A Prospective Study to Evaluate the Addition of Subcutaneous Recombinant Human-Luteinizing Hormone With Recombinant Human-Follicle Stimulating Hormone on Follicular Development in Women Undergoing Ovarian Stimulation for Assisted Reproductive Technologies

This study has been completed.

Sponsor:

Information provided by:

EMD Serono

ClinicalTrials.gov Identifier:

NCT01121991

First received: May 10, 2010

Last updated: June 8, 2011

Last verified: June 2011

History of Changes

Results First Received: February 17, 2011

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study; Intervention Model: Single Group Assignment; Masking: Open Label; Primary Purpose: Treatment
Conditions:	Infertility Ovarian Stimulation
Intervention:	Drug: Recombinant Human-Luteinizing Hormone (Luveris)

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were recruited in 4 study centers in Canada from September 2004 to October 2005.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
55 participants were enrolled in the study, 3 participants discontinued prior to study drug administration as they did not meet the eligibility criteria.

Reporting Groups

	Description
Recombinant Human-Luteinizing Hormone (Luveris)	All participants received Luveris 150 International Unit (IU) per day, subcutaneously (s.c) from stimulation day 6 (Day S6) of their assisted reproductive technology (ART) treatment cycle, continuing at the same dose until injection of hCG upto and including day of last FSH dose.

Participant Flow: Overall Study

	Recombinant Human-Luteinizing Hormone (Luveris)
STARTED	52 ^[1]
COMPLETED	46
NOT COMPLETED	6
Lack of Ovarian Response	2
No Oocytes Retrieved	3
No Fertilization	1

[1]	Number of participants treated

Baseline Characteristics

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Reporting Groups

	Description
Recombinant Human-Luteinizing Hormone (Luveris)	All participants received Luveris 150 International Unit (IU) per day, subcutaneously (s.c) from stimulation day 6 (Day S6) of their assisted reproductive technology (ART) treatment cycle, continuing at the same dose until injection of hCG upto and including day of last FSH dose.

Baseline Measures

	Recombinant Human-Luteinizing Hormone (Luveris)
Number of Participants [units: participants]	52
Age [units: years] Mean ± Standard Deviation	34.6 ± 3.6
Age, Customized [units: participants]
<35 years	22
>=35 years	30
Gender [units: participants]
Female	52
Male	0
Race/Ethnicity, Customized [units: participants]
Asian	3
White	47
Hispanic	1
Aboriginal	1
Region of Enrollment [units: participants]
Canada	52
Smoking ^[1] [units: participants]
0 cigarettes per day	50
6-20 cigarettes per day	1
>20 cigarettes per day	1

[1]	Consumption of cigarettes is inclusive of cigarillos and cigars.

Outcome Measures

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1. Primary:

Mean Number of Metaphase II Oocytes Per Participant Who Underwent Ovum Pick up for Intra-cytoplasmic Sperm Injection (ICSI) [ Time Frame: On the day of ovum pick up (Day 1 or 2 after human chorionic gonadotropin [hCG] administration). ]

Measure Type	Primary
Measure Title	Mean Number of Metaphase II Oocytes Per Participant Who Underwent Ovum Pick up for Intra-cytoplasmic Sperm Injection (ICSI)
Measure Description	Mean number of metaphase II oocytes was calculated for each participant undergoing ovum pick up for ICSI. ICSI is an in-vitro fertilization procedure in which a single sperm is injected directly into an egg under a microscope. Metaphase II stage of the oocyte was classified as the time at which the first polar body was observed microscopically. Metaphase II oocytes are a sub-group of the total number of oocytes.
Time Frame	On the day of ovum pick up (Day 1 or 2 after human chorionic gonadotropin [hCG] administration).
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis population includes those participants undergoing ICSI whose oocytes were assessed for maturity (Metaphase II) using a microscope.

Reporting Groups

	Description
Recombinant Human-Luteinizing Hormone (Luveris)	All participants received Luveris 150 International Unit (IU) per day, subcutaneously (s.c) from stimulation day 6 (Day S6) of their assisted reproductive technology (ART) treatment cycle, continuing at the same dose until injection of hCG upto and including day of last FSH dose.

Measured Values

	Recombinant Human-Luteinizing Hormone (Luveris)
Number of Participants Analyzed [units: participants]	22
Mean Number of Metaphase II Oocytes Per Participant Who Underwent Ovum Pick up for Intra-cytoplasmic Sperm Injection (ICSI) [units: Metaphase II Oocytes] Mean ± Standard Deviation	9.5 ± 4.2

No statistical analysis provided for Mean Number of Metaphase II Oocytes Per Participant Who Underwent Ovum Pick up for Intra-cytoplasmic Sperm Injection (ICSI)

2. Primary:

Mean Number of Mature Oocytes Per Participant Who Underwent Ovum Pick up for In Vitro Fertilization (IVF) [ Time Frame: On the day of ovum pick up (Day 1 or 2 after hCG administration). ]

Measure Type	Primary
Measure Title	Mean Number of Mature Oocytes Per Participant Who Underwent Ovum Pick up for In Vitro Fertilization (IVF)
Measure Description	Mean number of oocytes undergoing ovum pick up for IVF were calculated for each participant. IVF is a process by which egg cells are fertilized by sperm outside the body, in-vitro.
Time Frame	On the day of ovum pick up (Day 1 or 2 after hCG administration).
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis population includes those participants undergoing IVF whose oocytes were assessed for maturity. Mature oocytes can be considered as Metaphase II oocytes.

Reporting Groups

	Description
Recombinant Human-Luteinizing Hormone (Luveris)	All participants received Luveris 150 International Unit (IU) per day, subcutaneously (s.c) from stimulation day 6 (Day S6) of their assisted reproductive technology (ART) treatment cycle, continuing at the same dose until injection of hCG upto and including day of last FSH dose.

Measured Values

	Recombinant Human-Luteinizing Hormone (Luveris)
Number of Participants Analyzed [units: participants]	4
Mean Number of Mature Oocytes Per Participant Who Underwent Ovum Pick up for In Vitro Fertilization (IVF) [units: oocytes] Mean ± Standard Deviation	7.5 ± 6.8

No statistical analysis provided for Mean Number of Mature Oocytes Per Participant Who Underwent Ovum Pick up for In Vitro Fertilization (IVF)

3. Secondary:

Mean Number of Oocytes Retrieved Per Number of Follicles Aspirated on the Day of Ovum Pick up [ Time Frame: On day of ovum pick up (Day 1 or 2 after hCG administration) ]

Measure Type	Secondary
Measure Title	Mean Number of Oocytes Retrieved Per Number of Follicles Aspirated on the Day of Ovum Pick up
Measure Description	Mean number of oocytes retrieved per number of follicles aspirated on the day of ovum pick up 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.
Time Frame	On day of ovum pick up (Day 1 or 2 after hCG administration)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population: all participants who received at least one dose of the study drug and underwent vaginal ovum pick up.

Reporting Groups

	Description
Recombinant Human-Luteinizing Hormone (Luveris)	All participants received Luveris 150 International Unit (IU) per day, subcutaneously (s.c) from stimulation day 6 (Day S6) of their assisted reproductive technology (ART) treatment cycle, continuing at the same dose until injection of hCG upto and including day of last FSH dose.

Measured Values

	Recombinant Human-Luteinizing Hormone (Luveris)
Number of Participants Analyzed [units: participants]	50
Mean Number of Oocytes Retrieved Per Number of Follicles Aspirated on the Day of Ovum Pick up [units: oocytes per aspirated follicle] Mean ± Standard Deviation	0.9 ± 0.2

No statistical analysis provided for Mean Number of Oocytes Retrieved Per Number of Follicles Aspirated on the Day of Ovum Pick up

4. Secondary:

Number of Participants With Confirmed Pregnancies: Biochemical Pregnancies and Clinical Pregnancies [ Time Frame: Post-hCG days 15-20 and post-hCG days 35-42. ]

Measure Type	Secondary
Measure Title	Number of Participants With Confirmed Pregnancies: Biochemical Pregnancies and Clinical Pregnancies
Measure Description	Biochemical pregnancy: A positive pregnancy test defined as hCG level >10 IU/L in a sample taken at least 14 days after Day 3 embryo transfer or 12 days after Day 5/6 embryo transfer with no further ultrasound confirmation of the existence of a gestational sac in the uterus. Clinical pregnancy: Existence of at least one ultrasonography confirmed gestational sac in the uterus, with or without heartbeat.
Time Frame	Post-hCG days 15-20 and post-hCG days 35-42.
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population: all participants who received at least one dose of the study drug.

Reporting Groups

	Description
Recombinant Human-Luteinizing Hormone (Luveris)	All participants received Luveris 150 International Unit (IU) per day, subcutaneously (s.c) from stimulation day 6 (Day S6) of their assisted reproductive technology (ART) treatment cycle, continuing at the same dose until injection of hCG upto and including day of last FSH dose.

Measured Values

	Recombinant Human-Luteinizing Hormone (Luveris)
Number of Participants Analyzed [units: participants]	52
Number of Participants With Confirmed Pregnancies: Biochemical Pregnancies and Clinical Pregnancies [units: participants]
Participants with confirmed biochemical pregnancy	22
Participants with confirmed clinical pregnancy	14

No statistical analysis provided for Number of Participants With Confirmed Pregnancies: Biochemical Pregnancies and Clinical Pregnancies

5. Secondary:

Number of Participants With Multiple Pregnancies [ Time Frame: Post-hCG Day 35-42. ]

Measure Type	Secondary
Measure Title	Number of Participants With Multiple Pregnancies
Measure Description	Multiple pregnancy is a pregnancy where more than one fetus develops simultaneously in the womb. There are two types of twinning—identical and fraternal. Identical twins represent the splitting of a single fertilized zygote (union of two gametes or male/female sex cells that produce a developing fetus) into two separate individuals.
Time Frame	Post-hCG Day 35-42.
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population: all participants who received at least one dose of the study drug.

Reporting Groups

	Description
Recombinant Human-Luteinizing Hormone (Luveris)	All participants received Luveris 150 International Unit (IU) per day, subcutaneously (s.c) from stimulation day 6 (Day S6) of their assisted reproductive technology (ART) treatment cycle, continuing at the same dose until injection of hCG upto and including day of last FSH dose.

Measured Values

	Recombinant Human-Luteinizing Hormone (Luveris)
Number of Participants Analyzed [units: participants]	52
Number of Participants With Multiple Pregnancies [units: participants]	4

No statistical analysis provided for Number of Participants With Multiple Pregnancies

6. Secondary:

Number of Live Births [ Time Frame: Post-hCG days 15-20 to pregnancy follow up. ]

Measure Type	Secondary
Measure Title	Number of Live Births
Measure Description	A live birth occurs when a fetus, whatever its gestational age, exits the maternal body and subsequently shows any sign of life, such as voluntary movement, heartbeat, or pulsation of the umbilical cord, for however brief a time and regardless of whether the umbilical cord or placenta are intact.
Time Frame	Post-hCG days 15-20 to pregnancy follow up.
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population: all participants who received at least one dose of the study drug.

Reporting Groups

	Description
Recombinant Human-Luteinizing Hormone (Luveris)	All participants received Luveris 150 International Unit (IU) per day, subcutaneously (s.c) from stimulation day 6 (Day S6) of their assisted reproductive technology (ART) treatment cycle, continuing at the same dose until injection of hCG upto and including day of last FSH dose.

Measured Values

	Recombinant Human-Luteinizing Hormone (Luveris)
Number of Participants Analyzed [units: participants]	52
Number of Live Births [units: Live births]	13

No statistical analysis provided for Number of Live Births

7. Secondary:

Pregnancy Loss Per Clinical Pregnancy [ Time Frame: Post-hCG days 35-42. ]

Measure Type	Secondary
Measure Title	Pregnancy Loss Per Clinical Pregnancy
Measure Description	Preclinical miscarriage: Spontaneous cessation of a biochemical pregnancy. Early spontaneous abortion: Any spontaneous abortion occurring after confirmation of clinical pregnancy and before completion of 12 weeks of gestation. Late spontaneous abortion: any spontaneous abortion occurring between completion of 12 weeks of gestation and prior to a viable stage. Pregnancy loss per clinical pregnancy was measured as a percentage.
Time Frame	Post-hCG days 35-42.
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants with confirmed clinical pregnancies.

Reporting Groups

	Description
Recombinant Human-Luteinizing Hormone (Luveris)	All participants received Luveris 150 International Unit (IU) per day, subcutaneously (s.c) from stimulation day 6 (Day S6) of their assisted reproductive technology (ART) treatment cycle, continuing at the same dose until injection of hCG upto and including day of last FSH dose.

Measured Values

	Recombinant Human-Luteinizing Hormone (Luveris)
Number of Participants Analyzed [units: participants]	14
Pregnancy Loss Per Clinical Pregnancy [units: Percentage of pregnancy loss]	7.14

No statistical analysis provided for Pregnancy Loss Per Clinical Pregnancy

8. Secondary:

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Study Drug Discontinuation. [ Time Frame: From stimulation Day 1 (S1) to post-hCG days 35-42 (safety visit). ]

Measure Type	Secondary
Measure Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Study Drug Discontinuation.
Measure Description	AEs: Any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. TEAEs: AEs that occur during treatment with the study drug. It also included incidences of mild, moderate and severe ovarian hyperstimulation syndrome (OHSS). SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued from the study due to AE were also recorded.
Time Frame	From stimulation Day 1 (S1) to post-hCG days 35-42 (safety visit).
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population: all participants who received at least one dose of the study drug.

Reporting Groups

	Description
Recombinant Human-Luteinizing Hormone (Luveris)	All participants received Luveris 150 International Unit (IU) per day, subcutaneously (s.c) from stimulation day 6 (Day S6) of their assisted reproductive technology (ART) treatment cycle, continuing at the same dose until injection of hCG upto and including day of last FSH dose.

Measured Values

	Recombinant Human-Luteinizing Hormone (Luveris)
Number of Participants Analyzed [units: participants]	52
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Study Drug Discontinuation. [units: Number of participants]
TEAEs	15
SAEs	3
Discontinuation due to AEs	0

No statistical analysis provided for Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Study Drug Discontinuation.

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: No text entered.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Medical Responsible
Organization: EMD Serono Canada Inc., an affiliate of Merck KGaA, Darmstadt, Germany
phone: +1-888-737-6668 ext 5248
e-mail: david.sciberras@emdserono.com

No publications provided

Responsible Party:	Irene Kavanagh, Medical Research Manager, EMD Serono Canada Inc., an affiliate of Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier:	NCT01121991 History of Changes
Other Study ID Numbers:	IMP 25244
Study First Received:	May 10, 2010
Results First Received:	February 17, 2011
Last Updated:	June 8, 2011
Health Authority:	Canada: Health Canada

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