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

April 18, 2012 updated by: Ferring Pharmaceuticals

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

749

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Anderlecht, Belgium
        • Erasme Hospital
      • Brussels, Belgium
        • UZ Brussel
      • Edegem, Belgium
        • UZ Antwerpen
      • Gent, Belgium
        • UZ Gent
  • Czech Republic
      • Pilsen, Czech Republic
        • IVF Institute
      • Prague, Czech Republic
        • ISCARE IVF a.s.
      • Prague, Czech Republic
        • Pronatal
  • Denmark
      • Herlev, Denmark
        • Amtssygehuset Herlev
      • Holbæk, Denmark
        • Sygehus Vestsjælland
      • Hvidovre, Denmark
        • H:S Hvidovre Hospital
      • København, Denmark
        • H:S Rigshospitalet
  • Poland
      • Bialystok, Poland
        • KRIOBANK
      • Warsaw, Poland
        • NOVUM
  • Spain
      • Barcelona, Spain
        • IU Dexeus
      • Madrid, Spain
        • IVI Madrid
      • Madrid, Spain
        • GINEFIV, Madrid
      • Sevilla, Spain
        • IVI Sevilla
      • Sevilla, Spain
        • Ginemed
      • Valencia, Spain
        • IVI Valencia
  • Sweden
      • Gothenburg, Sweden
        • Fertilitetscentrum AB Gothenburg
      • Malmö, Sweden
        • IVF-kliniken CURA
      • Malmö, Sweden
        • RMC, Malmö
  • Turkey
      • Ankara, Turkey
        • Hacettepe University
      • Istanbul, Turkey
        • Memorial Hospital
      • Istanbul, Turkey
        • American Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

17 years to 30 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion criteria:

  • 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
  • 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

Exclusion criteria:

  • 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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Highly Purified Menotrophin
Drug: Highly purified menotrophin

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.

Other Names:
  • HP-hMG
  • MENOPUR
Active Comparator: Recombinant FSH
Drug: Recombinant FSH

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.

Other Names:
  • FOLLISTIM
  • Follitrophin-beta
  • PUREGON

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Transvaginal ultrasound showing at least one intrauterine viable fetus 10-11 weeks after embryo transfer at the blastocyst stage
10-11 weeks after embryo transfer at the blastocyst stage
Ongoing Pregnancy After One Fresh Embryo Replacement Cycle, Per-protocol (PP) Analysis Set
Time Frame: 10-11 weeks after embryo transfer at the blastocyst stage
Transvaginal ultrasound showing at least one intrauterine viable fetus 10-11 weeks after embryo transfer at the blastocyst stage
10-11 weeks after embryo transfer at the blastocyst stage

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Endocrine Profile (Estradiol), Intention-to-treat (ITT) Analysis Set
Time Frame: On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist
Blood samples for analysis of circulating concentrations of endocrine parameters were drawn
On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist
Endocrine Profile (FSH), Intention-to-treat (ITT) Analysis Set
Time Frame: On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist
Blood samples for analysis of circulating concentrations of endocrine parameters were drawn
On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist
Endocrine Profile (Free Androgen Index), Intention-to-treat (ITT) Analysis Set
Time Frame: On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist
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
On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist
Endocrine Profile (Luteinizing Hormone), Intention-to-treat (ITT) Analysis Set
Time Frame: On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist
Blood samples for analysis of circulating concentrations of endocrine parameters were drawn
On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist
Endocrine Profile (Progesterone), Intention-to-treat (ITT) Analysis Set
Time Frame: On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist
Blood samples for analysis of circulating concentrations of endocrine parameters were drawn
On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist
Endocrine Profile (Prolactin), Intention-to-treat (ITT) Analysis Set
Time Frame: On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist
Blood samples for analysis of circulating concentrations of endocrine parameters were drawn
On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist
Endocrine Profile (Sex Hormone Binding Globulin), Intention-to-treat (ITT) Analysis Set
Time Frame: On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist
Blood samples for analysis of circulating concentrations of endocrine parameters were drawn
On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist
Endocrine Profile (Testosterone), Intention-to-treat (ITT) Analysis Set
Time Frame: On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist
Blood samples for analysis of circulating concentrations of endocrine parameters were drawn
On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist
Number of Follicles of >= 12mm, 12-14 mm, 15-16 mm and >= 17 mm in Each Participant, Intention-to-treat (ITT) Analysis Set
Time Frame: Last stimulation day
During the controlled ovarian stimulation, transvaginal ultrasound was performed to count the number of follicles and measure the size of the follicles.
Last stimulation day
Number of Oocytes Retrieved in Each Participant, Intention-to-treat (ITT) Analysis Set
Time Frame: 36 h after hCG
Oocyte retrieval took place 36h (± 2h) after hCG administration. At oocyte retrieval, the number of oocytes retrieved was recorded.
36 h after hCG
Fertilization, Intention-to-treat (ITT) Analysis Set
Time Frame: 1 day after oocyte retrieval (19 h post-insemination)
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
1 day after oocyte retrieval (19 h post-insemination)
Blastocyst Quality, Intention-to-treat (ITT) Analysis Set
Time Frame: 5 days after oocyte retrieval (120h post-insemination)

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.
5 days after oocyte retrieval (120h post-insemination)
Live Birth for a Single Stimulation Cycle With Single Blastocyst Transfer From Fresh Embryo Replacement Cycle, Intention-to-treat (ITT) Analysis Set
Time Frame: Post-trial information
Post-trial information
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
Time Frame: Post-trial information
Post-trial information

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ferring Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2009

Primary Completion (Actual)

July 1, 2010

Study Completion (Actual)

January 1, 2011

Study Registration Dates

First Submitted

April 17, 2009

First Submitted That Met QC Criteria

April 17, 2009

First Posted (Estimate)

April 20, 2009

Study Record Updates

Last Update Posted (Estimate)

April 20, 2012

Last Update Submitted That Met QC Criteria

April 18, 2012

Last Verified

April 1, 2012

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FE999906 CS08
  • EudraCT Number: 2008-006775-67

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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