Infertility
Conditions
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.
Interventions
DRUGHighly 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.
DRUGRecombinant 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.
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
21 Years to 34 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 (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 |
| 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 |
| 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 |
| 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. |
| 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 |
| 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. |
| 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 | — |
| 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 | — |
| 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. |
| 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 |
Countries
Belgium, Czechia, Denmark, Poland, Spain, Sweden, Turkey (Türkiye)
Participant flow
Recruitment details
The participants were recruited among the patients attending the clinics included in the trial.
Pre-assignment details
810 participants were screened and 754 were randomised. 749 participants were exposed to highly purified menotrophin or recombinant FSH
Participants by arm
| Arm | Count |
|---|---|
| Highly Purified Menotrophin The gonadotrophin starting dose was 150 IU daily for the first 5 days. From stimulation day 6 and onwards, the 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 subjects could be treated with gonadotrophin for a maximum of 20 days. | 374 |
| Recombinant FSH The gonadotrophin starting dose was 150 IU daily for the first 5 days. From stimulation day 6 and onwards, the 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 subjects could be treated with gonadotrophin for a maximum of 20 days. | 375 |
| Total | 749 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 3 |
| Overall Study | Cancellation of Cycle and Other Reason | 12 | 13 |
| Overall Study | Protocol Violation | 16 | 13 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Highly Purified Menotrophin | Recombinant FSH | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 374 Participants | 375 Participants | 749 Participants |
| Age Continuous | 30.8 years STANDARD_DEVIATION 2.75 | 30.4 years STANDARD_DEVIATION 2.62 | 30.6 years STANDARD_DEVIATION 2.69 |
| Region of Enrollment Belgium | 20 participants | 20 participants | 40 participants |
| Region of Enrollment Czech Republic | 30 participants | 27 participants | 57 participants |
| Region of Enrollment Denmark | 33 participants | 33 participants | 66 participants |
| Region of Enrollment Poland | 72 participants | 71 participants | 143 participants |
| Region of Enrollment Spain | 179 participants | 178 participants | 357 participants |
| Region of Enrollment Sweden | 14 participants | 19 participants | 33 participants |
| Region of Enrollment Turkey | 26 participants | 27 participants | 53 participants |
| Sex: Female, Male Female | 374 Participants | 375 Participants | 749 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 66 / 374 | 47 / 375 |
| serious Total, serious adverse events | 5 / 374 | 7 / 375 |
Outcome results
Primary
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
Time frame: 10-11 weeks after embryo transfer at the blastocyst stage
Population: The intention-to-treat (ITT) analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Highly Purified Menotrophin | Ongoing Pregnancy After One Fresh Embryo Replacement Cycle, Intention-to-treat (ITT) Analysis Set | 29 Percentage of participants | Standard Deviation 2.3 |
| Recombinant FSH | Ongoing Pregnancy After One Fresh Embryo Replacement Cycle, Intention-to-treat (ITT) Analysis Set | 27 Percentage of participants | Standard Deviation 2.3 |
Comparison: The non-inferiority hypothesis to be tested for the primary endpoint was:~H0: π MENOPUR - π recombinant FSH ≤ -10.0% against the alternative H1: π MENOPUR - π recombinant FSH \> -10.0%,~where π MENOPUR and π recombinant FSH denote the ongoing pregnancy rate after treatment with MENOPUR and recombinant FSH, respectively, in a single fresh treatment cycle following a GnRH antagonist protocol.p-value: 0.49995% CI: [-4.2, 8.6]Sign test
Primary
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
Time frame: 10-11 weeks after embryo transfer at the blastocyst stage
Population: The per-protocol (PP) analysis set was defined as all randomized and exposed participants except those excluded as a result of major protocol deviations, such as significant non-compliance or other serious unforeseen deviations deemed to invalidate the data and affect the conclusions of the trial.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Highly Purified Menotrophin | Ongoing Pregnancy After One Fresh Embryo Replacement Cycle, Per-protocol (PP) Analysis Set | 30 Percentage of participants | Standard Deviation 2.5 |
| Recombinant FSH | Ongoing Pregnancy After One Fresh Embryo Replacement Cycle, Per-protocol (PP) Analysis Set | 27 Percentage of participants | Standard Deviation 2.4 |
Comparison: The non-inferiority hypothesis to be tested for the primary endpoint was:~H0: π MENOPUR - π recombinant FSH ≤ -10.0% against the alternative H1: π MENOPUR - π recombinant FSH \> -10.0%,~where π MENOPUR and π recombinant FSH denote the ongoing pregnancy rate after treatment with MENOPUR and recombinant FSH, respectively, in a single fresh treatment cycle following a GnRH antagonist protocol.p-value: 0.38795% CI: [-3.8, 9.8]Sign test
Secondary
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.
Time frame: 5 days after oocyte retrieval (120h post-insemination)
Population: The intention-to-treat (ITT) analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Highly Purified Menotrophin | Blastocyst Quality, Intention-to-treat (ITT) Analysis Set | Blastocyst 1 / 2 pn | 7 Number of blastocysts | Standard Deviation 17 |
| Highly Purified Menotrophin | Blastocyst Quality, Intention-to-treat (ITT) Analysis Set | Blastocyst 5 / 2pn | 7 Number of blastocysts | Standard Deviation 16 |
| Highly Purified Menotrophin | Blastocyst Quality, Intention-to-treat (ITT) Analysis Set | Blastocyst 3 / 2pn | 10 Number of blastocysts | Standard Deviation 16 |
| Highly Purified Menotrophin | Blastocyst Quality, Intention-to-treat (ITT) Analysis Set | Blastocyst 6 / 2pn | 0 Number of blastocysts | Standard Deviation 0 |
| Highly Purified Menotrophin | Blastocyst Quality, Intention-to-treat (ITT) Analysis Set | Blastocyst 2 / 2pn | 7 Number of blastocysts | Standard Deviation 15 |
| Highly Purified Menotrophin | Blastocyst Quality, Intention-to-treat (ITT) Analysis Set | Blastocyst 4AA/ 2pn | 5 Number of blastocysts | Standard Deviation 13 |
| Highly Purified Menotrophin | Blastocyst Quality, Intention-to-treat (ITT) Analysis Set | Blastocyst 4 / 2pn | 18 Number of blastocysts | Standard Deviation 22 |
| Highly Purified Menotrophin | Blastocyst Quality, Intention-to-treat (ITT) Analysis Set | Blastocyst 5AA / 2pn | 2 Number of blastocysts | Standard Deviation 7 |
| Recombinant FSH | Blastocyst Quality, Intention-to-treat (ITT) Analysis Set | Blastocyst 4 / 2pn | 20 Number of blastocysts | Standard Deviation 26 |
| Recombinant FSH | Blastocyst Quality, Intention-to-treat (ITT) Analysis Set | Blastocyst 1 / 2 pn | 7 Number of blastocysts | Standard Deviation 16 |
| Recombinant FSH | Blastocyst Quality, Intention-to-treat (ITT) Analysis Set | Blastocyst 2 / 2pn | 5 Number of blastocysts | Standard Deviation 11 |
| Recombinant FSH | Blastocyst Quality, Intention-to-treat (ITT) Analysis Set | Blastocyst 3 / 2pn | 10 Number of blastocysts | Standard Deviation 15 |
| Recombinant FSH | Blastocyst Quality, Intention-to-treat (ITT) Analysis Set | Blastocyst 5AA / 2pn | 2 Number of blastocysts | Standard Deviation 7 |
| Recombinant FSH | Blastocyst Quality, Intention-to-treat (ITT) Analysis Set | Blastocyst 5 / 2pn | 6 Number of blastocysts | Standard Deviation 13 |
| Recombinant FSH | Blastocyst Quality, Intention-to-treat (ITT) Analysis Set | Blastocyst 6 / 2pn | 0 Number of blastocysts | Standard Deviation 0 |
| Recombinant FSH | Blastocyst Quality, Intention-to-treat (ITT) Analysis Set | Blastocyst 4AA/ 2pn | 5 Number of blastocysts | Standard Deviation 14 |
Comparison: Comparison between treatments groups of percentage of blastocysts with expansion and hatching status 1 / 2pnp-value: 0.406Wilcoxon (Mann-Whitney)
Comparison: Comparison between treatments groups of percentage of blastocysts with expansion and hatching status 2 / 2pnp-value: 0.232Wilcoxon (Mann-Whitney)
Comparison: Comparison between treatments groups of percentage of blastocysts with expansion and hatching status 3 / 2pnp-value: 0.412Wilcoxon (Mann-Whitney)
Comparison: Comparison between treatments groups of percentage of blastocysts with expansion and hatching status 4 / 2pnp-value: 0.438Wilcoxon (Mann-Whitney)
Comparison: Comparison between treatments groups of percentage of blastocysts with expansion and hatching status 5 / 2pnp-value: 0.39Wilcoxon (Mann-Whitney)
Comparison: Comparison between treatments groups of percentage of blastocysts with expansion and hatching status, inner cell mass grading and trophectoderm grading 4AA / 2pnp-value: 0.958Wilcoxon (Mann-Whitney)
Comparison: Comparison between treatments groups of percentage of blastocysts with expansion and hatching status, inner cell mass grading and trophectoderm grading 5AA / 2pnp-value: 0.954Wilcoxon (Mann-Whitney)
Secondary
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
Population: The intention-to-treat (ITT) analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Highly Purified Menotrophin | 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 | 40 Percentage of participants | Standard Deviation 2.5 |
| Recombinant FSH | 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 | 38 Percentage of participants | Standard Deviation 2.5 |
p-value: 0.68695% CI: [-5.6, 9.2]Wilcoxon (Mann-Whitney)
Secondary
Endocrine Profile (Estradiol), Intention-to-treat (ITT) Analysis Set
Blood samples for analysis of circulating concentrations of endocrine parameters were drawn
Time frame: On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist
Population: The intention-to-treat (ITT) analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Highly Purified Menotrophin | Endocrine Profile (Estradiol), Intention-to-treat (ITT) Analysis Set | 8797 pmol/L | Standard Deviation 6030 |
| Recombinant FSH | Endocrine Profile (Estradiol), Intention-to-treat (ITT) Analysis Set | 7022 pmol/L | Standard Deviation 4945 |
Comparison: Estradiolp-value: <0.001Regression, Linear
Secondary
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
Time frame: On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist
Population: The intention-to-treat (ITT) analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Highly Purified Menotrophin | Endocrine Profile (Free Androgen Index), Intention-to-treat (ITT) Analysis Set | 2.8 Percentage of participants | Standard Deviation 2 |
| Recombinant FSH | Endocrine Profile (Free Androgen Index), Intention-to-treat (ITT) Analysis Set | 2.5 Percentage of participants | Standard Deviation 2.2 |
Comparison: Free Androgen Indexp-value: <0.001Regression, Linear
Secondary
Endocrine Profile (FSH), Intention-to-treat (ITT) Analysis Set
Blood samples for analysis of circulating concentrations of endocrine parameters were drawn
Time frame: On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist
Population: The intention-to-treat (ITT) analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Highly Purified Menotrophin | Endocrine Profile (FSH), Intention-to-treat (ITT) Analysis Set | 15.7 IU/L | Standard Deviation 4.1 |
| Recombinant FSH | Endocrine Profile (FSH), Intention-to-treat (ITT) Analysis Set | 12.6 IU/L | Standard Deviation 3.7 |
Comparison: FSHp-value: <0.001Regression, Linear
Secondary
Endocrine Profile (Luteinizing Hormone), Intention-to-treat (ITT) Analysis Set
Blood samples for analysis of circulating concentrations of endocrine parameters were drawn
Time frame: On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist
Population: The intention-to-treat (ITT) analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Highly Purified Menotrophin | Endocrine Profile (Luteinizing Hormone), Intention-to-treat (ITT) Analysis Set | 2.8 IU/L | Standard Deviation 2.8 |
| Recombinant FSH | Endocrine Profile (Luteinizing Hormone), Intention-to-treat (ITT) Analysis Set | 2.1 IU/L | Standard Deviation 1.6 |
Comparison: Luteinizing hormonep-value: <0.001Regression, Linear
Secondary
Endocrine Profile (Progesterone), Intention-to-treat (ITT) Analysis Set
Blood samples for analysis of circulating concentrations of endocrine parameters were drawn
Time frame: On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist
Population: The intention-to-treat (ITT) analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Highly Purified Menotrophin | Endocrine Profile (Progesterone), Intention-to-treat (ITT) Analysis Set | 3.1 nmol/L | Standard Deviation 3.4 |
| Recombinant FSH | Endocrine Profile (Progesterone), Intention-to-treat (ITT) Analysis Set | 3.1 nmol/L | Standard Deviation 3.3 |
Comparison: Progesteronep-value: 0.63Regression, Linear
Secondary
Endocrine Profile (Prolactin), Intention-to-treat (ITT) Analysis Set
Blood samples for analysis of circulating concentrations of endocrine parameters were drawn
Time frame: On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist
Population: The intention-to-treat (ITT) analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Highly Purified Menotrophin | Endocrine Profile (Prolactin), Intention-to-treat (ITT) Analysis Set | 1544 pmol/L | Standard Deviation 770 |
| Recombinant FSH | Endocrine Profile (Prolactin), Intention-to-treat (ITT) Analysis Set | 1410 pmol/L | Standard Deviation 689 |
Comparison: Prolactinp-value: 0.047Regression, Linear
Secondary
Endocrine Profile (Sex Hormone Binding Globulin), Intention-to-treat (ITT) Analysis Set
Blood samples for analysis of circulating concentrations of endocrine parameters were drawn
Time frame: On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist
Population: The intention-to-treat (ITT) analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Highly Purified Menotrophin | Endocrine Profile (Sex Hormone Binding Globulin), Intention-to-treat (ITT) Analysis Set | 111 nmol/L | Standard Deviation 51 |
| Recombinant FSH | Endocrine Profile (Sex Hormone Binding Globulin), Intention-to-treat (ITT) Analysis Set | 107 nmol/L | Standard Deviation 48 |
Comparison: Sex hormone binding globulinp-value: 0.009Regression, Linear
Secondary
Endocrine Profile (Testosterone), Intention-to-treat (ITT) Analysis Set
Blood samples for analysis of circulating concentrations of endocrine parameters were drawn
Time frame: On the last day of stimulation, blood was drawn at least 8 hours after the previous injection of gonadotrophin and GnRH antagonist
Population: The intention-to-treat (ITT) analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Highly Purified Menotrophin | Endocrine Profile (Testosterone), Intention-to-treat (ITT) Analysis Set | 2.5 nmol/L | Standard Deviation 1.2 |
| Recombinant FSH | Endocrine Profile (Testosterone), Intention-to-treat (ITT) Analysis Set | 2.1 nmol/L | Standard Deviation 1 |
Comparison: Testosteronep-value: <0.001Regression, Linear
Secondary
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
Time frame: 1 day after oocyte retrieval (19 h post-insemination)
Population: The intention-to-treat (ITT) analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Highly Purified Menotrophin | Fertilization, Intention-to-treat (ITT) Analysis Set | 75 Percentage of metaphase II oocytes | Standard Deviation 23 |
| Recombinant FSH | Fertilization, Intention-to-treat (ITT) Analysis Set | 76 Percentage of metaphase II oocytes | Standard Deviation 22 |
p-value: 0.969Wilcoxon (Mann-Whitney)
Secondary
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
Population: The intention-to-treat (ITT) analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Highly Purified Menotrophin | Live Birth for a Single Stimulation Cycle With Single Blastocyst Transfer From Fresh Embryo Replacement Cycle, Intention-to-treat (ITT) Analysis Set | 28 Percentage of participants | Standard Deviation 2.3 |
| Recombinant FSH | Live Birth for a Single Stimulation Cycle With Single Blastocyst Transfer From Fresh Embryo Replacement Cycle, Intention-to-treat (ITT) Analysis Set | 26 Percentage of participants | Standard Deviation 2.3 |
p-value: 0.39895% CI: [-3.6, 9.1]Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: Last stimulation day
Population: The intention-to-treat (ITT) analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Highly Purified Menotrophin | Number of Follicles of >= 12mm, 12-14 mm, 15-16 mm and >= 17 mm in Each Participant, Intention-to-treat (ITT) Analysis Set | >= 12 mm | 10.9 Follicles per participant | Standard Deviation 4.7 |
| Highly Purified Menotrophin | Number of Follicles of >= 12mm, 12-14 mm, 15-16 mm and >= 17 mm in Each Participant, Intention-to-treat (ITT) Analysis Set | 12-14 mm | 3.3 Follicles per participant | Standard Deviation 2.6 |
| Highly Purified Menotrophin | Number of Follicles of >= 12mm, 12-14 mm, 15-16 mm and >= 17 mm in Each Participant, Intention-to-treat (ITT) Analysis Set | 15-16 mm | 2.7 Follicles per participant | Standard Deviation 2.2 |
| Highly Purified Menotrophin | Number of Follicles of >= 12mm, 12-14 mm, 15-16 mm and >= 17 mm in Each Participant, Intention-to-treat (ITT) Analysis Set | >=17 mm | 4.9 Follicles per participant | Standard Deviation 2.2 |
| Recombinant FSH | Number of Follicles of >= 12mm, 12-14 mm, 15-16 mm and >= 17 mm in Each Participant, Intention-to-treat (ITT) Analysis Set | >=17 mm | 5.2 Follicles per participant | Standard Deviation 2.4 |
| Recombinant FSH | Number of Follicles of >= 12mm, 12-14 mm, 15-16 mm and >= 17 mm in Each Participant, Intention-to-treat (ITT) Analysis Set | >= 12 mm | 11.8 Follicles per participant | Standard Deviation 4.9 |
| Recombinant FSH | Number of Follicles of >= 12mm, 12-14 mm, 15-16 mm and >= 17 mm in Each Participant, Intention-to-treat (ITT) Analysis Set | 15-16 mm | 2.7 Follicles per participant | Standard Deviation 2.3 |
| Recombinant FSH | Number of Follicles of >= 12mm, 12-14 mm, 15-16 mm and >= 17 mm in Each Participant, Intention-to-treat (ITT) Analysis Set | 12-14 mm | 3.8 Follicles per participant | Standard Deviation 2.9 |
Comparison: Comparison between treatment groups of the average number of follicles \>= 12 mm on the last stimulation dayp-value: 0.025Wilcoxon (Mann-Whitney)
Comparison: Comparison between treatment groups of the average number of follicles 12-14 mm on the last stimulation dayp-value: 0.024Wilcoxon (Mann-Whitney)
Comparison: Comparison between treatment groups of the average number of follicles 15-16 mm on the last stimulation dayp-value: 0.728Wilcoxon (Mann-Whitney)
Comparison: Comparison between treatment groups of the average number of follicles \>=17 mm on the last stimulation dayp-value: 0.285Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: 36 h after hCG
Population: The intention-to-treat (ITT) analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Highly Purified Menotrophin | Number of Oocytes Retrieved in Each Participant, Intention-to-treat (ITT) Analysis Set | 9.1 Oocytes per participant | Standard Deviation 5.2 |
| Recombinant FSH | Number of Oocytes Retrieved in Each Participant, Intention-to-treat (ITT) Analysis Set | 10.7 Oocytes per participant | Standard Deviation 5.8 |
Comparison: Treatments were compared using the Wilcoxon test for the average number of oocytes retrieved.p-value: <0.001Wilcoxon (Mann-Whitney)