Premature LuteinisationPhase 1/2NCT05759871
Ovarian Stimulation With FSH Alone Versus FSH Plus GnRH Antagonist in an Oocyte Donor/Recipient Programme
A Phase 1/2 study testing GnRH antagonist in people with Premature Luteinisation and Progesterone Elevation, run by National and Kapodistrian University of Athens.
Trial summary
The aim of this study is to compare the efficacy of a protocol using FSH alone with that of a protocol using FSH plus a GnRH antagonist for controlled ovarian hyperstimulation in cycles of elective freezing in the context of a donor/recipient programme. Read more about this study
- Who is it for?
- Ages 21 to 32 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Premature Luteinisation, Progesterone Elevation
- What is being tested?
- GnRH antagonist
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 2023to 1 Jul 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 21 to 32 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- healthy women 21-32 years old with a BMI of 21 to 29 kg/m2 who wish to donate their oocytes
- normal ovarian reserve tests
- normal menstrual cycles of 26-32 days
- the women would not have received any hormonal treatment during the last three months before entering the study.
- absence of coagulation and/or autoimmune disorders.
Who cannot join
- Use of other protocols towards oocyte retrieval, such as natural, or modified natural cycles
- Poor ovarian response according to the Bologna criteria [22],
- History of endocrine or metabolic disorders, ovarian cystectomy or oophorectomy,
- Women with the diagnosis of polycystic ovary syndrome
- Clinical and/or laboratory markers of hereditary or acquired thrombophilia that complied to the standard protocols of each Unit.
- Non-hormonal medication for a serious medical condition
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Ovarian Stimulation With FSH Alone Versus FSH Plus a GnRH Antagonist in an Oocyte Donor/Recipient Programme: a Protocol for a Non-randomised Multicenter Study
The aim of this study is to compare the efficacy of a protocol using FSH alone with that of a protocol using FSH plus a GnRH antagonist for controlled ovarian hyperstimulation in cycles of elective freezing in the context of a donor/recipient programme.
Read the detailed description
The hypothesis to be tested is that an ovarian stimulation protocol that includes FSH alone without any LH surge prevention regimens is not inferior to a protocol including FSH plus a GnRH antagonist in terms of clinical outcome in a donor/recipient model.
The formal sample size is calculated as follows:
If there is a true difference in favour of the experimental treatment of 5% (20% vs 15%), then 160 patients (80 per group in case of 1:1 enrolment) are required to be 80% sure that the upper limit of a one-sided 95% confidence interval (or equivalently a 90% two-sided confidence interval) will exclude a difference in favour of the standard/control group of more than 10%.
In the context of the present pilot study (as a first stage), the investigators intend to study 50 patients (25 per group in case of 1:1 enrolment). At a second stage the above mentioned sample size will be used.
- Conditions
- Premature Luteinisation, Progesterone Elevation
- Being tested
- GnRH antagonist
- Keywords
- Controlled ovarian stimulation, GnRH antagonist, oocyte donation, LH surge
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GnRH antagonistOther
The GnRH antagonist in the control group (standard therapy) is administered from day 6 of FSH treatment at the dose of 0.25 mg per day until the triggering day and is injected each time immediately after the injection of FSH.
| Study group | Role | What they receive |
|---|---|---|
| FSH only (no GnRH antagonist) | Experimental | Women receive only FSH starting on day 2 of the cycle. The starting dose of FSH is 225-300 IU s.c. for the first 4 days adjusted thereafter according to the ovarian response. Receives: Other: GnRH antagonist |
| FSH + GnRH antagonist | Active comparator | Women receive 225-300 IU s.c. FSH, and a GnRH antagonist from day 6 of FSH treatment at the dose of 0.25 mg per day until the triggering day. The GnRH antagonist in group 2 is injected each time immediately after the injection of FSH. Receives: Other: GnRH antagonist |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of LH secretory peaks
A secretory peak of LH is defined as the increase at levels ≥10 IU/l.
Measured: 3 weeks after start of ovarian stimulation.
Rate of concentration of progesterone >1 ng/ml
Concentration of progesterone elevation >1 ng/ml
Measured: At any time within 3 weeks after start of ovarian stimulation.
Secondary outcomes (2)
Rate of ongoing clinical pregnancy
Clinical pregnancy (fetal heart beat) at ultrasound
Measured: 12 weeks after last menstrual period
Rate of miscarriage
Miscarriage / Loss of the embryo
Measured: Within 20 weeks after last menstrual period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2023
- Study start1 Apr 2023 (estimated)
- Primary completion1 Mar 2024 (estimated)
- Study completion1 Jul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Premature LuteinisationStudies of the same condition, open and under way.
- More trials run by National and Kapodistrian University of AthensThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Protocol using FSH alone with that of a protocol using FSH plus a GnRH antagonist for controlled ovarian hyperstimulation in cycles of elective freezing in the context of a donor/recipient programme.
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National and Kapodistrian University of Athens
- Sponsor type
- University, hospital or other
- Collaborators
- Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece, Embryoland, Athens, Greece, Embryolab IVF Unit, Thessaloniki, Greece, Assisting Nature IVF Unit, Thessaloniki, Greece, HYGEIA IVF - Embryogenesis A.R.T. Unit, Athens, Greece, Institute of Fertility, Athens, Greece, Mitosis IVF Centre, Pireas, Greece
- Responsible party
- Principal investigator, Siristatidis Charalampos, MD, PhD, National and Kapodistrian University of Athens
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05759871
- Sponsor's protocol ID
- Non-anta-D
- Status last verified
- Feb 2023
- First submitted
- 9 Feb 2023
- Last updated
- 10 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Wang HL, Lai HH, Chuang TH, Shih YW, Huang SC, Lee MJ, Chen SU. A Patient Friendly Corifollitropin Alfa Protocol without Routine Pituitary Suppression in Normal Responders. PLoS One. 2016 Apr 21;11(4):e0154123. doi: 10.1371/journal.pone.0154123. eCollection 2016.
PubMed 27100388Zhang Y, Xu Y, Yu J, Wang X, Xue Q, Shang J, Yang X, Shan X. A premature luteinizing hormone surge without elevated progesterone levels has no adverse effect on cumulative live birth rate in patient undergoing a flexible GnRH antagonist protocol: a retrospective study. J Ovarian Res. 2023 Jun 27;16(1):119. doi: 10.1186/s13048-023-01219-w.
PubMed 37370146Kuang Y, Chen Q, Fu Y, Wang Y, Hong Q, Lyu Q, Ai A, Shoham Z. Medroxyprogesterone acetate is an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Fertil Steril. 2015 Jul;104(1):62-70.e3. doi: 10.1016/j.fertnstert.2015.03.022. Epub 2015 May 5.
PubMed 25956370Messinis IE, Messini CI, Anifandis G, Daponte A. Exogenous progesterone for LH surge prevention is redundant in ovarian stimulation protocols. Reprod Biomed Online. 2021 Apr;42(4):694-697. doi: 10.1016/j.rbmo.2021.01.017. Epub 2021 Jan 30.
PubMed 33583700Messinis IE, Templeton A, Baird DT. Endogenous luteinizing hormone surge in women during induction of multiple follicular development with pulsatile follicle stimulating hormone. Clin Endocrinol (Oxf). 1986 Feb;24(2):193-201. doi: 10.1111/j.1365-2265.1986.tb00762.x.
PubMed 3085995
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ovarian Stimulation With FSH Alone Versus FSH Plus a GnRH Antagonist in an Oocyte Donor/Recipient Programme: a Protocol for a Non-randomised Multicenter Study
- ClinicalTrials.gov ID
- NCT05759871
- Acronym / sponsor ID
- Non-anta-D
- Conditions
- Premature Luteinisation, Progesterone Elevation
- Keywords
- Controlled ovarian stimulation, GnRH antagonist, oocyte donation, LH surge
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- National and Kapodistrian University of AthensUniversity, hospital or other
- Collaborators
- Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece, Embryoland, Athens, Greece, Embryolab IVF Unit, Thessaloniki, Greece, Assisting Nature IVF Unit, Thessaloniki, Greece, HYGEIA IVF - Embryogenesis A.R.T. Unit, Athens, Greece, Institute of Fertility, Athens, Greece, Mitosis IVF Centre, Pireas, Greece
- Study start
- 1 Apr 2023 (estimated)
- Primary completion
- 1 Mar 2024 (estimated)
- Study completion
- 1 Jul 2024 (estimated)
- First posted
- 8 Mar 2023 (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.
The aim of this study is to compare the efficacy of a protocol using FSH alone with that of a protocol using FSH plus a GnRH antagonist for controlled ovarian hyperstimulation in cycles of elective freezing in the context of a donor/recipient programme.
Detailed description
The hypothesis to be tested is that an ovarian stimulation protocol that includes FSH alone without any LH surge prevention regimens is not inferior to a protocol including FSH plus a GnRH antagonist in terms of clinical outcome in a donor/recipient model.
The formal sample size is calculated as follows:
If there is a true difference in favour of the experimental treatment of 5% (20% vs 15%), then 160 patients (80 per group in case of 1:1 enrolment) are required to be 80% sure that the upper limit of a one-sided 95% confidence interval (or equivalently a 90% two-sided confidence interval) will exclude a difference in favour of the standard/control group of more than 10%.
In the context of the present pilot study (as a first stage), the investigators intend to study 50 patients (25 per group in case of 1:1 enrolment). At a second stage the above mentioned sample size will be used.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Protocol using FSH alone with that of a protocol using FSH plus a GnRH antagonist for controlled ovarian hyperstimulation in cycles of elective freezing in the context of a donor/recipient programme.
| Arm | Type | Receives |
|---|---|---|
| FSH only (no GnRH antagonist) | Experimental | Other: GnRH antagonistWomen receive only FSH starting on day 2 of the cycle. The starting dose of FSH is 225-300 IU s.c. for the first 4 days adjusted thereafter according to the ovarian response. |
| FSH + GnRH antagonist | Active comparator | Other: GnRH antagonistWomen receive 225-300 IU s.c. FSH, and a GnRH antagonist from day 6 of FSH treatment at the dose of 0.25 mg per day until the triggering day. The GnRH antagonist in group 2 is injected each time immediately after the injection of FSH. |
Who may qualify
- Ages
- 21 to 32 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- healthy women 21-32 years old with a BMI of 21 to 29 kg/m2 who wish to donate their oocytes
- normal ovarian reserve tests
- normal menstrual cycles of 26-32 days
- the women would not have received any hormonal treatment during the last three months before entering the study.
Key exclusion criteria (6 listed)
- Use of other protocols towards oocyte retrieval, such as natural, or modified natural cycles
- Poor ovarian response according to the Bologna criteria [22],
- History of endocrine or metabolic disorders, ovarian cystectomy or oophorectomy,
- Women with the diagnosis of polycystic ovary syndrome
- Clinical and/or laboratory markers of hereditary or acquired thrombophilia that complied to the standard protocols of each Unit.
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 |
|---|---|---|
| GnRH antagonistThe GnRH antagonist in the control group (standard therapy) is administered from day 6 of FSH treatment at the dose of 0.25 mg per day until the triggering day and is injected each time immediately after the injection of FSH. | Other | FSH + GnRH antagonist, FSH only (no GnRH antagonist) |
Primary outcome
Rate of LH secretory peaks
Time frame: 3 weeks after start of ovarian stimulation.
A secretory peak of LH is defined as the increase at levels ≥10 IU/l.
Rate of concentration of progesterone >1 ng/ml
Time frame: At any time within 3 weeks after start of ovarian stimulation.
Concentration of progesterone elevation >1 ng/ml
2 secondary outcomes
Rate of ongoing clinical pregnancy
Time frame: 12 weeks after last menstrual period
Rate of miscarriage
Time frame: Within 20 weeks after last menstrual period
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2023.
- Background: PubMed 27100388Wang HL, Lai HH, Chuang TH, Shih YW, Huang SC, Lee MJ, Chen SU. A Patient Friendly Corifollitropin Alfa Protocol without Routine Pituitary Suppression in Normal Responders. PLoS One. 2016 Apr 21;11(4):e0154123. doi: 10.1371/journal.pone.0154123. eCollection 2016.
- Background: PubMed 37370146Zhang Y, Xu Y, Yu J, Wang X, Xue Q, Shang J, Yang X, Shan X. A premature luteinizing hormone surge without elevated progesterone levels has no adverse effect on cumulative live birth rate in patient undergoing a flexible GnRH antagonist protocol: a retrospective study. J Ovarian Res. 2023 Jun 27;16(1):119. doi: 10.1186/s13048-023-01219-w.
- Background: PubMed 25956370Kuang Y, Chen Q, Fu Y, Wang Y, Hong Q, Lyu Q, Ai A, Shoham Z. Medroxyprogesterone acetate is an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Fertil Steril. 2015 Jul;104(1):62-70.e3. doi: 10.1016/j.fertnstert.2015.03.022. Epub 2015 May 5.
- Background: PubMed 33583700Messinis IE, Messini CI, Anifandis G, Daponte A. Exogenous progesterone for LH surge prevention is redundant in ovarian stimulation protocols. Reprod Biomed Online. 2021 Apr;42(4):694-697. doi: 10.1016/j.rbmo.2021.01.017. Epub 2021 Jan 30.
- Background: PubMed 3085995Messinis IE, Templeton A, Baird DT. Endogenous luteinizing hormone surge in women during induction of multiple follicular development with pulsatile follicle stimulating hormone. Clin Endocrinol (Oxf). 1986 Feb;24(2):193-201. doi: 10.1111/j.1365-2265.1986.tb00762.x.
- Individual participant dataSharing planned: Undecided
Related trials for Premature Luteinisation
Recruiting
Usefulness of Corifollitropin α as Alternative to Conventional Daily rFSH Protocols in Oocyte Donors Undergoing Pituitary Suppression With Medroxiprogesterona Acetate (MPA)
Infertility, Female, Reproductive Sterility
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. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing GnRH antagonist in people with Premature Luteinisation and Progesterone Elevation, run by National and Kapodistrian University of Athens.
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 6 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: status not confirmed, as of the sponsor's last update on 10 Mar 2023. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ioannis Messinis, Prof (6944370627 ext. 0030, messinis.io@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of LH secretory peaks (time frame: 3 weeks after start of ovarian stimulation.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05759871, which also lists 5 linked publications.
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 10 Mar 2023.