InfertilityPhase 4NCT00441324
Efficacy and Safety of R-hLH (Luveris ®) Priming Prior to R-HFSH Treatment in Infertile Women Undergoing IVF-ET
A Phase 4 study testing recombinant human LH in people with Infertility, run by NHS Greater Glasgow and Clyde at 3 sites in 3 countries.
Trial summary
In programmes of IVF, normal women undergo controlled ovarian stimulation using exogenous FSH injections to obtain multiple eggs. The process results in eggs of mixed quality with a broad range of developmental and implantation potential. Read more about this study
- Who is it for?
- Ages 19 to 37 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Infertility
- What is being tested?
- recombinant human LH
- Type of treatment
- Surgery or procedure
- How many people
- 160 participants
- Where
- 3 sitesin 3 countries
- Study dates
- Mar 2003to Feb 2006
- 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 19 to 37 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- infertile undergoing IVF
- normal menstrual rhythm
Who cannot join
- polycystic ovaries
- known resistance to FSH
- other drug preparations
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
Denmark1 site
Fertility Clinic, Department of Obstetrics and Gynaecology, University Hospital of Odense, 5000
Odense
France1 site
Reproductive Medicine Unit, Department of Gynaecology and Obstetrics, Jean Verdier Hospital, University Paris XIII
Paris
United Kingdom1 site
Assisted Conception Unit., Royal Infirmary of Edinburgh
Edinburgh
About this study
In programmes of IVF, normal women undergo controlled ovarian stimulation using exogenous FSH injections to obtain multiple eggs. The process results in eggs of mixed quality with a broad range of developmental and implantation potential.
The aim of the study was to determine whether, treatment with recombinant human LH prior to the FSH injections can improve outcome for women undergoing IVF. High grade embryos implant with a higher frequency and baby delivery rate than poor quality embryos. The mature oocyte is the most important determinant of embryo quality. Early follicles, containing immature eggs, have LH receptors in the theca cells that surround the follicle, and LH stimulates these cells to produce factors essential for normal follicular development.
The intent of the study was to use recLH treatment prior to recFSH to treat a cohort of follicles, so that they can all mature together, thus increasing the proportion of high grade oocytes and their subsequent embryos
Read the detailed description
Normal women undergoing IVF (Total n = 146; GRI n = 43) were recruited in 4 centres in 3 countries, and all were started on treatment with a depo GnRH-agonist to suppress endogenous gonadotropin secretion. Block randomisation lead to a distribution 71 untreated cases and 75 cases treated with rec-hLH (Luveris,[Serono]; 300IU/d) for 7 days. On the following days recombinant follicle stimulating hormone (rec-hFSH) stimulation of the ovaries was initiated using Gonal-f (150IU/d) for approximately 12 days.
HCG (3500IU) was given when >2 mature follicles were seen by ovarian ultrasound, and oocytes (eggs) were fertilized in vitro after collection between 36 and 38h after the injection. Embryos were scored for quality, and a maximum of 2 embryos were transferred 2 or 3 days later.
Results During Luveris treatment the LH concentration was increased by approximately 3 IU/L, but there was no change in the hormone profiles of androgens or estrogens in blood samples measured in a central laboratory. Both groups of patients showed an increase in the circulating anti-mullerian hormone, although there was no difference between the groups.
The Luveris treated group showed a significant (p=0.007) increase in the number of small antral follicles, but to a degree that was not different from the control group.
During rec-hFSH stimulation, there was no difference in the duration of FSH injections required or the total dose, or the total number of follicles seen, or the hormone profiles observed.
The Luveris pre-treated group showed a slight (not significant) increase in oocyte yield. In this group there was a significant increase in the normally fertilized embryo yield (no treatment mean = 5.1; Luveris treatment mean = 7.0: p= 0.038).
Discussion The observations of negligible effects of LH upon the hormone profiles may be explained by the fact that the hormone concetrations were at the lower limit of sensitivity of the assay methods, and they do not preclude an effect within the follicles. We did observe effects upon follicular development in the ultrasound profiles. Effects upon hormone profiles may require both hormones (LH and FSH) to be present at the same time (instead of in sequence).
The small effect of the pre-treatment upon normal embryo yield may be an important observation.
Conclusion These results demonstrate that treating follicles with LH prior to FSH, may lead to the development of more viable follicles than with FSH treatment alone. This should lead to improved regimes of ovarian stimulation and improve the outcome potential for women undergoing IVF.
Future Research Exploration of this phenomenon will be required in order to maximise any potential benefit from the process. There are numerous sub-groups of patients who may possibly benefit, including poor responding patients, but further data are required.
- Conditions
- Infertility
- Being tested
- recombinant human LH
- Keywords
- Ovarian follicle, Thecal cells, Androgens, FSH sensitivity
- 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 LHProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Numbers of oocytes
Numbers of embryos
Numbers if high grade embryos
Secondary outcomes (2)
Duration of FSH injections
Numbers of FSH injections
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2007 (estimated)
- Study startMar 2003
- Study completionFeb 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- 160 participants
Sponsor and investigators
- Lead sponsor
- NHS Greater Glasgow and Clyde
- Sponsor type
- University, hospital or other
- Investigators
- Richard Fleming, PhD, Principal investigator, NHS Greater Glasgow and Clyde
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00441324
- Sponsor's protocol ID
- RN03B001
- Status last verified
- Feb 2007
- First submitted
- 27 Feb 2007
- Last updated
- 28 Feb 2007
- Results posted
- No
- Data monitoring committee
- No
Publications
Durnerin CI, Erb K, Fleming R, Hillier H, Hillier SG, Howles CM, Hugues JN, Lass A, Lyall H, Rasmussen P, Thong J, Traynor I, Westergaard L, Yates R; Luveris Pretreatment Group. Effects of recombinant LH treatment on folliculogenesis and responsiveness to FSH stimulation. Hum Reprod. 2008 Feb;23(2):421-6. doi: 10.1093/humrep/dem388. Epub 2007 Dec 15.
PubMed 18084048
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of R-hLH (Luveris ®) Priming Prior to R-HFSH Treatment in Infertile Women Undergoing IVF-ET
- ClinicalTrials.gov ID
- NCT00441324
- Acronym / sponsor ID
- RN03B001
- Conditions
- Infertility
- Keywords
- Ovarian follicle, Thecal cells, Androgens, FSH sensitivity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 160 participants
- Lead sponsor
- NHS Greater Glasgow and ClydeUniversity, hospital or other
- Study start
- Mar 2003
- Study completion
- Feb 2006
- First posted
- 28 Feb 2007 (estimated)
- 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.
In programmes of IVF, normal women undergo controlled ovarian stimulation using exogenous FSH injections to obtain multiple eggs. The process results in eggs of mixed quality with a broad range of developmental and implantation potential.
The aim of the study was to determine whether, treatment with recombinant human LH prior to the FSH injections can improve outcome for women undergoing IVF. High grade embryos implant with a higher frequency and baby delivery rate than poor quality embryos. The mature oocyte is the most important determinant of embryo quality. Early follicles, containing immature eggs, have LH receptors in the theca cells that surround the follicle, and LH stimulates these cells to produce factors essential for normal follicular development.
The intent of the study was to use recLH treatment prior to recFSH to treat a cohort of follicles, so that they can all mature together, thus increasing the proportion of high grade oocytes and their subsequent embryos
Detailed description
Normal women undergoing IVF (Total n = 146; GRI n = 43) were recruited in 4 centres in 3 countries, and all were started on treatment with a depo GnRH-agonist to suppress endogenous gonadotropin secretion. Block randomisation lead to a distribution 71 untreated cases and 75 cases treated with rec-hLH (Luveris,[Serono]; 300IU/d) for 7 days. On the following days recombinant follicle stimulating hormone (rec-hFSH) stimulation of the ovaries was initiated using Gonal-f (150IU/d) for approximately 12 days.
HCG (3500IU) was given when >2 mature follicles were seen by ovarian ultrasound, and oocytes (eggs) were fertilized in vitro after collection between 36 and 38h after the injection. Embryos were scored for quality, and a maximum of 2 embryos were transferred 2 or 3 days later.
Results During Luveris treatment the LH concentration was increased by approximately 3 IU/L, but there was no change in the hormone profiles of androgens or estrogens in blood samples measured in a central laboratory. Both groups of patients showed an increase in the circulating anti-mullerian hormone, although there was no difference between the groups.
The Luveris treated group showed a significant (p=0.007) increase in the number of small antral follicles, but to a degree that was not different from the control group.
During rec-hFSH stimulation, there was no difference in the duration of FSH injections required or the total dose, or the total number of follicles seen, or the hormone profiles observed.
The Luveris pre-treated group showed a slight (not significant) increase in oocyte yield. In this group there was a significant increase in the normally fertilized embryo yield (no treatment mean = 5.1; Luveris treatment mean = 7.0: p= 0.038).
Discussion The observations of negligible effects of LH upon the hormone profiles may be explained by the fact that the hormone concetrations were at the lower limit of sensitivity of the assay methods, and they do not preclude an effect within the follicles. We did observe effects upon follicular development in the ultrasound profiles. Effects upon hormone profiles may require both hormones (LH and FSH) to be present at the same time (instead of in sequence).
The small effect of the pre-treatment upon normal embryo yield may be an important observation.
Conclusion These results demonstrate that treating follicles with LH prior to FSH, may lead to the development of more viable follicles than with FSH treatment alone. This should lead to improved regimes of ovarian stimulation and improve the outcome potential for women undergoing IVF.
Future Research Exploration of this phenomenon will be required in order to maximise any potential benefit from the process. There are numerous sub-groups of patients who may possibly benefit, including poor responding patients, but further data are required.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 19 to 37 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- infertile undergoing IVF
- normal menstrual rhythm
Key exclusion criteria (3 listed)
- polycystic ovaries
- known resistance to FSH
- other drug preparations
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 LH | Procedure or surgery | – |
Primary outcome
Numbers of oocytes
Numbers of embryos
Numbers if high grade embryos
2 secondary outcomes
Duration of FSH injections
Numbers of FSH injections
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 28 Feb 2007.
- Derived from this study: PubMed 18084048Durnerin CI, Erb K, Fleming R, Hillier H, Hillier SG, Howles CM, Hugues JN, Lass A, Lyall H, Rasmussen P, Thong J, Traynor I, Westergaard L, Yates R; Luveris Pretreatment Group. Effects of recombinant LH treatment on folliculogenesis and responsiveness to FSH stimulation. Hum Reprod. 2008 Feb;23(2):421-6. doi: 10.1093/humrep/dem388. Epub 2007 Dec 15.
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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.
Richard Fleming, PhD principal investigator
NHS Greater Glasgow and Clyde
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing recombinant human LH in people with Infertility, run by NHS Greater Glasgow and Clyde at 3 sites in 3 countries.
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 2 inclusion and 3 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 28 Feb 2007. 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 Denmark, France, United Kingdom. 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?
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?
Numbers of oocytes. The study lists 3 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 NCT00441324, which also lists 1 linked publication.
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 2007.