A Clinical Trial to Determine the Effect of Lutropin Alfa... | NCT01075815

NCT01075815

ID	Type	Description	Link
2008-002281-55	EudraCT Number

Status Module

Sponsor/Collaborators Module

Name	Class
Merck, S.L., Spain	INDUSTRY

Oversight Module

Description Module

Detailed Description

This study will be carried out by the Grupo de Interés de Salud Embrionaria (GISE) group (part of the Spanish Fertility Society) who uses strict criteria to select the embryos most suitable for successful transference.

OBJECTIVES

Primary objective:

To determine the benefit of r-LH supplementation in COS prior to in-vitro fertilization (IVF)/intracytosolic sperm injection (ICSI) in advanced reproductive age, in terms of embryo competence to implant, as compared against no r-LH supplementation

Secondary objectives:

To evaluate the benefit of r-LH supplementation in COS, in terms of:

follicular development
length of the stimulation
oocyte number and their maturity
fertilization rate
embryo number and quality
gestational sacs
abortion
ongoing pregnancies
local and systemic safety of r-LH administration

The study will consist of 2 groups randomized in 1:1 ratio and each subject would be followed up until the confirmation of her pregnancy status. Each subject will be administered gonadotropin releasing hormone (GnRH) agonist subcutaneously daily from previous mid luteal phase to r-hCG administration as a standard practice to achieve down regulation. Each subject will also be administered recombinant follicle stimulating hormone (r-FSH) at a starting dose of 300 IU from S1 up to ovarian stimulation completion (r-hCG day) as a part of standard practice. In addition to the above concurrent therapies, one group will be administered experimental treatment (Luveris®) and the other group (control group) will not be administered any other drug (control treatment) during the stimulation period from stimulation start (S1) up to ovarian stimulation completion or stimulation cancellation respectively. Ovarian stimulation on an average takes 11 days and it is expected that stimulation period will not be extended beyond 15 days. A single injection of r-hCG will be administered intramuscularly or subcutaneously after the last injection of Luveris or r-FSH to achieve final follicular maturation. After, 34-36 hours of administration of r-hCG OPU will be done for oocyte retrieval and embryo transfer (ET) will be conducted within 5 days from OPU. Subjects will also be provided luteal support with natural progesterone and will be followed until delivery or miscarriage. Ultrasound and estradiol (E2) assessment of follicular growth will be conducted at various time points during the stimulation period with or without treatment adjustment.

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
rFSH + rhLH	Experimental	Recombinant human luteinizing hormone (rhLH,Luveris®) injection 150 IU subcutaneously daily along with rFSH 300 IU subcutaneously daily from S1 to S4 and then rFSH dose can be adjusted depending on the ovarian response till r-hCG administration day.	Drug: Recombinant human luteinizing hormone (rhLH) Drug: Recombinant follicle-stimulating hormone (rFSH)
rFSH	Active Comparator	rFSH injection 300 IU subcutaneously daily from S1 to S4 and then dose can be adjusted depending on the ovarian response till r-hCG administration day.	Drug: Recombinant follicle-stimulating hormone (rFSH)

Name	Type	Description	Arm Group Labels	Other Names
Recombinant human luteinizing hormone (rhLH)	Drug		rFSH + rhLH	Luveris® Lutropin alfa

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Implantation Rate	Implantation rate was measured as the number of gestational sacs observed, divided by the number of embryos transferred.	Day 35-42 post ovum pick-up (OPU) (34-38 hours post recombinant human choriogonadotropin day {end of stimulation cycle}[approximately 28 days])

Secondary Outcomes

Measure	Description	Time Frame
Mean Number of Follicles Greater Than or Equal to 14 Millimeter (mm) on Recombinant Human Choriogonadotropin (r-hCG) Day		r-hCG day (end of stimulation cycle [approximately 28 days])
Mean Number of Oocytes Retrieved	Mean number of oocytes retrieved per reporting group on the day of OPU (34-38 hours post r-hCG day (end of stimulation cycle [approximately 28 days]) was calculated. Oocyte retrieval is a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Pre-menopausal female subject aged greater than (>) 35 years
Subjects with baseline FSH serum level less than or equal to (<=) 10 IU/liter (l), LH and E2 levels within local normal range and plasma prolactin levels < 30 nanogram/milliliter (ng/ml)
Subjects with regular spontaneous menstrual cycles of 25-35 days
Subjects with infertility justifying IVF/ICSI-ET treatment
Subjects programmed for COS with r-FSH under GnRH agonist protocol
Sperm from current male partner suitable for IVF/ICSI according to local lab, unless sperm donor is foreseen
Subjects with presence of both ovaries
Subjects whose uterine cavity is able to sustain embryo implantation or pregnancy
Subjects with normal papanicolaou test (PAP) smear within previous 3 years
Subjects with body mass index (BMI) < 30 at stimulation start
Subjects who receive confirmation of not being pregnant by a negative beta-hCG test (urine or blood) prior to starting r-FSH administration
Subjects willing and able to comply with the protocol for the duration of the study
Subjects who have given informed consent prior to any study-related procedure not part of normal medical care

Exclusion Criteria:

Subjects or her male partners who are known to be human immunodeficiency virus, hepatitis B virus or hepatitis C virus positive
Subjects with any clinically significant systemic disease; tumors of the hypothalamus and pituitary gland; ovarian, uterine or mammary cancer; hormonal abnormality and/or medical, biochemical, hematological condition which in the judgment of the investigator may interfere with gonadotropin treatment
Subjects with more than 2 previous assisted reproductive technologies (ART) cycles
Subjects in which previous cycles were cancelled due to poor response (< 3 antral follicles after 15 day of stimulation)
Subjects with cryopreserved embryos from previous ART cycles
Subjects with unexplained gynecological bleeding
Subjects with polycystic ovaries, ovarian enlargement or cyst of unknown etiology
Subjects known to have any contraindication to being pregnant and/or carrying pregnancy to term
Subjects with known allergy to gonadotrophin preparations or any of the excipients
Subjects known to have any active substance abuse or history of drug, medication or alcohol abuse in the past 5 years
Subjects with previous entry into this study or simultaneous participation in another clinical drug trial
Subjects who have refused to or inability to comply with the protocol

Contacts/Locations Module

Name	Affiliation	Role
Medical Responsible	Merck, S.L., Spain	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
FivMadrid, C/ Marqués de Urquijo, 26,		Madrid		28008	Spain

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	rFSH + rhLH	Recombinant human luteinizing hormone (rhLH, Luveris®) injection 150 International Units (IU) subcutaneously daily along with recombinant follicle-stimulating hormone (rFSH) 300 IU subcutaneously daily from Day 1 of stimulation period (S1) to Day 4 of stimulation period (S4) and then rFSH dose adjusted depending on the ovarian response till recombinant human choriogonadotropin (r-hCG) administration day.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

FG00040 subjectsNumber of participants treated.

FG00135 subjectsNumber of participants treated.

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	rFSH + rhLH	Recombinant human luteinizing hormone (rhLH, Luveris®) injection 150 International Units (IU) subcutaneously daily along with recombinant follicle-stimulating hormone (rFSH) 300 IU subcutaneously daily from Day 1 of stimulation period (S1) to Day 4 of stimulation period (S4) and then rFSH dose adjusted depending on the ovarian response till recombinant human choriogonadotropin (r-hCG) administration day.
BG001	rFSH	Recombinant follicle stimulating hormone (rFSH) injection 300 IU subcutaneously daily from S1 to S4 and then dose adjusted depending on the ovarian response till r-hCG administration day.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00040 BG00135 BG00275

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG0000.2± 0.4 OG0010.2± 0.3

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Wilcoxon two sample test		0.8762		Mean Difference (Final Values)	0.0235			2-Sided	95	-0.1546	0.1568				No	Superiority or Other

Secondary

Mean Number of Follicles Greater Than or Equal to 14 Millimeter (mm) on Recombinant Human Choriogonadotropin (r-hCG) Day

ITT population included all randomized participants who had received at least 1 dose of the study medication.

Posted

Mean

Standard Deviation

follicles

r-hCG day (end of stimulation cycle [approximately 28 days])

ID	Title	Description
OG000	rFSH + rhLH	Recombinant human luteinizing hormone (rhLH, Luveris®) injection 150 International Units (IU) subcutaneously daily along with recombinant follicle-stimulating hormone (rFSH) 300 IU subcutaneously daily from Day 1 of stimulation period (S1) to Day 4 of stimulation period (S4) and then rFSH dose adjusted depending on the ovarian response till recombinant human choriogonadotropin (r-hCG) administration day.
OG001	rFSH	Recombinant follicle stimulating hormone (rFSH) injection 300 IU subcutaneously daily from S1 to S4 and then dose adjusted depending on the ovarian response till r-hCG administration day.

Units	Counts
Participants

Secondary

Mean Number of Oocytes Retrieved

Mean number of oocytes retrieved per reporting group on the day of OPU (34-38 hours post r-hCG day (end of stimulation cycle [approximately 28 days]) was calculated. Oocyte retrieval is a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body.

ITT population included all randomized participants who had received at least 1 dose of the study medication.

Posted

Mean

Standard Deviation

oocytes

34-38 hours post r-hCG day (end of stimulation cycle [approximately 28 days])

ID	Title	Description
OG000	rFSH + rhLH	Recombinant human luteinizing hormone (rhLH, Luveris®) injection 150 International Units (IU) subcutaneously daily along with recombinant follicle-stimulating hormone (rFSH) 300 IU subcutaneously daily from Day 1 of stimulation period (S1) to Day 4 of stimulation period (S4) and then rFSH dose adjusted depending on the ovarian response till recombinant human choriogonadotropin (r-hCG) administration day.
OG001	rFSH	Recombinant follicle stimulating hormone (rFSH) injection 300 IU subcutaneously daily from S1 to S4 and then dose adjusted depending on the ovarian response till r-hCG administration day.

Secondary

Number of Mature Oocytes Retrieved

Number of mature oocytes retrieved per reporting group on the day of OPU (34-38 hours post r-hCG day (end of stimulation cycle [approximately 28 days]) was calculated. Oocyte retrieval is a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body. The nuclear maturity was evaluated based on the presence of a germinal vesicle (GV) or whether oocytes were in metaphase I (Meta-I) or II (Meta-II) stage.

ITT population included all randomized participants who had received at least 1 dose of the study medication.

Posted

Number

mature oocytes

34-38 hours post r-hCG day (end of stimulation cycle [approximately 28 days])

ID	Title	Description
OG000	rFSH + rhLH	Recombinant human luteinizing hormone (rhLH, Luveris®) injection 150 International Units (IU) subcutaneously daily along with recombinant follicle-stimulating hormone (rFSH) 300 IU subcutaneously daily from Day 1 of stimulation period (S1) to Day 4 of stimulation period (S4) and then rFSH dose adjusted depending on the ovarian response till recombinant human choriogonadotropin (r-hCG) administration day.
OG001	rFSH	Recombinant follicle stimulating hormone (rFSH) injection 300 IU subcutaneously daily from S1 to S4 and then dose adjusted depending on the ovarian response till r-hCG administration day.

Secondary

Number of Fertilized Oocytes (2 Pronuclei [PN])

Oocytes were fertilized using Intra-cytoplasmic Sperm Injection (ICSI) technique which is an in-vitro fertilization procedure in which a single sperm is injected directly into an egg under a microscope. The appearance of two 2PN is the first sign of successful fertilization as observed during in vitro fertilization, and is usually observed after ICSI. The zygote is then termed 2PN.

ITT population included all randomized participants who had received at least 1 dose of the study medication.

Posted

Number

2PN oocytes

34-38 hours post r-hCG day (end of stimulation cycle [approximately 28 days])

ID	Title	Description
OG000	rFSH + rhLH	Recombinant human luteinizing hormone (rhLH, Luveris®) injection 150 International Units (IU) subcutaneously daily along with recombinant follicle-stimulating hormone (rFSH) 300 IU subcutaneously daily from Day 1 of stimulation period (S1) to Day 4 of stimulation period (S4) and then rFSH dose adjusted depending on the ovarian response till recombinant human choriogonadotropin (r-hCG) administration day.
OG001	rFSH	Recombinant follicle stimulating hormone (rFSH) injection 300 IU subcutaneously daily from S1 to S4 and then dose adjusted depending on the ovarian response till r-hCG administration day.

Secondary

Number and Quality of Embryos

Embryos were graded according to Spanish Association for the Study of Reproductive Biology (ASEBIR) criteria into different categories: (A) optimal quality with maximum capacity for implantation, (B) good quality with a high capacity for implantation, (C) regular with low possibility of implantation and (D) poor quality with very little possibility of implantation.

ITT population included all randomized participants who had received at least 1 dose of the study medication. Here "N" represents the number of participants who had at least one fertilized oocyte.

Posted

Number

embyros

Day 2-3 post OPU (34-38 hours post r-hCG day {end of stimulation cycle}[approximately 28 days])

ID	Title	Description
OG000	rFSH + rhLH	Recombinant human luteinizing hormone (rhLH, Luveris®) injection 150 International Units (IU) subcutaneously daily along with recombinant follicle-stimulating hormone (rFSH) 300 IU subcutaneously daily from Day 1 of stimulation period (S1) to Day 4 of stimulation period (S4) and then rFSH dose adjusted depending on the ovarian response till recombinant human choriogonadotropin (r-hCG) administration day.
OG001	rFSH	Recombinant follicle stimulating hormone (rFSH) injection 300 IU subcutaneously daily from S1 to S4 and then dose adjusted depending on the ovarian response till r-hCG administration day.

Secondary

Number of Participants With Biochemical Pregnancies

Biochemical pregnancy was defined as a pregnancy diagnosed only by the detection of hCG in serum or urine and that does not develop into a clinical pregnancy.

ITT population included all randomized participants who had received at least 1 dose of the study medication.

Posted

Number

participants

2 months after OPU (34-38 hours post r-hCG day {end of stimulation cycle} [approximately 28 days])

ID	Title	Description
OG000	rFSH + rhLH	Recombinant human luteinizing hormone (rhLH, Luveris®) injection 150 International Units (IU) subcutaneously daily along with recombinant follicle-stimulating hormone (rFSH) 300 IU subcutaneously daily from Day 1 of stimulation period (S1) to Day 4 of stimulation period (S4) and then rFSH dose adjusted depending on the ovarian response till recombinant human choriogonadotropin (r-hCG) administration day.
OG001	rFSH	Recombinant follicle stimulating hormone (rFSH) injection 300 IU subcutaneously daily from S1 to S4 and then dose adjusted depending on the ovarian response till r-hCG administration day.

Units	Counts
Participants

Secondary

Number of Participants With Clinical Pregnancies

Clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It includes ectopic pregnancy.

ITT population included all randomized participants who had received at least 1 dose of the study medication.

Posted

Number

participants

2 months after OPU (34-38 hours post r-hCG day {end of stimulation cycle} [approximately 28 days])

ID	Title	Description
OG000	rFSH + rhLH	Recombinant human luteinizing hormone (rhLH, Luveris®) injection 150 International Units (IU) subcutaneously daily along with recombinant follicle-stimulating hormone (rFSH) 300 IU subcutaneously daily from Day 1 of stimulation period (S1) to Day 4 of stimulation period (S4) and then rFSH dose adjusted depending on the ovarian response till recombinant human choriogonadotropin (r-hCG) administration day.
OG001	rFSH	Recombinant follicle stimulating hormone (rFSH) injection 300 IU subcutaneously daily from S1 to S4 and then dose adjusted depending on the ovarian response till r-hCG administration day.

Units	Counts

Secondary

Total Dose of Recombinant Follicle Stimulating Hormone (r-FSH)

ITT population included all randomized participants who had received at least 1 dose of the study medication.

Posted

Mean

Standard Deviation

2 months after OPU (34-38 hours post r-hCG day {end of stimulation cycle} [approximately 28 days])

ID	Title	Description
OG000	rFSH + rhLH	Recombinant human luteinizing hormone (rhLH, Luveris®) injection 150 International Units (IU) subcutaneously daily along with recombinant follicle-stimulating hormone (rFSH) 300 IU subcutaneously daily from Day 1 of stimulation period (S1) to Day 4 of stimulation period (S4) and then rFSH dose adjusted depending on the ovarian response till recombinant human choriogonadotropin (r-hCG) administration day.
OG001	rFSH	Recombinant follicle stimulating hormone (rFSH) injection 300 IU subcutaneously daily from S1 to S4 and then dose adjusted depending on the ovarian response till r-hCG administration day.

Units	Counts
Participants

Secondary

Estradiol (E2) Levels on r-hCG Day

ITT population included all randomized participants who had received at least 1 dose of the study medication. Here "N" represents the number of participants with plasma E2 levels at r-hCG day.

Posted

Mean

Standard Deviation

picogram/milliter (pg/mL)

r-hCG day (end of stimulation cycle [approximately 28 days])

ID	Title	Description
OG000	rFSH + rhLH	Recombinant human luteinizing hormone (rhLH, Luveris®) injection 150 International Units (IU) subcutaneously daily along with recombinant follicle-stimulating hormone (rFSH) 300 IU subcutaneously daily from Day 1 of stimulation period (S1) to Day 4 of stimulation period (S4) and then rFSH dose adjusted depending on the ovarian response till recombinant human choriogonadotropin (r-hCG) administration day.
OG001	rFSH	Recombinant follicle stimulating hormone (rFSH) injection 300 IU subcutaneously daily from S1 to S4 and then dose adjusted depending on the ovarian response till r-hCG administration day.

Units	Counts
Participants

Secondary

Number of Ovarian Stimulation Days

Ovarian stimulation included from first rFSH injection (S1) until day on which r-hCG was administered (r-hCG day). This period was divided into 2 parts: the first period in which 300 International Unit (IU) rFSH dose was constant and which covered from S1 to Day 4 of stimulation period (S4); the second period in which the rFSH dose could be adjusted depending on the ovarian response and which began on S4 and finished on the day on which the criteria for administration of r-hCG to induce the final follicular maturation were met.

ITT population included all randomized participants who had received at least 1 dose of the study medication.

Posted

Mean

Standard Deviation

Days

S1 up to r-hCG day (end of stimulation cycle [approximately 28 days])

ID	Title	Description
OG000	rFSH + rhLH	Recombinant human luteinizing hormone (rhLH, Luveris®) injection 150 International Units (IU) subcutaneously daily along with recombinant follicle-stimulating hormone (rFSH) 300 IU subcutaneously daily from Day 1 of stimulation period (S1) to Day 4 of stimulation period (S4) and then rFSH dose adjusted depending on the ovarian response till recombinant human choriogonadotropin (r-hCG) administration day.
OG001	rFSH	Recombinant follicle stimulating hormone (rFSH) injection 300 IU subcutaneously daily from S1 to S4 and then dose adjusted depending on the ovarian response till r-hCG administration day.

Secondary

Number of Recombinant Human Choriogonadotropin (r-hCG) Cycles Cancelled Due to Poor Response

Poor response was defined as 3 or less follicles of greater than or equal to 12 mm developing following at least 7 days of study treatment.

ITT population included all randomized participants who had received at least 1 dose of the study medication.

Posted

Number

cycles

Up to 2 months after OPU (34-38 hours post r-hCG day {end of stimulation cycle} [approximately 28 days])

ID	Title	Description
OG000	rFSH + rhLH	Recombinant human luteinizing hormone (rhLH, Luveris®) injection 150 International Units (IU) subcutaneously daily along with recombinant follicle-stimulating hormone (rFSH) 300 IU subcutaneously daily from Day 1 of stimulation period (S1) to Day 4 of stimulation period (S4) and then rFSH dose adjusted depending on the ovarian response till recombinant human choriogonadotropin (r-hCG) administration day.
OG001	rFSH	Recombinant follicle stimulating hormone (rFSH) injection 300 IU subcutaneously daily from S1 to S4 and then dose adjusted depending on the ovarian response till r-hCG administration day.

Units	Counts

Secondary

Total Number of Births

Total number of births per reporting group was calculated.

ITT population included all randomized participants who had received at least 1 dose of the study medication. Here "N" represents number of participants evaluated for this measure.

Posted

Number

births

Up to 2 months after OPU (34-38 hours post r-hCG day {end of stimulation cycle} [approximately 28 days])

ID	Title	Description
OG000	rFSH + rhLH	Recombinant human luteinizing hormone (rhLH, Luveris®) injection 150 International Units (IU) subcutaneously daily along with recombinant follicle-stimulating hormone (rFSH) 300 IU subcutaneously daily from Day 1 of stimulation period (S1) to Day 4 of stimulation period (S4) and then rFSH dose adjusted depending on the ovarian response till recombinant human choriogonadotropin (r-hCG) administration day.
OG001	rFSH	Recombinant follicle stimulating hormone (rFSH) injection 300 IU subcutaneously daily from S1 to S4 and then dose adjusted depending on the ovarian response till r-hCG administration day.

Units	Counts
Participants

Secondary

Number of Participants With Adverse Events (AEs)

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

Safety population included all participants who had received at least 1 dose of the study medication.

Posted

Number

participants

Baseline up to 2 months after OPU (34-38 hours post r-hCG day {end of stimulation cycle} [approximately 28 days])

ID	Title	Description
OG000	rFSH + rhLH	Recombinant human luteinizing hormone (rhLH, Luveris®) injection 150 International Units (IU) subcutaneously daily along with recombinant follicle-stimulating hormone (rFSH) 300 IU subcutaneously daily from Day 1 of stimulation period (S1) to Day 4 of stimulation period (S4) and then rFSH dose adjusted depending on the ovarian response till recombinant human choriogonadotropin (r-hCG) administration day.
OG001	rFSH	Recombinant follicle stimulating hormone (rFSH) injection 300 IU subcutaneously daily from S1 to S4 and then dose adjusted depending on the ovarian response till r-hCG administration day.

Units	Counts
Participants

Secondary

Number of Participants With Ovarian Hyper Stimulation Syndrome (OHSS)

OHSS is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting.

Safety population included all participants who had received at least 1 dose of the study medication.

Posted

Number

participants

Baseline up to 2 months after OPU (34-38 hours post r-hCG day {end of stimulation cycle} [approximately 28 days])

ID	Title	Description
OG000	rFSH + rhLH	Recombinant human luteinizing hormone (rhLH, Luveris®) injection 150 International Units (IU) subcutaneously daily along with recombinant follicle-stimulating hormone (rFSH) 300 IU subcutaneously daily from Day 1 of stimulation period (S1) to Day 4 of stimulation period (S4) and then rFSH dose adjusted depending on the ovarian response till recombinant human choriogonadotropin (r-hCG) administration day.
OG001	rFSH	Recombinant follicle stimulating hormone (rFSH) injection 300 IU subcutaneously daily from S1 to S4 and then dose adjusted depending on the ovarian response till r-hCG administration day.

Units	Counts

Secondary

Number of Cycles Cancelled Due to Risk of Ovarian Hyper Stimulation Syndrome (OHSS)

OHSS is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting.

Safety population included all participants who had received at least 1 dose of the study medication.

Posted

Number

cycles

Baseline up to 2 months after OPU (34-38 hours post r-hCG day {end of stimulation cycle} [approximately 28 days])

ID	Title	Description
OG000	rFSH + rhLH	Recombinant human luteinizing hormone (rhLH, Luveris®) injection 150 International Units (IU) subcutaneously daily along with recombinant follicle-stimulating hormone (rFSH) 300 IU subcutaneously daily from Day 1 of stimulation period (S1) to Day 4 of stimulation period (S4) and then rFSH dose adjusted depending on the ovarian response till recombinant human choriogonadotropin (r-hCG) administration day.
OG001	rFSH	Recombinant follicle stimulating hormone (rFSH) injection 300 IU subcutaneously daily from S1 to S4 and then dose adjusted depending on the ovarian response till r-hCG administration day.

Units	Counts

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	rFSH + rhLH	Recombinant human luteinizing hormone (rhLH, Luveris®) injection 150 International Units (IU) subcutaneously daily along with recombinant follicle-stimulating hormone (rFSH) 300 IU subcutaneously daily from Day 1 of stimulation period (S1) to Day 4 of stimulation period (S4) and then rFSH dose adjusted depending on the ovarian response till recombinant human choriogonadotropin (r-hCG) administration day.			2	40	17	40
EG001	rFSH	Recombinant follicle stimulating hormone (rFSH) injection 300 IU subcutaneously daily from S1 to S4 and then dose adjusted depending on the ovarian response till r-hCG administration day.			1	35	8	35

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
New born hip dysplasia	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected40 at risk EG0010 affected35 at risk
Cutaneous anginoma	Skin and subcutaneous tissue disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected40 at risk EG0010 affected35 at risk
Trisomy 13	Congenital, familial and genetic disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected40 at risk EG0011 affected35 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Premature birth	Pregnancy, puerperium and perinatal conditions	MedDRA 13.0	Non-systematic Assessment	EG0002 affected40 at risk EG0011 affected35 at risk
Subcutaneous haematoma	Injury, poisoning and procedural complications	MedDRA 13.0	Non-systematic Assessment	EG0002 affected40 at risk EG0012 affected35 at risk
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA 13.0	Non-systematic Assessment	EG0003 affected40 at risk EG0010 affected35 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 13.0	Non-systematic Assessment	EG0005 affected40 at risk EG0010 affected35 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 13.0	Non-systematic Assessment	EG0004 affected40 at risk EG0011 affected35 at risk
Ovarian hyperstimulation syndrome	Reproductive system and breast disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected40 at risk EG0010 affected35 at risk
Headache	Nervous system disorders	MedDRA 13.0	Non-systematic Assessment	EG0004 affected40 at risk EG0013 affected35 at risk
Dizziness	Nervous system disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected40 at risk EG0012 affected35 at risk
Bloating	Gastrointestinal disorders	MedDRA 13.0	Non-systematic Assessment	EG0002 affected40 at risk EG0010 affected35 at risk
Pain	General disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected40 at risk EG0012 affected35 at risk
Pain at the injection site	General disorders	MedDRA 13.0	Non-systematic Assessment	EG0005 affected40 at risk EG0010 affected35 at risk
Erythema at the injection site	General disorders	MedDRA 13.0	Non-systematic Assessment	EG0002 affected40 at risk EG0010 affected35 at risk
Pruritus at the injection site	General disorders	MedDRA 13.0	Non-systematic Assessment	EG0002 affected40 at risk EG0010 affected35 at risk
Haematoma	Vascular disorders	MedDRA 13.0	Non-systematic Assessment	EG0004 affected40 at risk EG0011 affected35 at risk
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected40 at risk EG0011 affected35 at risk
Pelvic pain	Reproductive system and breast disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected40 at risk EG0010 affected35 at risk
Genital secretion	Reproductive system and breast disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected40 at risk EG0011 affected35 at risk
Burning sensation	Nervous system disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected40 at risk EG0010 affected35 at risk
Retching	Gastrointestinal disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected40 at risk EG0010 affected35 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected40 at risk EG0010 affected35 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected40 at risk EG0010 affected35 at risk
Odynophagia	Gastrointestinal disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected40 at risk EG0010 affected35 at risk
Oedema	General disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected40 at risk EG0010 affected35 at risk
Haematoma at the injection site	General disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected40 at risk EG0010 affected35 at risk
Swelling	General disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected40 at risk EG0011 affected35 at risk
Inflammation	General disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected40 at risk EG0011 affected35 at risk
Inflammation at the injection site	General disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected40 at risk EG0010 affected35 at risk
General malaise	General disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected40 at risk EG0010 affected35 at risk
Reaction at the injection site	General disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected40 at risk EG0010 affected35 at risk
Mood change	Psychiatric disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected40 at risk EG0011 affected35 at risk

ID	Term
D007246	Infertility
D006379	Helping Behavior

ID	Term
D037101	Luteinizing Hormone, beta Subunit
D015292	Glycoprotein Hormones, alpha Subunit

Ancestor Terms

ID	Term
D007986	Luteinizing Hormone
D006065	Gonadotropins, Pituitary
D006062	Gonadotropins
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D010908	Pituitary Hormones, Anterior
D010907	Pituitary Hormones
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D006063	Chorionic Gonadotropin
D005640	Follicle Stimulating Hormone
D013972	Thyrotropin
D010926	Placental Hormones

Units	Counts
Participants	OG00040 OG00135

Units	Counts
Participants	OG00031 OG00132

ID	Term
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D012919	Social Behavior
D001519	Behavior