Infertility, FemaleNCT07732348
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)
A study testing Ganirelix ; Cetrorelix, Medroxyprogesterone Acetate ; Micronized Progesterone and Linzagolix in people with Infertility, Female and Ovulation Induction, run by Centro A.M.B.R.A. (Associazione Medici e Biologi per la Riproduzione Assistita).
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 42 years, women only
- Conditions the study is for
- Infertility, Female, Ovulation Induction
- What is being tested?
- Ganirelix ; Cetrorelix, Medroxyprogesterone Acetate ; Micronized Progesterone and Linzagolix
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- No sites listed yet
- Study dates
- Sep 2026to Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 42 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
About this study
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.
Read the detailed description
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."
- Conditions
- Infertility, Female, Ovulation Induction
- Being tested
- Ganirelix ; Cetrorelix, Medroxyprogesterone Acetate ; Micronized Progesterone, Linzagolix
- Keywords
- Oral GnRH Antagonist, Linzagolix, Controlled Ovarian Stimulation, In Vitro Fertilization, ICSI, Progestin-Primed Ovarian Stimulation, Oocyte Maturation, OHSS Prevention
- Medical subject headings
- Infertility, Female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ganirelix ; CetrorelixDrug
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.
Medroxyprogesterone Acetate ; Micronized ProgesteroneDrug
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.
LinzagolixDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| B - Injectable GnRH Antagonist (Ganirelix/Cetrorelix) | Active comparator | Not described Receives: Drug: Ganirelix ; Cetrorelix |
| C - PPOS (Progestin-Primed Ovarian Stimulation) Cohort | Active comparator | Not described Receives: Drug: Medroxyprogesterone Acetate ; Micronized Progesterone |
| A - Linzagolix | Experimental | Not described Receives: Drug: Linzagolix |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At oocyte retrieval, approximately 36 hours after trigger (first study cycle)
Secondary outcomes (1)
Incidence of Premature LH Rise
Measured: From initiation of LH-suppressive treatment to the day of trigger (up to approximately 12 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2026
- Study startSep 2026 (estimated)
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infertility, FemaleStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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).
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centro A.M.B.R.A. (Associazione Medici e Biologi per la Riproduzione Assistita)
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07732348
- Sponsor's protocol ID
- LINZA-COS
- Status last verified
- Sep 2026
- First submitted
- 24 Jul 2026
- Last updated
- 30 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT07732348
- Acronym / sponsor ID
- LINZA-COS
- 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
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Centro A.M.B.R.A. (Associazione Medici e Biologi per la Riproduzione Assistita)University, hospital or other
- Study start
- Sep 2026 (estimated)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 28 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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."
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 42 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ganirelix ; CetrorelixGanirelix 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. | Drug | B - Injectable GnRH Antagonist (Ganirelix/Cetrorelix) |
| Medroxyprogesterone Acetate ; Micronized ProgesteroneThis 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. | Drug | C - PPOS (Progestin-Primed Ovarian Stimulation) Cohort |
| LinzagolixDescription: 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. | Drug | A - Linzagolix |
Primary outcome
Number of Mature (MII) Oocytes Retrieved
Time frame: 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.
1 secondary outcome
Incidence of Premature LH Rise
Time frame: From initiation of LH-suppressive treatment to the day of trigger (up to approximately 12 days)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A study testing Ganirelix ; Cetrorelix, Medroxyprogesterone Acetate ; Micronized Progesterone and Linzagolix in people with Infertility, Female and Ovulation Induction, run by Centro A.M.B.R.A. (Associazione Medici e Biologi per la Riproduzione Assistita).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 30 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Mature (MII) Oocytes Retrieved (time frame: At oocyte retrieval, approximately 36 hours after trigger (first study cycle)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2026.