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A Clinical Trial to Determine the Effect of Lutropin Alfa on Embryo Quality and Implantation Rate in Advanced Reproductive Age

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ClinicalTrials.gov Identifier: NCT01075815
Recruitment Status : Terminated
First Posted : February 25, 2010
Results First Posted : November 20, 2012
Last Update Posted : February 13, 2014
Sponsor:
Collaborator:
Merck, S.L., Spain
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Infertility
Ovulation Induction
Interventions Drug: Recombinant human luteinizing hormone (rhLH)
Drug: Recombinant follicle-stimulating hormone (rFSH)
Enrollment 76
Recruitment Details  
Pre-assignment Details One out of 76 randomized participants did not receive study medication.
Arm/Group Title rFSH + rhLH rFSH
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 40 [1] 35 [1]
Completed 30 31
Not Completed 10 4
Reason Not Completed
Withdrawal before r-hCG administration             6             1
Withdrawal between rhCG-ovum pickup(OPU)             1             1
Withdrawal between OPU - embryo transfer             3             2
[1]
Number of participants treated.
Arm/Group Title rFSH + rhLH rFSH Total
Hide Arm/Group Description 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 40 35 75
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 40 participants 35 participants 75 participants
37.2  (2.2) 37.3  (1.5) 37.2  (1.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 35 participants 75 participants
Female
40
 100.0%
35
 100.0%
75
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Implantation Rate
Hide Description Implantation rate was measured as the number of gestational sacs observed, divided by the number of embryos transferred.
Time Frame Day 35-42 post ovum pick-up (OPU) (34-38 hours post recombinant human choriogonadotropin day {end of stimulation cycle}[approximately 28 days])
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT) population included all randomized participants who had received at least 1 dose of the study medication.
Arm/Group Title rFSH + rhLH rFSH
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 40 35
Mean (Standard Deviation)
Unit of Measure: sacs per embryo
0.2  (0.4) 0.2  (0.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection rFSH + rhLH, rFSH
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8762
Comments [Not Specified]
Method Wilcoxon two sample test
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0235
Confidence Interval (2-Sided) 95%
-0.1546 to 0.1568
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Mean Number of Follicles Greater Than or Equal to 14 Millimeter (mm) on Recombinant Human Choriogonadotropin (r-hCG) Day
Hide Description [Not Specified]
Time Frame r-hCG day (end of stimulation cycle [approximately 28 days])
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants who had received at least 1 dose of the study medication.
Arm/Group Title rFSH + rhLH rFSH
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 40 35
Mean (Standard Deviation)
Unit of Measure: follicles
7.7  (4.9) 8.7  (4.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection rFSH + rhLH, rFSH
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3589
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
3.Secondary Outcome
Title Mean Number of Oocytes Retrieved
Hide Description 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.
Time Frame 34-38 hours post r-hCG day (end of stimulation cycle [approximately 28 days])
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants who had received at least 1 dose of the study medication.
Arm/Group Title rFSH + rhLH rFSH
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 40 35
Mean (Standard Deviation)
Unit of Measure: oocytes
5.9  (3.9) 7.7  (4.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection rFSH + rhLH, rFSH
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0629
Comments [Not Specified]
Method Wilcoxon two sample test
Comments [Not Specified]
4.Secondary Outcome
Title Number of Mature Oocytes Retrieved
Hide Description 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.
Time Frame 34-38 hours post r-hCG day (end of stimulation cycle [approximately 28 days])
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants who had received at least 1 dose of the study medication.
Arm/Group Title rFSH + rhLH rFSH
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 40 35
Measure Type: Number
Unit of Measure: mature oocytes
234 271
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection rFSH + rhLH, rFSH
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4728
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
5.Secondary Outcome
Title Number of Fertilized Oocytes (2 Pronuclei [PN])
Hide Description 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.
Time Frame 34-38 hours post r-hCG day (end of stimulation cycle [approximately 28 days])
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants who had received at least 1 dose of the study medication.
Arm/Group Title rFSH + rhLH rFSH
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 40 35
Measure Type: Number
Unit of Measure: 2PN oocytes
128 136
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection rFSH + rhLH, rFSH
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0950
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
6.Secondary Outcome
Title Number and Quality of Embryos
Hide Description 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.
Time Frame Day 2-3 post OPU (34-38 hours post r-hCG day {end of stimulation cycle}[approximately 28 days])
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title rFSH + rhLH rFSH
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 31 32
Measure Type: Number
Unit of Measure: embyros
A + B (good quality) 69 65
C + D (poor quality) 56 73
Total embryos 125 138
7.Secondary Outcome
Title Number of Participants With Biochemical Pregnancies
Hide Description 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.
Time Frame 2 months after OPU (34-38 hours post r-hCG day {end of stimulation cycle} [approximately 28 days])
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants who had received at least 1 dose of the study medication.
Arm/Group Title rFSH + rhLH rFSH
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 40 35
Measure Type: Number
Unit of Measure: participants
11 10
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection rFSH + rhLH, rFSH
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9179
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.9625
Confidence Interval (2-Sided) 95%
0.4655 to 1.9900
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Number of Participants With Clinical Pregnancies
Hide Description 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.
Time Frame 2 months after OPU (34-38 hours post r-hCG day {end of stimulation cycle} [approximately 28 days])
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants who had received at least 1 dose of the study medication.
Arm/Group Title rFSH + rhLH rFSH
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 40 35
Measure Type: Number
Unit of Measure: participants
10 10
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection rFSH + rhLH, rFSH
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7271
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.8750
Confidence Interval (2-Sided) 95%
0.4133 to 1.8524
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Total Dose of Recombinant Follicle Stimulating Hormone (r-FSH)
Hide Description [Not Specified]
Time Frame 2 months after OPU (34-38 hours post r-hCG day {end of stimulation cycle} [approximately 28 days])
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants who had received at least 1 dose of the study medication.
Arm/Group Title rFSH + rhLH rFSH
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 40 35
Mean (Standard Deviation)
Unit of Measure: IU
2812.2  (719.4) 2970.3  (748.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection rFSH + rhLH, rFSH
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3267
Comments [Not Specified]
Method Wilcoxon two sample test
Comments [Not Specified]
10.Secondary Outcome
Title Estradiol (E2) Levels on r-hCG Day
Hide Description [Not Specified]
Time Frame r-hCG day (end of stimulation cycle [approximately 28 days])
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title rFSH + rhLH rFSH
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 33 29
Mean (Standard Deviation)
Unit of Measure: picogram/milliter (pg/mL)
1890.2  (1084.4) 1621  (827.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection rFSH + rhLH, rFSH
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4164
Comments [Not Specified]
Method Wilcoxon two sample test
Comments [Not Specified]
11.Secondary Outcome
Title Number of Ovarian Stimulation Days
Hide Description 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.
Time Frame S1 up to r-hCG day (end of stimulation cycle [approximately 28 days])
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants who had received at least 1 dose of the study medication.
Arm/Group Title rFSH + rhLH rFSH
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 40 35
Mean (Standard Deviation)
Unit of Measure: Days
9.7  (2.1) 9.8  (1.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection rFSH + rhLH, rFSH
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5952
Comments [Not Specified]
Method Wilcoxon two sample test
Comments [Not Specified]
12.Secondary Outcome
Title Number of Recombinant Human Choriogonadotropin (r-hCG) Cycles Cancelled Due to Poor Response
Hide Description 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.
Time Frame Up to 2 months after OPU (34-38 hours post r-hCG day {end of stimulation cycle} [approximately 28 days])
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants who had received at least 1 dose of the study medication.
Arm/Group Title rFSH + rhLH rFSH
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 40 35
Measure Type: Number
Unit of Measure: cycles
4 1
13.Secondary Outcome
Title Total Number of Births
Hide Description Total number of births per reporting group was calculated.
Time Frame Up to 2 months after OPU (34-38 hours post r-hCG day {end of stimulation cycle} [approximately 28 days])
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title rFSH + rhLH rFSH
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 40 34
Measure Type: Number
Unit of Measure: births
10 9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection rFSH + rhLH, rFSH
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8852
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.9444
Confidence Interval (2-Sided) 95%
0.4347 to 2.0518
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Number of Participants With Adverse Events (AEs)
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Time Frame Baseline up to 2 months after OPU (34-38 hours post r-hCG day {end of stimulation cycle} [approximately 28 days])
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who had received at least 1 dose of the study medication.
Arm/Group Title rFSH + rhLH rFSH
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 40 35
Measure Type: Number
Unit of Measure: participants
19 9
15.Secondary Outcome
Title Number of Participants With Ovarian Hyper Stimulation Syndrome (OHSS)
Hide Description OHSS is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting.
Time Frame Baseline up to 2 months after OPU (34-38 hours post r-hCG day {end of stimulation cycle} [approximately 28 days])
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who had received at least 1 dose of the study medication.
Arm/Group Title rFSH + rhLH rFSH
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 40 35
Measure Type: Number
Unit of Measure: participants
1 0
16.Secondary Outcome
Title Number of Cycles Cancelled Due to Risk of Ovarian Hyper Stimulation Syndrome (OHSS)
Hide Description OHSS is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting.
Time Frame Baseline up to 2 months after OPU (34-38 hours post r-hCG day {end of stimulation cycle} [approximately 28 days])
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who had received at least 1 dose of the study medication.
Arm/Group Title rFSH + rhLH rFSH
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 40 35
Measure Type: Number
Unit of Measure: cycles
1 0
Time Frame AEs are collected on an ongoing basis from day of written informed consent. All new AEs must be recorded until the post-treatment safety, on day 35-42 post-hCG administration. AEs are classified as pre-treatment, treatment-emergent and post-treatment.
Adverse Event Reporting Description Pre-Treatment:Medical conditions present at the initial study visit that did not worsen in severity or frequency during the study;Treatment-Emergent: If the onset date of the AE was on or after the first dose date of the study medication; Post-Treatment: If the onset date of the AE was post-hCG Days 35- 42 for participants who completed the study.
 
Arm/Group Title rFSH + rhLH rFSH
Hide Arm/Group Description 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. 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.
All-Cause Mortality
rFSH + rhLH rFSH
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
rFSH + rhLH rFSH
Affected / at Risk (%) Affected / at Risk (%)
Total   2/40 (5.00%)   1/35 (2.86%) 
Congenital, familial and genetic disorders     
Trisomy 13 * 1  0/40 (0.00%)  1/35 (2.86%) 
Musculoskeletal and connective tissue disorders     
New born hip dysplasia * 1  1/40 (2.50%)  0/35 (0.00%) 
Skin and subcutaneous tissue disorders     
Cutaneous anginoma * 1  1/40 (2.50%)  0/35 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
rFSH + rhLH rFSH
Affected / at Risk (%) Affected / at Risk (%)
Total   17/40 (42.50%)   8/35 (22.86%) 
Gastrointestinal disorders     
Bloating * 1  2/40 (5.00%)  0/35 (0.00%) 
Retching * 1  1/40 (2.50%)  0/35 (0.00%) 
Diarrhoea * 1  1/40 (2.50%)  0/35 (0.00%) 
Abdominal pain * 1  1/40 (2.50%)  0/35 (0.00%) 
Odynophagia * 1  1/40 (2.50%)  0/35 (0.00%) 
General disorders     
Pain * 1  1/40 (2.50%)  2/35 (5.71%) 
Pain at the injection site * 1  5/40 (12.50%)  0/35 (0.00%) 
Erythema at the injection site * 1  2/40 (5.00%)  0/35 (0.00%) 
Pruritus at the injection site * 1  2/40 (5.00%)  0/35 (0.00%) 
Oedema * 1  1/40 (2.50%)  0/35 (0.00%) 
Haematoma at the injection site * 1  1/40 (2.50%)  0/35 (0.00%) 
Swelling * 1  0/40 (0.00%)  1/35 (2.86%) 
Inflammation * 1  1/40 (2.50%)  1/35 (2.86%) 
Inflammation at the injection site * 1  1/40 (2.50%)  0/35 (0.00%) 
General malaise * 1  1/40 (2.50%)  0/35 (0.00%) 
Reaction at the injection site * 1  1/40 (2.50%)  0/35 (0.00%) 
Injury, poisoning and procedural complications     
Subcutaneous haematoma * 1  2/40 (5.00%)  2/35 (5.71%) 
Nervous system disorders     
Headache * 1  4/40 (10.00%)  3/35 (8.57%) 
Dizziness * 1  1/40 (2.50%)  2/35 (5.71%) 
Burning sensation * 1  1/40 (2.50%)  0/35 (0.00%) 
Pregnancy, puerperium and perinatal conditions     
Premature birth * 1  2/40 (5.00%)  1/35 (2.86%) 
Psychiatric disorders     
Mood change * 1  0/40 (0.00%)  1/35 (2.86%) 
Reproductive system and breast disorders     
Ovarian hyperstimulation syndrome * 1  1/40 (2.50%)  0/35 (0.00%) 
Dysmenorrhoea * 1  0/40 (0.00%)  1/35 (2.86%) 
Pelvic pain * 1  1/40 (2.50%)  0/35 (0.00%) 
Genital secretion * 1  0/40 (0.00%)  1/35 (2.86%) 
Skin and subcutaneous tissue disorders     
Ecchymosis * 1  3/40 (7.50%)  0/35 (0.00%) 
Erythema * 1  5/40 (12.50%)  0/35 (0.00%) 
Pruritus * 1  4/40 (10.00%)  1/35 (2.86%) 
Vascular disorders     
Haematoma * 1  4/40 (10.00%)  1/35 (2.86%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.0
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.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Merck KGaA Communication Center
Organization: Merck Serono, a division of Merck KGaA
Phone: +49-6151-72-5200
EMail: service@merckgroup.com
Layout table for additonal information
Responsible Party: Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT01075815    
Other Study ID Numbers: 700642-500
2008-002281-55 ( EudraCT Number )
First Submitted: February 24, 2010
First Posted: February 25, 2010
Results First Submitted: August 29, 2012
Results First Posted: November 20, 2012
Last Update Posted: February 13, 2014