Arm: 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.

A - Linzagolix

Ganirelix ; Cetrorelix DRUG

Ganirelix Type: Drug Arm: 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.

B - Injectable GnRH Antagonist (Ganirelix/Cetrorelix)

Medroxyprogesterone Acetate ; Dienogest ; Micronized Progesterone DRUG

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. Dienogest Type: Drug Arm: C Description: Dienogest 2 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.

C - PPOS (Progestin-Primed Ovarian Stimulation) Cohort

Eligibility Criteria

• Age: 18 Years - 42 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centro A.M.B.R.A. (Associazione Medici e Biologi per la Riproduzione Assistita): lead

MeSH Terms

Conditions

Infertility, Female

Interventions

linzagolix; ganirelix; cetrorelix; Medroxyprogesterone Acetate; dienogest; Progesterone

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Infertility

Intervention Hierarchy (Ancestors)

Medroxyprogesterone; Hydroxyprogesterones; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2026
• First Posted: July 28, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: July 28, 2026

Record last verified: 2026-07