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

• Sponsor: Ferring Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00805935
• Collaborator: (none)
• Enrollment: 110
• Locations: 6
• Arms: 4
• Duration (Months): 20
• Patients Per Site: 18.3
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This multicenter, randomized, open-label exploratory study will be performed in approximately 200 polycystic ovary syndrome (PCOS) but otherwise healthy females undergoing in vitro fertilization (IVF). Each study center will follow its standard practice for in vitro fertilization (IVF) within the study parameters as noted in this protocol. The study centers will use marketed products purchased from Schraft's Pharmacy for all phases of the study (down-regulation, stimulation, ovulation induction, and luteal support). Subjects will be randomly assigned to highly purified menotropin (Menopur®) or follitropin beta (Follistim Pen®) for stimulation and progesterone vaginal insert (Endometrin®) or progesterone in oil for luteal support. Subjects will return to the study center for regular scheduled clinic visits as required per in vitro fertilization (IVF) protocol at the site and at specified times during the cycle (Stimulation Day 6, Day of human chorionic gonadotropin (hCG), and first serum pregnancy test) for estradiol (E2), progesterone (P4) and human chorionic gonadotropin (hCG) labs. All subjects will be required to complete a final study visit at completion of luteal support or negative serum pregnancy test following embryo transfer.

Condition or Disease	Intervention/Treatment	Phase
Polycystic Ovarian Syndrome; Infertility	Drug: Menotropin; Drug: Progesterone vaginal insert; Drug: Follitropin beta; Drug: Progesterone in oil; Drug: leuprolide acetate	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 110 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-Center, Randomized, Open-Label Evaluation of MENOPUR® Versus FOLLISTIM® in Polycystic Ovarian Syndrome (PCOS) Patients
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Menotropin/Progesterone vaginal insert 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.	Drug: Menotropin; 225 IU (up to 450 IU) by subcutaneous injection once per day for up to about 15 days.; Other Names: Menopur® ; Drug: Progesterone vaginal insert; 100 mg inserted vaginally 2 or 3 times daily (BID or TID) (start on the day after oocyte retrieval) until 10 weeks gestation or confirmation of negative pregnancy test.; Other Names: Endometrin® ; Drug: leuprolide acetate; Daily administration of 0.5mg of leuprolide acetate (depot formulations were not permitted) began on Day 21 following onset of menses, and then decreased to 0.25 mg when gonadotropin therapy was initiated.; Other Names: Lupron
Experimental: Menotropin/Progesterone in oil 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.	Drug: Menotropin; 225 IU (up to 450 IU) by subcutaneous injection once per day for up to about 15 days.; Other Names: Menopur® ; Drug: Progesterone in oil; 50 mg by intramuscular injection once per day, starting on the day after oocyte retrieval until 10 weeks gestation or confirmation of negative pregnancy test.; Drug: leuprolide acetate; Daily administration of 0.5mg of leuprolide acetate (depot formulations were not permitted) began on Day 21 following onset of menses, and then decreased to 0.25 mg when gonadotropin therapy was initiated.; Other Names: Lupron
Active Comparator: Follitropin beta/Progesterone vaginal insert Follitropin beta (Follistim Pen®) 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.	Drug: Progesterone vaginal insert; 100 mg inserted vaginally 2 or 3 times daily (BID or TID) (start on the day after oocyte retrieval) until 10 weeks gestation or confirmation of negative pregnancy test.; Other Names: Endometrin® ; Drug: Follitropin beta; 225 IU (up to 450 IU) by subcutaneous injection once per day for up to about 15 days.; Other Names: Follistim Pen® ; Drug: leuprolide acetate; Daily administration of 0.5mg of leuprolide acetate (depot formulations were not permitted) began on Day 21 following onset of menses, and then decreased to 0.25 mg when gonadotropin therapy was initiated.; Other Names: Lupron
Active Comparator: Follitropin beta/Progesterone in oil Follitropin beta (Follistim Pen®) 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.	Drug: Follitropin beta; 225 IU (up to 450 IU) by subcutaneous injection once per day for up to about 15 days.; Other Names: Follistim Pen® ; Drug: Progesterone in oil; 50 mg by intramuscular injection once per day, starting on the day after oocyte retrieval until 10 weeks gestation or confirmation of negative pregnancy test.; Drug: leuprolide acetate; Daily administration of 0.5mg of leuprolide acetate (depot formulations were not permitted) began on Day 21 following onset of menses, and then decreased to 0.25 mg when gonadotropin therapy was initiated.; Other Names: Lupron

Outcome Measures

Primary Outcome Measures

1. Participants With Cycle Cancellation Due to Risk of Ovarian Hyperstimulation Syndrome (OHSS) Between Weeks 1 - 3 [weeks 1-3]

   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).

Secondary Outcome Measures

1. Number of Follicles Observed at Day 15 [approximately day 15]

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

2. Number of Oocytes Retrieved at Day 18 [approximately day 18]

   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.

3. Percentage of Oocytes Fertilized of the Total Number of Oocytes Retrieved [approximately day 19]

   The fertilization rate for each participant was the percentage of the number of oocytes inseminated of the total number of oocytes retrieved.

4. Number of Embryos Transferred at Three Stages of Development Before Implantation [approximately day 24]

   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.

5. Number of Embryos Frozen [approximately day 24]

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

6. Percentage of Participants With Biochemical Pregnancy at Approximately Day 38 [approximately day 38 (Day 14 post embryo transfer)]

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

7. Percentage of Participants With Clinical Pregnancy at Week 7 [approximately Day 52]

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

8. Percentage of Participants With Ongoing Pregnancy at Week 9 [approximately Day 65]

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

9. Estradiol Levels at Day 6 [Day 6]

   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.

10. Human Chorionic Gonadotropin (hCG) Levels at Day 6 [Day 6]

    Blood tests were sent to a central laboratory to obtain hCG levels.

11. Progesterone Levels at Human Chorionic Gonadotropin (hCG) Administration [approximately day 16]

    Blood tests were sent to a central laboratory to obtain progesterone levels.

12. Number of Live Births Resulting From the In Vitro Fertilization Process [Approximately 10 months]

    Number of live births resulting from the IVF process

13. Participants With Treatment Emergent Adverse Events [Week 1 to week12]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 42 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Pre-menopausal females between the ages of 18 and 42 years

2. Diagnosed with polycystic ovary syndrome (PCOS), using criteria adopted as the 2003 Rotterdam PCOS Consensus (2 out of 3, excluding other etiologies [congenital adrenal hyperplasia, androgen-secreting tumors, Cushing's syndrome])

• Oligo- or anovulation

• Clinical and/or biochemical signs of hyperandrogenism

• Polycystic ovaries

1. Body mass index (BMI) of 18-39

2. Early follicular phase (Day 3) follicle stimulating hormone (FSH) < 15 IU/L and estradiol (E2) within normal limits

3. Documented history of infertility (e.g., unable to conceive for at least one year, or for 6 months for women > 38 years of age, or bilateral tubal occlusion or absence, or male factor but excluding severe male factor requiring invasive or surgical sperm retrieval. Donor sperm may be used.)

4. Transvaginal ultrasound at screening consistent with findings adequate for assisted reproductive technology (ART) with respect to uterus and adnexa

5. Signed informed consent

Exclusion Criteria:

1. Gestational or surrogate carrier, donor oocyte

2. Presence of any clinically relevant systemic disease (e.g., uncontrolled thyroid or adrenal dysfunction, an organic intracranial lesion such as a pituitary tumor, insulin-dependent diabetes mellitus, uterine cancer)

3. Surgical or medical condition which, in the judgment of the Investigator or Sponsor, may interfere with absorption, distribution, metabolism, or excretion of the drugs to be used

4. Two or more previous failed in vitro fertilization (IVF) cycles or in vitro fertilization (IVF)/assisted reproductive technology (ART) failure due to a poor response to gonadotropins, defined as development of 2 mature follicles

5. History of recurrent pregnancy loss, defined as more than two clinical losses

6. Presence of abnormal uterine bleeding of undetermined origin

7. Current or recent substance abuse, including alcohol or smoking > 10 cigarettes per day

8. Refusal or inability to comply with the requirements of the Protocol for any reason, including scheduled clinic visits and laboratory tests

9. Participation in any experimental drug study within 30 days prior to Screening

10. Severe male factor requiring invasive or surgical sperm retrieval (e.g., microsurgical epididymal sperm aspiration [MESA], testicular sperm extraction [TESE])

11. Prior hypersensitivity to any of the protocol drugs

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Conceptions Reproductive Associates of Colorado	Littleton	Colorado	United States	80129
2	Women's Medical Research Group LLC, Florida	Clearwater	Florida	United States	33759
3	Fertility Center of Illinois	Chicago	Illinois	United States	60610
4	Weill Cornell Medical College	New York	New York	United States	10021
5	Women & Infants' Hospital of RI	Providence	Rhode Island	United States	02905
6	Center for Assisted Reproduction	Bedford	Texas	United States	76022

Sponsors and Collaborators

• Ferring Pharmaceuticals

Investigators

• Study Director: Clinical Development Support, Ferring Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ferring Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00805935
• Other Study ID Numbers: 2008-05
• First Posted: Dec 10, 2008
• Last Update Posted: Jan 27, 2012
• Last Verified: Jan 1, 2012

• Keywords provided by Ferring Pharmaceuticals: pre-menopausal women; PCOS; polycystic ovarian syndrome; infertility; IVF; in vitro fertilization
• Additional relevant MeSH terms: Polycystic Ovary Syndrome; Infertility; Syndrome; Leuprolide; Menotropins; Progesterone; Follicle Stimulating Hormone

Study Results

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 Detail	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

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 Participants	25	27	28	30	110
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	25 100%	27 100%	28 100%	30 100%	110 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	25 100%	27 100%	28 100%	30 100%	110 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Number) [Number]
Caucasian	18 72%	18 66.7%	20 71.4%	25 83.3%	81 73.6%
African American	0 0%	1 3.7%	0 0%	0 0%	1 0.9%
Asian	5 20%	1 3.7%	4 14.3%	1 3.3%	11 10%
Hispanic	2 8%	7 25.9%	4 14.3%	3 10%	16 14.5%
Other	0 0%	0 0%	0 0%	1 3.3%	1 0.9%

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.
Measure Participants	25	27	28	30
Yes	1 4%	0 0%	1 3.6%	0 0%
No	24 96%	27 100%	27 96.4%	30 100%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Menotropin/Progesterone Vaginal Insert, Follitropin Beta/Progesterone Vaginal Insert
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Menotropin/Progesterone in Oil, Follitropin Beta/Progesterone in Oil
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Fisher Exact
	Comments

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
Statistical Test of Hypothesis	p-Value	0.481
	Comments
	Method	Fisher Exact
	Comments

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
Statistical Test of Hypothesis	p-Value	0.483
	Comments
	Method	Fisher Exact
	Comments

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.
Measure Participants	52	58
Mean (Standard Deviation) [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.
Measure Participants	52	58
Mean (Standard Deviation) [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.
Measure Participants	52	58
Number [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.
Measure Participants	52	58
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.
Measure Participants	52	58
Mean (Standard Deviation) [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.
Measure Participants	25	27	28	30
Number [Percentage of participants]	60.0 240%	55.6 205.9%	60.7 216.8%	73.3 244.3%

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.
Measure Participants	25	27	28	30
Number [Percentage of participants]	56.0 224%	33.3 123.3%	46.4 165.7%	66.7 222.3%

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.
Measure Participants	25	27	28	30
Number [Percentage of participants]	48.0 192%	33.3 123.3%	46.4 165.7%	63.3 211%

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.
Measure Participants	25	27	28	30
Mean (Standard Deviation) [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.
Measure Participants	25	27	28	30
Mean (Standard Deviation) [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.
Measure Participants	23	21	23	28
Mean (Standard Deviation) [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.
Measure Participants	0	0	0	0

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.
Measure Participants	25	27	28	30
With at least one adverse event	9 36%	12 44.4%	15 53.6%	14 46.7%
With at least one mild or moderate adverse event	9 36%	11 40.7%	15 53.6%	14 46.7%
With at least one severe adverse event	0 0%	2 7.4%	1 3.6%	0 0%
With at least one serious adverse event	0 0%	1 3.7%	0 0%	0 0%
With at least one unrelated or unlikely AE	8 32%	11 40.7%	12 42.9%	13 43.3%
With at least one possibly or probably related AE	3 12%	7 25.9%	8 28.6%	6 20%

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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
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%)		1/27 (3.7%)		0/28 (0%)		0/30 (0%)
Congenital, familial and genetic disorders
Conjoined Twins	0/25 (0%)	0	1/27 (3.7%)	1	0/28 (0%)	0	0/30 (0%)	0
Other (Not Including 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	9/25 (36%)		11/27 (40.7%)		15/28 (53.6%)		14/30 (46.7%)
Blood and lymphatic system disorders
Lymphadenopathy	1/25 (4%)		0/27 (0%)		0/28 (0%)		0/30 (0%)
Gastrointestinal disorders
Abdominal discomfort	1/25 (4%)		0/27 (0%)		0/28 (0%)		0/30 (0%)
Abdominal Distension	1/25 (4%)		1/27 (3.7%)		3/28 (10.7%)		2/30 (6.7%)
Abdominal pain	0/25 (0%)		0/27 (0%)		1/28 (3.6%)		0/30 (0%)
Abdominal pain lower	1/25 (4%)		2/27 (7.4%)		0/28 (0%)		1/30 (3.3%)
Diarrhoea	0/25 (0%)		1/27 (3.7%)		0/28 (0%)		0/30 (0%)
Dyspepsia	0/25 (0%)		0/27 (0%)		1/28 (3.6%)		1/30 (3.3%)
Nausea	0/25 (0%)		2/27 (7.4%)		2/28 (7.1%)		3/30 (10%)
Stomach discomfort	1/25 (4%)		0/27 (0%)		0/28 (0%)		0/30 (0%)
Vomiting	0/25 (0%)		1/27 (3.7%)		1/28 (3.6%)		0/30 (0%)
General disorders
Injection site anaesthesia	0/25 (0%)		0/27 (0%)		0/28 (0%)		1/30 (3.3%)
Oedema Peripheral	1/25 (4%)		0/27 (0%)		0/28 (0%)		1/30 (3.3%)
Suprapubic pain	0/25 (0%)		1/27 (3.7%)		0/28 (0%)		0/30 (0%)
Infections and infestations
Nasopharyngitis	0/25 (0%)		1/27 (3.7%)		0/28 (0%)		0/30 (0%)
Sinusitis	0/25 (0%)		0/27 (0%)		1/28 (3.6%)		0/30 (0%)
Injury, poisoning and procedural complications
Exposure to toxic agent	0/25 (0%)		0/27 (0%)		1/28 (3.6%)		0/30 (0%)
Post procedural discomfort	1/25 (4%)		3/27 (11.1%)		3/28 (10.7%)		3/30 (10%)
Procedural pain	4/25 (16%)		5/27 (18.5%)		6/28 (21.4%)		4/30 (13.3%)
Musculoskeletal and connective tissue disorders
Back pain	0/25 (0%)		2/27 (7.4%)		0/28 (0%)		0/30 (0%)
Myalgia	0/25 (0%)		0/27 (0%)		1/28 (3.6%)		0/30 (0%)
Pain in extremity	0/25 (0%)		1/27 (3.7%)		0/28 (0%)		0/30 (0%)
Nervous system disorders
Headache	1/25 (4%)		2/27 (7.4%)		2/28 (7.1%)		2/30 (6.7%)
Pregnancy, puerperium and perinatal conditions
Antepartum Haemorrhage	0/25 (0%)		0/27 (0%)		0/28 (0%)		1/30 (3.3%)
Psychiatric disorders
Insomnia	0/25 (0%)		0/27 (0%)		0/28 (0%)		1/30 (3.3%)
Sleep disorder	0/25 (0%)		0/27 (0%)		0/28 (0%)		1/30 (3.3%)
Reproductive system and breast disorders
Dysmenorrhoea	1/25 (4%)		0/27 (0%)		0/28 (0%)		0/30 (0%)
Ovarian hyperstimulation	2/25 (8%)		2/27 (7.4%)		2/28 (7.1%)		2/30 (6.7%)
Pelvic Discomfort	0/25 (0%)		0/27 (0%)		0/28 (0%)		1/30 (3.3%)
Uterine Spasm	0/25 (0%)		0/27 (0%)		0/28 (0%)		1/30 (3.3%)
Respiratory, thoracic and mediastinal disorders
Cough	0/25 (0%)		1/27 (3.7%)		0/28 (0%)		0/30 (0%)
Dyspnoea	0/25 (0%)		1/27 (3.7%)		0/28 (0%)		0/30 (0%)
Skin and subcutaneous tissue disorders
Dermatitis	0/25 (0%)		0/27 (0%)		1/28 (3.6%)		0/30 (0%)
Pruritus	0/25 (0%)		1/27 (3.7%)		1/28 (3.6%)		0/30 (0%)
Rash	0/25 (0%)		0/27 (0%)		1/28 (3.6%)		0/30 (0%)
Rash generalised	0/25 (0%)		1/27 (3.7%)		0/28 (0%)		0/30 (0%)
Hot flush	0/25 (0%)		1/27 (3.7%)		0/28 (0%)		0/30 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.