InfertilityPhase 4NCT06571214
Potential Benefit of r-hLH Addition in Patients Aged 35 to 40 Under Ovarian Stimulation Treatment
A Phase 4 study testing Recombinant Human Follitropin Alfa Solution for Injection (Gonal-f®) and Recombinant Human Lutropin alfa for Injection (r-hLH, Luveris®) in people with Infertility, run by Nanjing University at 1 site in China.
Trial summary
This will be an exploratory, prospective, randomized, open-label and controlled trial to evaluate the potential benefit of r-hFSH:r-hLH 2:1 co-treatment starting from COS D1 versus r-hFSH alone in patients aged 35 to 40 under ovarian stimulation treatment. Read more about this study
- Who is it for?
- Ages 35 to 40 years, women only
- Conditions the study is for
- Infertility
- What is being tested?
- Recombinant Human Follitropin Alfa Solution for Injection (Gonal-f®) and Recombinant Human Lutropin alfa for Injection (r-hLH, Luveris®)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteChina
- Study dates
- 1 Sep 2024to 30 Jan 2027
- Phase
- Phase 4
- 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 35 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Age 35 to 40 (including 40)
- 18.5<BMI<28 kg/m2
- AFC up to 14
- First or second ART cycle
- Planned for ovarian stimulation with GnRH-antagonist for down-regulation
- Ejaculated sperm
Who cannot join
- Contraindications to ART treatment
- History of two or more spontaneous miscarriages
- History of two or more implantation failures after fresh or frozen-warmed embryo transfers
- Diagnosis of severe endometriosis
- Patients with endocrine and metabolic diseases (diabetes mellitus, hypogonadotropic amenorrhea, genital system tumors, hyperprolactinemia, etc.)
- Confirmed chromosomal abnormalities
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Nanjing Drum Tower Hospital
Nanjing, Jiangsu, 210008
Haixiang Sun, Dr., +8683106666
About this study
Official title: An Exploratory, Randomized, Open-label, Controlled Study to Evaluate the Potential Benefit of r-hLH Addition in Patients Aged 35 to 40 Under Ovarian Stimulation Treatment
This will be an exploratory, prospective, randomized, open-label and controlled trial to evaluate the potential benefit of r-hFSH:r-hLH 2:1 co-treatment starting from COS D1 versus r-hFSH alone in patients aged 35 to 40 under ovarian stimulation treatment.
After signing informed consent form (ICF), all eligible participants will be randomly assigned in a 1:1 ratio to either treatment or control group, and GnRH antagonist protocol will be used in both treatment and control groups.
Read the detailed description
This will be an exploratory, prospective, randomized, open-label and controlled trial to evaluate the potential benefit of r-hFSH:r-hLH 2:1 co-treatment starting from COS D1 versus r-hFSH alone in patients aged 35 to 40 under ovarian stimulation treatment.
After signing informed consent form (ICF), all eligible participants will be randomly assigned in a 1:1 ratio to either treatment or control group, and GnRH antagonist protocol will be used in both treatment and control groups.
- Treatment group: The r-hFSH starting dose will be based on the patient's profile and physician's experience. r-hLH will be added at a ratio of 2:1 starting from day 1 of r-hFSH administration; the dose of r-hFSH during COS will be adjusted by the physician based on clinical experience and the patient's ovarian response, and the r-hFSH: r-hLH dose will be 2:1, continuing to 24~48 hours prior to trigger drug injection.
- Control group: r-hFSH alone will be administrated for ovarian stimulation. The r-hFSH starting dose will be based on the patient's profile and physician's experience. The dose of r-hFSH during COS will be adjusted by the physician based on clinical experience and the patient's ovarian response, continuing to 24~48 hours prior to trigger drug injection.
The estimated treatment duration is 11 days from the first day of COS until 24~48 h prior to trigger drug injection, and this may vary depending on individual circumstances.
Follicular development, serum E2 and P levels will be monitored during COS according to the investigator site's ART practice until the criteria to administer trigger drug are met to induce final oocyte maturation. Trigger drug administration is to be performed according to the site's routine clinical practice.
Oocyte pick-up (OPU), IVF/ICSI, ET, and luteal phase support (LPS) will be performed according to the site's routine practice. LPS will be started after oocyte retrieval in fresh embryo transfer.
- Conditions
- Infertility
- Being tested
- Recombinant Human Follitropin Alfa Solution for Injection (Gonal-f®), Recombinant Human Lutropin alfa for Injection (r-hLH, Luveris®)
- Keywords
- recombinant human LH, recombinant human FSH, ovarian stimulation treatment, advanced maternal age population
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant Human Follitropin Alfa Solution for Injection (Gonal-f®)Drug
As a r-hFSH agent, Gonal-f® is used for COS. It is a prefilled ready to use pen device containing follitropin alfa for injection and is designed for subcutaneous self-administration by patients undergoing COS for ART. It is available as dose presentations of 150 IU and 450 IU. The investigators and/or his/her delegate/s will explain the use of Gonal-f® prefilled pen. Gonal-f® will be prescribed by the investigator based on clinical diagnosis and treatment routines, and will not be provided free of charge.
Recombinant Human Lutropin alfa for Injection (r-hLH, Luveris®)Drug
This product is a white freeze-dried powder and a colorless and clear injection solvent, and stored away from light under 25℃ in the original packaging. Luveris® will be provided free of charge.
| Study group | Role | What they receive |
|---|---|---|
| Treatment group | Experimental | The r-hFSH starting dose will be based on the patient's profile and physician's experience. r-hLH will be added at a ratio of 2:1 starting from day 1 of r-hFSH administration; the dose of r-hFSH during COS will be adjusted by the physician based on clinical experience and the patient's ovarian response, and the r-hFSH: r-hLH dose will be 2:1, continuing to 24~48 hours prior to trigger drug injection.
For both groups, daily injection of 0.25 mg of cetrorelix (Cetrotide®, Merck Serono S.A.) will be administrated subcutaneously when at least one follicle with diameter ≥ 14 mm or serum LH level exceeds 10 IU/L or LH level is 2 folder than basal LH level or P level exceeds 0.8 ng/ml, continuing until ovulation triggering day. Cetrorelix can be administrated earlier in patients with advanced age or diminished ovarian reserve according to judgment of clinicians. Receives: Drug: Recombinant Human Follitropin Alfa Solution for Injection (Gonal-f®); Drug: Recombinant Human Lutropin alfa for Injection (r-hLH, Luveris®) |
| Control group | Active comparator | r-hFSH alone will be administrated for ovarian stimulation. The r-hFSH starting dose will be based on the patient's profile and physician's experience. The dose of r-hFSH during COS will be adjusted by the physician based on clinical experience and the patient's ovarian response, continuing to 24~48 hours prior to trigger drug injection.
For both groups, daily injection of 0.25 mg of cetrorelix (Cetrotide®, Merck Serono S.A.) will be administrated subcutaneously when at least one follicle with diameter ≥ 14 mm or serum LH level exceeds 10 IU/L or LH level is 2 folder than basal LH level or P level exceeds 0.8 ng/ml, continuing until ovulation triggering day. Cetrorelix can be administrated earlier in patients with advanced age or diminished ovarian reserve according to judgment of clinicians. Receives: Drug: Recombinant Human Lutropin alfa for Injection (r-hLH, Luveris®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Good quality embryo rate (cleavage stage)
Cleavage stage good-quality embryos are defined as embryos derived from normally fertilized zygotes with 7~9 cells on day 3 post-fertilization, stage-specific cell size, less than 10% fragmentation, and no multinucleation. Cleavage stage good-quality embryo rate is defined as the number of cleavage stage good-quality embryos divided by the number of normally fertilized zygotes. Embryos will be assessed by two independent experienced embryologists to minimize intra-observation variability.
Measured: Day 3 after fertilization
Secondary outcomes (13)
Number of oocytes
Number of oocytes is defined as the total number of oocytes obtained through transvaginal ultrasound guided puncture on the day of OPU. All follicles with an estimated diameter of ≥12 mm should be punctured.
Measured: 24 hours after Oocytes pick up
Number of MII oocytes (analyzed in ICSI subgroup only)
Number of MII oocyte is defined as the total number of an oocyte at metaphase of meiosis II, exhibiting the first polar body and with the ability to become fertilized
Measured: 24 hours after Oocytes pick up
Total r-hFSH dose
Total r-hFSH dose is defined as the total dose of r-hFSH used for subcutaneous injection during COS period.
Measured: 24 hours after ovulation triggering
Fertilization rate
- IVF normal fertilization rate is defined as the number of oocytes with 2PN and 2PB divided by the number of COCs inseminated.
- ICSI normal fertilization rate is defined as the number of oocytes with 2PN and 2PB divided by the number of MII oocytes injected.
Measured: 24 hours after fertilization
Blastocyst development rate
Blastocyst development rate is defined as the proportion of blastocysts observed at 116 ± 2 h post-insemination as a function of the number of normally fertilized oocytes.
Measured: 5 days after fertilization, up to 7 days
Utilizable embryo rate
Utilizable embryo rate is defined as the number of embryos (or blastocysts) suitable for transfer or cryopreservation as a function of the number of normally fertilized (2PN) oocytes observed on Day 1.
Measured: 5 days after fertilization, up to 7 days
Implantation rate
Implantation rate is defined as the number of gestational sacs observed divided by the number of embryos transferred using transvaginal ultrasound 4~6 weeks after embryo transfer.
Measured: At 4-6 weeks of amenorrhea after customized timing of embryo transfer
Clinical pregnancy rate (per transfer cycle and per oocyte retrieval cycle)
Clinical pregnancy rate is defined as the number of clinical pregnancies expressed per 100 initiated cycles, aspiration cycles, or embryo transfer cycles. Clinical pregnancy is defined as the presence of gestational sac (intrauterine or ectopic) using ultrasound examination at 4~6 weeks after embryo transfer.
Measured: At 4-6 weeks of amenorrhea after customized timing of embryo transfer
Ongoing pregnancy rate
Ongoing pregnancy rate is defined as the number of intrauterine pregnancies continued for 12 gestational weeks divided by the number of embryo transfer cycles.
Measured: At 12 weeks of amenorrhea after customized timing of embryo transfer
Ovarian sensitivity index (OSI)
OSI is defined as the total r-hFSH dose divided by the number of oocytes retrieved.
Measured: 24 hours after fertilization
Follicular output rate (FORT)
FORT is defined as the number of pre-ovulatory follicles (16~22 mm) on the day of trigger divided by the AFC (3~8 mm)
Measured: 24 hours after fertilization
Follicle oocyte index (FOI)
FOI is defined as the number of total oocytes retrieved divided by the AFC
Measured: 24 hours after fertilization
Safety Assessments
AE, SAE and OHSS
Measured: During the COS cycle (average cycle range 11 days), Up to 12 weeks after transfer
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2024
- Study start1 Sep 2024 (estimated)
- Primary completion30 Dec 2026 (estimated)
- Study completion30 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InfertilityStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nanjing University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Li-jun Ding, Nanjing University
- Investigators
- Haiming Xia, Dr., Principal investigator, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06571214
- Sponsor's protocol ID
- MS700642_0020
- Status last verified
- Aug 2024
- First submitted
- 5 Aug 2024
- Last updated
- 27 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory, Randomized, Open-label, Controlled Study to Evaluate the Potential Benefit of r-hLH Addition in Patients Aged 35 to 40 Under Ovarian Stimulation Treatment
- ClinicalTrials.gov ID
- NCT06571214
- Acronym / sponsor ID
- MS700642_0020
- Conditions
- Infertility
- Keywords
- recombinant human LH, recombinant human FSH, ovarian stimulation treatment, advanced maternal age population
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Nanjing UniversityUniversity, hospital or other
- Study start
- 1 Sep 2024 (estimated)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 30 Jan 2027 (estimated)
- First posted
- 26 Aug 2024 (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.
This will be an exploratory, prospective, randomized, open-label and controlled trial to evaluate the potential benefit of r-hFSH:r-hLH 2:1 co-treatment starting from COS D1 versus r-hFSH alone in patients aged 35 to 40 under ovarian stimulation treatment.
After signing informed consent form (ICF), all eligible participants will be randomly assigned in a 1:1 ratio to either treatment or control group, and GnRH antagonist protocol will be used in both treatment and control groups.
Detailed description
This will be an exploratory, prospective, randomized, open-label and controlled trial to evaluate the potential benefit of r-hFSH:r-hLH 2:1 co-treatment starting from COS D1 versus r-hFSH alone in patients aged 35 to 40 under ovarian stimulation treatment.
After signing informed consent form (ICF), all eligible participants will be randomly assigned in a 1:1 ratio to either treatment or control group, and GnRH antagonist protocol will be used in both treatment and control groups.
- Treatment group: The r-hFSH starting dose will be based on the patient's profile and physician's experience. r-hLH will be added at a ratio of 2:1 starting from day 1 of r-hFSH administration; the dose of r-hFSH during COS will be adjusted by the physician based on clinical experience and the patient's ovarian response, and the r-hFSH: r-hLH dose will be 2:1, continuing to 24~48 hours prior to trigger drug injection.
- Control group: r-hFSH alone will be administrated for ovarian stimulation. The r-hFSH starting dose will be based on the patient's profile and physician's experience. The dose of r-hFSH during COS will be adjusted by the physician based on clinical experience and the patient's ovarian response, continuing to 24~48 hours prior to trigger drug injection.
The estimated treatment duration is 11 days from the first day of COS until 24~48 h prior to trigger drug injection, and this may vary depending on individual circumstances.
Follicular development, serum E2 and P levels will be monitored during COS according to the investigator site's ART practice until the criteria to administer trigger drug are met to induce final oocyte maturation. Trigger drug administration is to be performed according to the site's routine clinical practice.
Oocyte pick-up (OPU), IVF/ICSI, ET, and luteal phase support (LPS) will be performed according to the site's routine practice. LPS will be started after oocyte retrieval in fresh embryo transfer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment group | Experimental | Drug: Recombinant Human Follitropin Alfa Solution for Injection (Gonal-f®), Drug: Recombinant Human Lutropin alfa for Injection (r-hLH, Luveris®)The r-hFSH starting dose will be based on the patient's profile and physician's experience. r-hLH will be added at a ratio of 2:1 starting from day 1 of r-hFSH administration; the dose of r-hFSH during COS will be adjusted by the physician based on clinical experience and the patient's ovarian response, and the r-hFSH: r-hLH dose will be 2:1, continuing to 24~48 hours prior to trigger drug injection. For both groups, daily injection of 0.25 mg of cetrorelix (Cetrotide®, Merck Serono S.A.) will be administrated subcutaneously when at least one follicle with diameter ≥ 14 mm or serum LH level exceeds 10 IU/L or LH level is 2 folder than basal LH level or P level exceeds 0.8 ng/ml, continuing until ovulation triggering day. Cetrorelix can be administrated earlier in patients with advanced age or diminished ovarian reserve according to judgment of clinicians. |
| Control group | Active comparator | Drug: Recombinant Human Lutropin alfa for Injection (r-hLH, Luveris®)r-hFSH alone will be administrated for ovarian stimulation. The r-hFSH starting dose will be based on the patient's profile and physician's experience. The dose of r-hFSH during COS will be adjusted by the physician based on clinical experience and the patient's ovarian response, continuing to 24~48 hours prior to trigger drug injection. For both groups, daily injection of 0.25 mg of cetrorelix (Cetrotide®, Merck Serono S.A.) will be administrated subcutaneously when at least one follicle with diameter ≥ 14 mm or serum LH level exceeds 10 IU/L or LH level is 2 folder than basal LH level or P level exceeds 0.8 ng/ml, continuing until ovulation triggering day. Cetrorelix can be administrated earlier in patients with advanced age or diminished ovarian reserve according to judgment of clinicians. |
Who may qualify
- Ages
- 35 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Age 35 to 40 (including 40)
- 18.5<BMI<28 kg/m2
- AFC up to 14
- First or second ART cycle
- Planned for ovarian stimulation with GnRH-antagonist for down-regulation
Key exclusion criteria (6 listed)
- Contraindications to ART treatment
- History of two or more spontaneous miscarriages
- History of two or more implantation failures after fresh or frozen-warmed embryo transfers
- Diagnosis of severe endometriosis
- Patients with endocrine and metabolic diseases (diabetes mellitus, hypogonadotropic amenorrhea, genital system tumors, hyperprolactinemia, etc.)
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 |
|---|---|---|
| Recombinant Human Follitropin Alfa Solution for Injection (Gonal-f®)As a r-hFSH agent, Gonal-f® is used for COS. It is a prefilled ready to use pen device containing follitropin alfa for injection and is designed for subcutaneous self-administration by patients undergoing COS for ART. It is available as dose presentations of 150 IU and 450 IU. The investigators and/or his/her delegate/s will explain the use of Gonal-f® prefilled pen. Gonal-f® will be prescribed by the investigator based on clinical diagnosis and treatment routines, and will not be provided free of charge. | Drug | Treatment group |
| Recombinant Human Lutropin alfa for Injection (r-hLH, Luveris®)This product is a white freeze-dried powder and a colorless and clear injection solvent, and stored away from light under 25℃ in the original packaging. Luveris® will be provided free of charge. | Drug | Control group, Treatment group |
Primary outcome
Good quality embryo rate (cleavage stage)
Time frame: Day 3 after fertilization
Cleavage stage good-quality embryos are defined as embryos derived from normally fertilized zygotes with 7~9 cells on day 3 post-fertilization, stage-specific cell size, less than 10% fragmentation, and no multinucleation. Cleavage stage good-quality embryo rate is defined as the number of cleavage stage good-quality embryos divided by the number of normally fertilized zygotes. Embryos will be assessed by two independent experienced embryologists to minimize intra-observation variability.
13 secondary outcomes
Number of oocytes
Time frame: 24 hours after Oocytes pick up
Number of MII oocytes (analyzed in ICSI subgroup only)
Time frame: 24 hours after Oocytes pick up
Total r-hFSH dose
Time frame: 24 hours after ovulation triggering
Fertilization rate
Time frame: 24 hours after fertilization
Blastocyst development rate
Time frame: 5 days after fertilization, up to 7 days
Utilizable embryo rate
Time frame: 5 days after fertilization, up to 7 days
Implantation rate
Time frame: At 4-6 weeks of amenorrhea after customized timing of embryo transfer
Clinical pregnancy rate (per transfer cycle and per oocyte retrieval cycle)
Time frame: At 4-6 weeks of amenorrhea after customized timing of embryo transfer
Ongoing pregnancy rate
Time frame: At 12 weeks of amenorrhea after customized timing of embryo transfer
Ovarian sensitivity index (OSI)
Time frame: 24 hours after fertilization
Follicular output rate (FORT)
Time frame: 24 hours after fertilization
Follicle oocyte index (FOI)
Time frame: 24 hours after fertilization
Safety Assessments
Time frame: During the COS cycle (average cycle range 11 days), Up to 12 weeks after transfer
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 27 Aug 2024.
- Individual participant dataSharing planned: No
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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.
Haiming Xia, Dr. principal investigator
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Recombinant Human Follitropin Alfa Solution for Injection (Gonal-f®) and Recombinant Human Lutropin alfa for Injection (r-hLH, Luveris®) in people with Infertility, run by Nanjing University at 1 site in China.
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 6 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: opening soon, as of the sponsor's last update on 27 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Contact Haixiang Sun, Dr. (13851622008, stevensunz@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Good quality embryo rate (cleavage stage) (time frame: Day 3 after fertilization). 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 27 Aug 2024.