Poor Response to Ovulation InductionPhase 4NCT05405686
Effect of LH Supplementation on the Endometrial Gene Expression Profile in Poor Ovarian Responders
A Phase 4 study testing Lutropin alfa, Follitropin alfa and Endometrial biopsy in people with Poor Response to Ovulation Induction, run by CRG UZ Brussel.
Trial summary
This is a prospective randomized open-label cross-over study. Poor responder patients will undergo two ovarian stimulation cycles. One with recombinant follicle stimulation hormone (FSH), and an other stimulation with recombinant FSH and recombinant luteinizing hormone (LH). Read more about this study
- Who is it for?
- Ages 35 to 40 years, women only
- Conditions the study is for
- Poor Response to Ovulation Induction
- What is being tested?
- Lutropin alfa, Follitropin alfa and Endometrial biopsy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 May 2023to 1 Aug 2024
- Phase
- Phase 4
- 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 35 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Age 35-40 years
- Undergoing IVF/ICSI
- BMI ≥ 19 and ≤ 30
- AMH <1.2 ng/mL
- Previous conventional ovarian stimulation (OS) with < 4 metaphase II (MII) oocytes
- Regular menstrual cycle (26-35 days)
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- Non-smokers
- Acceptance to do 2 consecutive ovarian stimulation cycles (between 1-6 months)
- Signed informed consent
Who cannot join
- Endometriosis > rAFS grade II
- Testicular sperm extraction
- Recurrent miscarriage (>2 previous miscarriages)
- Ovarian stimulation for pre-implantation genetic testing (PGT-A/M)
- Medical/social oocyte vitrification
- In vitro maturation (IVM)
- Untreated auto-immune, endocrine or metabolic disorders
- Asherman's syndrome
About this study
Official title: Endometrial Gene Expression Profiles During Ovarian Stimulation With Recombinant FSH With or Without the Addition of Recombinant LH in Genuine Poor Responders
This is a prospective randomized open-label cross-over study. Poor responder patients will undergo two ovarian stimulation cycles. One with recombinant follicle stimulation hormone (FSH), and an other stimulation with recombinant FSH and recombinant luteinizing hormone (LH). In both groups, a freeze-all strategy will be applied and an endometrial biopsy will be taken 7 days after final oocyte maturation trigger. Endometrial gene expression analysis will be performed on both biopsies. After completion of both treatment cycles, a frozen embryo transfer of a single embryo will be performed.
Read the detailed description
This is a prospective randomized open-label cross-over study, in which patients will be randomized to either start in the control group or in the study group. Participants will undergo both treatments with an interval of minimum 1 and maximum 6 months. In both treatment arms, ovarian stimulation will be started at day 2/3 of the menstrual cycle. In the control group, 225 IU of recombinant FSH will be administered in a fixed antagonist protocol. In the study group, 225 IU of recombinant FSH plus 112,5 IU of recombinant LH will be administered. Cycle monitoring will be performed through serum estradiol (E2), progesterone (P), and luteinizing hormone (LH) assessments, combined with serial ultrasound examinations. Both groups will undergo dual triggering with gonadotropin releasing hormone agonist (GnRHa) 0,2ml and human chorionic gonadotrophin (hCG) 6500IU if one or more follicles of ≥ 17 mm are observed. The oocyte retrieval (OR) will be performed between 34 and 36 hours after final oocyte maturation trigger. At each OR, follicles will be individually meas-ured, aspirated and searched for the presence of cumulus oocyte complexes (COC). Metaphase II (MII) oocytes will then be injected to standard intra-cytoplasmatic sperm injection (ICSI) procedures. In both groups, a freeze-all strategy will be applied. An endometrial biopsy (Pipelle de Cornier ®) will be taken 7 days after final oocyte maturation trigger. After completion of both treatment cycles, a frozen embryo transfer of a single embryo will be performed.
- Conditions
- Poor Response to Ovulation Induction
- Being tested
- Lutropin alfa, Follitropin alfa, Endometrial biopsy
- Keywords
- IVF, LH supplementation, endometrial gene expression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lutropin alfaDrug
addition of recombinant luteinizing hormone
Follitropin alfaDrug
recombinant follicle stimulating hormone (FSH)
Endometrial biopsyDiagnostic test
pipelle de cornier biopsy
| Study group | Role | What they receive |
|---|---|---|
| Control arm | Active comparator | In the control group, 225 IU of recombinant FSH will be administered in a fixed antagonist protocol. Receives: Drug: Follitropin alfa; Diagnostic Test: Endometrial biopsy |
| Study arm | Experimental | In the study group, 225 IU of recombinant FSH plus 112,5 IU of recombinant LH will be administered. Receives: Drug: Lutropin alfa; Drug: Follitropin alfa; Diagnostic Test: Endometrial biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
endometrial gene expression
gene expression profile of the endometrium
Measured: 7 days after finale oocyte maturation trigger
Secondary outcomes (14)
cumulus cell gene expression
Measured: 3-6 months
endometrial histologic analysis based on Noyes' classification system
Measured: 3-6 months
progesterone level at oocyte triggering
Measured: 3-6 months
follicular fluid (FF) hormonal analysis
Measured: 3-6 months
number of preovulatory follicles
Measured: 3-6 months
number of MII oocytes
Measured: 3-6 months
number of oocytes fertilized
Measured: 3-6 months
number of good quality embryos
Measured: 3-6 months
total dose of gonadotropins administered
Measured: 3-6 months
duration of stimulation
Measured: 3-6 months
endometrial thickness at the day of endometrial biopsy
Measured: 3-6 months
implantation rate
Measured: 6-12 months
clinical pregnancy rate
Measured: 6-12 months
live birth rate
Measured: 20 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2022
- Study start1 May 2023 (estimated)
- Primary completion1 Aug 2023 (estimated)
- Study completion1 Aug 2024 (estimated)
Why it stopped: withdrawn due to practical reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Poor Response to Ovulation InductionStudies 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
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Model description
- prospective randomized open-label cross-over study
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- CRG UZ Brussel
- Sponsor type
- University, hospital or other
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Responsible party
- Principal investigator, Liese Boudry, CRG UZ Brussel
- Investigators
- Christophe Blockeel, Principal investigator, UZ Brussels
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05405686
- Sponsor's protocol ID
- LHinPOR
- Status last verified
- Feb 2024
- First submitted
- 1 Jun 2022
- Last updated
- 28 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endometrial Gene Expression Profiles During Ovarian Stimulation With Recombinant FSH With or Without the Addition of Recombinant LH in Genuine Poor Responders
- ClinicalTrials.gov ID
- NCT05405686
- Acronym / sponsor ID
- LHinPOR
- Conditions
- Poor Response to Ovulation Induction
- Keywords
- IVF, LH supplementation, endometrial gene expression
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: withdrawn due to practical reasons
- Enrolment
- 0 participants (actual)
- Lead sponsor
- CRG UZ BrusselUniversity, hospital or other
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Study start
- 1 May 2023 (estimated)
- Primary completion
- 1 Aug 2023 (estimated)
- Study completion
- 1 Aug 2024 (estimated)
- First posted
- 6 Jun 2022 (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 is a prospective randomized open-label cross-over study. Poor responder patients will undergo two ovarian stimulation cycles. One with recombinant follicle stimulation hormone (FSH), and an other stimulation with recombinant FSH and recombinant luteinizing hormone (LH). In both groups, a freeze-all strategy will be applied and an endometrial biopsy will be taken 7 days after final oocyte maturation trigger. Endometrial gene expression analysis will be performed on both biopsies. After completion of both treatment cycles, a frozen embryo transfer of a single embryo will be performed.
Detailed description
This is a prospective randomized open-label cross-over study, in which patients will be randomized to either start in the control group or in the study group. Participants will undergo both treatments with an interval of minimum 1 and maximum 6 months. In both treatment arms, ovarian stimulation will be started at day 2/3 of the menstrual cycle. In the control group, 225 IU of recombinant FSH will be administered in a fixed antagonist protocol. In the study group, 225 IU of recombinant FSH plus 112,5 IU of recombinant LH will be administered. Cycle monitoring will be performed through serum estradiol (E2), progesterone (P), and luteinizing hormone (LH) assessments, combined with serial ultrasound examinations. Both groups will undergo dual triggering with gonadotropin releasing hormone agonist (GnRHa) 0,2ml and human chorionic gonadotrophin (hCG) 6500IU if one or more follicles of ≥ 17 mm are observed. The oocyte retrieval (OR) will be performed between 34 and 36 hours after final oocyte maturation trigger. At each OR, follicles will be individually meas-ured, aspirated and searched for the presence of cumulus oocyte complexes (COC). Metaphase II (MII) oocytes will then be injected to standard intra-cytoplasmatic sperm injection (ICSI) procedures. In both groups, a freeze-all strategy will be applied. An endometrial biopsy (Pipelle de Cornier ®) will be taken 7 days after final oocyte maturation trigger. After completion of both treatment cycles, a frozen embryo transfer of a single embryo will be performed.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- prospective randomized open-label cross-over study
| Arm | Type | Receives |
|---|---|---|
| Control arm | Active comparator | Drug: Follitropin alfa, Diagnostic Test: Endometrial biopsyIn the control group, 225 IU of recombinant FSH will be administered in a fixed antagonist protocol. |
| Study arm | Experimental | Drug: Lutropin alfa, Drug: Follitropin alfa, Diagnostic Test: Endometrial biopsyIn the study group, 225 IU of recombinant FSH plus 112,5 IU of recombinant LH will be administered. |
Who may qualify
- Ages
- 35 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Age 35-40 years
- Undergoing IVF/ICSI
- BMI ≥ 19 and ≤ 30
- AMH <1.2 ng/mL
- Previous conventional ovarian stimulation (OS) with < 4 metaphase II (MII) oocytes
Key exclusion criteria (8 listed)
- Endometriosis > rAFS grade II
- Testicular sperm extraction
- Recurrent miscarriage (>2 previous miscarriages)
- Ovarian stimulation for pre-implantation genetic testing (PGT-A/M)
- Medical/social oocyte vitrification
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 |
|---|---|---|
| Lutropin alfaaddition of recombinant luteinizing hormone | Drug | Study arm |
| Follitropin alfarecombinant follicle stimulating hormone (FSH) | Drug | Control arm, Study arm |
| Endometrial biopsypipelle de cornier biopsy | Diagnostic test | Control arm, Study arm |
Primary outcome
endometrial gene expression
Time frame: 7 days after finale oocyte maturation trigger
gene expression profile of the endometrium
14 secondary outcomes
cumulus cell gene expression
Time frame: 3-6 months
endometrial histologic analysis based on Noyes' classification system
Time frame: 3-6 months
progesterone level at oocyte triggering
Time frame: 3-6 months
follicular fluid (FF) hormonal analysis
Time frame: 3-6 months
number of preovulatory follicles
Time frame: 3-6 months
number of MII oocytes
Time frame: 3-6 months
number of oocytes fertilized
Time frame: 3-6 months
number of good quality embryos
Time frame: 3-6 months
total dose of gonadotropins administered
Time frame: 3-6 months
duration of stimulation
Time frame: 3-6 months
endometrial thickness at the day of endometrial biopsy
Time frame: 3-6 months
implantation rate
Time frame: 6-12 months
clinical pregnancy rate
Time frame: 6-12 months
live birth rate
Time frame: 20 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2024.
- Individual participant dataSharing planned: Undecided
Related trials for Poor Response to Ovulation Induction
RecruitingPhase 2/3
Autologous Platelet Rich Plasma Intraovarian Infusion for Poor Responders
Poor Response to Ovulation Induction, Infertility, Female
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.
Christophe Blockeel principal investigator
UZ Brussels
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Lutropin alfa, Follitropin alfa and Endometrial biopsy in people with Poor Response to Ovulation Induction, run by CRG UZ Brussel.
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 9 inclusion and 8 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: withdrawn, as of the sponsor's last update on 28 Feb 2024. 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 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
endometrial gene expression (time frame: 7 days after finale oocyte maturation trigger). 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 28 Feb 2024.