Menopur® Versus Follistim® in Polycystic Ovarian Syndrome (PCOS)

• ClinicalTrials.gov Identifier: NCT00805935
• Recruitment Status: Completed
• First Posted: December 10, 2008
• Results First Posted: January 25, 2012
• Last Update Posted: January 27, 2012
• 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
• Conditions: Polycystic Ovarian Syndrome; Infertility
• Interventions: Drug: Menotropin; Drug: Progesterone vaginal insert; Drug: Follitropin beta; Drug: Progesterone in oil; Drug: leuprolide acetate
• Enrollment: 110

Participant Flow

Recruitment Details	The original plan was for 200 participants to be enrolled across six (6) women's reproductive study centers across the US.
Pre-assignment Details	127 patients were screened. 120 patients were randomized. Of the randomized patients, 10 did not receive treatment. 110 randomized participants started the study on treatment.

Arm/Group Title	Menotropin/Progesterone Vaginal Insert	Menotropin/Progesterone in Oil	Follitropin Beta/Progesterone Vaginal Insert	Follitropin Beta/Progesterone in Oil
Arm/Group Description	Highly purified menotropin (Menopur®) 225 IU 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 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 (Menopur®) 225 IU 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 50 mg injections 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 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®) 50 mg injections 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 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 50 mg injections 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	25	27	28	30
Completed	12	8	13	19
Not Completed	13	19	15	11
Reason Not Completed
Stimulation Failure	1	5	2	2
Cycle cancelled	0	0	2	0
Cycle cancellation for risk of OHSS	1	0	1	0
Ovarian hyperstimulation syndrome(OHSS)	0	0	0	1
Lost to Follow-up	1	0	0	0
No positive serum pregnancy	8	7	6	5
Pregnancy not confirmed by ultrasound	0	0	0	1
Pregnancy loss/miscarriage	2	0	0	0
Biochemical pregnancy	0	1	0	0
Chemical pregnancy	0	5	3	2
Ectopic pregnancy	0	0	1	0
Serious Adverse Event-congenital anomaly	0	1	0	0

Baseline Characteristics

Arm/Group Title		Menotropin/Progesterone Vaginal Insert	Menotropin/Progesterone in Oil	Follitropin Beta/Progesterone Vaginal Insert	Follitropin Beta/Progesterone in Oil	Total
Arm/Group Description		Highly purified menotropin (Menopur®) 225 IU 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 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 (Menopur®) 225 IU 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 50 mg injections 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 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®) 50 mg injections 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 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 50 mg injections 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		25	27	28	30	110
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	25 participants	27 participants	28 participants	30 participants	110 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	25 100.0%	27 100.0%	28 100.0%	30 100.0%	110 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	25 participants	27 participants	28 participants	30 participants	110 participants
	Female	25 100.0%	27 100.0%	28 100.0%	30 100.0%	110 100.0%
	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	25 participants	27 participants	28 participants	30 participants	110 participants
Caucasian		18	18	20	25	81
African American		0	1	0	0	1
Asian		5	1	4	1	11
Hispanic		2	7	4	3	16
Other		0	0	0	1	1

Outcome Measures

1. Primary Outcome

Title	Participants With Cycle Cancellation Due to Risk of Ovarian Hyperstimulation Syndrome (OHSS) Between Weeks 1 - 3
Description	A count of participants whose discontinuation was clearly documented on the study completion/termination form as cycle cancellation for risk of ovarian hyperstimulation syndrome (OHSS).
Time Frame	weeks 1-3

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	Menotropin/Progesterone Vaginal Insert	Menotropin/Progesterone in Oil	Follitropin Beta/Progesterone Vaginal Insert	Follitropin Beta/Progesterone in Oil
Arm/Group Description:	Highly purified menotropin (Menopur®) 225 IU 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 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 (Menopur®) 225 IU 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 50 mg injections 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 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®) 50 mg injections 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 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 50 mg injections 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	25	27	28	30
Measure Type: Number; Unit of Measure: Participants
Yes	1	0	1	0
No	24	27	27	30

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Menotropin/Progesterone Vaginal Insert, Follitropin Beta/Progesterone Vaginal Insert
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	1.000
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Menotropin/Progesterone in Oil, Follitropin Beta/Progesterone in Oil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	1.000
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Menotropin/Progesterone Vaginal Insert, Menotropin/Progesterone in Oil
	Comments	Comparing Progesterone vaginal insert to Progesterone in oil within the menotropin treatments arms.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.481
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Follitropin Beta/Progesterone Vaginal Insert, Follitropin Beta/Progesterone in Oil
	Comments	Comparing Progesterone vaginal insert to Progesterone in oil within the follitropin beta treatment group.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.483
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

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	approximately 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	Menotropin	Follitropin Beta
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 Highly purified menotropin (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 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 Follitropin beta (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	52	58
Mean (Standard Deviation); Unit of Measure: Follicles
	27.7 (12.8)	30.5 (16.1)

3. Secondary Outcome

Title	Number of Oocytes Retrieved at Day 18
Description	The mean number of oocytes retrieved approximately 36 hours after hCG (Novarel®) administration and fertilized (by insemination or intra cytoplasmic sperm injection (ICSI)) according to site-specific procedures.
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

Arm/Group Title	Menotropin	Follitropin Beta
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 Highly purified menotropin (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 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 Follitropin beta (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	52	58
Mean (Standard Deviation); Unit of Measure: Oocytes
	13.0 (7.7)	15.6 (8.6)

4. Secondary Outcome

Title	Percentage of Oocytes Fertilized of the Total Number of Oocytes Retrieved
Description	The fertilization rate for each participant was the percentage of the number of oocytes inseminated 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

Arm/Group Title	Menotropin	Follitropin Beta
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 Highly purified menotropin (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 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 Follitropin beta (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	52	58
Measure Type: Number; Unit of Measure: Percentage of oocytes retrieved
	17.1	24.8

5. Secondary Outcome

Title	Number of Embryos Transferred at Three Stages of Development Before Implantation
Description	The number of embryos, morulas and blastocysts transferred to the study participant on either day 3 or day 5 following fertilization. Embryos represent the earliest development stage and contain 2-8 cells. Morulas, the next stage, continued cellular cleavage results in a 16-30 cell solid sphere. Morula further develop into blastocyst, which contains 70-100 cells in a hollow spherical shape.
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

Arm/Group Title	Menotropin	Follitropin Beta
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 Highly purified menotropin (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 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 Follitropin beta (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	52	58
Mean (Standard Deviation); Unit of Measure: Embryos
Number of embryos transferred	2.0 (0.7)	2.0 (0.5)
Number of morula transferred	0.0 (0.1)	0.1 (0.4)
Number of blastocyst transferred	0.8 (0.9)	1.1 (0.9)

6. Secondary Outcome

Title	Number of Embryos Frozen
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

Arm/Group Title	Menotropin	Follitropin Beta
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 Highly purified menotropin (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 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 Follitropin beta (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	52	58
Mean (Standard Deviation); Unit of Measure: Embryos
	1.9 (2.3)	1.9 (2.6)

7. Secondary Outcome

Title	Percentage of Participants With Biochemical Pregnancy at Approximately 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

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

Arm/Group Title	Menotropin/Progesterone Vaginal Insert	Menotropin/Progesterone in Oil	Follitropin Beta/Progesterone Vaginal Insert	Follitropin Beta/Progesterone in Oil
Arm/Group Description:	Highly purified menotropin (Menopur®) 225 IU 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 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 (Menopur®) 225 IU 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 50 mg injections 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 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®) 50 mg injections 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 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 50 mg injections 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	25	27	28	30
Measure Type: Number; Unit of Measure: Percentage of participants
	60.0	55.6	60.7	73.3

8. Secondary Outcome

Title	Percentage of 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 Day 52

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	Menotropin/Progesterone Vaginal Insert	Menotropin/Progesterone in Oil	Follitropin Beta/Progesterone Vaginal Insert	Follitropin Beta/Progesterone in Oil
Arm/Group Description:	Highly purified menotropin (Menopur®) 225 IU 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 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 (Menopur®) 225 IU 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 50 mg injections 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 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®) 50 mg injections 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 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 50 mg injections 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	25	27	28	30
Measure Type: Number; Unit of Measure: Percentage of participants
	56.0	33.3	46.4	66.7

9. Secondary Outcome

Title	Percentage of Participants With Ongoing Pregnancy at Week 9
Description	Clinical pregnancy is the confirmation of the presence of intrauterine gestational sacs on pregnancy ultrasound examination.
Time Frame	approximately Day 65

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	Menotropin/Progesterone Vaginal Insert	Menotropin/Progesterone in Oil	Follitropin Beta/Progesterone Vaginal Insert	Follitropin Beta/Progesterone in Oil
Arm/Group Description:	Highly purified menotropin (Menopur®) 225 IU 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 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 (Menopur®) 225 IU 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 50 mg injections 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 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®) 50 mg injections 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 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 50 mg injections 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	25	27	28	30
Measure Type: Number; Unit of Measure: Percentage of participants
	48.0	33.3	46.4	63.3

10. Secondary Outcome

Title	Estradiol Levels at Day 6
Description	Estradiol monitoring during fertility therapy assesses follicular growth and is useful in monitoring the treatment. Blood tests sent to a central laboratory to obtain estradiol levels.
Time Frame	Day 6

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	Menotropin/Progesterone Vaginal Insert	Menotropin/Progesterone in Oil	Follitropin Beta/Progesterone Vaginal Insert	Follitropin Beta/Progesterone in Oil
Arm/Group Description:	Highly purified menotropin (Menopur®) 225 IU 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 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 (Menopur®) 225 IU 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 50 mg injections 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 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®) 50 mg injections 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 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 50 mg injections 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	25	27	28	30
Mean (Standard Deviation); Unit of Measure: pg/mL
	354.6 (331.3)	268.2 (260.7)	617.5 (409.6)	550.5 (486.9)

11. Secondary Outcome

Title	Human Chorionic Gonadotropin (hCG) Levels at Day 6
Description	Blood tests were sent to a central laboratory to obtain hCG levels.
Time Frame	Day 6

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	Menotropin/Progesterone Vaginal Insert	Menotropin/Progesterone in Oil	Follitropin Beta/Progesterone Vaginal Insert	Follitropin Beta/Progesterone in Oil
Arm/Group Description:	Highly purified menotropin (Menopur®) 225 IU 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 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 (Menopur®) 225 IU 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 50 mg injections 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 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®) 50 mg injections 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 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 50 mg injections 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	25	27	28	30
Mean (Standard Deviation); Unit of Measure: mIU/ml
	1.0 (0.2)	1.0 (0.0)	1.0 (0.0)	1.0 (0.0)

12. Secondary Outcome

Title	Progesterone Levels at Human Chorionic Gonadotropin (hCG) Administration
Description	Blood tests were sent to a central laboratory to obtain progesterone levels.
Time Frame	approximately day 16

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Menotropin/Progesterone Vaginal Insert	Menotropin/Progesterone in Oil	Follitropin Beta/Progesterone Vaginal Insert	Follitropin Beta/Progesterone in Oil
Arm/Group Description:	Highly purified menotropin (Menopur®) 225 IU 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 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 (Menopur®) 225 IU 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 50 mg injections 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 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®) 50 mg injections 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 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 50 mg injections 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	23	21	23	28
Mean (Standard Deviation); Unit of Measure: ng/mL
	1.3 (0.7)	1.1 (0.4)	1.7 (0.9)	1.3 (0.6)

13. Secondary Outcome

Title	Number of Live Births Resulting From the In Vitro Fertilization Process
Description	Number of live births resulting from the IVF process
Time Frame	Approximately 10 months

Outcome Measure Data

Analysis Population Description

Database was locked prior to most participants giving birth.

Arm/Group Title	Menotropin/Progesterone Vaginal Insert	Menotropin/Progesterone in Oil	Follitropin Beta/Progesterone Vaginal Insert	Follitropin Beta/Progesterone in Oil
Arm/Group Description:	Highly purified menotropin (Menopur®) 225 IU 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 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 (Menopur®) 225 IU 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 50 mg injections 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 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®) 50 mg injections 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 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 50 mg injections 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.

14. Secondary Outcome

Title	Participants With Treatment Emergent Adverse Events
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	Week 1 to week12

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	Menotropin/Progesterone Vaginal Insert	Menotropin/Progesterone in Oil	Follitropin Beta/Progesterone Vaginal Insert	Follitropin Beta/Progesterone in Oil
Arm/Group Description:	Highly purified menotropin (Menopur®) 225 IU 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 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 (Menopur®) 225 IU 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 50 mg injections 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 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®) 50 mg injections 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 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 50 mg injections 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	25	27	28	30
Measure Type: Number; Unit of Measure: Participants
With at least one adverse event	9	12	15	14
With at least one mild or moderate adverse event	9	11	15	14
With at least one severe adverse event	0	2	1	0
With at least one serious adverse event	0	1	0	0
With at least one unrelated or unlikely AE	8	11	12	13
With at least one possibly or probably related AE	3	7	8	6

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	Menotropin/Progesterone Vaginal Insert		Menotropin/Progesterone in Oil		Follitropin Beta/Progesterone Vaginal Insert		Follitropin Beta/Progesterone in Oil
Arm/Group Description	Highly purified menotropin (Menopur®) 225 IU 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 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 (Menopur®) 225 IU 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 50 mg injections 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 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®) 50 mg injections 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 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 50 mg injections 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
	Menotropin/Progesterone Vaginal Insert		Menotropin/Progesterone in Oil		Follitropin Beta/Progesterone Vaginal Insert		Follitropin Beta/Progesterone in Oil
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--		--/--
Serious Adverse Events
	Menotropin/Progesterone Vaginal Insert		Menotropin/Progesterone in Oil		Follitropin Beta/Progesterone Vaginal Insert		Follitropin Beta/Progesterone in Oil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0.00%)		1/27 (3.70%)		0/28 (0.00%)		0/30 (0.00%)
Congenital, familial and genetic disorders
Conjoined Twins † 1	0/25 (0.00%)	0	1/27 (3.70%)	1	0/28 (0.00%)	0	0/30 (0.00%)	0
† 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%
	Menotropin/Progesterone Vaginal Insert		Menotropin/Progesterone in Oil		Follitropin Beta/Progesterone Vaginal Insert		Follitropin Beta/Progesterone in Oil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/25 (36.00%)		11/27 (40.74%)		15/28 (53.57%)		14/30 (46.67%)
Blood and lymphatic system disorders
Lymphadenopathy † 1	1/25 (4.00%)		0/27 (0.00%)		0/28 (0.00%)		0/30 (0.00%)
Gastrointestinal disorders
Abdominal discomfort † 1	1/25 (4.00%)		0/27 (0.00%)		0/28 (0.00%)		0/30 (0.00%)
Abdominal Distension † 1	1/25 (4.00%)		1/27 (3.70%)		3/28 (10.71%)		2/30 (6.67%)
Abdominal pain † 1	0/25 (0.00%)		0/27 (0.00%)		1/28 (3.57%)		0/30 (0.00%)
Abdominal pain lower † 1	1/25 (4.00%)		2/27 (7.41%)		0/28 (0.00%)		1/30 (3.33%)
Diarrhoea † 1	0/25 (0.00%)		1/27 (3.70%)		0/28 (0.00%)		0/30 (0.00%)
Dyspepsia † 1	0/25 (0.00%)		0/27 (0.00%)		1/28 (3.57%)		1/30 (3.33%)
Nausea † 1	0/25 (0.00%)		2/27 (7.41%)		2/28 (7.14%)		3/30 (10.00%)
Stomach discomfort † 1	1/25 (4.00%)		0/27 (0.00%)		0/28 (0.00%)		0/30 (0.00%)
Vomiting † 1	0/25 (0.00%)		1/27 (3.70%)		1/28 (3.57%)		0/30 (0.00%)
General disorders
Injection site anaesthesia † 1	0/25 (0.00%)		0/27 (0.00%)		0/28 (0.00%)		1/30 (3.33%)
Oedema Peripheral † 1	1/25 (4.00%)		0/27 (0.00%)		0/28 (0.00%)		1/30 (3.33%)
Suprapubic pain † 1	0/25 (0.00%)		1/27 (3.70%)		0/28 (0.00%)		0/30 (0.00%)
Infections and infestations
Nasopharyngitis † 1	0/25 (0.00%)		1/27 (3.70%)		0/28 (0.00%)		0/30 (0.00%)
Sinusitis † 1	0/25 (0.00%)		0/27 (0.00%)		1/28 (3.57%)		0/30 (0.00%)
Injury, poisoning and procedural complications
Exposure to toxic agent † 1	0/25 (0.00%)		0/27 (0.00%)		1/28 (3.57%)		0/30 (0.00%)
Post procedural discomfort † 1	1/25 (4.00%)		3/27 (11.11%)		3/28 (10.71%)		3/30 (10.00%)
Procedural pain † 1	4/25 (16.00%)		5/27 (18.52%)		6/28 (21.43%)		4/30 (13.33%)
Musculoskeletal and connective tissue disorders
Back pain † 1	0/25 (0.00%)		2/27 (7.41%)		0/28 (0.00%)		0/30 (0.00%)
Myalgia † 1	0/25 (0.00%)		0/27 (0.00%)		1/28 (3.57%)		0/30 (0.00%)
Pain in extremity † 1	0/25 (0.00%)		1/27 (3.70%)		0/28 (0.00%)		0/30 (0.00%)
Nervous system disorders
Headache † 1	1/25 (4.00%)		2/27 (7.41%)		2/28 (7.14%)		2/30 (6.67%)
Pregnancy, puerperium and perinatal conditions
Antepartum Haemorrhage † 1	0/25 (0.00%)		0/27 (0.00%)		0/28 (0.00%)		1/30 (3.33%)
Psychiatric disorders
Insomnia † 1	0/25 (0.00%)		0/27 (0.00%)		0/28 (0.00%)		1/30 (3.33%)
Sleep disorder † 1	0/25 (0.00%)		0/27 (0.00%)		0/28 (0.00%)		1/30 (3.33%)
Reproductive system and breast disorders
Dysmenorrhoea † 1	1/25 (4.00%)		0/27 (0.00%)		0/28 (0.00%)		0/30 (0.00%)
Ovarian hyperstimulation † 1	2/25 (8.00%)		2/27 (7.41%)		2/28 (7.14%)		2/30 (6.67%)
Pelvic Discomfort † 1	0/25 (0.00%)		0/27 (0.00%)		0/28 (0.00%)		1/30 (3.33%)
Uterine Spasm † 1	0/25 (0.00%)		0/27 (0.00%)		0/28 (0.00%)		1/30 (3.33%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	0/25 (0.00%)		1/27 (3.70%)		0/28 (0.00%)		0/30 (0.00%)
Dyspnoea † 1	0/25 (0.00%)		1/27 (3.70%)		0/28 (0.00%)		0/30 (0.00%)
Skin and subcutaneous tissue disorders
Dermatitis † 1	0/25 (0.00%)		0/27 (0.00%)		1/28 (3.57%)		0/30 (0.00%)
Pruritus † 1	0/25 (0.00%)		1/27 (3.70%)		1/28 (3.57%)		0/30 (0.00%)
Rash † 1	0/25 (0.00%)		0/27 (0.00%)		1/28 (3.57%)		0/30 (0.00%)
Rash generalised † 1	0/25 (0.00%)		1/27 (3.70%)		0/28 (0.00%)		0/30 (0.00%)
Hot flush † 1	0/25 (0.00%)		1/27 (3.70%)		0/28 (0.00%)		0/30 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (Unspecified)

Limitations and Caveats

[Not Specified]

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Beltsos AN, Sanchez MD, Doody KJ, Bush MR, Domar AD, Collins MG. Patients' administration preferences: progesterone vaginal insert (Endometrin(R)) compared to intramuscular progesterone for Luteal phase support. Reprod Health. 2014 Nov 11;11:78. doi: 10.1186/1742-4755-11-78.

• Responsible Party: Ferring Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00805935
• Other Study ID Numbers: 2008-05
• First Submitted: December 9, 2008
• First Posted: December 10, 2008
• Results First Submitted: November 28, 2011
• Results First Posted: January 25, 2012
• Last Update Posted: January 27, 2012