Trial to Assess the Clinical Efficacy and Safety of MSJ-0011 in Inducing Ovulation in Anovulatory or Oligo-ovulatory Japanese Women

• Sponsor: Merck KGaA, Darmstadt, Germany (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01653743
• Collaborator: Merck Serono Co., Ltd., Japan (Industry)
• Enrollment: 81
• Locations: 6
• Arms: 2
• Duration (Months): 27
• Patients Per Site: 13.5
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This is an open-label, parallel-group, randomized, multicenter Phase III trial to compare the efficacy and safety of a single 250 microgram (mcg) subcutaneous dose of MSJ-0011 to a single 5,000 international units (IU) intramuscular dose of urinary human chorionic gonadotropin (hCG) in inducing ovulation in Japanese women diagnosed with anovulation or oligo-ovulation. Ovulation induction therapy will be undertaken with follitropin alfa. The primary objective is to show that MSJ-0011 is non-inferior to urinary hCG, as assessed by the ovulation rate.

Condition or Disease	Intervention/Treatment	Phase
Anovulation; Oligo-ovulation; Hypothalamic-pituitary Dysfunction; Polycystic Ovarian Syndrome	Drug: MSJ-0011; Drug: urinary hCG (u-hCG); Drug: Follitropin alpha	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 81 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-Label, Parallel-Group, Randomized, Multicenter Phase III Trial to Compare the Efficacy and Safety of a 250 mcg SC Dose of MSJ-0011 to a 5,000 IU IM Dose of Urinary Human Chorionic Gonadotropin in Inducing Ovulation in Japanese Women Diagnosed With Anovulation or Oligo-Ovulation Secondary to Hypothalamic-Pituitary Dysfunction or Polycystic Ovarian Syndrome, and Who Are Undergoing Ovulation Induction With Follitropin Alfa
• Study Start Date: Sep 1, 2012
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MSJ-0011	Drug: MSJ-0011; Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol for maximum of 28 days will receive a single dose of 250 microgram (mcg) MSJ-0011 (choriogonadotropin alfa [recombinant human Chorionic Gonadotropin, r-hCG]) subcutaneously (SC) within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of greater than or equal to (>=) 18 millimeter (mm); not more than 3 follicles each with a mean diameter of >=16 mm and serum Estradiol (E2) level within an acceptable range for the number of follicle present, and not more than 2,000 picogram per milliliter (pg/mL).; Drug: Follitropin alpha; Low-dose step-up protocol involves starting dose of follitropin alfa as 75 International Units (IU) subcutaneously per day ,increments by 37.5 IU every 7 days (Day 8, 15, 28) will be done if no ovarian response will be observed for maximum of 28 days.
Active Comparator: urinary hCG	Drug: urinary hCG (u-hCG); Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol for maximum of 28 days will receive a single dose of 5,000 IU u-hCG intramuscularly dose within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of >=18 mm; not more than 3 follicles each with a mean diameter of >=16 mm and serum E2 level within an acceptable range for the number of follicle present, and not more than 2,000 pg/mL.; Drug: Follitropin alpha; Low-dose step-up protocol involves starting dose of follitropin alfa as 75 International Units (IU) subcutaneously per day ,increments by 37.5 IU every 7 days (Day 8, 15, 28) will be done if no ovarian response will be observed for maximum of 28 days.

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects With Ovulation Mid-luteal Serum Progesterone (P4) Level of Greater Than or Equal (>=) 5 Nanogram Per Milliliter (ng/mL) or Clinical Pregnancy [Mid-luteal phase progesterone assessed (Day 5 to 10) or clinical pregnancy (Day 35 to 42) post hCG treatment]

   Ovulation was defined as mid-luteal serum progesterone level of >= 5 ng/mL or clinical pregnancy. Clinical pregnancy was defined as the presence of at least a fetal sac on transvaginal ultrasound (TVUS).

Secondary Outcome Measures

1. Percentage of Subjects With Ovulation Mid-Luteal Serum Progesterone (P4) Level of Greater Than or Equal (>=) 9.4 Nanogram Per Milliliter (ng/mL) or Clinical Pregnancy [Mid-luteal phase progesterone assessed (Day 5 to 10) or clinical pregnancy (Day 35 to 42) post hCG treatment]

   Ovulation was defined as mid-luteal serum progesterone level of >= 9.4 ng/mL or clinical pregnancy. Clinical pregnancy was defined as the presence of at least a fetal sac on TVUS.

2. Mid-luteal Endometrial Thickness [Day 5 to 7 post hCG treatment]

   Endometrial thickness was measured using TVUS.

3. Percentage of Participants With Biochemical Pregnancy [Day 35 to 42 post hCG treatment]

   Percentage of subjects with biochemical pregnancy was assessed. Biochemical pregnancy was defined as any miscarriage without any evidence of a fetal sac on TVUS on the Day 35 to 42 post hCG treatment, but with a positive serum β-hCG pregnancy test on Day 15 to 20 post hCG treatment (Beta-hCG level greater than [>] 10 IU/Liter)

4. Percentage of Participants With Clinical Pregnancy [Day 35 to 42 post hCG treatment]

   Percentage of subjects with clinical pregnancy was assessed. Clinical pregnancy was defined as the presence of at least a fetal sac on TVUS.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 39 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Premenopausal women aged between 20 to 39 years inclusive and wishing to conceive

• Body Mass Index (BMI) of 17.0 to 29.0 kilogram per square meter (kg/m^2) inclusive (value up to first decimal place)

• No clinically significant abnormalities in serum thyroid stimulating hormone (TSH), dehydroepiandrosterone sulfate (DHEA-S), 17-hydroxyProgesterone (17-OHP), prolactin (PRL) and follicle-stimulating hormone (FSH) levels in the early follicular phase

• Anovulation or oligo-ovulation

• Any one of the following: spontaneous menstruation (at least twice per year) or a positive response to progestin as evidenced by menstruation.

• Eligible for ovarian stimulation with gonadotropins (e.g. documented failure to ovulate or achieve pregnancy with anti-estrogenic therapy such as clomiphene citrate)

• Male partner with normal semen analysis, as defined by World Health Organization (WHO) standards, within 12 months prior to date of informed consent

• Normal cervical smear results (Papanicolaou [PAP] score less than or equal to [<=] II) taken within 12 months prior to date of informed consent; if not available a cervical smear will be performed as part of screening

• Full comprehension of the trial and voluntary consent obtained in writing prior to participation in this trial

Exclusion Criteria:

• Infertility involving gynecological factors other than anovulation or oligo-ovulation secondary to hypothalamic-pituitary dysfunction (Grade 1 Amenorrhea, Oligomenorrhea or Anovulatory Cycles) or polycystic ovarian syndrome (PCOS) and for whom ovulation induction (OI) therapy is contraindicated

• Subjects with known surgical/histological diagnosis of endometriosis greater than Stage II (American Fertility Society classification), or endometriosis requiring treatment

• Infertility secondary to amenorrhea of uterine cause

• Infertility secondary to primary or premature ovarian failure

• Infertility secondary to known adrenal or thyroid dysfunction, or hyperprolactinemia

• Failure of ovulation in 2 or more consecutive previous cycles with any gonadotropins

• Subjects in whom pregnancy is contraindicated, e.g. malformations of sexual organs or fibroid tumors of the uterus incompatible with pregnancy

• Extrauterine pregnancy in the previous 3 months

• History or presence of intracranial tumor (e.g. hypothalamic or pituitary tumor)

• Presence of or suspected gonadotropin- or estrogen-dependent malignancy (e.g. ovarian, uterine or mammary carcinoma)

• Untreated endometrial hyperplasia

• Abnormal hemorrhage of the reproductive tract of unknown origin

• History of severe ovarian hyper stimulation syndrome (OHSS) (Classification of OHSS Severity, Japan Reproductive/Endocrine Working Group)

• Clinically significant systemic disease (e.g. insulin-dependent diabetes, epilepsy, severe migraine, intermittent porphyria, hepatic, renal or cardiovascular disease, severe corticosteroid-dependent asthma)

• Participation in another clinical trial within 3 months prior to date of informed consent or simultaneous participation in another clinical trial

• Gonadotropin treatment within 2 months prior to date of informed consent

• Legal incapacity or limited legal capacity

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hanabusa Women's Central Fertility Clinic	Hyogo		Japan
2	Bashamichi Ladies Clinic	Kanagawa		Japan
3	Sophia Ladies Clinic	Kanagawa		Japan
4	Ivf Namba Clinic	Osaka		Japan
5	Ivf Osaka Clinic	Osaka		Japan
6	Department of Obstetrics and Gynecology, Saitama Medical University Hospital	Saitama		Japan

Sponsors and Collaborators

• Merck KGaA, Darmstadt, Germany
• Merck Serono Co., Ltd., Japan

Investigators

• Study Director: Medical Responsible, Merck Serono Co., Ltd., Japan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck KGaA, Darmstadt, Germany
• ClinicalTrials.gov Identifier: NCT01653743
• Other Study ID Numbers: EMR701173_002
• First Posted: Jul 31, 2012
• Last Update Posted: Jan 7, 2016
• Last Verified: Dec 1, 2015

• Keywords provided by Merck KGaA, Darmstadt, Germany: Japanese
• Additional relevant MeSH terms: Polycystic Ovary Syndrome; Pituitary Diseases; Anovulation; Syndrome; Chorionic Gonadotropin; Follicle Stimulating Hormone

Study Results

Participant Flow

Arm/Group Title	MSJ-0011	u-hCG
Arm/Group Description	Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 International Units (IU) subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 250 microgram (mcg) MSJ-0011 subcutaneously (SC) within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of greater than or equal to (>=) 18 millimeter (mm); not more than 3 follicles each with a mean diameter of >=16 mm and serum Estradiol (E2) level within an acceptable range for the number of follicle present, and not more than 2,000 picogram per milliliter (pg/mL).	Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 IIU subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 5,000 IU u-hCG intramuscularly dose within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of >=18 mm; not more than 3 follicles each with a mean diameter of >=16 mm and serum E2 level within an acceptable range for the number of follicle present, and not more than 2,000 pg/mL.
Period Title: Overall Study
STARTED	54	27
COMPLETED	50	27
NOT COMPLETED	4	0

Baseline Characteristics

Arm/Group Title	MSJ-0011	Urinary Human Chorionic Gonadotropin (u-hCG)	Total
Arm/Group Description	Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 International Units (IU) subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 250 microgram (mcg) MSJ-0011 subcutaneously (SC) within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of greater than or equal to (>=) 18 millimeter (mm); not more than 3 follicles each with a mean diameter of >=16 mm and serum Estradiol (E2) level within an acceptable range for the number of follicle present, and not more than 2,000 picogram per milliliter (pg/mL).	Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 IIU subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 5,000 IU u-hCG intramuscularly dose within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of >=18 mm; not more than 3 follicles each with a mean diameter of >=16 mm and serum E2 level within an acceptable range for the number of follicle present, and not more than 2,000 pg/mL.	Total of all reporting groups
Overall Participants	54	27	81
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.61 (3.303)	30.67 (3.603)	31.96 (3.506)
Sex: Female, Male (Count of Participants)
Female	54 100%	27 100%	81 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects With Ovulation Mid-luteal Serum Progesterone (P4) Level of Greater Than or Equal (>=) 5 Nanogram Per Milliliter (ng/mL) or Clinical Pregnancy
Description	Ovulation was defined as mid-luteal serum progesterone level of >= 5 ng/mL or clinical pregnancy. Clinical pregnancy was defined as the presence of at least a fetal sac on transvaginal ultrasound (TVUS).
Time Frame	Mid-luteal phase progesterone assessed (Day 5 to 10) or clinical pregnancy (Day 35 to 42) post hCG treatment

Outcome Measure Data

Analysis Population Description

The modified intent to treat (Mod ITT) population was defined as all subjects randomized to IMP (MSJ-0011 or u-hCG) and who completed the primary efficacy assessment.

Arm/Group Title	MSJ-0011	u-hCG
Arm/Group Description	Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 International Units (IU) subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 250 microgram (mcg) MSJ-0011 subcutaneously (SC) within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of greater than or equal to (>=) 18 millimeter (mm); not more than 3 follicles each with a mean diameter of >=16 mm and serum Estradiol (E2) level within an acceptable range for the number of follicle present, and not more than 2,000 picogram per milliliter (pg/mL).	Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 IIU subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 5,000 IU u-hCG intramuscularly dose within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of >=18 mm; not more than 3 follicles each with a mean diameter of >=16 mm and serum E2 level within an acceptable range for the number of follicle present, and not more than 2,000 pg/mL.
Measure Participants	54	27
Number (95% Confidence Interval) [percentage of subjects]	100	100

2. Secondary Outcome

Title	Percentage of Subjects With Ovulation Mid-Luteal Serum Progesterone (P4) Level of Greater Than or Equal (>=) 9.4 Nanogram Per Milliliter (ng/mL) or Clinical Pregnancy
Description	Ovulation was defined as mid-luteal serum progesterone level of >= 9.4 ng/mL or clinical pregnancy. Clinical pregnancy was defined as the presence of at least a fetal sac on TVUS.
Time Frame	Mid-luteal phase progesterone assessed (Day 5 to 10) or clinical pregnancy (Day 35 to 42) post hCG treatment

Outcome Measure Data

Analysis Population Description

The Mod ITT population was defined as all subjects randomized to IMP (MSJ-0011 or u-hCG) and who completed the primary efficacy assessment.

Arm/Group Title	MSJ-0011	u-hCG
Arm/Group Description	Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 International Units (IU) subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 250 microgram (mcg) MSJ-0011 subcutaneously (SC) within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of greater than or equal to (>=) 18 millimeter (mm); not more than 3 follicles each with a mean diameter of >=16 mm and serum Estradiol (E2) level within an acceptable range for the number of follicle present, and not more than 2,000 picogram per milliliter (pg/mL).	Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 IIU subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 5,000 IU u-hCG intramuscularly dose within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of >=18 mm; not more than 3 follicles each with a mean diameter of >=16 mm and serum E2 level within an acceptable range for the number of follicle present, and not more than 2,000 pg/mL.
Measure Participants	54	27
Number (95% Confidence Interval) [percentage of subjects]	96.3	88.9

3. Secondary Outcome

Title	Mid-luteal Endometrial Thickness
Description	Endometrial thickness was measured using TVUS.
Time Frame	Day 5 to 7 post hCG treatment

Outcome Measure Data

Analysis Population Description

The Mod ITT population was defined as all subjects randomized to IMP (MSJ-0011 or u-hCG) and who completed the primary efficacy assessment.

Arm/Group Title	MSJ-0011	u-hCG
Arm/Group Description	Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 International Units (IU) subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 250 microgram (mcg) MSJ-0011 subcutaneously (SC) within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of greater than or equal to (>=) 18 millimeter (mm); not more than 3 follicles each with a mean diameter of >=16 mm and serum Estradiol (E2) level within an acceptable range for the number of follicle present, and not more than 2,000 picogram per milliliter (pg/mL).	Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 IIU subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 5,000 IU u-hCG intramuscularly dose within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of >=18 mm; not more than 3 follicles each with a mean diameter of >=16 mm and serum E2 level within an acceptable range for the number of follicle present, and not more than 2,000 pg/mL.
Measure Participants	54	27
Mean (Standard Deviation) [millimeter]	11.6 (2.64)	12.4 (2.58)

4. Secondary Outcome

Title	Percentage of Participants With Biochemical Pregnancy
Description	Percentage of subjects with biochemical pregnancy was assessed. Biochemical pregnancy was defined as any miscarriage without any evidence of a fetal sac on TVUS on the Day 35 to 42 post hCG treatment, but with a positive serum β-hCG pregnancy test on Day 15 to 20 post hCG treatment (Beta-hCG level greater than [>] 10 IU/Liter)
Time Frame	Day 35 to 42 post hCG treatment

Outcome Measure Data

Analysis Population Description

The Mod ITT population was defined as all subjects randomized to IMP (MSJ-0011 or u-hCG) and who completed the primary efficacy assessment.

Arm/Group Title	MSJ-0011	u-hCG
Arm/Group Description	Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 International Units (IU) subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 250 microgram (mcg) MSJ-0011 subcutaneously (SC) within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of greater than or equal to (>=) 18 millimeter (mm); not more than 3 follicles each with a mean diameter of >=16 mm and serum Estradiol (E2) level within an acceptable range for the number of follicle present, and not more than 2,000 picogram per milliliter (pg/mL).	Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 IIU subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 5,000 IU u-hCG intramuscularly dose within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of >=18 mm; not more than 3 follicles each with a mean diameter of >=16 mm and serum E2 level within an acceptable range for the number of follicle present, and not more than 2,000 pg/mL.
Measure Participants	54	27
Number (95% Confidence Interval) [percentage of subjects]	3.7	3.7

5. Secondary Outcome

Title	Percentage of Participants With Clinical Pregnancy
Description	Percentage of subjects with clinical pregnancy was assessed. Clinical pregnancy was defined as the presence of at least a fetal sac on TVUS.
Time Frame	Day 35 to 42 post hCG treatment

Outcome Measure Data

Analysis Population Description

The Mod ITT population was defined as all subjects randomized to IMP (MSJ-0011 or u-hCG) and who completed the primary efficacy assessment.

Arm/Group Title	MSJ-0011	u-hCG
Arm/Group Description	Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 International Units (IU) subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 250 microgram (mcg) MSJ-0011 subcutaneously (SC) within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of greater than or equal to (>=) 18 millimeter (mm); not more than 3 follicles each with a mean diameter of >=16 mm and serum Estradiol (E2) level within an acceptable range for the number of follicle present, and not more than 2,000 picogram per milliliter (pg/mL).	Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 IIU subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 5,000 IU u-hCG intramuscularly dose within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of >=18 mm; not more than 3 follicles each with a mean diameter of >=16 mm and serum E2 level within an acceptable range for the number of follicle present, and not more than 2,000 pg/mL.
Measure Participants	54	27
Number (95% Confidence Interval) [percentage of subjects]	29.6	33.3

Adverse Events

Time Frame	From signing of the informed consent document until Day 28-31 (for subjects who had a negative serum β-hCG pregnancy test on Day 15-20), or up to the Day 35-42 post hCG treatment (for subjects who have a positive serum β-hCG pregnancy test on Day 15-20).
Arm/Group Title	MSJ-0011		u-hCG
Arm/Group Description	Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 International Units (IU) subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 250 microgram (mcg) MSJ-0011 subcutaneously (SC) within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of greater than or equal to (>=) 18 millimeter (mm); not more than 3 follicles each with a mean diameter of >=16 mm and serum Estradiol (E2) level within an acceptable range for the number of follicle present, and not more than 2,000 picogram per milliliter (pg/mL).		Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol (starting dose of follitropin alfa as 75 IIU subcutaneously per day ,increments by 37.5 IU every 7 days was done if no ovarian response was observed) for maximum of 28 days received a single dose of 5,000 IU u-hCG intramuscularly dose within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of >=18 mm; not more than 3 follicles each with a mean diameter of >=16 mm and serum E2 level within an acceptable range for the number of follicle present, and not more than 2,000 pg/mL.
All Cause Mortality
	MSJ-0011		u-hCG
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	MSJ-0011		u-hCG
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/54 (1.9%)		0/27 (0%)
Reproductive system and breast disorders
Ovarian hyperstimulation syndrome	1/54 (1.9%)		0/27 (0%)
Other (Not Including Serious) Adverse Events
	MSJ-0011		u-hCG
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/54 (59.3%)		11/27 (40.7%)
Gastrointestinal disorders
Abdominal distension	0/54 (0%)		1/27 (3.7%)
Abdominal pain	2/54 (3.7%)		0/27 (0%)
Abdominal pain upper	1/54 (1.9%)		0/27 (0%)
Ascites	1/54 (1.9%)		0/27 (0%)
Constipation	2/54 (3.7%)		0/27 (0%)
Diarrhoea	1/54 (1.9%)		0/27 (0%)
Nausea	1/54 (1.9%)		0/27 (0%)
Vomiting	1/54 (1.9%)		0/27 (0%)
General disorders
Injection site bruising	1/54 (1.9%)		0/27 (0%)
Injection site erythema	5/54 (9.3%)		2/27 (7.4%)
Injection site pain	2/54 (3.7%)		3/27 (11.1%)
Injection site swelling	1/54 (1.9%)		0/27 (0%)
Infections and infestations
Acute tonsillitis	1/54 (1.9%)		0/27 (0%)
Cystitis	4/54 (7.4%)		0/27 (0%)
Nasopharyngitis	4/54 (7.4%)		1/27 (3.7%)
Nervous system disorders
Dizziness	1/54 (1.9%)		0/27 (0%)
Headache	1/54 (1.9%)		0/27 (0%)
Pregnancy, puerperium and perinatal conditions
Haemorrhage in pregnancy	1/54 (1.9%)		0/27 (0%)
Reproductive system and breast disorders
Dysmenorrhoea	1/54 (1.9%)		0/27 (0%)
Genital haemorrhage	1/54 (1.9%)		0/27 (0%)
Haemorrhagic ovarian cyst	1/54 (1.9%)		0/27 (0%)
Ovarian cyst	6/54 (11.1%)		3/27 (11.1%)
Ovarian enlargement	1/54 (1.9%)		0/27 (0%)
Ovarian hyperstimulation syndrome	7/54 (13%)		4/27 (14.8%)
Uterine haemorrhage	1/54 (1.9%)		0/27 (0%)
Skin and subcutaneous tissue disorders
Drug eruption	1/54 (1.9%)		0/27 (0%)
Eczema	1/54 (1.9%)		0/27 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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