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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ferring Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00884221
First received: April 17, 2009
Last updated: April 18, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Infertility
Drug: Highly purified menotrophin
Drug: Recombinant FSH
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Ferring Pharmaceuticals:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Transvaginal ultrasound showing at least one intrauterine viable fetus 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 ] [ Designated as safety issue: No ]
    Transvaginal ultrasound showing at least one intrauterine viable fetus 10-11 weeks after embryo transfer at the blastocyst stage


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Blood samples for analysis of circulating concentrations of endocrine parameters were drawn

  • 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 ] [ Designated as safety issue: No ]
    Blood samples for analysis of circulating concentrations of endocrine parameters were drawn

  • 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 ] [ Designated as safety issue: No ]
    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

  • 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 ] [ Designated as safety issue: No ]
    Blood samples for analysis of circulating concentrations of endocrine parameters were drawn

  • 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 ] [ Designated as safety issue: No ]
    Blood samples for analysis of circulating concentrations of endocrine parameters were drawn

  • 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 ] [ Designated as safety issue: No ]
    Blood samples for analysis of circulating concentrations of endocrine parameters were drawn

  • 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 ] [ Designated as safety issue: No ]
    Blood samples for analysis of circulating concentrations of endocrine parameters were drawn

  • 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 ] [ Designated as safety issue: No ]
    Blood samples for analysis of circulating concentrations of endocrine parameters were drawn

  • 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 ] [ Designated as safety issue: No ]
    During the controlled ovarian stimulation, transvaginal ultrasound was performed to count the number of follicles and measure the size of the follicles.

  • Number of Oocytes Retrieved in Each Participant, Intention-to-treat (ITT) Analysis Set [ Time Frame: 36 h after hCG ] [ Designated as safety issue: No ]
    Oocyte retrieval took place 36h (± 2h) after hCG administration. At oocyte retrieval, the number of oocytes retrieved was recorded.

  • Fertilization, Intention-to-treat (ITT) Analysis Set [ Time Frame: 1 day after oocyte retrieval (19 h post-insemination) ] [ Designated as safety issue: No ]
    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

  • Blastocyst Quality, Intention-to-treat (ITT) Analysis Set [ Time Frame: 5 days after oocyte retrieval (120h post-insemination) ] [ Designated as safety issue: No ]

    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.


  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 749
Study Start Date: July 2009
Study Completion Date: January 2011
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • Follitrophin-beta
  • PUREGON
  • FOLLISTIM

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.

  Eligibility

Ages Eligible for Study:   21 Years to 34 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00884221

Locations
Belgium
ERASME Hospital
Anderlecht, Belgium
UZ Brussel
Brussels, Belgium
UZ Antwerpen
Edegem, Belgium
UZ Gent
Gent, Belgium
Czech Republic
IVF Institute
Pilsen, Czech Republic
Pronatal
Prague, Czech Republic
ISCARE IVF a.s.
Prague, Czech Republic
Denmark
Amtssygehuset Herlev
Herlev, Denmark
Sygehus Vestsjælland
Holbæk, Denmark
H:S Hvidovre Hospital
Hvidovre, Denmark
H:S Rigshospitalet
København, Denmark
Poland
KRIOBANK
Bialystok, Poland
nOvum
Warsaw, Poland
Spain
IU Dexeus
Barcelona, Spain
IVI Madrid
Madrid, Spain
GINEFIV, Madrid
Madrid, Spain
IVI Sevilla
Sevilla, Spain
Ginemed
Sevilla, Spain
IVI Valencia
Valencia, Spain
Sweden
Fertilitetscentrum AB Gothenburg
Gothenburg, Sweden
RMC, Malmö
Malmö, Sweden
IVF-kliniken CURA
Malmö, Sweden
Turkey
Hacettepe University
Ankara, Turkey
Memorial Hospital
Istanbul, Turkey
American Hospital
Istanbul, Turkey
Sponsors and Collaborators
Ferring Pharmaceuticals
Investigators
Study Director: Clinical Development Support Ferring Pharmaceuticals
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ferring Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00884221     History of Changes
Other Study ID Numbers: FE999906 CS08, EudraCT Number: 2008-006775-67
Study First Received: April 17, 2009
Results First Received: February 14, 2012
Last Updated: April 18, 2012
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Belgium: Institutional Review Board
Czech Republic: Ethics Committee
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
Denmark: Ethics Committee
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Spain: Ethics Committee
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Sweden: Regional Ethical Review Board
Turkey: Ethics Committee
Turkey: Ministry of Health

Additional relevant MeSH terms:
Infertility
Genital Diseases, Female
Genital Diseases, Male

ClinicalTrials.gov processed this record on October 23, 2014