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InfertilityPhase 3MEGASETNCT00884221

MENOPUR in Gonadotrophin-releasing Hormone (GnRH) Antagonist Cycles With Single Embryo Transfer

A Phase 3 study testing Highly purified menotrophin and Recombinant FSH in people with Infertility, run by Ferring Pharmaceuticals at 25 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The main purpose of this clinical research trial was to compare the ongoing pregnancy rate between two gonadotrophins for controlled ovarian stimulation (MENOPUR and recombinant follicle-stimulating hormone (FSH)), in cycles where a gonadotrophin-releasing hormone (GnRH) antagonist was used for prevention of premature… Read more about this study

Who is it for?
Ages 21 to 34 years, women only
Conditions the study is for
Infertility
What is being tested?
Highly purified menotrophin and Recombinant FSH
Could I receive a placebo?
No, everyone receives an active treatment
How many people
749 participants
Where
25 sitesin 7 countries
Study dates
Jul 2009to Jan 2011
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 21 to 34 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • Informed Consent Documents signed prior to screening evaluations
  • In good physical and mental health
  • Pre-menopausal females 21-34 years of age
  • Body mass index (BMI)18-25 kg/m2
  • Eligible for intracytoplasmic sperm injection (ICSI)
  • Unexplained infertility or partner with mild male factor infertility
Show all 14Show fewer
  • Infertility for at least 12 months before randomization
  • Regular menstrual cycles of 24-35 days, presumed to be ovulatory
  • Hysterosalpingography, hysteroscopy, or transvaginal ultrasound documenting a uterus consistent with expected normal function
  • Transvaginal ultrasound documenting expected normal function of the ovaries
  • Early follicular phase serum levels of FSH between 1 and 12 IU/L
  • Early follicular phase total antral follicle (diameter 2-10 mm) count ≥ 10 for both ovaries combined
  • Willing to accept transfer of one blastocyst in the fresh cycle
  • Willing to undergo frozen embryo replacement cycles with transfer of one blastocyst per cycle within the first year after randomisation

Who cannot join

  • Known polycystic ovarian syndrome or known endometriosis stage I-IV
  • Diagnosed as "poor responder" in a previous controlled ovarian stimulation (COS) cycle
  • Severe ovarian hyperstimulation syndrome (OHSS)in a previous COS cycle
  • History of recurrent miscarriage
  • Current or past (12 months prior to randomization) abuse of alcohol or drugs, and/or current (last month) intake of more than 14 units of alcohol per week
  • Current or past smoking habit of more than 10 cigarettes per day
Show all 10Show fewer
  • Hypersensitivity to any active ingredient or excipients in the medicinal products used in the trial
  • Hypersensitivity to gonadotrophin-releasing hormone (GnRH) or any other GnRH analogue
  • Previous participation in the trial
  • Use of any non registered investigational drugs during 3 months before randomization

Trial locations and contacts

25 sites in 7 countries.

25 sites in 7 countries

Spain6 sites

  • IU Dexeus

    Barcelona

  • GINEFIV, Madrid

    Madrid

  • IVI Madrid

    Madrid

  • Ginemed

    Seville

  • IVI Sevilla

    Seville

  • IVI Valencia

    Valencia

Other trials in Spain

Belgium4 sites

  • ERASME Hospital

    Anderlecht

  • UZ Brussel

    Brussels

  • UZ Antwerpen

    Edegem

  • UZ Gent

    Ghent

Other trials in Belgium

Denmark4 sites

  • H:S Rigshospitalet

    Copenhagen

  • Amtssygehuset Herlev

    Herlev

  • Sygehus Vestsjælland

    Holbæk

  • H:S Hvidovre Hospital

    Hvidovre

Other trials in Denmark

Czechia3 sites

  • IVF Institute

    Pilsen

  • ISCARE IVF a.s.

    Prague

  • Pronatal

    Prague

Other trials in Czechia

Sweden3 sites

  • Fertilitetscentrum AB Gothenburg

    Gothenburg

  • IVF-kliniken CURA

    Malmö

  • RMC, Malmö

    Malmö

Other trials in Sweden

Turkey (Türkiye)3 sites

  • Hacettepe University

    Ankara

  • American Hospital

    Istanbul

  • Memorial Hospital

    Istanbul

Other trials in Turkey (Türkiye)

Poland2 sites

  • KRIOBANK

    Bialystok

  • nOvum

    Warsaw

Other trials in Poland

About this study

Official title: A Randomized, Open-label, Assessor-blind, Parallel Groups, Multicentre Trial Comparing the Efficacy of MENOPUR Versus Recombinant FSH in Controlled Ovarian Stimulation Following a GnRH Antagonist Protocol and Single Embryo Transfer

The main purpose of this clinical research trial was to compare the ongoing pregnancy rate between two gonadotrophins for controlled ovarian stimulation (MENOPUR and recombinant follicle-stimulating hormone (FSH)), in cycles where a gonadotrophin-releasing hormone (GnRH) antagonist was used for prevention of premature luteinizing hormone (LH) surge and where a single embryo was transferred at the blastocyst stage.

Read the detailed description

This was a randomized, open-label, assessor-blind, parallel groups, multicentre trial comparing the efficacy of highly purified menotrophin (MENOPUR; Ferring) and recombinant FSH (PUREGON/FOLLISTIM; MSD/Merck) in women undergoing controlled ovarian stimulation following a GnRH antagonist protocol.

The use of oral contraceptives for programming of the trial cycle was prohibited. On day 2-3 of the menstrual cycle, participants were randomized in a 1:1 fashion to treatment with either highly purified menotrophin (MENOPUR) or recombinant FSH, and stimulation was initiated.

The gonadotrophin starting dose was 150 international units (IU) daily for the first 5 days. Hereafter, the participants were seen on stimulation day 6 and subsequently at least every 2 days when a transvaginal ultrasound was made to monitor response to stimulation. From stimulation day 6 and onwards, dosing could be adjusted according to individual patient response with the purpose of achieving 8-10 oocytes at the time of oocyte retrieval. The dose adjustment could be by 75 IU per adjustment and could not be done more frequently than every 4 days. The maximum allowed gonadotrophin dose was 375 IU daily and participants could be treated with gonadotrophin for a maximum of 20 days. Coasting was prohibited.

The GnRH antagonist (ORGALUTRAN/GANIRELIX ACETATE INJECTION; MSD/Merck) was initiated on stimulation day 6 at a daily dose of 0.25 mg and continued throughout the gonadotrophin treatment period. A single injection of recombinant human chorionic gonadotrophin (hCG) 250 µg (OVITRELLE/OVIDREL; Merck Serono/EMD Serono) was administered to induce final follicular maturation as soon as 3 follicles of ≥ 17 mm were observed; i.e., the day of reaching the hCG criterion or the next day. Oocyte retrieval took place 36h (± 2h) after hCG administration. Oocytes were inseminated using partner sperm by intracytoplasmic sperm injection (ICSI) 4h (± 1h) after retrieval. Oocyte, embryo and blastocyst quality was assessed daily from oocyte retrieval till 5 days after. On day 5 after oocyte retrieval, a single blastocyst of the best quality available was transferred and all remaining blastocysts were frozen. Vaginal progesterone capsules (UTROGESTAN; Seid) 600 mg/day were provided for luteal phase support from the day after oocyte retrieval till the day of the beta human chorionic gonadotrophin (βhCG) test (13-15 days after embryo transfer); prolonged luteal phase support beyond this time point was not allowed. Clinical pregnancy was confirmed by transvaginal ultrasound 5-6 weeks after embryo transfer and ongoing pregnancy was confirmed by transvaginal ultrasound 10-11 weeks after embryo transfer. Post-trial follow-up included pregnancy outcome (e.g. live birth) and neonatal health from the fresh trial cycle. Additional post-trial activities included follow-up of frozen embryo replacement cycles initiated within 1 year after the participant's randomization date.

Conditions
Infertility
Being tested
Highly purified menotrophin, Recombinant FSH
Medical subject headings
Infertility

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Highly purified menotrophinDrug

    Also called HP-hMG, MENOPUR

    The gonadotrophin starting dose was 150 IU daily for the first 5 days. From stimulation day 6 and onwards, dosing could be adjusted according to individual participant response. The dose adjustment could be by 75 IU per adjustment and could not be done more frequently than every 4 days. The maximum allowed gonadotrophin dose was 375 IU daily and participants could be treated with gonadotrophin for a maximum of 20 days.

    NOTE: The gonadotrophins (highly purified menotrophin and the active comparator recombinant FSH) were administered in an identical fashion.

  • Recombinant FSHDrug

    Also called Follitrophin-beta, PUREGON, FOLLISTIM

    The gonadotrophin starting dose was 150 IU daily for the first 5 days. From stimulation day 6 and onwards, dosing could be adjusted according to individual participant response. The dose adjustment could be by 75 IU per adjustment and could not be done more frequently than every 4 days. The maximum allowed gonadotrophin dose was 375 IU daily and participants could be treated with gonadotrophin for a maximum of 20 days.

    NOTE: The gonadotrophins (highly purified menotrophin and the active comparator recombinant FSH) were administered in an identical fashion.

Study groups in NCT00884221
Study groupRoleWhat they receive
Highly Purified MenotrophinExperimentalNot described
Receives: Drug: Highly purified menotrophin
Recombinant FSHActive comparatorNot described
Receives: Drug: Recombinant FSH

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Ongoing Pregnancy After One Fresh Embryo Replacement Cycle, Intention-to-treat (ITT) Analysis Set

    Transvaginal ultrasound showing at least one intrauterine viable fetus 10-11 weeks after embryo transfer at the blastocyst stage

    Measured: 10-11 weeks after embryo transfer at the blastocyst stage

  2. Ongoing Pregnancy After One Fresh Embryo Replacement Cycle, Per-protocol (PP) Analysis Set

    Transvaginal ultrasound showing at least one intrauterine viable fetus 10-11 weeks after embryo transfer at the blastocyst stage

    Measured: 10-11 weeks after embryo transfer at the blastocyst stage

Secondary outcomes (14)

  1. Endocrine Profile (Estradiol), Intention-to-treat (ITT) Analysis Set

    Blood samples for analysis of circulating concentrations of endocrine parameters were drawn

    Measured: On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist

  2. Endocrine Profile (FSH), Intention-to-treat (ITT) Analysis Set

    Blood samples for analysis of circulating concentrations of endocrine parameters were drawn

    Measured: On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist

  3. Endocrine Profile (Free Androgen Index), Intention-to-treat (ITT) Analysis Set

    Blood samples for analysis of circulating concentrations of endocrine parameters were drawn. Free androgen index = (testosterone (nmol/L)/ sex hormone binding globulin (nmol/L))*100

    Measured: On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist

  4. Endocrine Profile (Luteinizing Hormone), Intention-to-treat (ITT) Analysis Set

    Blood samples for analysis of circulating concentrations of endocrine parameters were drawn

    Measured: On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist

  5. Endocrine Profile (Progesterone), Intention-to-treat (ITT) Analysis Set

    Blood samples for analysis of circulating concentrations of endocrine parameters were drawn

    Measured: On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist

  6. Endocrine Profile (Prolactin), Intention-to-treat (ITT) Analysis Set

    Blood samples for analysis of circulating concentrations of endocrine parameters were drawn

    Measured: On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist

  7. Endocrine Profile (Sex Hormone Binding Globulin), Intention-to-treat (ITT) Analysis Set

    Blood samples for analysis of circulating concentrations of endocrine parameters were drawn

    Measured: On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist

  8. Endocrine Profile (Testosterone), Intention-to-treat (ITT) Analysis Set

    Blood samples for analysis of circulating concentrations of endocrine parameters were drawn

    Measured: On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist

  9. Number of Follicles of >= 12mm, 12-14 mm, 15-16 mm and >= 17 mm in Each Participant, Intention-to-treat (ITT) Analysis Set

    During the controlled ovarian stimulation, transvaginal ultrasound was performed to count the number of follicles and measure the size of the follicles.

    Measured: Last stimulation day

  10. Number of Oocytes Retrieved in Each Participant, Intention-to-treat (ITT) Analysis Set

    Oocyte retrieval took place 36h (± 2h) after hCG administration. At oocyte retrieval, the number of oocytes retrieved was recorded.

    Measured: 36 h after hCG

  11. Fertilization, Intention-to-treat (ITT) Analysis Set

    Fertilized oocytes with 2 pronuclei were regarded as correctly fertilized. Fertilization was estimated as (Number of oocytes with 2 pronuclei / number of metaphase II oocytes)*100

    Measured: 1 day after oocyte retrieval (19 h post-insemination)

  12. Blastocyst Quality, Intention-to-treat (ITT) Analysis Set

    Blastocyst quality on day 5 was based on the blastocyst expansion and hatching status, inner cell mass grading and trophectoderm grading.

    Excellent-quality blastocysts were defined as those with blastocyst expansion and hatching status 4, 5 or 6, inner cell mass grading A, and trophectoderm grading A or B. Good-quality blastocysts were defined as those with blastocyst expansion and hatching status 3, 4, 5 or 6, inner cell mass grading A or B, and trophectoderm grading A or B.

    Measured: 5 days after oocyte retrieval (120h post-insemination)

  13. Live Birth for a Single Stimulation Cycle With Single Blastocyst Transfer From Fresh Embryo Replacement Cycle, Intention-to-treat (ITT) Analysis Set

    Measured: Post-trial information

  14. Cumulative Live Birth for a Single Stimulation Cycle With Single Blastocyst Transfer From Fresh and 1 Year Frozen Embryo Replacement Cycles, Intention-to-treat (ITT) Analysis Set

    Measured: Post-trial information

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Apr 2009 (estimated)
  2. Study startJul 2009
  3. Primary completionJul 2010
  4. Study completionJan 2011

Resources

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
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
749 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00884221
Sponsor's protocol ID
FE999906 CS08
Other IDs
EudraCT Number: 2008-006775-67
Acronym
MEGASET
Status last verified
Apr 2012
First submitted
17 Apr 2009
Last updated
20 Apr 2012
Data monitoring committee
No

Publications

  • Devroey P, Pellicer A, Nyboe Andersen A, Arce JC; Menopur in GnRH Antagonist Cycles with Single Embryo Transfer Trial Group. A randomized assessor-blind trial comparing highly purified hMG and recombinant FSH in a GnRH antagonist cycle with compulsory single-blastocyst transfer. Fertil Steril. 2012 Mar;97(3):561-71. doi: 10.1016/j.fertnstert.2011.12.016. Epub 2012 Jan 13.

    PubMed 22244781

  • Arce JC, La Marca A, Mirner Klein B, Nyboe Andersen A, Fleming R. Antimullerian hormone in gonadotropin releasing-hormone antagonist cycles: prediction of ovarian response and cumulative treatment outcome in good-prognosis patients. Fertil Steril. 2013 May;99(6):1644-53. doi: 10.1016/j.fertnstert.2012.12.048. Epub 2013 Feb 5.

    PubMed 23394782

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Highly purified menotrophin and Recombinant FSH in people with Infertility, run by Ferring Pharmaceuticals at 25 sites in 7 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 14 inclusion and 10 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 20 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in Spain, Belgium, Denmark, Czechia, Sweden and 2 more countries. 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?

Yes. Results are posted in the registry (first posted 18 Apr 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Ongoing Pregnancy After One Fresh Embryo Replacement Cycle, Intention-to-treat (ITT) Analysis Set (time frame: 10-11 weeks after embryo transfer at the blastocyst stage). The study lists 2 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 NCT00884221, which also lists 2 linked publications.

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 20 Apr 2012.

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