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

Phase 3

Completed

Conditions: Infertility

Interventions: Drug: Highly purified menotrophin
Drug: Recombinant FSH

Registration Number: NCT00884221

Lead Sponsor: Ferring Pharmaceuticals

Brief 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 luteinizing hormone (LH) surge and where a single embryo was transferred at the blastocyst stage.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 749

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Highly Purified Menotrophin	Highly purified menotrophin	-
Recombinant FSH	Recombinant FSH	-

Primary Outcome Measures

Name	Time	Method
Ongoing Pregnancy After One Fresh Embryo Replacement Cycle, Intention-to-treat (ITT) Analysis Set	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
Ongoing Pregnancy After One Fresh Embryo Replacement Cycle, Per-protocol (PP) Analysis Set	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

Secondary Outcome Measures

Name	Time	Method
Endocrine Profile (Prolactin), Intention-to-treat (ITT) Analysis Set	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
Endocrine Profile (Luteinizing Hormone), Intention-to-treat (ITT) Analysis Set	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
Endocrine Profile (Progesterone), Intention-to-treat (ITT) Analysis Set	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
Number of Follicles of >= 12mm, 12-14 mm, 15-16 mm and >= 17 mm in Each Participant, Intention-to-treat (ITT) Analysis Set	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.
Fertilization, Intention-to-treat (ITT) Analysis Set	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
Endocrine Profile (FSH), Intention-to-treat (ITT) Analysis Set	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
Endocrine Profile (Free Androgen Index), Intention-to-treat (ITT) Analysis Set	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
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	Post-trial information
Endocrine Profile (Estradiol), Intention-to-treat (ITT) Analysis Set	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
Endocrine Profile (Testosterone), Intention-to-treat (ITT) Analysis Set	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
Blastocyst Quality, Intention-to-treat (ITT) Analysis Set	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.
Endocrine Profile (Sex Hormone Binding Globulin), Intention-to-treat (ITT) Analysis Set	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
Number of Oocytes Retrieved in Each Participant, Intention-to-treat (ITT) Analysis Set	36 h after hCG	Oocyte retrieval took place 36h (± 2h) after hCG administration. At oocyte retrieval, the number of oocytes retrieved was recorded.
Live Birth for a Single Stimulation Cycle With Single Blastocyst Transfer From Fresh Embryo Replacement Cycle, Intention-to-treat (ITT) Analysis Set	Post-trial information

Trial Locations

Locations (25): IU Dexeus
🇪🇸
Barcelona, Spain
IVI Valencia
🇪🇸
Valencia, Spain
GINEFIV, Madrid
🇪🇸
Madrid, Spain
IVI Sevilla
🇪🇸
Sevilla, Spain
IVF-kliniken CURA
🇸🇪
Malmö, Sweden
RMC, Malmö
🇸🇪
Malmö, Sweden
Hacettepe University
🇹🇷
Ankara, Turkey
IVI Madrid
🇪🇸
Madrid, Spain
Ginemed
🇪🇸
Sevilla, Spain
American Hospital
🇹🇷
Istanbul, Turkey
Memorial Hospital
🇹🇷
Istanbul, Turkey
Fertilitetscentrum AB Gothenburg
🇸🇪
Gothenburg, Sweden
Amtssygehuset Herlev
🇩🇰
Herlev, Denmark
Sygehus Vestsjælland
🇩🇰
Holbæk, Denmark
H:S Hvidovre Hospital
🇩🇰
Hvidovre, Denmark
H:S Rigshospitalet
🇩🇰
København, Denmark
Pronatal
🇨🇿
Prague, Czech Republic
ERASME Hospital
🇧🇪
Anderlecht, Belgium
UZ Antwerpen
🇧🇪
Edegem, Belgium
UZ Brussel
🇧🇪
Brussels, Belgium
IVF Institute
🇨🇿
Pilsen, Czech Republic
UZ Gent
🇧🇪
Gent, Belgium
ISCARE IVF a.s.
🇨🇿
Prague, Czech Republic
KRIOBANK
🇵🇱
Bialystok, Poland
nOvum
🇵🇱
Warsaw, Poland