Trial Outcomes & Findings for MENOPUR® Versus FOLLISTIM® (NCT NCT00802360)

Last Updated: 2011-11-02

Results Overview

The ongoing pregnancy was defined as a positive fetal heart movement (motion) at approximately six weeks of gestation and confirmed in a follow-up pregnancy ultrasound.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

173 participants

Primary outcome timeframe

Week 8 (Week 6 of gestation)

Results posted on

2011-11-02

Participant Flow

One hundred ninety one (191) participants were screened from 6 study centers in the US; 173 of these participants were eligible for randomization. Six subjects did not receive their respected treatment and two subjects withdrew consent, 165 subjects were included in the statistical analyses

Participant milestones

Participant milestones
Measure	Menopur/Endometrin Highly purified menotropin (Menopur®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Menopur/Progesterone in Oil Highly purified menotropin 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follistim/Endometrin Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follistim/Progesterone in Oil Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Overall Study STARTED	42	42	42	39
Overall Study COMPLETED	18	16	17	17
Overall Study NOT COMPLETED	24	26	25	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Menopur/Endometrin Highly purified menotropin (Menopur®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Menopur/Progesterone in Oil Highly purified menotropin 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follistim/Endometrin Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follistim/Progesterone in Oil Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Overall Study Stimulation failure	4	0	3	3
Overall Study Inadequate number of oocytes retrieved	0	0	0	1
Overall Study Cycle cancelled	0	1	1	1
Overall Study Risk of ovarian hyperstimulation syndrom	0	0	0	1
Overall Study No positive serum pregnancy	17	20	14	10
Overall Study Pregnancy not confirmed by ultrasound	1	0	1	0
Overall Study Pregnancy loss/miscarriage	0	2	0	3
Overall Study Other	2	3	6	3

Baseline Characteristics

MENOPUR® Versus FOLLISTIM®

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Menopur/Endometrin n=42 Participants Highly purified menotropin (Menopur®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Menopur/Progesterone in Oil n=42 Participants Highly purified menotropin 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follistim/Endometrin n=42 Participants Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follistim/Progesterone in Oil n=39 Participants Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Total n=165 Participants Total of all reporting groups
Age Continuous	33.5 years STANDARD_DEVIATION 4.1 • n=93 Participants	33.2 years STANDARD_DEVIATION 4.8 • n=4 Participants	34.0 years STANDARD_DEVIATION 4.3 • n=27 Participants	33.9 years STANDARD_DEVIATION 4.3 • n=483 Participants	33.9 years STANDARD_DEVIATION 7.4 • n=36 Participants
Sex: Female, Male Female	42 Participants n=93 Participants	42 Participants n=4 Participants	42 Participants n=27 Participants	39 Participants n=483 Participants	165 Participants n=36 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race/Ethnicity, Customized Caucasian	32 Participants n=93 Participants	35 Participants n=4 Participants	31 Participants n=27 Participants	32 Participants n=483 Participants	130 Participants n=36 Participants
Race/Ethnicity, Customized African American	5 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants	2 Participants n=483 Participants	10 Participants n=36 Participants
Race/Ethnicity, Customized Asian	4 Participants n=93 Participants	2 Participants n=4 Participants	6 Participants n=27 Participants	2 Participants n=483 Participants	14 Participants n=36 Participants
Race/Ethnicity, Customized Hispanic	1 Participants n=93 Participants	4 Participants n=4 Participants	3 Participants n=27 Participants	1 Participants n=483 Participants	9 Participants n=36 Participants
Race/Ethnicity, Customized Other	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants	2 Participants n=36 Participants
Body Mass Index (BMI)	24.6 kg/m^2 STANDARD_DEVIATION 4.1 • n=93 Participants	23.8 kg/m^2 STANDARD_DEVIATION 3.0 • n=4 Participants	25.0 kg/m^2 STANDARD_DEVIATION 3.3 • n=27 Participants	25.6 kg/m^2 STANDARD_DEVIATION 4.5 • n=483 Participants	24.6 kg/m^2 STANDARD_DEVIATION 3.8 • n=36 Participants
Follicle-stimulating hormone level	7.4 mIU/mL STANDARD_DEVIATION 2.3 • n=93 Participants	7.1 mIU/mL STANDARD_DEVIATION 2.2 • n=4 Participants	6.9 mIU/mL STANDARD_DEVIATION 2.0 • n=27 Participants	6.9 mIU/mL STANDARD_DEVIATION 2.9 • n=483 Participants	7.3 mIU/mL STANDARD_DEVIATION 2.3 • n=36 Participants

PRIMARY outcome

Timeframe: Week 8 (Week 6 of gestation)

Population: Intent to treat population

The ongoing pregnancy was defined as a positive fetal heart movement (motion) at approximately six weeks of gestation and confirmed in a follow-up pregnancy ultrasound.

Outcome measures

Outcome measures
Measure	Menopur n=42 Participants Highly purified menotropin (Menopur) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Menopur for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follistim n=42 Participants Follitropin beta (Follistim®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Follistim for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follistim/Endometrin n=42 Participants Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follistim/Progesterone in Oil n=39 Participants Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Percentage of Participants With Ongoing Pregnancy at Week 8	45.2 percentage of participants	45.2 percentage of participants	42.9 percentage of participants	48.7 percentage of participants

SECONDARY outcome

Timeframe: Day 15

Population: Intend-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication

The mean number of follicles observed in both ovaries at the last transvaginal ultrasound in the stimulation phase.

Outcome measures

Outcome measures
Measure	Menopur n=84 Participants Highly purified menotropin (Menopur) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Menopur for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follistim n=81 Participants Follitropin beta (Follistim®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Follistim for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follistim/Endometrin Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follistim/Progesterone in Oil Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Number of Follicles Observed at Day 15	15.6 follicles Standard Deviation 8.6	16.2 follicles Standard Deviation 8.4	—	—

SECONDARY outcome

Timeframe: Approximately Day 18

Population: Intend-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication and had oocytes retrieved.

The mean number of oocytes retrieved within 34-36 hours of human chorionic gonadotropin (hCG) administration.

Outcome measures

Outcome measures
Measure	Menopur n=79 Participants Highly purified menotropin (Menopur) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Menopur for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follistim n=74 Participants Follitropin beta (Follistim®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Follistim for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follistim/Endometrin Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follistim/Progesterone in Oil Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Number of Oocytes Retrieved at Day 18	11.5 oocytes Standard Deviation 6.3	13.8 oocytes Standard Deviation 7.9	—	—

SECONDARY outcome

Timeframe: Approximately Day 19

Population: Intend-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication and had oocytes retrieved.

The proportion of the number of oocytes inseminated (fertilized) of the total number of oocytes retrieved.

Outcome measures

Outcome measures
Measure	Menopur n=79 Participants Highly purified menotropin (Menopur) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Menopur for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follistim n=73 Participants Follitropin beta (Follistim®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Follistim for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follistim/Endometrin Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follistim/Progesterone in Oil Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Proportion of Oocytes Fertilized of the Total Number of Oocytes Retrieved	0.3 proportion of oocytes retrieved Standard Deviation 0.4	0.3 proportion of oocytes retrieved Standard Deviation 0.4	—	—

SECONDARY outcome

Timeframe: Approximately Day 24

Population: Intend-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication and had embryos transferred.

The number of embryos, morula and blastocytes transferred to the study participant on either day 3 or day 5 following fertilization.

Outcome measures

Outcome measures
Measure	Menopur n=78 Participants Highly purified menotropin (Menopur) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Menopur for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follistim n=69 Participants Follitropin beta (Follistim®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Follistim for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follistim/Endometrin Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follistim/Progesterone in Oil Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Number of Embryos Transferred at Three Stages of Development Number of Embryos transferred	2.1 embryos Standard Deviation 0.7	2.4 embryos Standard Deviation 0.7	—	—
Number of Embryos Transferred at Three Stages of Development Number of Morula transferred	0.0 embryos Standard Deviation 0.1	0.1 embryos Standard Deviation 0.4	—	—
Number of Embryos Transferred at Three Stages of Development Number of Blastocytes transferred	0.9 embryos Standard Deviation 1	0.9 embryos Standard Deviation 1	—	—

SECONDARY outcome

Timeframe: Approximately Day 24

Population: Intend-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication and had oocytes fertilized

The number of embryos that were not transferred but instead were frozen for future use.

Outcome measures

Outcome measures
Measure	Menopur n=78 Participants Highly purified menotropin (Menopur) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Menopur for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follistim n=69 Participants Follitropin beta (Follistim®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Follistim for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follistim/Endometrin Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follistim/Progesterone in Oil Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Number of Embryos Frozen at Day 24	1.9 embryos Standard Deviation 2.9	1.6 embryos Standard Deviation 2.5	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 24

Population: Intend-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication

A count of participants whose discontinuation was clearly documented on the study completion/termination form as 1) due to cycle cancelled or 2) cycle cancellation for risk of ovarian hyperstimulation syndrome (OHSS).

Outcome measures

Outcome measures
Measure	Menopur n=42 Participants Highly purified menotropin (Menopur) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Menopur for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follistim n=42 Participants Follitropin beta (Follistim®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Follistim for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follistim/Endometrin n=42 Participants Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follistim/Progesterone in Oil n=39 Participants Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Participants With Cycle Cancellation Following One In Vitro Fertilization (IVF) Treatment Cycle	0 participants	1 participants	1 participants	2 participants

SECONDARY outcome

Timeframe: approximately day 38 (Day 14 post embryo transfer)

Population: Intent-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication and had an embryo transfer

Biochemical pregnancy is a positive β-hCG pregnancy test 12-14 days post embryo transfer.

Outcome measures

Outcome measures
Measure	Menopur n=38 Participants Highly purified menotropin (Menopur) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Menopur for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follistim n=40 Participants Follitropin beta (Follistim®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Follistim for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follistim/Endometrin n=36 Participants Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follistim/Progesterone in Oil n=33 Participants Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Participants With Biochemical Pregnancy at Day 38	21 participants	20 participants	22 participants	23 participants

SECONDARY outcome

Timeframe: approximately week 7

Population: Intent-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication and had an embryo transfer

Clinical pregnancy is the confirmation of the presence of intrauterine gestational sacs on pregnancy ultrasound examination.

Outcome measures

Outcome measures
Measure	Menopur n=38 Participants Highly purified menotropin (Menopur) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Menopur for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follistim n=40 Participants Follitropin beta (Follistim®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Follistim for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follistim/Endometrin n=36 Participants Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follistim/Progesterone in Oil n=33 Participants Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Participants With Clinical Pregnancy at Week 7	19 participants	19 participants	18 participants	20 participants

SECONDARY outcome

Timeframe: Day 1 - week 12

Population: Safety population all randomized and treated participants. The safety population is identical intent-to- treat (ITT) population in this study

Number of participants with adverse events (AEs) that started after first treatment. Severity used a three point scale: mild=awareness of signs/symptoms, but no disruption of usual activity moderate=event sufficient to affect usual activity (disturbing) severe=event causes inability to work or perform usual activities (unacceptable) Relatedness to study treatment used a four point scale: unrelated, unlikely, possible, probable. Seriousness refers to death, hospitalization, a life-threatening experience, persistent or significant disability/incapacity, or congenital anomaly.

Outcome measures

Outcome measures
Measure	Menopur n=42 Participants Highly purified menotropin (Menopur) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Menopur for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follistim n=42 Participants Follitropin beta (Follistim®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. This group combines the two treatment arms that use Follistim for ovarian stimulation. This treatment is followed by luteal support using either progesterone vaginal insert (Endometrin®) or progesterone in oil.	Follistim/Endometrin n=42 Participants Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follistim/Progesterone in Oil n=39 Participants Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Participants With Adverse Events (AEs), Including Ovarian Hyperstimulation Syndrome (OHSS) Possibly or probably related adverse event	10 participants	8 participants	7 participants	15 participants
Participants With Adverse Events (AEs), Including Ovarian Hyperstimulation Syndrome (OHSS) With at least one adverse event	20 participants	18 participants	18 participants	21 participants
Participants With Adverse Events (AEs), Including Ovarian Hyperstimulation Syndrome (OHSS) Mild or moderate adverse event	20 participants	18 participants	18 participants	21 participants
Participants With Adverse Events (AEs), Including Ovarian Hyperstimulation Syndrome (OHSS) Severe adverse event	1 participants	0 participants	2 participants	0 participants
Participants With Adverse Events (AEs), Including Ovarian Hyperstimulation Syndrome (OHSS) Serious adverse event	0 participants	1 participants	1 participants	0 participants
Participants With Adverse Events (AEs), Including Ovarian Hyperstimulation Syndrome (OHSS) Unrelated or unlikely adverse event	15 participants	13 participants	17 participants	14 participants

SECONDARY outcome

Timeframe: Approximately 10 months

Population: Database was locked prior to all participants giving birth.

Outcome measures

Outcome data not reported

Adverse Events

Menopur/Endometrin

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Menopur/Progesterone in Oil

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Follistim/Endometrin

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Follistim/Progesterone in Oil

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Menopur/Endometrin n=42 participants at risk Highly purified menotropin (Menopur®) 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Menopur/Progesterone in Oil n=42 participants at risk Highly purified menotropin 225 IU by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follistim/Endometrin n=42 participants at risk Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg inserted vaginally 2 or 3 times daily (BID or TID) starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.	Follistim/Progesterone in Oil n=39 participants at risk Follitropin beta (Follistim®) 225 IU (up to 450 IU) by subcutaneous injection once per day from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil injections 50 mg by intramuscular injection (IM) once per day start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Reproductive system and breast disorders Ovarian hyperstimulation syndrome with ascites	0.00% 0/42 • Treatment-emergent adverse events were collected from Day 1 to Week 12. Multiple events in the same system organ class for a subject are only counted once for that system organ class.	2.4% 1/42 • Treatment-emergent adverse events were collected from Day 1 to Week 12. Multiple events in the same system organ class for a subject are only counted once for that system organ class.	0.00% 0/42 • Treatment-emergent adverse events were collected from Day 1 to Week 12. Multiple events in the same system organ class for a subject are only counted once for that system organ class.	0.00% 0/39 • Treatment-emergent adverse events were collected from Day 1 to Week 12. Multiple events in the same system organ class for a subject are only counted once for that system organ class.
Gastrointestinal disorders Hyperemesis gravidarum	0.00% 0/42 • Treatment-emergent adverse events were collected from Day 1 to Week 12. Multiple events in the same system organ class for a subject are only counted once for that system organ class.	0.00% 0/42 • Treatment-emergent adverse events were collected from Day 1 to Week 12. Multiple events in the same system organ class for a subject are only counted once for that system organ class.	2.4% 1/42 • Treatment-emergent adverse events were collected from Day 1 to Week 12. Multiple events in the same system organ class for a subject are only counted once for that system organ class.	0.00% 0/39 • Treatment-emergent adverse events were collected from Day 1 to Week 12. Multiple events in the same system organ class for a subject are only counted once for that system organ class.

Other adverse events

Additional Information

Clinical Development Support

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