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)

NCT07732348 | Not Yet Recruiting

• 1 other identifier: LINZA-COS
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

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

  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)

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)

B - Injectable GnRH Antagonist (Ganirelix/Cetrorelix)

ACTIVE COMPARATOR

Drug: Ganirelix ; Cetrorelix

C - PPOS (Progestin-Primed Ovarian Stimulation) Cohort

ACTIVE COMPARATOR

Drug: Medroxyprogesterone Acetate ; Micronized Progesterone

A - Linzagolix

EXPERIMENTAL

Drug: Linzagolix

Interventions

Linzagolix DRUG

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.

A - Linzagolix

Ganirelix ; Cetrorelix DRUG

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.

B - Injectable GnRH Antagonist (Ganirelix/Cetrorelix)

Medroxyprogesterone Acetate ; Micronized Progesterone DRUG

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.

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

ganirelix; cetrorelix; Medroxyprogesterone Acetate; Progesterone; linzagolix

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: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Arms A and B are allocated by 1:1 randomization; Group C is a non-randomized, concurrently enrolled comparator cohort assigned by clinical indication (e.g., need for a freeze-all strategy).

Study Record Dates

• First Submitted: July 24, 2026
• First Posted: July 28, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 30, 2026

Record last verified: 2026-09