Female Infertilitylate-rLHNCT03204253
Effects of Recombinant LH in Patients With Repeated Implantation Failure
A study testing rFSH + r-LH in combination and rFSH alone in people with Female Infertility and Female Subfertility, run by University of Roma La Sapienza.
Trial summary
Pregnancy rates fall dramatically in women after 35 years undergoing to IVF or ICSI. While ovarian aging obviously plays the major role in this phenomenon, over suppression of endogenous LH concentrations with GnRH agonists or antagonists-an integral part of standard IVF/ ICSI protocols-may also play a pivotal role. Read more about this study
- Who is it for?
- Ages 18 to 42 years, women only
- Conditions the study is for
- Female Infertility, Female Subfertility
- What is being tested?
- rFSH + r-LH in combination and rFSH alone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- Jan 2016to Sep 2016
- Phase
- Interventional
- 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 18 to 42 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Only patients with repeated implantation failure in at least two previous IVF cycles were included.
Who cannot join
- Patients were excluded from the study if they had any clinically significant systemic disease, polycystic ovarian syndrome (PCOS), a previous history of severe ovarian hyperstimulation syndrome (OHSS), abnormal gynaecological bleeding of unknown origin, a previous history of intolerance to any of the agents used in the study.
About this study
Official title: Effects of Recombinant LH in Late Phase of Ovarian Stimulation in Patients With Repeated Implantation Failure, Clinical Results
Pregnancy rates fall dramatically in women after 35 years undergoing to IVF or ICSI. While ovarian aging obviously plays the major role in this phenomenon, over suppression of endogenous LH concentrations with GnRH agonists or antagonists-an integral part of standard IVF/ ICSI protocols-may also play a pivotal role.
Assisted reproduction technology protocols using GnRH agonists have been considered as the standard protocol during the last two decades, but the use of GnRH antagonists offers the opportunity to control the endogenous LH surge in a rapid and more convenient way.
Read more
LH plays a key role in the intermediate-late phases of folliculogenesis. The presence of receptors for LH in cumulus granulosa cells and its correlation with oocyte maturation has been demonstrated. Although ovarian stimulation is efficiently achieved in most cases by the administration of exogenous FSH alone, specific subgroups of women may benefit from LH activity supplementation during ovarian stimulation. Some authors have found improved outcome with LH activity supplementation in advanced reproductive age women.
LH has a number of roles in follicular development, induction of ovulation, completion of meiosis I, early luteinization and the production of progesterone.
The efficacy of recombinant human follicle-stimulating hormone (r-hFSH) for ovarian stimulation is well established however, the role of supplementary recombinant human luteinizing hormone (r-hLH) is less clear.
Aim of the present study is to evaluate If adding rLH in the late phase of stimulation can benefit in some patient awith repeated implantation failure.
Read the detailed description
Study Design, Size and Duration
The study was conducted at the - Bio fertility IVF Center, Rome, Italy, on infertile couples due to male factor undergoing ICSI treatment.
The study was reviewed and approved by the institutional review board at the - Biofertilty IVF Center.
All patients undergoing ICSI and participating in the study gave informed consent.
Patients included in the study had regular spontaneous menstrual cycles (26-39 days) and were aged < 42 years.
All patients had acceptable follicular phase serum concentrations of FSH (≤10IU/L), LH (<10IU/L) and oestradiol (<60pg/ml), body mass index (BMI) ≤ 30 kg/m2, presence of both ovaries and normal uterine cavity.
Only patients with repeated implantation failure in at least two previous IVF cycles were included.
Patients were excluded from the study if they had any clinically significant systemic disease, polycystic ovarian syndrome (PCOS), a previous history of severe ovarian hyperstimulation syndrome (OHSS), abnormal gynaecological bleeding of unknown origin, a previous history of intolerance to any of the agents used in the study.
This was a prospective, randomized study.
All patient sighed a detailed informed consent.
The study is in accordance to the GCP guidelines
They were randomly divided into two groups (A and B).
All patients were stimulated in GnRH antagonist flexible protocol cycles using rFSH started on day 2 of a spontaneous or induced cycle. HCG (10000 iu ) was administered by I.M route when at least 2 folliclesreached 18 mm in diameter.
Group A included 29 women stimulated with rFSH supplemented by rLH in the late follicular phase started at the same time of starting the antagonist administration.
Those patients received 75 iu of rLH (Luveris serono) daily and 150 iu about 12 hours before triggering ovulation with HCG while Group B included 32 women who were stimulated with recombinant FSH (gonal F serono) only. The oocytes were decumulated and assessed for the maturation two hours after pick up which was done 36 hours after hcg injection. Mature oocyte should have an intact first polar body and homogeneously fine granular and light-colored ooplasm
The rate of metaphase II oocytes was calculated and the MII oocytes were assessed for cytoplasmic morphology and maturity. MII oocytes with a light color and fine homogeneous granulate ooplasm were considered oocytes normal morphology and classified as oocytes that have completed their cytoplasmic maturation.
Embryo transfer was done after 2 days of icsi. Pregnancy test was done after 12 days and clinical pregnancy and number of gestional sacs were assured after 2 weeks of positive pregnancy test with presence of featal heart beats. The mean, SD, T-test and Chi square test were used for statistic calculations of the results.
- Conditions
- Female Infertility, Female Subfertility
- Being tested
- rFSH + r-LH in combination, rFSH alone
- Medical subject headings
- Infertility, Female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rFSH + r-LH in combinationDrug
29 women stimulated with rFSH supplemented by rLH in the late follicular phase started at the same time of starting the antagonist administration.
rFSH aloneDrug
32 women who were stimulated with recombinant FSH alone
| Study group | Role | What they receive |
|---|---|---|
| rFSH + r-LH in combination | Experimental | treatment group Receives: Drug: rFSH + r-LH in combination |
| rFSH alone | Active comparator | control group Receives: Drug: rFSH alone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of ovocites retrived
Possible beneficial effects of rLH in the late phase of stimulation in patient with repeated implantation failure
Measured: 1 cicle of stimulation of 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2017
- Study startJan 2016
- Primary completionSep 2016
- Study completionSep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Female InfertilityStudies of the same condition, open and under way.
- More trials run by University of Roma La SapienzaThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Roma La Sapienza
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Davide Francomano, University of Roma La Sapienza
- Investigators
- Davide Francomano, Principal investigator, University of Roma La Sapienza
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03204253
- Sponsor's protocol ID
- Biofertility
- Acronym
- late-rLH
- Status last verified
- Jun 2017
- First submitted
- 9 Dec 2016
- Last updated
- 29 Jun 2017
- 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 29 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Recombinant LH in Late Phase of Ovarian Stimulation in Patients With Repeated Implantation Failure, Clinical Results
- ClinicalTrials.gov ID
- NCT03204253
- Acronym / sponsor ID
- late-rLH / Biofertility
- Conditions
- Female Infertility, Female Subfertility
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University of Roma La SapienzaUniversity, hospital or other
- Study start
- Jan 2016
- Primary completion
- Sep 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 29 Jun 2017 (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.
Pregnancy rates fall dramatically in women after 35 years undergoing to IVF or ICSI. While ovarian aging obviously plays the major role in this phenomenon, over suppression of endogenous LH concentrations with GnRH agonists or antagonists-an integral part of standard IVF/ ICSI protocols-may also play a pivotal role.
Assisted reproduction technology protocols using GnRH agonists have been considered as the standard protocol during the last two decades, but the use of GnRH antagonists offers the opportunity to control the endogenous LH surge in a rapid and more convenient way.
LH plays a key role in the intermediate-late phases of folliculogenesis. The presence of receptors for LH in cumulus granulosa cells and its correlation with oocyte maturation has been demonstrated. Although ovarian stimulation is efficiently achieved in most cases by the administration of exogenous FSH alone, specific subgroups of women may benefit from LH activity supplementation during ovarian stimulation. Some authors have found improved outcome with LH activity supplementation in advanced reproductive age women.
LH has a number of roles in follicular development, induction of ovulation, completion of meiosis I, early luteinization and the production of progesterone.
The efficacy of recombinant human follicle-stimulating hormone (r-hFSH) for ovarian stimulation is well established however, the role of supplementary recombinant human luteinizing hormone (r-hLH) is less clear.
Aim of the present study is to evaluate If adding rLH in the late phase of stimulation can benefit in some patient awith repeated implantation failure.
Detailed description
Study Design, Size and Duration
The study was conducted at the - Bio fertility IVF Center, Rome, Italy, on infertile couples due to male factor undergoing ICSI treatment.
The study was reviewed and approved by the institutional review board at the - Biofertilty IVF Center.
All patients undergoing ICSI and participating in the study gave informed consent.
Patients included in the study had regular spontaneous menstrual cycles (26-39 days) and were aged < 42 years.
All patients had acceptable follicular phase serum concentrations of FSH (≤10IU/L), LH (<10IU/L) and oestradiol (<60pg/ml), body mass index (BMI) ≤ 30 kg/m2, presence of both ovaries and normal uterine cavity.
Only patients with repeated implantation failure in at least two previous IVF cycles were included.
Patients were excluded from the study if they had any clinically significant systemic disease, polycystic ovarian syndrome (PCOS), a previous history of severe ovarian hyperstimulation syndrome (OHSS), abnormal gynaecological bleeding of unknown origin, a previous history of intolerance to any of the agents used in the study.
This was a prospective, randomized study.
All patient sighed a detailed informed consent.
The study is in accordance to the GCP guidelines
They were randomly divided into two groups (A and B).
All patients were stimulated in GnRH antagonist flexible protocol cycles using rFSH started on day 2 of a spontaneous or induced cycle. HCG (10000 iu ) was administered by I.M route when at least 2 folliclesreached 18 mm in diameter.
Group A included 29 women stimulated with rFSH supplemented by rLH in the late follicular phase started at the same time of starting the antagonist administration.
Those patients received 75 iu of rLH (Luveris serono) daily and 150 iu about 12 hours before triggering ovulation with HCG while Group B included 32 women who were stimulated with recombinant FSH (gonal F serono) only. The oocytes were decumulated and assessed for the maturation two hours after pick up which was done 36 hours after hcg injection. Mature oocyte should have an intact first polar body and homogeneously fine granular and light-colored ooplasm
The rate of metaphase II oocytes was calculated and the MII oocytes were assessed for cytoplasmic morphology and maturity. MII oocytes with a light color and fine homogeneous granulate ooplasm were considered oocytes normal morphology and classified as oocytes that have completed their cytoplasmic maturation.
Embryo transfer was done after 2 days of icsi. Pregnancy test was done after 12 days and clinical pregnancy and number of gestional sacs were assured after 2 weeks of positive pregnancy test with presence of featal heart beats. The mean, SD, T-test and Chi square test were used for statistic calculations of the results.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| rFSH + r-LH in combination | Experimental | Drug: rFSH + r-LH in combinationtreatment group |
| rFSH alone | Active comparator | Drug: rFSH alonecontrol group |
Who may qualify
- Ages
- 18 to 42 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Only patients with repeated implantation failure in at least two previous IVF cycles were included.
Key exclusion criteria (1 listed)
- Patients were excluded from the study if they had any clinically significant systemic disease, polycystic ovarian syndrome (PCOS), a previous history of severe ovarian hyperstimulation syndrome (OHSS), abnormal gynaecological bleeding of unknown origin, a previous history of intolerance to any of the agents used in the study.
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 |
|---|---|---|
| rFSH + r-LH in combination29 women stimulated with rFSH supplemented by rLH in the late follicular phase started at the same time of starting the antagonist administration. | Drug | rFSH + r-LH in combination |
| rFSH alone32 women who were stimulated with recombinant FSH alone | Drug | rFSH alone |
Primary outcome
Number of ovocites retrived
Time frame: 1 cicle of stimulation of 14 days
Possible beneficial effects of rLH in the late phase of stimulation in patient with repeated implantation failure
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 29 Jun 2017.
- 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. This study is not recruiting at the moment.
Davide Francomano principal investigator
University of Roma La Sapienza
Questions about this trial
What is this clinical trial studying?
A study testing rFSH + r-LH in combination and rFSH alone in people with Female Infertility and Female Subfertility, run by University of Roma La Sapienza.
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 1 inclusion and 1 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 29 Jun 2017. 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.
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 ovocites retrived (time frame: 1 cicle of stimulation of 14 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 29 Jun 2017.