Infertility, FemalePhase 3PRE-LHNCT03741699
Recombinant LH Prior to Ovarian Stimulation in Poor Ovarian Responders (PRE-LH)
A Phase 3 study testing Pre-treatment with rLH (Luveris 75 IU), in people with Infertility, Female, run by Instituto Valenciano de Infertilidad, IVI Alicante at 3 sites in Spain.
Trial summary
Controlled ovarian stimulation (COS) is one of the first stages of assisted reproductive treatment. The goal is to mimic the ovarian cycle while stimulating the ovaries to overproduce eggs capable of being fertilized, thus maximizing the chances of reproductive success. Read more about this study
- Who is it for?
- Ages 35 to 43 years, women only
- Conditions the study is for
- Infertility, Female
- What is being tested?
- Pre-treatment with rLH (Luveris 75 IU),
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 3 sitesSpain
- Study dates
- 18 Feb 2019to 11 May 2024
- Phase
- Phase 3
- 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 43 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- -Patients with POR according to specific criteria that are in line with the criteria defined by the ESHRE (Bologna Criteria), according to which a patient is classified as a poor ovarian responder when she meets two of the three of the following criteria: I.- Previous episode of POR (≤3 oocytes) with conventional stimulation protocol II.- Abnormal ovarian reserve test with an antral follicle count (AFC) <5-7 and/or anti-mullerian hormone values (AMH) <0.5-1.1 ng/mL.
- III.- Women ≥40 years old and/or who have any other risk factor for POR. In addition, two episodes of POR after maximal stimulation are sufficient to define a patient as poor responder in the absence of advanced maternal age or abnormal ovarian reserve test.
- - Women ≥35 to ≤43 years for COS and assisted reproduction techniques (ART).
- - Couple or single woman, accepting preimplantation genetic diagnosis (PGS) after blastocyst biopsy and delayed transfer for selection of euploid embryos.
- - Body Mass Index (BMI) between18 and 30 kg/m 2 , inclusive.
- - Ejaculatory sperm with concentration ≥ 5 mill spermatozoa/mL and ≥ 5 mill total spermatozoa progressive motility. Bank and cryopreserved semen allowed.
- - Informed consent completed, signed and dated.
Who cannot join
- - Cases of recurrent spontaneous miscarriage (≥2 clinical miscarriages) or implantation failure (after transfer of 6 good D3 embryos or 4 good blastocysts) will be excluded.
- - Use of testicular or epididymal spermatozoa as well as ejaculate with concentration < 5 mill spermatozoa/mL and < 5 mill total spermatozoa progressive motility.
- - Primary ovarian failure, PCOS (in accordance with the Rotterdam criteria) or ovary/s inaccessible for oocyte retrieval.
- - Anatomical uterine abnormalities and any endometrium or myometrium pathology (adenomyosis, polyps, myoma, etc.) that may interfere with implantation or pregnancy. Patients with previous polypectomy, myomectomy or surgery for septate/subseptate/arcuatus uterus should not be excluded.
- - Presence of unilateral or bilateral hydrosalpinx that has not been surgically removed or ligated.
- - Presence of level III-IV endometriosis.
Show all 14Show fewer
- - History of tumours in the hypothalamus or pituitary gland, or ovarian, uterine or breast cancer.
- - Abnormal bleeding of undetermined origin.
- - Known infection with human immunodeficiency virus, active hepatitis B or C virus in the woman or her partner.
- - Known allergy or hypersensitivity to the drugs administered during the trial.
- - Concurrent significant medical pathologies that would endanger the patient's safety (uncontrolled thyroid or adrenal dysfunction, severe hepatic or renal impairment, etc.) or interfere with the test evaluations or the clinical outcomes (i.e. confirmed thrombophilia).
- - Use of concomitant medication or any other circumstances that, in the opinion of the investigator, interferes with the development of the trial or does not ensure the safety and efficacy of the data.
- - Simultaneous participation in another clinical trial or previous participation in this study.
- - Participation in another clinical study two months before inclusion in the present study that could affect its objectives.
Trial locations and contacts
3 sites in 1 country.
Spain3 sites
IVI Alicante
Alicante, Valencia, 03015
IVI Madrid
Madrid, 28023
IVI Murcia
Murcia, 30007
About this study
Official title: A Phase III Multicentre, Randomized, Unblinded Clinical Trial to Test the Effect of Treatment with Recombinant LH Prior to Controlled Ovarian Stimulation in Poor Ovarian Responder Women with an Advanced Maternal Age
Controlled ovarian stimulation (COS) is one of the first stages of assisted reproductive treatment. The goal is to mimic the ovarian cycle while stimulating the ovaries to overproduce eggs capable of being fertilized, thus maximizing the chances of reproductive success. The stimulation phase involves the use of different hormonal medications but requires tests to check the development of follicles, and hormonal adjustment to get the optimal ovarian response to stimulation.
However, between 9 to 24% of patients fail to respond adequately to standard stimulation protocols, resulting in Poor Ovarian Response (POR). In addition to the low oocyte production, POR results in a restricted number of good quality embryos with appropriate implantation potential, suggesting a compromised oocyte quality.
Read more
POR is one of the most challenging problems in reproductive medicine. Poor responders are difficult to treat since their response to stimulation tend to be deficient even when using different drugs or protocols. In recent years, different therapeutic alternatives have been proposed for these patients. However, to date, the optimal stimulation protocol has not yet been described and oocyte donation is often offered as their only option to achieve pregnancy.
Recently, evidence has emerged that supplementation with a specific hormone, luteinizing hormone (LH), during or prior to COS could lead to improved reproductive outcomes in poor responders by increasing the number of oocytes retrieved and improving their quality.
The present study aims to evaluate the effect of the treatment with LH prior to COS on the ovarian response in patients with POR and advanced maternal age, the worst prognosis but more frequent group of poor responders attending fertility clinics. We will assess whether LH treatment prior to COS increases the number and quality of oocytes retrieved in those patients and, finally, analyse the impact in their chances of getting pregnant and having a baby.
- Conditions
- Infertility, Female
- Being tested
- Pre-treatment with rLH (Luveris 75 IU),
- Keywords
- Poor ovarian response, Recombinant LH, Advanced maternal age, Oocyte retrieved
- Medical subject headings
- Infertility, Female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pre-treatment with rLH (Luveris 75 IU),Drug
Treatment with 150 IU/day rLH (Luveris 75 IU), administered subcutaneously for 4 consecutive days prior to COS (Controlled ovarian stimulation)
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 - experimental group | Experimental | Treatment with 150 IU/day rLH, administered subcutaneously for 4 consecutive days prior to COS (with a starting dose of 225 IU/day rFSH and 75 IU/day rLH for 18 days maximum in a short antagonist protocol). Receives: Drug: Pre-treatment with rLH (Luveris 75 IU), |
| Arm 2 - control (no pre-treatment) group | No intervention | The subjects assigned to this group will not receive any treatment in the four days prior to COS (with a starting dose of 225 IU/day rFSH and 75 IU/day rLH for 18 days maximum in a short antagonist protocol). |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of oocytes retrieved
number of oocytes retrieved
Measured: 37 days
Secondary outcomes (24)
Number of follicles >17 mm on the previous day or the day of GnRH agonist injection (Decapeptyl)
Measured: from day 8-12 to day 33-37
P 4 and E 2 levels on the previous day or the day of GnRH agonist injection
Measured: from day 8-12 to day 33-37
Duration of stimulation and total gonadotropin dose during COS
Measured: from day 8-12 to day 33-37
Serum hormonal profile before and after IMP treatment and after stimulation
Measured: from day 8-12 to day 33-37
Cycle cancellation rates (stimulation cycle cancelled prior to oocyte retrieval if there is no follicular response after 10 days of stimulation or due to premature ovulation at any time before oocyte retrieval)
Measured: from day 8-12 to day 33-37
Number of mature or metaphase II (MII) oocytes/number of oocytes retrieved per puncture
Measured: Day 37
Number of retrieved oocytes/number of expected oocytes (follicles >15 mm on the day of GnRH agonist injection)
Measured: Day 37
Fertilization rate
Measured: Day 38
Hormonal profile in follicular fluid on the day of the puncture
Measured: Day 37
Gene expression profile in granulosa cells
Measured: Day 37
Apoptosis rate in granulosa cells
Measured: Day 37
Morphological variables of embryonic quality
Measured: Day 38 to 43
Blastocyst rate
Measured: Day 43
Number of optimal embryos (type A or B, according to ASEBIR classification)
Measured: Day 43
Number of euploid and aneuploid embryos
Measured: Day 50
Stimulation cycle yield (number of frozen embryos).
Measured: Day 43
Number of cycles with embryo transferred/ number of stimulation cycle started
Measured: Day 43
Pregnancy rates (per stimulation cycle and embryo transfer)
Measured: Throughout the study, estimate 1 year
Implantation rates
Measured: Throughout the study, estimate 1 year
Ongoing pregnancy rates (per stimulation cycle and embryo transfer)
Measured: Throughout the study, estimate 1 year
Clinical and biochemical miscarriages rates (per stimulation cycle and embryo transfer)
Measured: Throughout the study, estimate 1 year
Ectopic pregnancy rates (per stimulation cycle and embryo transfer)
Measured: Throughout the study, estimate 1 year
Live birth rates
Measured: Throughout the study, estimate 18 +/-3 months
Assessment and recording of adverse events
Measured: Throughout the study, estimate 18 +/-3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2018
- Study start18 Feb 2019
- Primary completion11 May 2024
- Study completion11 May 2024
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- prospective, interventional, randomised, unblinded and controlled study with 2 parallel groups
- Masking
- None (open label)
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- Instituto Valenciano de Infertilidad, IVI Alicante
- Sponsor type
- University, hospital or other
- Collaborators
- Merck, S.L., Spain, Syntax for Science, S.L, Fundación IVI
- Responsible party
- Sponsor
- Investigators
- Manuel Muñoz, Dr., Principal investigator, Physician - Investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03741699
- Sponsor's protocol ID
- 1601-ALC-002-MM
- Other IDs
- 2017-004298-15, 2017
- Acronym
- PRE-LH
- Status last verified
- Oct 2024
- First submitted
- 5 Nov 2018
- Last updated
- 9 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- 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 9 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Multicentre, Randomized, Unblinded Clinical Trial to Test the Effect of Treatment with Recombinant LH Prior to Controlled Ovarian Stimulation in Poor Ovarian Responder Women with an Advanced Maternal Age
- ClinicalTrials.gov ID
- NCT03741699
- Acronym / sponsor ID
- PRE-LH / 1601-ALC-002-MM
- Conditions
- Infertility, Female
- Keywords
- Poor ovarian response, Recombinant LH, Advanced maternal age, Oocyte retrieved
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- Instituto Valenciano de Infertilidad, IVI AlicanteUniversity, hospital or other
- Collaborators
- Merck, S.L., Spain, Syntax for Science, S.L, Fundación IVI
- Study start
- 18 Feb 2019 (actual)
- Primary completion
- 11 May 2024 (actual)
- Study completion
- 11 May 2024 (actual)
- First posted
- 15 Nov 2018 (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.
Controlled ovarian stimulation (COS) is one of the first stages of assisted reproductive treatment. The goal is to mimic the ovarian cycle while stimulating the ovaries to overproduce eggs capable of being fertilized, thus maximizing the chances of reproductive success. The stimulation phase involves the use of different hormonal medications but requires tests to check the development of follicles, and hormonal adjustment to get the optimal ovarian response to stimulation.
However, between 9 to 24% of patients fail to respond adequately to standard stimulation protocols, resulting in Poor Ovarian Response (POR). In addition to the low oocyte production, POR results in a restricted number of good quality embryos with appropriate implantation potential, suggesting a compromised oocyte quality.
POR is one of the most challenging problems in reproductive medicine. Poor responders are difficult to treat since their response to stimulation tend to be deficient even when using different drugs or protocols. In recent years, different therapeutic alternatives have been proposed for these patients. However, to date, the optimal stimulation protocol has not yet been described and oocyte donation is often offered as their only option to achieve pregnancy.
Recently, evidence has emerged that supplementation with a specific hormone, luteinizing hormone (LH), during or prior to COS could lead to improved reproductive outcomes in poor responders by increasing the number of oocytes retrieved and improving their quality.
The present study aims to evaluate the effect of the treatment with LH prior to COS on the ovarian response in patients with POR and advanced maternal age, the worst prognosis but more frequent group of poor responders attending fertility clinics. We will assess whether LH treatment prior to COS increases the number and quality of oocytes retrieved in those patients and, finally, analyse the impact in their chances of getting pregnant and having a baby.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- prospective, interventional, randomised, unblinded and controlled study with 2 parallel groups
| Arm | Type | Receives |
|---|---|---|
| Arm 1 - experimental group | Experimental | Drug: Pre-treatment with rLH (Luveris 75 IU),Treatment with 150 IU/day rLH, administered subcutaneously for 4 consecutive days prior to COS (with a starting dose of 225 IU/day rFSH and 75 IU/day rLH for 18 days maximum in a short antagonist protocol). |
| Arm 2 - control (no pre-treatment) group | No intervention | –The subjects assigned to this group will not receive any treatment in the four days prior to COS (with a starting dose of 225 IU/day rFSH and 75 IU/day rLH for 18 days maximum in a short antagonist protocol). |
Who may qualify
- Ages
- 35 to 43 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- -Patients with POR according to specific criteria that are in line with the criteria defined by the ESHRE (Bologna Criteria), according to which a patient is classified as a poor ovarian responder when she meets two of the three of the following criteria: I.- Previous episode of POR (≤3 oocytes) with conventional stimulation protocol II.- Abnormal ovarian reserve test with an antral follicle count (AFC) <5-7 and/or anti-mullerian hormone values (AMH) <0.5-1.1 ng/mL.
- III.- Women ≥40 years old and/or who have any other risk factor for POR. In addition, two episodes of POR after maximal stimulation are sufficient to define a patient as poor responder in the absence of advanced maternal age or abnormal ovarian reserve test.
- - Women ≥35 to ≤43 years for COS and assisted reproduction techniques (ART).
- - Couple or single woman, accepting preimplantation genetic diagnosis (PGS) after blastocyst biopsy and delayed transfer for selection of euploid embryos.
- - Body Mass Index (BMI) between18 and 30 kg/m 2 , inclusive.
Key exclusion criteria (14 listed)
- - Cases of recurrent spontaneous miscarriage (≥2 clinical miscarriages) or implantation failure (after transfer of 6 good D3 embryos or 4 good blastocysts) will be excluded.
- - Use of testicular or epididymal spermatozoa as well as ejaculate with concentration < 5 mill spermatozoa/mL and < 5 mill total spermatozoa progressive motility.
- - Primary ovarian failure, PCOS (in accordance with the Rotterdam criteria) or ovary/s inaccessible for oocyte retrieval.
- - Anatomical uterine abnormalities and any endometrium or myometrium pathology (adenomyosis, polyps, myoma, etc.) that may interfere with implantation or pregnancy. Patients with previous polypectomy, myomectomy or surgery for septate/subseptate/arcuatus uterus should not be excluded.
- - Presence of unilateral or bilateral hydrosalpinx that has not been surgically removed or ligated.
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 |
|---|---|---|
| Pre-treatment with rLH (Luveris 75 IU),Treatment with 150 IU/day rLH (Luveris 75 IU), administered subcutaneously for 4 consecutive days prior to COS (Controlled ovarian stimulation) | Drug | Arm 1 - experimental group |
Primary outcome
number of oocytes retrieved
Time frame: 37 days
number of oocytes retrieved
24 secondary outcomes
Number of follicles >17 mm on the previous day or the day of GnRH agonist injection (Decapeptyl)
Time frame: from day 8-12 to day 33-37
P 4 and E 2 levels on the previous day or the day of GnRH agonist injection
Time frame: from day 8-12 to day 33-37
Duration of stimulation and total gonadotropin dose during COS
Time frame: from day 8-12 to day 33-37
Serum hormonal profile before and after IMP treatment and after stimulation
Time frame: from day 8-12 to day 33-37
Cycle cancellation rates (stimulation cycle cancelled prior to oocyte retrieval if there is no follicular response after 10 days of stimulation or due to premature ovulation at any time before oocyte retrieval)
Time frame: from day 8-12 to day 33-37
Number of mature or metaphase II (MII) oocytes/number of oocytes retrieved per puncture
Time frame: Day 37
Number of retrieved oocytes/number of expected oocytes (follicles >15 mm on the day of GnRH agonist injection)
Time frame: Day 37
Fertilization rate
Time frame: Day 38
Hormonal profile in follicular fluid on the day of the puncture
Time frame: Day 37
Gene expression profile in granulosa cells
Time frame: Day 37
Apoptosis rate in granulosa cells
Time frame: Day 37
Morphological variables of embryonic quality
Time frame: Day 38 to 43
Blastocyst rate
Time frame: Day 43
Number of optimal embryos (type A or B, according to ASEBIR classification)
Time frame: Day 43
Number of euploid and aneuploid embryos
Time frame: Day 50
Stimulation cycle yield (number of frozen embryos).
Time frame: Day 43
Number of cycles with embryo transferred/ number of stimulation cycle started
Time frame: Day 43
Pregnancy rates (per stimulation cycle and embryo transfer)
Time frame: Throughout the study, estimate 1 year
Implantation rates
Time frame: Throughout the study, estimate 1 year
Ongoing pregnancy rates (per stimulation cycle and embryo transfer)
Time frame: Throughout the study, estimate 1 year
Clinical and biochemical miscarriages rates (per stimulation cycle and embryo transfer)
Time frame: Throughout the study, estimate 1 year
Ectopic pregnancy rates (per stimulation cycle and embryo transfer)
Time frame: Throughout the study, estimate 1 year
Live birth rates
Time frame: Throughout the study, estimate 18 +/-3 months
Assessment and recording of adverse events
Time frame: Throughout the study, estimate 18 +/-3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2024.
- Individual participant dataSharing planned: Undecided
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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. This study is not recruiting at the moment.
Manuel Muñoz, Dr. principal investigator
Physician - Investigator
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pre-treatment with rLH (Luveris 75 IU), in people with Infertility, Female, run by Instituto Valenciano de Infertilidad, IVI Alicante at 3 sites in Spain.
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 7 inclusion and 14 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: finished, as of the sponsor's last update on 9 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Spain. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 oocytes retrieved (time frame: 37 days). 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 9 Oct 2024.