Trial Outcomes & Findings for MENOPUR in Gonadotrophin-releasing Hormone (GnRH) Antagonist Cycles With Single Embryo Transfer (NCT NCT00884221)

NCT ID: NCT00884221

Last Updated: 2012-04-20

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 749 participants
• Primary outcome timeframe: 10-11 weeks after embryo transfer at the blastocyst stage
• Results posted on: 2012-04-20

Participant Flow

The participants were recruited among the patients attending the clinics included in the trial.

810 participants were screened and 754 were randomised. 749 participants were exposed to highly purified menotrophin or recombinant FSH

Participant milestones

Measure	Highly Purified Menotrophin The gonadotrophin starting dose was 150 IU daily for the first 5 days. Hereafter, the subjects 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 subjects could be treated with gonadotrophin for a maximum of 20 days. Coasting was prohibited.	Recombinant FSH The gonadotrophin starting dose was 150 IU daily for the first 5 days. Hereafter, the subjects 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 subjects could be treated with gonadotrophin for a maximum of 20 days. Coasting was prohibited.
Overall Study STARTED	374	375
Overall Study COMPLETED	340	343
Overall Study NOT COMPLETED	34	32

Reasons for withdrawal

Measure	Highly Purified Menotrophin The gonadotrophin starting dose was 150 IU daily for the first 5 days. Hereafter, the subjects 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 subjects could be treated with gonadotrophin for a maximum of 20 days. Coasting was prohibited.	Recombinant FSH The gonadotrophin starting dose was 150 IU daily for the first 5 days. Hereafter, the subjects 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 subjects could be treated with gonadotrophin for a maximum of 20 days. Coasting was prohibited.
Overall Study Withdrawal by Subject	0	3
Overall Study Adverse Event	6	3
Overall Study Protocol Violation	16	13
Overall Study Cancellation of Cycle and Other Reason	12	13

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Highly Purified Menotrophin n=374 Participants 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.	Recombinant FSH n=375 Participants 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.	Total n=749 Participants Total of all reporting groups
Age Continuous	30.8 years STANDARD_DEVIATION 2.75 • n=5 Participants	30.4 years STANDARD_DEVIATION 2.62 • n=7 Participants	30.6 years STANDARD_DEVIATION 2.69 • n=5 Participants
Sex: Female, Male Female	374 Participants n=5 Participants	375 Participants n=7 Participants	749 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Belgium	20 participants n=5 Participants	20 participants n=7 Participants	40 participants n=5 Participants
Region of Enrollment Czech Republic	30 participants n=5 Participants	27 participants n=7 Participants	57 participants n=5 Participants
Region of Enrollment Denmark	33 participants n=5 Participants	33 participants n=7 Participants	66 participants n=5 Participants
Region of Enrollment Poland	72 participants n=5 Participants	71 participants n=7 Participants	143 participants n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	374 Participants n=5 Participants	375 Participants n=7 Participants	749 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Spain	179 participants n=5 Participants	178 participants n=7 Participants	357 participants n=5 Participants
Region of Enrollment Sweden	14 participants n=5 Participants	19 participants n=7 Participants	33 participants n=5 Participants
Region of Enrollment Turkey	26 participants n=5 Participants	27 participants n=7 Participants	53 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Highly Purified Menotrophin n=374 Participants 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 participant 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.	Recombinant FSH n=375 Participants 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 participant 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.
Ongoing Pregnancy After One Fresh Embryo Replacement Cycle, Intention-to-treat (ITT) Analysis Set	29 Percentage of participants Standard Deviation 2.3 • Interval -4.2 to 8.6	27 Percentage of participants Standard Deviation 2.3

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Highly Purified Menotrophin n=343 Participants 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 participant 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.	Recombinant FSH n=333 Participants 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 participant 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.
Ongoing Pregnancy After One Fresh Embryo Replacement Cycle, Per-protocol (PP) Analysis Set	30 Percentage of participants Standard Deviation 2.5	27 Percentage of participants Standard Deviation 2.4

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Highly Purified Menotrophin n=374 Participants 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 participant 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.	Recombinant FSH n=375 Participants 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 participant 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.
Endocrine Profile (Estradiol), Intention-to-treat (ITT) Analysis Set	8797 pmol/L Standard Deviation 6030 • Interval 4993.0 to 10136.0	7022 pmol/L Standard Deviation 4945 • Interval 4023.0 to 8234.0

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Highly Purified Menotrophin n=374 Participants 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 participant 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.	Recombinant FSH n=375 Participants 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 participant 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.
Endocrine Profile (FSH), Intention-to-treat (ITT) Analysis Set	15.7 IU/L Standard Deviation 4.1	12.6 IU/L Standard Deviation 3.7

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Highly Purified Menotrophin n=374 Participants 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 participant 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.	Recombinant FSH n=375 Participants 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 participant 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.
Endocrine Profile (Free Androgen Index), Intention-to-treat (ITT) Analysis Set	2.8 Percentage of participants Standard Deviation 2.0	2.5 Percentage of participants Standard Deviation 2.2

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Highly Purified Menotrophin n=374 Participants 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 participant 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.	Recombinant FSH n=375 Participants 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 participant 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.
Endocrine Profile (Luteinizing Hormone), Intention-to-treat (ITT) Analysis Set	2.8 IU/L Standard Deviation 2.8	2.1 IU/L Standard Deviation 1.6

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Highly Purified Menotrophin n=374 Participants 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 participant 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.	Recombinant FSH n=375 Participants 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 participant 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.
Endocrine Profile (Progesterone), Intention-to-treat (ITT) Analysis Set	3.1 nmol/L Standard Deviation 3.4	3.1 nmol/L Standard Deviation 3.3

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Highly Purified Menotrophin n=374 Participants 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 participant 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.	Recombinant FSH n=375 Participants 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 participant 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.
Endocrine Profile (Prolactin), Intention-to-treat (ITT) Analysis Set	1544 pmol/L Standard Deviation 770	1410 pmol/L Standard Deviation 689

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Highly Purified Menotrophin n=374 Participants 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 participant 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.	Recombinant FSH n=375 Participants 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 participant 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.
Endocrine Profile (Sex Hormone Binding Globulin), Intention-to-treat (ITT) Analysis Set	111 nmol/L Standard Deviation 51	107 nmol/L Standard Deviation 48

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Highly Purified Menotrophin n=374 Participants 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 participant 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.	Recombinant FSH n=375 Participants 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 participant 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.
Endocrine Profile (Testosterone), Intention-to-treat (ITT) Analysis Set	2.5 nmol/L Standard Deviation 1.2	2.1 nmol/L Standard Deviation 1.0

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Highly Purified Menotrophin n=374 Participants 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 participant 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.	Recombinant FSH n=375 Participants 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 participant 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.
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	11.8 Follicles per participant Standard Deviation 4.9
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	3.8 Follicles per participant Standard Deviation 2.9
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	2.7 Follicles per participant Standard Deviation 2.3
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	5.2 Follicles per participant Standard Deviation 2.4

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Highly Purified Menotrophin n=374 Participants 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 participant 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.	Recombinant FSH n=375 Participants 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 participant 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.
Number of Oocytes Retrieved in Each Participant, Intention-to-treat (ITT) Analysis Set	9.1 Oocytes per participant Standard Deviation 5.2	10.7 Oocytes per participant Standard Deviation 5.8

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Highly Purified Menotrophin n=374 Participants 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 participant 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.	Recombinant FSH n=375 Participants 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 participant 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.
Fertilization, Intention-to-treat (ITT) Analysis Set	75 Percentage of metaphase II oocytes Standard Deviation 23	76 Percentage of metaphase II oocytes Standard Deviation 22

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Highly Purified Menotrophin n=374 Participants 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 participant 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.	Recombinant FSH n=375 Participants 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 participant 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.
Blastocyst Quality, Intention-to-treat (ITT) Analysis Set Blastocyst 1 / 2 pn	7 Number of blastocysts Standard Deviation 17	7 Number of blastocysts Standard Deviation 16
Blastocyst Quality, Intention-to-treat (ITT) Analysis Set Blastocyst 2 / 2pn	7 Number of blastocysts Standard Deviation 15	5 Number of blastocysts Standard Deviation 11
Blastocyst Quality, Intention-to-treat (ITT) Analysis Set Blastocyst 3 / 2pn	10 Number of blastocysts Standard Deviation 16	10 Number of blastocysts Standard Deviation 15
Blastocyst Quality, Intention-to-treat (ITT) Analysis Set Blastocyst 4 / 2pn	18 Number of blastocysts Standard Deviation 22	20 Number of blastocysts Standard Deviation 26
Blastocyst Quality, Intention-to-treat (ITT) Analysis Set Blastocyst 5 / 2pn	7 Number of blastocysts Standard Deviation 16	6 Number of blastocysts Standard Deviation 13
Blastocyst Quality, Intention-to-treat (ITT) Analysis Set Blastocyst 6 / 2pn	0 Number of blastocysts Standard Deviation 0	0 Number of blastocysts Standard Deviation 0
Blastocyst Quality, Intention-to-treat (ITT) Analysis Set Blastocyst 4AA/ 2pn	5 Number of blastocysts Standard Deviation 13	5 Number of blastocysts Standard Deviation 14
Blastocyst Quality, Intention-to-treat (ITT) Analysis Set Blastocyst 5AA / 2pn	2 Number of blastocysts Standard Deviation 7	2 Number of blastocysts Standard Deviation 7

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Highly Purified Menotrophin n=374 Participants 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 participant 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.	Recombinant FSH n=375 Participants 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 participant 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.
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	26 Percentage of participants Standard Deviation 2.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Highly Purified Menotrophin n=374 Participants 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 participant 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.	Recombinant FSH n=375 Participants 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 participant 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.
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	38 Percentage of participants Standard Deviation 2.5

Adverse Events

Highly Purified Menotrophin

Serious events: 5 serious events

Other events: 66 other events

Deaths: 0 deaths

Recombinant FSH

Serious events: 7 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Measure	Highly Purified Menotrophin n=374 participants at risk 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 participant 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.	Recombinant FSH n=375 participants at risk 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 participant 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.
Gastrointestinal disorders Abdominal pain	0.27% 1/374 • Number of events 1 • Adverse events were recorded from signed informed consent until the end-of-trial visit. Adverse events were evaluated at each visit.	0.00% 0/375 • Adverse events were recorded from signed informed consent until the end-of-trial visit. Adverse events were evaluated at each visit.
Pregnancy, puerperium and perinatal conditions Abortion missed	0.00% 0/374 • Adverse events were recorded from signed informed consent until the end-of-trial visit. Adverse events were evaluated at each visit.	0.53% 2/375 • Number of events 2 • Adverse events were recorded from signed informed consent until the end-of-trial visit. Adverse events were evaluated at each visit.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.00% 0/374 • Adverse events were recorded from signed informed consent until the end-of-trial visit. Adverse events were evaluated at each visit.	0.27% 1/375 • Number of events 1 • Adverse events were recorded from signed informed consent until the end-of-trial visit. Adverse events were evaluated at each visit.
Pregnancy, puerperium and perinatal conditions Abortion threatened	0.00% 0/374 • Adverse events were recorded from signed informed consent until the end-of-trial visit. Adverse events were evaluated at each visit.	0.27% 1/375 • Number of events 1 • Adverse events were recorded from signed informed consent until the end-of-trial visit. Adverse events were evaluated at each visit.
Pregnancy, puerperium and perinatal conditions Ectopic pregnancy	0.00% 0/374 • Adverse events were recorded from signed informed consent until the end-of-trial visit. Adverse events were evaluated at each visit.	0.27% 1/375 • Number of events 1 • Adverse events were recorded from signed informed consent until the end-of-trial visit. Adverse events were evaluated at each visit.
Reproductive system and breast disorders Ovarian hyperstimulation syndrome	0.80% 3/374 • Number of events 3 • Adverse events were recorded from signed informed consent until the end-of-trial visit. Adverse events were evaluated at each visit.	0.53% 2/375 • Number of events 2 • Adverse events were recorded from signed informed consent until the end-of-trial visit. Adverse events were evaluated at each visit.
Reproductive system and breast disorders Ovarian cyst	0.27% 1/374 • Number of events 1 • Adverse events were recorded from signed informed consent until the end-of-trial visit. Adverse events were evaluated at each visit.	0.00% 0/375 • Adverse events were recorded from signed informed consent until the end-of-trial visit. Adverse events were evaluated at each visit.

Other adverse events

Measure	Highly Purified Menotrophin n=374 participants at risk 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 participant 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.	Recombinant FSH n=375 participants at risk 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 participant 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.
Gastrointestinal disorders Nausea	4.8% 18/374 • Number of events 19 • Adverse events were recorded from signed informed consent until the end-of-trial visit. Adverse events were evaluated at each visit.	4.0% 15/375 • Number of events 16 • Adverse events were recorded from signed informed consent until the end-of-trial visit. Adverse events were evaluated at each visit.
Nervous system disorders Headache	6.7% 25/374 • Number of events 30 • Adverse events were recorded from signed informed consent until the end-of-trial visit. Adverse events were evaluated at each visit.	5.1% 19/375 • Number of events 23 • Adverse events were recorded from signed informed consent until the end-of-trial visit. Adverse events were evaluated at each visit.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	7.2% 27/374 • Number of events 27 • Adverse events were recorded from signed informed consent until the end-of-trial visit. Adverse events were evaluated at each visit.	5.1% 19/375 • Number of events 19 • Adverse events were recorded from signed informed consent until the end-of-trial visit. Adverse events were evaluated at each visit.
Reproductive system and breast disorders Pelvic pain	4.8% 18/374 • Number of events 23 • Adverse events were recorded from signed informed consent until the end-of-trial visit. Adverse events were evaluated at each visit.	4.3% 16/375 • Number of events 20 • Adverse events were recorded from signed informed consent until the end-of-trial visit. Adverse events were evaluated at each visit.
Reproductive system and breast disorders Vaginal haemorrhage	5.6% 21/374 • Number of events 25 • Adverse events were recorded from signed informed consent until the end-of-trial visit. Adverse events were evaluated at each visit.	2.7% 10/375 • Number of events 13 • Adverse events were recorded from signed informed consent until the end-of-trial visit. Adverse events were evaluated at each visit.

Additional Information

Ferring Pharmaceuticals

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