Lutropin Alfa in Women at Risk of Poor Response

• Sponsor: Merck KGaA, Darmstadt, Germany (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01112358
• Collaborator: (none)
• Enrollment: 58
• Location: 1
• Arms: 2
• Actual Duration (Months): 13.8
• Patients Per Site Per Month: 4.2

Study Details

Study Description

Brief Summary

Evaluate the effectiveness of adding lutropin alfa (recombinant human luteinizing hormone [r-hLH]) in the middle of the follicular phase compared to no addition, in infertile women at risk of poor response stimulated with follitropin alfa (recombinant Follicle-Stimulating Hormone [r-FSH]) under Gonadotropin Releasing Hormone (GnRH) antagonist in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), in the number and quality of oocytes, follicular development, fertilization oocyte, embryo quality, and pregnancy rate.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Stimulation	Drug: r-FSH; Drug: r-hLH; Drug: Analogous GnRH antagonist; Drug: r-hCG; Drug: Progesterone	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Lutropin Alfa (Luveris®) in Women at Risk of Poor Response Suppressed With Cetrorelix: an Exploratory Trial
• Actual Study Start Date: Dec 7, 2005
• Actual Primary Completion Date: Jan 30, 2007
• Actual Study Completion Date: Jan 30, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: r-FSH + r-hLH Lutropin alfa (r-hLH) will be administered at a daily dose of 150 International Units (IU) from the presence of at least one follicle greater than (>) 14 millimeter (mm) to complete ovarian stimulation. Follitropin alfa (r-FSH) will be administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose will then be adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants will also receive analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 milligrams (mg) of recombinant Human Chorionic Gonadotropin (r-hCG) will be administered subcutaneously at 12 hours after the last injection of lutropin alfa and/or follitropin alfa and analogous GnRH antagonist.	Drug: r-FSH; r-FSH will be administered as specified in the arm description.; Other Names: Follitropin alfa; Gonal-F® ; Drug: r-hLH; r-hLH will be administered as specified in the arm description.; Other Names: Lutropin alfa; Luveris® ; Drug: Analogous GnRH antagonist; Analogous GnRH antagonist will be administered as specified in the arm description.; Other Names: Cetrotide® ; Drug: r-hCG; r-hCG will be administered as specified in the arm description.; Drug: Progesterone; Progesterone will be administered as specified in the arm description.
Active Comparator: r-FSH Follitropin alfa (r-FSH) will be administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose will then be adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants will also receive analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 mg of r-hCG will be administered subcutaneously at 12 hours after the last injection of follitropin alfa and analogous GnRH antagonist.	Drug: r-FSH; r-FSH will be administered as specified in the arm description.; Other Names: Follitropin alfa; Gonal-F® ; Drug: Analogous GnRH antagonist; Analogous GnRH antagonist will be administered as specified in the arm description.; Other Names: Cetrotide® ; Drug: r-hCG; r-hCG will be administered as specified in the arm description.; Drug: Progesterone; Progesterone will be administered as specified in the arm description.

Outcome Measures

Primary Outcome Measures

1. Number of Oocytes Retrieved [At the end of stimulation (Day 2 up to Day 8)]

2. Number of Follicles Greater Than (>) 14 Millimeter (mm) in Diameter [At the end of stimulation (Day 2 up to Day 8)]

3. Oocytes Recovery Rate [At the end of stimulation (Day 2 up to Day 8)]

   Oocytes recovery rate (oocytes per >14 mm follicle) is defined as number of oocytes retrieved divided by number of follicles >14 mm in diameter.

Secondary Outcome Measures

1. Oocyte Nuclear Maturity Rate [At the end of stimulation (Day 2 up to Day 8)]

   Oocyte nuclear maturity rate (metaphase II oocytes per retrieved oocyte) is defined as number of metaphase II oocytes divided by total number of oocytes retrieved.

2. Fertilization Rate [Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)]

   The fertilization rate (2 pronuclei [PN] fertilized oocytes per inseminated oocyte) was defined as number of 2 PN fertilized oocytes divided by number of inseminated oocytes.

3. Number of Embryos by Quality [Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)]

   Embryo quality was graded according to morphological classification of Veeck. Grade 1: even blastomeres with no fragmentation; Grade 2: even blastomeres with slight fragmentation (less than 20%); Grade 3: uneven size blastomeres with no fragmentation; Grade 4: even or uneven size blastomeres with moderate fragmentation (20-25%); and Grade 5: unrecognizable blastomeres with severe fragmentation (>50%).

4. Number of Embryos Transferred by In Vitro Fertilization (IVF) [Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)]

5. Number of Participants With Positive Pregnancy Test [Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)]

   The beta Human Chorionic Gonadotropin (beta-hCG) test was used as pregnancy test.

6. Number of Participants With Clinical Pregnancy [Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)]

   A clinical pregnancy is a pregnancy that is confirmed by both pregnancy test (beta-hCG test) and sonographic confirmation of a gestational sac or heartbeat (fetal sac).

7. Implementation Rate [Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)]

   Implementation rate (clinical pregnancy/embryo transferred) was defined as the number of clinical pregnancies divided by number of embryos transferred.

8. Plasma Level of Estradiol [At the time of r-hCG administration (any days between Day 2 to Day 8)]

9. Endometrial Thickness [At the time of r-hCG administration (any days between Day 2 to Day 8)]

10. Duration of Ovarian Stimulation [Randomization to Day 8]

    Duration of ovarian stimulation was defined as the time from start of study treatment to time of r-hCG administration.

11. rFSH Cumulative Dose [Randomization to Day 8]

12. Plasma Levels of LH [At the time of r-hCG administration (any days between Day 2 to Day 8)]

13. Number of Participants in Whom At Least 1 Stimulation Cycle Was Cancelled [Randomization to Day 8]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 38 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants who were at risk of poor response by at least one of the following criteria: a) <3 follicles in last cycle, or less than or equal to (</=) 2 metaphase II oocytes, or estradiol (E2) <600 pg/mL; b) Cancellation of previous cycle; c) Early follicular serum Follicle-Stimulating Hormone (FSH) >8.5 milli IU/L

• Participants with normal baseline luteinizing hormone and E2 levels

• Regular menstrual cycles of 25-35 days

• Presence of both ovaries and uterus able to withstand pregnancy

Exclusion Criteria:

• Participants who had any clinically significant disease including known human immunodeficiency virus (HIV), hepatitis-B virus (HBV)/hepatitis-C virus (HCV) positivity

• Participants with more than 3 previous assisted reproductive techniques (ART) cycles

• Participants with polycystic ovaries or cyst of unknown etiology; unexplained gynecological bleeding

• Participants who had any contraindication to being pregnant

• Active substance abuse

• Participants who had simultaneously participated in another clinical drug trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Universitario de La Fe	Valencia		Spain

Sponsors and Collaborators

• Merck KGaA, Darmstadt, Germany

Investigators

• Study Director: Medical Responsible, Merck KGaA, Darmstadt, Germany

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Results publication in spanish language

Publications

None provided.

• Responsible Party: Merck KGaA, Darmstadt, Germany
• ClinicalTrials.gov Identifier: NCT01112358
• Other Study ID Numbers: IMP26170 (INI25954); 2005-002229-30
• First Posted: Apr 28, 2010
• Last Update Posted: Aug 28, 2018
• Last Verified: Jul 1, 2018

• Keywords provided by Merck KGaA, Darmstadt, Germany: Lutropin alfa; Fertilization in vitro; Intracytoplasmic sperm injection; Reproductive techniques, assisted
• Additional relevant MeSH terms: Cetrorelix; Progesterone

Study Results

Participant Flow

Arm/Group Title	r-FSH + r-hLH	r-FSH
Arm/Group Description	Lutropin alfa (recombinant human luteinizing hormone [r-hLH]) was administered at a daily dose of 150 International Units (IU) from the presence of at least one follicle greater than (>) 14 millimeter (mm) to complete ovarian stimulation. Follitropin alfa (recombinant Follicle-Stimulating Hormone [r-FSH]) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous Gonadotropin Releasing Hormone (GnRH) antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 milligrams (mg) of recombinant Human Chorionic Gonadotropin (r-hCG) was administered subcutaneously at 12 hours after the last injection of lutropin alfa and/or follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).	Follitropin alfa (r-FSH) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 mg of r-hCG was administered subcutaneously at 12 hours after the last injection of follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).
Period Title: Overall Study
STARTED	25	33
COMPLETED	25	33
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	r-FSH + r-hLH	r-FSH	Total
Arm/Group Description	Lutropin alfa (recombinant human luteinizing hormone [r-hLH]) was administered at a daily dose of 150 International Units (IU) from the presence of at least one follicle greater than (>) 14 millimeter (mm) to complete ovarian stimulation. Follitropin alfa (recombinant Follicle-Stimulating Hormone [r-FSH]) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous Gonadotropin Releasing Hormone (GnRH) antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 milligrams (mg) of recombinant Human Chorionic Gonadotropin (r-hCG) was administered subcutaneously at 12 hours after the last injection of lutropin alfa and/or follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).	Follitropin alfa (r-FSH) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 mg of r-hCG was administered subcutaneously at 12 hours after the last injection of follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).	Total of all reporting groups
Overall Participants	25	33	58
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	34.9 (2.2)	34.4 (2.0)	34.65 (2.1)
Sex: Female, Male (Count of Participants)
Female	25 100%	33 100%	58 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Oocytes Retrieved
Time Frame	At the end of stimulation (Day 2 up to Day 8)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	r-FSH + r-hLH	r-FSH
Arm/Group Description	Lutropin alfa (recombinant human luteinizing hormone [r-hLH]) was administered at a daily dose of 150 International Units (IU) from the presence of at least one follicle greater than (>) 14 millimeter (mm) to complete ovarian stimulation. Follitropin alfa (recombinant Follicle-Stimulating Hormone [r-FSH]) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous Gonadotropin Releasing Hormone (GnRH) antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 milligrams (mg) of recombinant Human Chorionic Gonadotropin (r-hCG) was administered subcutaneously at 12 hours after the last injection of lutropin alfa and/or follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).	Follitropin alfa (r-FSH) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 mg of r-hCG was administered subcutaneously at 12 hours after the last injection of follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).
Measure Participants	25	33
Mean (Standard Deviation) [Oocytes]	4.0 (5.3)	3.5 (3.1)

2. Primary Outcome

Title	Number of Follicles Greater Than (>) 14 Millimeter (mm) in Diameter
Time Frame	At the end of stimulation (Day 2 up to Day 8)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	r-FSH + r-hLH	r-FSH
Arm/Group Description	Lutropin alfa (recombinant human luteinizing hormone [r-hLH]) was administered at a daily dose of 150 International Units (IU) from the presence of at least one follicle greater than (>) 14 millimeter (mm) to complete ovarian stimulation. Follitropin alfa (recombinant Follicle-Stimulating Hormone [r-FSH]) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous Gonadotropin Releasing Hormone (GnRH) antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 milligrams (mg) of recombinant Human Chorionic Gonadotropin (r-hCG) was administered subcutaneously at 12 hours after the last injection of lutropin alfa and/or follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).	Follitropin alfa (r-FSH) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 mg of r-hCG was administered subcutaneously at 12 hours after the last injection of follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).
Measure Participants	25	33
Mean (Standard Deviation) [Follicles]	7.2 (1.1)	7.0 (0.8)

3. Primary Outcome

Title	Oocytes Recovery Rate
Description	Oocytes recovery rate (oocytes per >14 mm follicle) is defined as number of oocytes retrieved divided by number of follicles >14 mm in diameter.
Time Frame	At the end of stimulation (Day 2 up to Day 8)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	r-FSH + r-hLH	r-FSH
Arm/Group Description	Lutropin alfa (recombinant human luteinizing hormone [r-hLH]) was administered at a daily dose of 150 International Units (IU) from the presence of at least one follicle greater than (>) 14 millimeter (mm) to complete ovarian stimulation. Follitropin alfa (recombinant Follicle-Stimulating Hormone [r-FSH]) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous Gonadotropin Releasing Hormone (GnRH) antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 milligrams (mg) of recombinant Human Chorionic Gonadotropin (r-hCG) was administered subcutaneously at 12 hours after the last injection of lutropin alfa and/or follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).	Follitropin alfa (r-FSH) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 mg of r-hCG was administered subcutaneously at 12 hours after the last injection of follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).
Measure Participants	25	33
Mean (Standard Deviation) [oocytes per >14 mm follicle]	0.56 (0.42)	0.50 (0.41)

4. Secondary Outcome

Title	Oocyte Nuclear Maturity Rate
Description	Oocyte nuclear maturity rate (metaphase II oocytes per retrieved oocyte) is defined as number of metaphase II oocytes divided by total number of oocytes retrieved.
Time Frame	At the end of stimulation (Day 2 up to Day 8)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	r-FSH + r-hLH	r-FSH
Arm/Group Description	Lutropin alfa (recombinant human luteinizing hormone [r-hLH]) was administered at a daily dose of 150 International Units (IU) from the presence of at least one follicle greater than (>) 14 millimeter (mm) to complete ovarian stimulation. Follitropin alfa (recombinant Follicle-Stimulating Hormone [r-FSH]) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous Gonadotropin Releasing Hormone (GnRH) antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 milligrams (mg) of recombinant Human Chorionic Gonadotropin (r-hCG) was administered subcutaneously at 12 hours after the last injection of lutropin alfa and/or follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).	Follitropin alfa (r-FSH) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 mg of r-hCG was administered subcutaneously at 12 hours after the last injection of follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).
Measure Participants	25	33
Mean (Standard Deviation) [metaphase II oocytes/retrieved oocyte]	0.73 (0.75)	0.61 (0.26)

5. Secondary Outcome

Title	Fertilization Rate
Description	The fertilization rate (2 pronuclei [PN] fertilized oocytes per inseminated oocyte) was defined as number of 2 PN fertilized oocytes divided by number of inseminated oocytes.
Time Frame	Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	r-FSH + r-hLH	r-FSH
Arm/Group Description	Lutropin alfa (recombinant human luteinizing hormone [r-hLH]) was administered at a daily dose of 150 International Units (IU) from the presence of at least one follicle greater than (>) 14 millimeter (mm) to complete ovarian stimulation. Follitropin alfa (recombinant Follicle-Stimulating Hormone [r-FSH]) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous Gonadotropin Releasing Hormone (GnRH) antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 milligrams (mg) of recombinant Human Chorionic Gonadotropin (r-hCG) was administered subcutaneously at 12 hours after the last injection of lutropin alfa and/or follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).	Follitropin alfa (r-FSH) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 mg of r-hCG was administered subcutaneously at 12 hours after the last injection of follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).
Measure Participants	25	33
Mean (Standard Deviation) [2PN fertilized oocyte/inseminated oocyte]	0.70 (0.35)	0.64 (0.33)

6. Secondary Outcome

Title	Number of Embryos by Quality
Description	Embryo quality was graded according to morphological classification of Veeck. Grade 1: even blastomeres with no fragmentation; Grade 2: even blastomeres with slight fragmentation (less than 20%); Grade 3: uneven size blastomeres with no fragmentation; Grade 4: even or uneven size blastomeres with moderate fragmentation (20-25%); and Grade 5: unrecognizable blastomeres with severe fragmentation (>50%).
Time Frame	Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	r-FSH + r-hLH	r-FSH
Arm/Group Description	Lutropin alfa (recombinant human luteinizing hormone [r-hLH]) was administered at a daily dose of 150 International Units (IU) from the presence of at least one follicle greater than (>) 14 millimeter (mm) to complete ovarian stimulation. Follitropin alfa (recombinant Follicle-Stimulating Hormone [r-FSH]) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous Gonadotropin Releasing Hormone (GnRH) antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 milligrams (mg) of recombinant Human Chorionic Gonadotropin (r-hCG) was administered subcutaneously at 12 hours after the last injection of lutropin alfa and/or follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).	Follitropin alfa (r-FSH) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 mg of r-hCG was administered subcutaneously at 12 hours after the last injection of follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).
Measure Participants	25	33
Grade 1	0.6 (0.7)	0.8 (1.0)
Grade 2	1.4 (1.8)	0.7 (0.76)
Grade 3	1.8 (2.0)	0.6 (0.8)
Grade 4	0.1 (0.2)	0.2 (0.3)
Grade 5	0.1 (0.2)	0.0 (0.2)

7. Secondary Outcome

Title	Number of Embryos Transferred by In Vitro Fertilization (IVF)
Time Frame	Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	r-FSH + r-hLH	r-FSH
Arm/Group Description	Lutropin alfa (recombinant human luteinizing hormone [r-hLH]) was administered at a daily dose of 150 International Units (IU) from the presence of at least one follicle greater than (>) 14 millimeter (mm) to complete ovarian stimulation. Follitropin alfa (recombinant Follicle-Stimulating Hormone [r-FSH]) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous Gonadotropin Releasing Hormone (GnRH) antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 milligrams (mg) of recombinant Human Chorionic Gonadotropin (r-hCG) was administered subcutaneously at 12 hours after the last injection of lutropin alfa and/or follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).	Follitropin alfa (r-FSH) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 mg of r-hCG was administered subcutaneously at 12 hours after the last injection of follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).
Measure Participants	25	33
Mean (Standard Deviation) [Embroys]	2.0 (1.0)	1.6 (0.8)

8. Secondary Outcome

Title	Number of Participants With Positive Pregnancy Test
Description	The beta Human Chorionic Gonadotropin (beta-hCG) test was used as pregnancy test.
Time Frame	Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	r-FSH + r-hLH	r-FSH
Arm/Group Description	Lutropin alfa (recombinant human luteinizing hormone [r-hLH]) was administered at a daily dose of 150 International Units (IU) from the presence of at least one follicle greater than (>) 14 millimeter (mm) to complete ovarian stimulation. Follitropin alfa (recombinant Follicle-Stimulating Hormone [r-FSH]) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous Gonadotropin Releasing Hormone (GnRH) antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 milligrams (mg) of recombinant Human Chorionic Gonadotropin (r-hCG) was administered subcutaneously at 12 hours after the last injection of lutropin alfa and/or follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).	Follitropin alfa (r-FSH) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 mg of r-hCG was administered subcutaneously at 12 hours after the last injection of follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).
Measure Participants	25	33
Number [Participants]	3 12%	5 15.2%

9. Secondary Outcome

Title	Number of Participants With Clinical Pregnancy
Description	A clinical pregnancy is a pregnancy that is confirmed by both pregnancy test (beta-hCG test) and sonographic confirmation of a gestational sac or heartbeat (fetal sac).
Time Frame	Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	r-FSH + r-hLH	r-FSH
Arm/Group Description	Lutropin alfa (recombinant human luteinizing hormone [r-hLH]) was administered at a daily dose of 150 International Units (IU) from the presence of at least one follicle greater than (>) 14 millimeter (mm) to complete ovarian stimulation. Follitropin alfa (recombinant Follicle-Stimulating Hormone [r-FSH]) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous Gonadotropin Releasing Hormone (GnRH) antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 milligrams (mg) of recombinant Human Chorionic Gonadotropin (r-hCG) was administered subcutaneously at 12 hours after the last injection of lutropin alfa and/or follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).	Follitropin alfa (r-FSH) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 mg of r-hCG was administered subcutaneously at 12 hours after the last injection of follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).
Measure Participants	25	33
Number [Participants]	3 12%	5 15.2%

10. Secondary Outcome

Title	Implementation Rate
Description	Implementation rate (clinical pregnancy/embryo transferred) was defined as the number of clinical pregnancies divided by number of embryos transferred.
Time Frame	Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	r-FSH + r-hLH	r-FSH
Arm/Group Description	Lutropin alfa (recombinant human luteinizing hormone [r-hLH]) was administered at a daily dose of 150 International Units (IU) from the presence of at least one follicle greater than (>) 14 millimeter (mm) to complete ovarian stimulation. Follitropin alfa (recombinant Follicle-Stimulating Hormone [r-FSH]) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous Gonadotropin Releasing Hormone (GnRH) antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 milligrams (mg) of recombinant Human Chorionic Gonadotropin (r-hCG) was administered subcutaneously at 12 hours after the last injection of lutropin alfa and/or follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).	Follitropin alfa (r-FSH) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 mg of r-hCG was administered subcutaneously at 12 hours after the last injection of follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).
Measure Participants	25	33
Number (95% Confidence Interval) [Clinical pregnancy/embryo transferred]	0.15	0.14

11. Secondary Outcome

Title	Plasma Level of Estradiol
Time Frame	At the time of r-hCG administration (any days between Day 2 to Day 8)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	r-FSH + r-hLH	r-FSH
Arm/Group Description	Lutropin alfa (recombinant human luteinizing hormone [r-hLH]) was administered at a daily dose of 150 International Units (IU) from the presence of at least one follicle greater than (>) 14 millimeter (mm) to complete ovarian stimulation. Follitropin alfa (recombinant Follicle-Stimulating Hormone [r-FSH]) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous Gonadotropin Releasing Hormone (GnRH) antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 milligrams (mg) of recombinant Human Chorionic Gonadotropin (r-hCG) was administered subcutaneously at 12 hours after the last injection of lutropin alfa and/or follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).	Follitropin alfa (r-FSH) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 mg of r-hCG was administered subcutaneously at 12 hours after the last injection of follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).
Measure Participants	25	33
Mean (Standard Deviation) [Picograms per milliliters (pg/mL)]	1218 (699)	1029 (336)

12. Secondary Outcome

Title	Endometrial Thickness
Time Frame	At the time of r-hCG administration (any days between Day 2 to Day 8)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	r-FSH + r-hLH	r-FSH
Arm/Group Description	Lutropin alfa (recombinant human luteinizing hormone [r-hLH]) was administered at a daily dose of 150 International Units (IU) from the presence of at least one follicle greater than (>) 14 millimeter (mm) to complete ovarian stimulation. Follitropin alfa (recombinant Follicle-Stimulating Hormone [r-FSH]) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous Gonadotropin Releasing Hormone (GnRH) antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 milligrams (mg) of recombinant Human Chorionic Gonadotropin (r-hCG) was administered subcutaneously at 12 hours after the last injection of lutropin alfa and/or follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).	Follitropin alfa (r-FSH) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 mg of r-hCG was administered subcutaneously at 12 hours after the last injection of follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).
Measure Participants	25	33
Mean (Standard Deviation) [millimeters (mm)]	12.3 (1.8)	11.2 (2.1)

13. Secondary Outcome

Title	Duration of Ovarian Stimulation
Description	Duration of ovarian stimulation was defined as the time from start of study treatment to time of r-hCG administration.
Time Frame	Randomization to Day 8

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	r-FSH + r-hLH	r-FSH
Arm/Group Description	Lutropin alfa (recombinant human luteinizing hormone [r-hLH]) was administered at a daily dose of 150 International Units (IU) from the presence of at least one follicle greater than (>) 14 millimeter (mm) to complete ovarian stimulation. Follitropin alfa (recombinant Follicle-Stimulating Hormone [r-FSH]) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous Gonadotropin Releasing Hormone (GnRH) antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 milligrams (mg) of recombinant Human Chorionic Gonadotropin (r-hCG) was administered subcutaneously at 12 hours after the last injection of lutropin alfa and/or follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).	Follitropin alfa (r-FSH) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 mg of r-hCG was administered subcutaneously at 12 hours after the last injection of follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).
Measure Participants	25	33
Mean (Standard Deviation) [days]	4.8 (1.7)	4.8 (1.7)

14. Secondary Outcome

Title	rFSH Cumulative Dose
Time Frame	Randomization to Day 8

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	r-FSH + r-hLH	r-FSH
Arm/Group Description	Lutropin alfa (recombinant human luteinizing hormone [r-hLH]) was administered at a daily dose of 150 International Units (IU) from the presence of at least one follicle greater than (>) 14 millimeter (mm) to complete ovarian stimulation. Follitropin alfa (recombinant Follicle-Stimulating Hormone [r-FSH]) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous Gonadotropin Releasing Hormone (GnRH) antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 milligrams (mg) of recombinant Human Chorionic Gonadotropin (r-hCG) was administered subcutaneously at 12 hours after the last injection of lutropin alfa and/or follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).	Follitropin alfa (r-FSH) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 mg of r-hCG was administered subcutaneously at 12 hours after the last injection of follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).
Measure Participants	25	33
Mean (Standard Deviation) [IU]	4338 (1241)	4298 (1137)

15. Secondary Outcome

Title	Plasma Levels of LH
Time Frame	At the time of r-hCG administration (any days between Day 2 to Day 8)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	r-FSH + r-hLH	r-FSH
Arm/Group Description	Lutropin alfa (recombinant human luteinizing hormone [r-hLH]) was administered at a daily dose of 150 International Units (IU) from the presence of at least one follicle greater than (>) 14 millimeter (mm) to complete ovarian stimulation. Follitropin alfa (recombinant Follicle-Stimulating Hormone [r-FSH]) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous Gonadotropin Releasing Hormone (GnRH) antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 milligrams (mg) of recombinant Human Chorionic Gonadotropin (r-hCG) was administered subcutaneously at 12 hours after the last injection of lutropin alfa and/or follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).	Follitropin alfa (r-FSH) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 mg of r-hCG was administered subcutaneously at 12 hours after the last injection of follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).
Measure Participants	25	33
Mean (Standard Deviation) [IU per liter (IU/L)]	2.8 (1.0)	2.1 (2.1)

16. Secondary Outcome

Title	Number of Participants in Whom At Least 1 Stimulation Cycle Was Cancelled
Time Frame	Randomization to Day 8

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	r-FSH + r-hLH	r-FSH
Arm/Group Description	Lutropin alfa (recombinant human luteinizing hormone [r-hLH]) was administered at a daily dose of 150 International Units (IU) from the presence of at least one follicle greater than (>) 14 millimeter (mm) to complete ovarian stimulation. Follitropin alfa (recombinant Follicle-Stimulating Hormone [r-FSH]) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous Gonadotropin Releasing Hormone (GnRH) antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 milligrams (mg) of recombinant Human Chorionic Gonadotropin (r-hCG) was administered subcutaneously at 12 hours after the last injection of lutropin alfa and/or follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).	Follitropin alfa (r-FSH) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 mg of r-hCG was administered subcutaneously at 12 hours after the last injection of follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).
Measure Participants	25	33
Number [Participants]	8 32%	8 24.2%

Adverse Events

Arm/Group Title	r-FSH + r-hLH		r-FSH
Arm/Group Description	Lutropin alfa (recombinant human luteinizing hormone [r-hLH]) was administered at a daily dose of 150 International Units (IU) from the presence of at least one follicle greater than (>) 14 millimeter (mm) to complete ovarian stimulation. Follitropin alfa (recombinant Follicle-Stimulating Hormone [r-FSH]) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous Gonadotropin Releasing Hormone (GnRH) antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 milligrams (mg) of recombinant Human Chorionic Gonadotropin (r-hCG) was administered subcutaneously at 12 hours after the last injection of lutropin alfa and/or follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).		Follitropin alfa (r-FSH) was administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose was then adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants also received analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 mg of r-hCG was administered subcutaneously at 12 hours after the last injection of follitropin alfa and analogous GnRH antagonist (on Days 2 to 8).
All Cause Mortality
	r-FSH + r-hLH		r-FSH
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	r-FSH + r-hLH		r-FSH
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/33 (0%)
Other (Not Including Serious) Adverse Events
	r-FSH + r-hLH		r-FSH
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/33 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.