MENOPUR® Versus FOLLISTIM®

• ClinicalTrials.gov Identifier: NCT00802360
• Recruitment Status: Completed
• First Posted: December 4, 2008
• Results First Posted: August 30, 2011
• Last Update Posted: November 2, 2011
• Sponsor: Ferring Pharmaceuticals
• Information provided by (Responsible Party): Ferring Pharmaceuticals

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Infertility
• Interventions: Drug: Menotropin; Drug: Progestrone vaginal insert; Drug: follitropin beta; Drug: Progesterone in oil; Drug: Ganirelix
• Enrollment: 173

Participant Flow

Recruitment Details	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
Pre-assignment Details

Arm/Group Title	Menopur/Endometrin	Menopur/Progesterone in Oil	Follistim/Endometrin	Follistim/Progesterone in Oil
Arm/Group Description	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.	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.	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.	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.
Period Title: Overall Study
Started	42	42	42	39
Completed	18	16	17	17
Not Completed	24	26	25	22
Reason Not Completed
Stimulation failure	4	0	3	3
Inadequate number of oocytes retrieved	0	0	0	1
Cycle cancelled	0	1	1	1
Risk of ovarian hyperstimulation syndrom	0	0	0	1
No positive serum pregnancy	17	20	14	10
Pregnancy not confirmed by ultrasound	1	0	1	0
Pregnancy loss/miscarriage	0	2	0	3
Other	2	3	6	3

Baseline Characteristics

Arm/Group Title		Menopur/Endometrin	Menopur/Progesterone in Oil	Follistim/Endometrin	Follistim/Progesterone in Oil	Total
Arm/Group Description		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.	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.	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.	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 of all reporting groups
Overall Number of Baseline Participants		42	42	42	39	165
Baseline Analysis Population Description		[Not Specified]
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	42 participants	42 participants	42 participants	39 participants	165 participants
		33.5 (4.1)	33.2 (4.8)	34.0 (4.3)	33.9 (4.3)	33.9 (7.4)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	42 participants	42 participants	42 participants	39 participants	165 participants
	Female	42 100.0%	42 100.0%	42 100.0%	39 100.0%	165 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	42 participants	42 participants	42 participants	39 participants	165 participants
Caucasian		32	35	31	32	130
African American		5	1	2	2	10
Asian		4	2	6	2	14
Hispanic		1	4	3	1	9
Other		0	0	0	2	2
Body Mass Index (BMI); Mean (Standard Deviation); Unit of measure: Kg/m^2
	Number Analyzed	42 participants	42 participants	42 participants	39 participants	165 participants
		24.6 (4.1)	23.8 (3.0)	25.0 (3.3)	25.6 (4.5)	24.6 (3.8)
Follicle-stimulating hormone level; Mean (Standard Deviation); Unit of measure: mIU/mL
	Number Analyzed	42 participants	42 participants	42 participants	39 participants	165 participants
		7.4 (2.3)	7.1 (2.2)	6.9 (2.0)	6.9 (2.9)	7.3 (2.3)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Ongoing Pregnancy at Week 8
Description	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.
Time Frame	Week 8 (Week 6 of gestation)

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	Menopur/Endometrin	Menopur/Progesterone in Oil	Follistim/Endometrin	Follistim/Progesterone in Oil
Arm/Group Description:	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.	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.	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.	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 Number of Participants Analyzed	42	42	42	39
Measure Type: Number; Unit of Measure: percentage of participants
	45.2	45.2	42.9	48.7

2. Secondary Outcome

Title	Number of Follicles Observed at Day 15
Description	The mean number of follicles observed in both ovaries at the last transvaginal ultrasound in the stimulation phase.
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Menopur	Follistim
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	84	81
Mean (Standard Deviation); Unit of Measure: follicles
	15.6 (8.6)	16.2 (8.4)

3. Secondary Outcome

Title	Number of Oocytes Retrieved at Day 18
Description	The mean number of oocytes retrieved within 34-36 hours of human chorionic gonadotropin (hCG) administration.
Time Frame	Approximately Day 18

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Menopur	Follistim
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	79	74
Mean (Standard Deviation); Unit of Measure: oocytes
	11.5 (6.3)	13.8 (7.9)

4. Secondary Outcome

Title	Proportion of Oocytes Fertilized of the Total Number of Oocytes Retrieved
Description	The proportion of the number of oocytes inseminated (fertilized) of the total number of oocytes retrieved.
Time Frame	Approximately Day 19

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Menopur	Follistim
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	79	73
Mean (Standard Deviation); Unit of Measure: proportion of oocytes retrieved
	0.3 (0.4)	0.3 (0.4)

5. Secondary Outcome

Title	Number of Embryos Transferred at Three Stages of Development
Description	The number of embryos, morula and blastocytes transferred to the study participant on either day 3 or day 5 following fertilization.
Time Frame	Approximately Day 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Menopur	Follistim
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	78	69
Mean (Standard Deviation); Unit of Measure: embryos
Number of Embryos transferred	2.1 (0.7)	2.4 (0.7)
Number of Morula transferred	0.0 (0.1)	0.1 (0.4)
Number of Blastocytes transferred	0.9 (1)	0.9 (1)

6. Secondary Outcome

Title	Number of Embryos Frozen at Day 24
Description	The number of embryos that were not transferred but instead were frozen for future use.
Time Frame	Approximately Day 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Menopur	Follistim
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	78	69
Mean (Standard Deviation); Unit of Measure: embryos
	1.9 (2.9)	1.6 (2.5)

7. Secondary Outcome

Title	Participants With Cycle Cancellation Following One In Vitro Fertilization (IVF) Treatment Cycle
Description	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).
Time Frame	Day 1 to Day 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Menopur/Endometrin	Menopur/Progesterone in Oil	Follistim/Endometrin	Follistim/Progesterone in Oil
Arm/Group Description:	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.	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.	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.	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 Number of Participants Analyzed	42	42	42	39
Measure Type: Number; Unit of Measure: participants
	0	1	1	2

8. Secondary Outcome

Title	Participants With Biochemical Pregnancy at Day 38
Description	Biochemical pregnancy is a positive β-hCG pregnancy test 12-14 days post embryo transfer.
Time Frame	approximately day 38 (Day 14 post embryo transfer)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Menopur/Endometrin	Menopur/Progesterone in Oil	Follistim/Endometrin	Follistim/Progesterone in Oil
Arm/Group Description:	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.	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.	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.	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 Number of Participants Analyzed	38	40	36	33
Measure Type: Number; Unit of Measure: participants
	21	20	22	23

9. Secondary Outcome

Title	Participants With Clinical Pregnancy at Week 7
Description	Clinical pregnancy is the confirmation of the presence of intrauterine gestational sacs on pregnancy ultrasound examination.
Time Frame	approximately week 7

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Menopur/Endometrin	Menopur/Progesterone in Oil	Follistim/Endometrin	Follistim/Progesterone in Oil
Arm/Group Description:	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.	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.	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.	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 Number of Participants Analyzed	38	40	36	33
Measure Type: Number; Unit of Measure: participants
	19	19	18	20

10. Secondary Outcome

Title	Participants With Adverse Events (AEs), Including Ovarian Hyperstimulation Syndrome (OHSS)
Description	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.
Time Frame	Day 1 - week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Menopur/Endometrin	Menopur/Progesterone in Oil	Follistim/Endometrin	Follistim/Progesterone in Oil
Arm/Group Description:	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.	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.	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.	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 Number of Participants Analyzed	42	42	42	39
Measure Type: Number; Unit of Measure: participants
With at least one adverse event	20	18	18	21
Mild or moderate adverse event	20	18	18	21
Severe adverse event	1	0	2	0
Serious adverse event	0	1	1	0
Unrelated or unlikely adverse event	15	13	17	14
Possibly or probably related adverse event	10	8	7	15

11. Secondary Outcome

Title	Number of Live Births
Description	[Not Specified]
Time Frame	Approximately 10 months

Outcome Measure Data

Analysis Population Description

Database was locked prior to all participants giving birth.

Arm/Group Title	Menopur/Endometrin	Menopur/Progesterone in Oil	Follistim/Endometrin	Follistim/Progesterone in Oil
Arm/Group Description:	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.	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.	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.	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 Number of Participants Analyzed	0	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

Adverse Events

Time Frame	Treatment-emergent adverse events were collected from Day 1 to Week 12.
Adverse Event Reporting Description	Multiple events in the same system organ class for a subject are only counted once for that system organ class.
Arm/Group Title	Menopur/Endometrin	Menopur/Progesterone in Oil	Follistim/Endometrin	Follistim/Progesterone in Oil
Arm/Group Description	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.	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.	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.	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.
All-Cause Mortality
	Menopur/Endometrin	Menopur/Progesterone in Oil	Follistim/Endometrin	Follistim/Progesterone in Oil
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--	--/--
Serious Adverse Events
	Menopur/Endometrin	Menopur/Progesterone in Oil	Follistim/Endometrin	Follistim/Progesterone in Oil
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/42 (0.00%)	1/42 (2.38%)	1/42 (2.38%)	0/39 (0.00%)
Gastrointestinal disorders
Hyperemesis gravidarum † 1	0/42 (0.00%)	0/42 (0.00%)	1/42 (2.38%)	0/39 (0.00%)
Reproductive system and breast disorders
Ovarian hyperstimulation syndrome with ascites † 1	0/42 (0.00%)	1/42 (2.38%)	0/42 (0.00%)	0/39 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (Unspecified)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Menopur/Endometrin	Menopur/Progesterone in Oil	Follistim/Endometrin	Follistim/Progesterone in Oil
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	20/42 (47.62%)	18/42 (42.86%)	18/42 (42.86%)	21/39 (53.85%)
Gastrointestinal disorders
Abdominal distension † 1	4/42 (9.52%)	6/42 (14.29%)	3/42 (7.14%)	5/39 (12.82%)
Abdominal pain lower † 1	3/42 (7.14%)	0/42 (0.00%)	0/42 (0.00%)	0/39 (0.00%)
Abdominal pain upper † 1	1/42 (2.38%)	0/42 (0.00%)	0/42 (0.00%)	2/39 (5.13%)
Nausea † 1	3/42 (7.14%)	5/42 (11.90%)	3/42 (7.14%)	8/39 (20.51%)
Abdominal discomfort † 1	1/42 (2.38%)	0/42 (0.00%)	0/42 (0.00%)	0/39 (0.00%)
Abdominal pain † 1	0/42 (0.00%)	0/42 (0.00%)	2/42 (4.76%)	0/39 (0.00%)
Ascites † 1	0/42 (0.00%)	0/42 (0.00%)	1/42 (2.38%)	0/39 (0.00%)
Constipation † 1	1/42 (2.38%)	1/42 (2.38%)	2/42 (4.76%)	0/39 (0.00%)
Dyspepsia † 1	0/42 (0.00%)	1/42 (2.38%)	0/42 (0.00%)	0/39 (0.00%)
Flatulence † 1	1/42 (2.38%)	0/42 (0.00%)	0/42 (0.00%)	0/39 (0.00%)
Stomach discomfort † 1	0/42 (0.00%)	0/42 (0.00%)	1/42 (2.38%)	0/39 (0.00%)
Vomiting † 1	1/42 (2.38%)	2/42 (4.76%)	2/42 (4.76%)	1/39 (2.56%)
General disorders
Adverse drug reaction † 1	0/42 (0.00%)	1/42 (2.38%)	0/42 (0.00%)	0/39 (0.00%)
Fatigue † 1	0/42 (0.00%)	0/42 (0.00%)	0/42 (0.00%)	1/39 (2.56%)
Injection site discomfort † 1	0/42 (0.00%)	0/42 (0.00%)	0/42 (0.00%)	1/39 (2.56%)
Injection site erythema † 1	0/42 (0.00%)	0/42 (0.00%)	0/42 (0.00%)	1/39 (2.56%)
Injection site oedema † 1	0/42 (0.00%)	1/42 (2.38%)	0/42 (0.00%)	0/39 (0.00%)
Injection site pruritus † 1	0/42 (0.00%)	0/42 (0.00%)	0/42 (0.00%)	1/39 (2.56%)
Injection site rash † 1	0/42 (0.00%)	0/42 (0.00%)	0/42 (0.00%)	1/39 (2.56%)
Irritability † 1	1/42 (2.38%)	0/42 (0.00%)	0/42 (0.00%)	0/39 (0.00%)
Oedema peripheral † 1	0/42 (0.00%)	0/42 (0.00%)	1/42 (2.38%)	0/39 (0.00%)
Immune system disorders
Drug hypersensitivity † 1	0/42 (0.00%)	0/42 (0.00%)	1/42 (2.38%)	0/39 (0.00%)
Infections and infestations
Fungal infection † 1	1/42 (2.38%)	0/42 (0.00%)	0/42 (0.00%)	1/39 (2.56%)
Nasopharyngitis † 1	0/42 (0.00%)	0/42 (0.00%)	1/42 (2.38%)	1/39 (2.56%)
Urinary tract infection † 1	0/42 (0.00%)	0/42 (0.00%)	1/42 (2.38%)	0/39 (0.00%)
Vulvovaginal mycotic infection † 1	1/42 (2.38%)	2/42 (4.76%)	1/42 (2.38%)	1/39 (2.56%)
Injury, poisoning and procedural complications
Procedural pain † 1	1/42 (2.38%)	3/42 (7.14%)	5/42 (11.90%)	2/39 (5.13%)
Incision site complication † 1	0/42 (0.00%)	1/42 (2.38%)	0/42 (0.00%)	0/39 (0.00%)
Injection site anaesthesia † 1	0/42 (0.00%)	0/42 (0.00%)	0/42 (0.00%)	1/39 (2.56%)
Procedural nausea † 1	1/42 (2.38%)	1/42 (2.38%)	2/42 (4.76%)	0/39 (0.00%)
Investigations
Alanine aminotransferase increased † 1	0/42 (0.00%)	0/42 (0.00%)	0/42 (0.00%)	1/39 (2.56%)
Metabolism and nutrition disorders
Decreased appetite † 1	0/42 (0.00%)	1/42 (2.38%)	0/42 (0.00%)	0/39 (0.00%)
Musculoskeletal and connective tissue disorders
Back pain † 1	2/42 (4.76%)	2/42 (4.76%)	0/42 (0.00%)	0/39 (0.00%)
Musculoskeletal pain † 1	0/42 (0.00%)	0/42 (0.00%)	1/42 (2.38%)	0/39 (0.00%)
Myalgia † 1	0/42 (0.00%)	0/42 (0.00%)	1/42 (2.38%)	0/39 (0.00%)
Nervous system disorders
Dizziness † 1	1/42 (2.38%)	0/42 (0.00%)	1/42 (2.38%)	2/39 (5.13%)
Headache † 1	1/42 (2.38%)	1/42 (2.38%)	2/42 (4.76%)	1/39 (2.56%)
Migraine † 1	0/42 (0.00%)	0/42 (0.00%)	0/42 (0.00%)	1/39 (2.56%)
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy † 1	0/42 (0.00%)	1/42 (2.38%)	1/42 (2.38%)	0/39 (0.00%)
Psychiatric disorders
Depression † 1	1/42 (2.38%)	0/42 (0.00%)	0/42 (0.00%)	0/39 (0.00%)
Insomnia † 1	0/42 (0.00%)	1/42 (2.38%)	1/42 (2.38%)	0/39 (0.00%)
Renal and urinary disorders
Bladder pain † 1	1/42 (2.38%)	0/42 (0.00%)	0/42 (0.00%)	0/39 (0.00%)
Reproductive system and breast disorders
Adnexa uteri pain † 1	6/42 (14.29%)	7/42 (16.67%)	6/42 (14.29%)	9/39 (23.08%)
Ovarian hyperstimulation syndrome † 1	3/42 (7.14%)	1/42 (2.38%)	1/42 (2.38%)	8/39 (20.51%)
Pelvic pain † 1	0/42 (0.00%)	0/42 (0.00%)	0/42 (0.00%)	2/39 (5.13%)
Breast tenderness † 1	2/42 (4.76%)	0/42 (0.00%)	0/42 (0.00%)	0/39 (0.00%)
Metrorrhagia † 1	1/42 (2.38%)	0/42 (0.00%)	1/42 (2.38%)	1/39 (2.56%)
Pelvic discomfort † 1	0/42 (0.00%)	1/42 (2.38%)	0/42 (0.00%)	0/39 (0.00%)
Uterine spasm † 1	1/42 (2.38%)	1/42 (2.38%)	2/42 (4.76%)	1/39 (2.56%)
Vaginal discharge † 1	0/42 (0.00%)	1/42 (2.38%)	0/42 (0.00%)	0/39 (0.00%)
Vaginal haemorrhage † 1	2/42 (4.76%)	0/42 (0.00%)	2/42 (4.76%)	0/39 (0.00%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	1/42 (2.38%)	0/42 (0.00%)	0/42 (0.00%)	0/39 (0.00%)
Dyspnoea † 1	1/42 (2.38%)	0/42 (0.00%)	1/42 (2.38%)	0/39 (0.00%)
Nasal congestion † 1	0/42 (0.00%)	0/42 (0.00%)	0/42 (0.00%)	1/39 (2.56%)
Pharyngolaryngeal pain † 1	2/42 (4.76%)	0/42 (0.00%)	1/42 (2.38%)	1/39 (2.56%)
Sinus congestion † 1	0/42 (0.00%)	0/42 (0.00%)	1/42 (2.38%)	0/39 (0.00%)
Skin and subcutaneous tissue disorders
Acne † 1	1/42 (2.38%)	1/42 (2.38%)	0/42 (0.00%)	0/39 (0.00%)
Vascular disorders
Haematoma † 1	0/42 (0.00%)	1/42 (2.38%)	0/42 (0.00%)	0/39 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (Unspecified)

Limitations and Caveats

This was an exploratory study that could be used as the basis for larger, adequately-powered studies. This limitation is the reason no statistical analyses are offered for study outcomes.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The only disclosure restriction on the PI is that the sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the sponsor.

Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow Ferring to seek patent protection of the invention.

Results Point of Contact

• Name/Title: Clinical Development Support
• Organization: Ferring Pharmaceuticals
• EMail: DK0-Disclosure@ferring.com

• Responsible Party: Ferring Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00802360
• Other Study ID Numbers: 2008-04
• First Submitted: December 3, 2008
• First Posted: December 4, 2008
• Results First Submitted: May 3, 2011
• Results First Posted: August 30, 2011
• Last Update Posted: November 2, 2011