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PERgoveriS In Stratified Treatment for Assisted Reproductive Technique (PERSIST)

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ClinicalTrials.gov Identifier: NCT01297465
Recruitment Status : Completed
First Posted : February 16, 2011
Results First Posted : February 24, 2014
Last Update Posted : February 24, 2014
Sponsor:
Collaborators:
Merck Serono S.A., Geneva
Merck A/S, Denmark
Merck OY, Finland
Merck Serono S.A.S, France
Merck Serono GmbH, Germany
Merck A.E., Greece
Merck B.V., Netherlands
Merck SP. Z.O.O., Poland
Merck Serono S.P.A., Italy
Merck Services U.K. Ltd, UK
LLC Merck, Russia
Merck spol. s r.o., Slovakia
Merck Pharma, K.S., Slovakia
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 Assisted Reproductive Techniques
Reproductive Technology, Assisted
Interventions Drug: Gonal-f®
Drug: Pergoveris®
Drug: Recombinant human chorionic gonadotropin (r-hCG)
Enrollment 202
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Gonal-f® Plus Pergoveris® Pergoveris®
Hide Arm/Group Description Gonal-f® (follitropin alfa) 300 International Unit (IU) was administered subcutaneously once daily from stimulation day 1 (S1) to stimulation day 5 (S5) followed by subsequent daily administration of Pergoveris® (follitropin alfa and lutropin alfa) 300 IU subcutaneously starting from S6 until recombinant human chorionic gonadotropin (r-hCG) (Ovidrel®/Ovitrelle®) administration day (at least 1 follicles greater than or equal to (>=) 18 millimeter [mm]). On r-hCG day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted based upon the participant's ovarian response and according to the site's standard practice. Pergoveris® (follitropin alfa and lutropin alfa) 300 IU was administered subcutaneously once daily from S1 until r-hCG administration day (at least 1 follicles >= 18 mm). On r-hCG (Ovidrel®/Ovitrelle®) day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted starting from S6 based upon the participant's ovarian response and according to the site's standard practice.
Period Title: Overall Study
Started 99 103
Completed 91 93
Not Completed 8 10
Reason Not Completed
Lack of Ovarian Response             1             1
Ovarian hyperstimulation syndrome risk             0             1
No Oocytes Retrieved             1             1
Poor oocyte quality             0             1
No Fertilization             6             4
All Embryos Discarded             0             1
Intention to Freeze all Embryos             0             1
Arm/Group Title Gonal-f® Plus Pergoveris® Pergoveris® Total
Hide Arm/Group Description Gonal-f® (follitropin alfa) 300 International Unit (IU) was administered subcutaneously once daily from stimulation day 1 (S1) to stimulation day 5 (S5) followed by subsequent daily administration of Pergoveris® (follitropin alfa and lutropin alfa) 300 IU subcutaneously starting from S6 until recombinant human chorionic gonadotropin (r-hCG) (Ovidrel®/Ovitrelle®) administration day (at least 1 follicles greater than or equal to (>=) 18 millimeter [mm]). On r-hCG day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted based upon the participant's ovarian response and according to the site's standard practice. Pergoveris® (follitropin alfa and lutropin alfa) 300 IU was administered subcutaneously once daily from S1 until r-hCG administration day (at least 1 follicles >= 18 mm). On r-hCG (Ovidrel®/Ovitrelle®) day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted starting from S6 based upon the participant's ovarian response and according to the site's standard practice. Total of all reporting groups
Overall Number of Baseline Participants 99 103 202
Hide Baseline Analysis Population Description
Safety Population included all the randomized participants who had received at least 1 dose of Pergoveris® or Gonal-f®.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 99 participants 103 participants 202 participants
37.6  (1.16) 37.4  (1.14) 37.5  (1.15)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 99 participants 103 participants 202 participants
Female
99
 100.0%
103
 100.0%
202
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 99 participants 103 participants 202 participants
Black 4 3 7
Asian 4 6 10
Other 2 2 4
White 89 92 181
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeter
Number Analyzed 99 participants 103 participants 202 participants
166.1  (6.49) 166.3  (6.47) 166.2  (6.46)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilogram
Number Analyzed 99 participants 103 participants 202 participants
64.81  (10.364) 65.82  (8.923) 65.33  (9.645)
1.Primary Outcome
Title Total Number of Oocytes Retrieved
Hide Description The total number of oocytes retrieved per reporting group on the day of ovum pick-up (OPU) (34-38 hours post r-hCG day) was calculated. Oocyte retrieval is a technique used in in-vitro fertilization (IVF) in order to remove oocytes from the ovary of the female participant, enabling fertilization outside the body.
Time Frame OPU day (34-38 hours post r-hCG day [end of stimulation cycle {approximately 11 days}])
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intention-to-treat (Mod-ITT) population included all the randomized participants who had received at least one dose of GONAL-f® or Pergoveris®, and completed the primary efficacy assessment.
Arm/Group Title Gonal-f® Plus Pergoveris® Pergoveris®
Hide Arm/Group Description:
Gonal-f® (follitropin alfa) 300 International Unit (IU) was administered subcutaneously once daily from stimulation day 1 (S1) to stimulation day 5 (S5) followed by subsequent daily administration of Pergoveris® (follitropin alfa and lutropin alfa) 300 IU subcutaneously starting from S6 until recombinant human chorionic gonadotropin (r-hCG) (Ovidrel®/Ovitrelle®) administration day (at least 1 follicles greater than or equal to (>=) 18 millimeter [mm]). On r-hCG day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted based upon the participant's ovarian response and according to the site's standard practice.
Pergoveris® (follitropin alfa and lutropin alfa) 300 IU was administered subcutaneously once daily from S1 until r-hCG administration day (at least 1 follicles >= 18 mm). On r-hCG (Ovidrel®/Ovitrelle®) day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted starting from S6 based upon the participant's ovarian response and according to the site's standard practice.
Overall Number of Participants Analyzed 98 101
Mean (Standard Deviation)
Unit of Measure: oocytes
10.9  (6.5) 9.7  (6.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gonal-f® Plus Pergoveris®, Pergoveris®
Comments The null hypothesis was that the difference between the mean number of oocytes is less than (-3) or greater than (+3) between the two treatment arm. The alternate hypothesis was that the difference is between (-3) and (+3). The study had 80% power to show that the group randomized to Pergoveris® has an absolute difference of no more than 3 oocytes retrieved in comparison to the group randomized to GONAL-f®/Pergoveris®
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments ANOVA model adjusted for treatment and country
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.28
Confidence Interval (2-Sided) 95%
-3.15 to 0.59
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.947
Estimation Comments The primary efficacy variable was to be analyzed using an analysis of variance (ANOVA) model, adjusted for treatment and country.
2.Secondary Outcome
Title Total Dose and Mean Daily Dose of Follicle Stimulating Hormone (FSH)
Hide Description [Not Specified]
Time Frame Day 1 up to r-hCG day (end of stimulation cycle [approximately 11 days])
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all the randomized participants who had received at least 1 dose of Pergoveris® or Gonal-f®.
Arm/Group Title Gonal-f® Plus Pergoveris® Pergoveris®
Hide Arm/Group Description:
Gonal-f® (follitropin alfa) 300 International Unit (IU) was administered subcutaneously once daily from stimulation day 1 (S1) to stimulation day 5 (S5) followed by subsequent daily administration of Pergoveris® (follitropin alfa and lutropin alfa) 300 IU subcutaneously starting from S6 until recombinant human chorionic gonadotropin (r-hCG) (Ovidrel®/Ovitrelle®) administration day (at least 1 follicles greater than or equal to (>=) 18 millimeter [mm]). On r-hCG day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted based upon the participant's ovarian response and according to the site's standard practice.
Pergoveris® (follitropin alfa and lutropin alfa) 300 IU was administered subcutaneously once daily from S1 until r-hCG administration day (at least 1 follicles >= 18 mm). On r-hCG (Ovidrel®/Ovitrelle®) day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted starting from S6 based upon the participant's ovarian response and according to the site's standard practice.
Overall Number of Participants Analyzed 99 103
Mean (Standard Deviation)
Unit of Measure: IU
Total Dose 3292  (851) 3321  (850)
Mean Daily Dose 307  (43) 311  (41)
3.Secondary Outcome
Title Total Number of Stimulation Treatment Days
Hide Description [Not Specified]
Time Frame Day 1 up to r-hCG day (end of stimulation cycle [approximately 11 days])
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all the randomized participants who had received at least 1 dose of Pergoveris® or Gonal-f®.
Arm/Group Title Gonal-f® Plus Pergoveris® Pergoveris®
Hide Arm/Group Description:
Gonal-f® (follitropin alfa) 300 International Unit (IU) was administered subcutaneously once daily from stimulation day 1 (S1) to stimulation day 5 (S5) followed by subsequent daily administration of Pergoveris® (follitropin alfa and lutropin alfa) 300 IU subcutaneously starting from S6 until recombinant human chorionic gonadotropin (r-hCG) (Ovidrel®/Ovitrelle®) administration day (at least 1 follicles greater than or equal to (>=) 18 millimeter [mm]). On r-hCG day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted based upon the participant's ovarian response and according to the site's standard practice.
Pergoveris® (follitropin alfa and lutropin alfa) 300 IU was administered subcutaneously once daily from S1 until r-hCG administration day (at least 1 follicles >= 18 mm). On r-hCG (Ovidrel®/Ovitrelle®) day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted starting from S6 based upon the participant's ovarian response and according to the site's standard practice.
Overall Number of Participants Analyzed 99 103
Mean (Standard Deviation)
Unit of Measure: days
10.6  (1.6) 10.6  (1.7)
4.Secondary Outcome
Title Implantation Rate
Hide Description Implantation rate per reporting group was measured as the number of fetal sacs observed, divided by the number of embryos transferred multiplied by 100.
Time Frame Days 35-42 post r-hCG day (end of stimulation cycle [approximately 11 days])
Hide Outcome Measure Data
Hide Analysis Population Description
Mod-ITT population included all the randomized participants who had received at least one dose of GONAL-f® or Pergoveris®, and completed the primary efficacy assessment.
Arm/Group Title Gonal-f® Plus Pergoveris® Pergoveris®
Hide Arm/Group Description:
Gonal-f® (follitropin alfa) 300 International Unit (IU) was administered subcutaneously once daily from stimulation day 1 (S1) to stimulation day 5 (S5) followed by subsequent daily administration of Pergoveris® (follitropin alfa and lutropin alfa) 300 IU subcutaneously starting from S6 until recombinant human chorionic gonadotropin (r-hCG) (Ovidrel®/Ovitrelle®) administration day (at least 1 follicles greater than or equal to (>=) 18 millimeter [mm]). On r-hCG day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted based upon the participant's ovarian response and according to the site's standard practice.
Pergoveris® (follitropin alfa and lutropin alfa) 300 IU was administered subcutaneously once daily from S1 until r-hCG administration day (at least 1 follicles >= 18 mm). On r-hCG (Ovidrel®/Ovitrelle®) day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted starting from S6 based upon the participant's ovarian response and according to the site's standard practice.
Overall Number of Participants Analyzed 90 93
Mean (Standard Deviation)
Unit of Measure: percent sacs per embryo
13.3  (29.1) 24.7  (36.1)
5.Secondary Outcome
Title Number of Fetal Sacs With Activity
Hide Description Number of fetal sacs with activity was evaluated by ultrasound scan
Time Frame Days 35-42 post r-hCG day [end of stimulation cycle {approximately 11 days}])
Hide Outcome Measure Data
Hide Analysis Population Description
Mod-ITT population included all the randomized participants who had received at least one dose of GONAL-f® or Pergoveris®, and completed the primary efficacy assessment."N" (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Gonal-f® Plus Pergoveris® Pergoveris®
Hide Arm/Group Description:
Gonal-f® (follitropin alfa) 300 International Unit (IU) was administered subcutaneously once daily from stimulation day 1 (S1) to stimulation day 5 (S5) followed by subsequent daily administration of Pergoveris® (follitropin alfa and lutropin alfa) 300 IU subcutaneously starting from S6 until recombinant human chorionic gonadotropin (r-hCG) (Ovidrel®/Ovitrelle®) administration day (at least 1 follicles greater than or equal to (>=) 18 millimeter [mm]). On r-hCG day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted based upon the participant's ovarian response and according to the site's standard practice.
Pergoveris® (follitropin alfa and lutropin alfa) 300 IU was administered subcutaneously once daily from S1 until r-hCG administration day (at least 1 follicles >= 18 mm). On r-hCG (Ovidrel®/Ovitrelle®) day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted starting from S6 based upon the participant's ovarian response and according to the site's standard practice.
Overall Number of Participants Analyzed 18 35
Mean (Standard Deviation)
Unit of Measure: fetal sacs
1.4  (0.5) 1.2  (0.4)
6.Secondary Outcome
Title Number of Fetal Hearts With Activity
Hide Description Number of fetal hearts with activity was evaluated by ultrasound scan
Time Frame Days 35-42 post r-hCG day [end of stimulation cycle {approximately 11 days}])
Hide Outcome Measure Data
Hide Analysis Population Description
Mod-ITT population included all the randomized participants who had received at least one dose of GONAL-f® or Pergoveris®, and completed the primary efficacy assessment."N" (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Gonal-f® Plus Pergoveris® Pergoveris®
Hide Arm/Group Description:
Gonal-f® (follitropin alfa) 300 International Unit (IU) was administered subcutaneously once daily from stimulation day 1 (S1) to stimulation day 5 (S5) followed by subsequent daily administration of Pergoveris® (follitropin alfa and lutropin alfa) 300 IU subcutaneously starting from S6 until recombinant human chorionic gonadotropin (r-hCG) (Ovidrel®/Ovitrelle®) administration day (at least 1 follicles greater than or equal to (>=) 18 millimeter [mm]). On r-hCG day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted based upon the participant's ovarian response and according to the site's standard practice.
Pergoveris® (follitropin alfa and lutropin alfa) 300 IU was administered subcutaneously once daily from S1 until r-hCG administration day (at least 1 follicles >= 18 mm). On r-hCG (Ovidrel®/Ovitrelle®) day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted starting from S6 based upon the participant's ovarian response and according to the site's standard practice.
Overall Number of Participants Analyzed 17 32
Mean (Standard Deviation)
Unit of Measure: fetal hearts
1.4  (0.5) 1.3  (0.5)
7.Secondary Outcome
Title Clinical Pregnancy Rate
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. Clinical pregnancy rate was reported as total clinical pregnancy rate, clinical pregnancy rate per cycle started and per embryo transfer [ET]).
Time Frame Days 35-42 post r-hCG day (end of stimulation cycle [approximately 11 days])
Hide Outcome Measure Data
Hide Analysis Population Description
Mod-ITT population included all the randomized participants who had received at least one dose of GONAL-f® or Pergoveris®, and had completed the primary efficacy assessment. "N" signifies those participants who had their ET in study treatment cycle. "n" signifies those participants who were evaluated for this measure in specified categories.
Arm/Group Title Gonal-f® Plus Pergoveris® Pergoveris®
Hide Arm/Group Description:
Gonal-f® (follitropin alfa) 300 International Unit (IU) was administered subcutaneously once daily from stimulation day 1 (S1) to stimulation day 5 (S5) followed by subsequent daily administration of Pergoveris® (follitropin alfa and lutropin alfa) 300 IU subcutaneously starting from S6 until recombinant human chorionic gonadotropin (r-hCG) (Ovidrel®/Ovitrelle®) administration day (at least 1 follicles greater than or equal to (>=) 18 millimeter [mm]). On r-hCG day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted based upon the participant's ovarian response and according to the site's standard practice.
Pergoveris® (follitropin alfa and lutropin alfa) 300 IU was administered subcutaneously once daily from S1 until r-hCG administration day (at least 1 follicles >= 18 mm). On r-hCG (Ovidrel®/Ovitrelle®) day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted starting from S6 based upon the participant's ovarian response and according to the site's standard practice.
Overall Number of Participants Analyzed 97 101
Measure Type: Number
Unit of Measure: percentage of participants
Total clinical pregnancy rate (n=97, 101) 17.5 31.7
Clinical pregnancy rate per cycle (n=97, 101) 17.5 31.7
Clinical pregnancy rate per ET (n=90, 93) 18.9 34.4
8.Secondary Outcome
Title Number of Participants With Cancelled Cycles Due to Excessive or Insufficient Ovarian Response to Treatment
Hide Description An excessive ovarian response: greater than or equal to 25 oocytes which could put the participant at risk of OHSS; An insufficient ovarian response: defined as 3 or less follicles of greater than or equal to 12 millimeter developing following at least 7 days of treatment.
Time Frame S1 until Day 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days])
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all the randomized participants who had received at least 1 dose of Pergoveris® or Gonal-f®.
Arm/Group Title Gonal-f® Plus Pergoveris® Pergoveris®
Hide Arm/Group Description:
Gonal-f® (follitropin alfa) 300 International Unit (IU) was administered subcutaneously once daily from stimulation day 1 (S1) to stimulation day 5 (S5) followed by subsequent daily administration of Pergoveris® (follitropin alfa and lutropin alfa) 300 IU subcutaneously starting from S6 until recombinant human chorionic gonadotropin (r-hCG) (Ovidrel®/Ovitrelle®) administration day (at least 1 follicles greater than or equal to (>=) 18 millimeter [mm]). On r-hCG day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted based upon the participant's ovarian response and according to the site's standard practice.
Pergoveris® (follitropin alfa and lutropin alfa) 300 IU was administered subcutaneously once daily from S1 until r-hCG administration day (at least 1 follicles >= 18 mm). On r-hCG (Ovidrel®/Ovitrelle®) day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted starting from S6 based upon the participant's ovarian response and according to the site's standard practice.
Overall Number of Participants Analyzed 99 103
Measure Type: Number
Unit of Measure: participants
Insufficient ovarian response 1 1
Excessive ovarian response 0 1
9.Secondary Outcome
Title Biochemical Pregnancies Rate
Hide Description Biochemical pregnancy was defined as the pregnancy diagnosed only by the detection of human chorionic gonadotropin (hCG) in serum or urine and that does not develop into a clinical pregnancy. Participants with beta- hCG concentration greater than 10 international units per liter (IU/L) were considered as biochemical pregnant.
Time Frame Days 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days])
Hide Outcome Measure Data
Hide Analysis Population Description
Mod-ITT population included all the randomized participants who had received at least one dose of GONAL-f® or Pergoveris®, and completed the primary efficacy assessment. . "N" (number of participants analyzed) signifies those participants who had their embryo transfer in study treatment cycle.
Arm/Group Title Gonal-f® Plus Pergoveris® Pergoveris®
Hide Arm/Group Description:
Gonal-f® (follitropin alfa) 300 International Unit (IU) was administered subcutaneously once daily from stimulation day 1 (S1) to stimulation day 5 (S5) followed by subsequent daily administration of Pergoveris® (follitropin alfa and lutropin alfa) 300 IU subcutaneously starting from S6 until recombinant human chorionic gonadotropin (r-hCG) (Ovidrel®/Ovitrelle®) administration day (at least 1 follicles greater than or equal to (>=) 18 millimeter [mm]). On r-hCG day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted based upon the participant's ovarian response and according to the site's standard practice.
Pergoveris® (follitropin alfa and lutropin alfa) 300 IU was administered subcutaneously once daily from S1 until r-hCG administration day (at least 1 follicles >= 18 mm). On r-hCG (Ovidrel®/Ovitrelle®) day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted starting from S6 based upon the participant's ovarian response and according to the site's standard practice.
Overall Number of Participants Analyzed 97 101
Measure Type: Number
Unit of Measure: participants
23 41
10.Secondary Outcome
Title Number of Participants With Multiple Pregnancies
Hide Description Multiple pregnancy was defined as the existence of more than one fetal sac with fetal heart activity.
Time Frame Days 35-42 post r-hCG day (end of stimulation cycle [approximately 11 days])
Hide Outcome Measure Data
Hide Analysis Population Description
Mod-ITT population included all the randomized participants who had received at least one dose of GONAL-f® or Pergoveris®, and completed the primary efficacy assessment. "N" (number of participants analyzed) signifies those participants who had their embryo transfer in study treatment cycle.
Arm/Group Title Gonal-f® Plus Pergoveris® Pergoveris®
Hide Arm/Group Description:
Gonal-f® (follitropin alfa) 300 International Unit (IU) was administered subcutaneously once daily from stimulation day 1 (S1) to stimulation day 5 (S5) followed by subsequent daily administration of Pergoveris® (follitropin alfa and lutropin alfa) 300 IU subcutaneously starting from S6 until recombinant human chorionic gonadotropin (r-hCG) (Ovidrel®/Ovitrelle®) administration day (at least 1 follicles greater than or equal to (>=) 18 millimeter [mm]). On r-hCG day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted based upon the participant's ovarian response and according to the site's standard practice.
Pergoveris® (follitropin alfa and lutropin alfa) 300 IU was administered subcutaneously once daily from S1 until r-hCG administration day (at least 1 follicles >= 18 mm). On r-hCG (Ovidrel®/Ovitrelle®) day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted starting from S6 based upon the participant's ovarian response and according to the site's standard practice.
Overall Number of Participants Analyzed 97 101
Measure Type: Number
Unit of Measure: participants
6 8
11.Secondary Outcome
Title Number of Participants With Early and Late Ovarian Hyper Stimulation Syndrome (OHSS)
Hide Description Ovarian Hyper Stimulation Syndrome (OHSS) is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting. Early OHSS was defined as the onset of OHSS occurring within 9 days after oocyte retrieval and late OHSS was defined as the onset of OHSS occurring on or after day 10 from oocyte retrieval.
Time Frame Days 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days])
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all the randomized participants who had received at least 1 dose of Pergoveris® or Gonal-f®.
Arm/Group Title Gonal-f® Plus Pergoveris® Pergoveris®
Hide Arm/Group Description:
Gonal-f® (follitropin alfa) 300 International Unit (IU) was administered subcutaneously once daily from stimulation day 1 (S1) to stimulation day 5 (S5) followed by subsequent daily administration of Pergoveris® (follitropin alfa and lutropin alfa) 300 IU subcutaneously starting from S6 until recombinant human chorionic gonadotropin (r-hCG) (Ovidrel®/Ovitrelle®) administration day (at least 1 follicles greater than or equal to (>=) 18 millimeter [mm]). On r-hCG day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted based upon the participant's ovarian response and according to the site's standard practice.
Pergoveris® (follitropin alfa and lutropin alfa) 300 IU was administered subcutaneously once daily from S1 until r-hCG administration day (at least 1 follicles >= 18 mm). On r-hCG (Ovidrel®/Ovitrelle®) day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted starting from S6 based upon the participant's ovarian response and according to the site's standard practice.
Overall Number of Participants Analyzed 99 103
Measure Type: Number
Unit of Measure: participants
Early Ovarian hyperstimulation syndrome 4 1
Late Ovarian hyperstimulation syndrome 0 1
12.Secondary Outcome
Title Number of Participants With Treatment-emergent Adverse Events
Hide Description An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Time Frame Day 1 up to days 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days])
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all the randomized participants who had received at least 1 dose of Pergoveris® or Gonal-f®.
Arm/Group Title Gonal-f® Plus Pergoveris® Pergoveris®
Hide Arm/Group Description:
Gonal-f® (follitropin alfa) 300 International Unit (IU) was administered subcutaneously once daily from stimulation day 1 (S1) to stimulation day 5 (S5) followed by subsequent daily administration of Pergoveris® (follitropin alfa and lutropin alfa) 300 IU subcutaneously starting from S6 until recombinant human chorionic gonadotropin (r-hCG) (Ovidrel®/Ovitrelle®) administration day (at least 1 follicles greater than or equal to (>=) 18 millimeter [mm]). On r-hCG day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted based upon the participant's ovarian response and according to the site's standard practice.
Pergoveris® (follitropin alfa and lutropin alfa) 300 IU was administered subcutaneously once daily from S1 until r-hCG administration day (at least 1 follicles >= 18 mm). On r-hCG (Ovidrel®/Ovitrelle®) day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted starting from S6 based upon the participant's ovarian response and according to the site's standard practice.
Overall Number of Participants Analyzed 99 103
Measure Type: Number
Unit of Measure: participants
26 23
13.Secondary Outcome
Title Systolic and Diastolic Arterial Blood Pressure Assessments
Hide Description [Not Specified]
Time Frame Days 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days])
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all the randomized participants who had received at least 1 dose of Pergoveris® or Gonal-f®. ."N" (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Gonal-f® Plus Pergoveris® Pergoveris®
Hide Arm/Group Description:
Gonal-f® (follitropin alfa) 300 International Unit (IU) was administered subcutaneously once daily from stimulation day 1 (S1) to stimulation day 5 (S5) followed by subsequent daily administration of Pergoveris® (follitropin alfa and lutropin alfa) 300 IU subcutaneously starting from S6 until recombinant human chorionic gonadotropin (r-hCG) (Ovidrel®/Ovitrelle®) administration day (at least 1 follicles greater than or equal to (>=) 18 millimeter [mm]). On r-hCG day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted based upon the participant's ovarian response and according to the site's standard practice.
Pergoveris® (follitropin alfa and lutropin alfa) 300 IU was administered subcutaneously once daily from S1 until r-hCG administration day (at least 1 follicles >= 18 mm). On r-hCG (Ovidrel®/Ovitrelle®) day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted starting from S6 based upon the participant's ovarian response and according to the site's standard practice.
Overall Number of Participants Analyzed 93 99
Mean (Standard Deviation)
Unit of Measure: millimeter of mercury ( mm Hg)
Systolic Blood Pressure 118.9  (12.8) 121.2  (14.8)
Diastolic Blood Pressure 74.8  (9.8) 76.8  (9.5)
14.Secondary Outcome
Title Heart Rate Assessments
Hide Description [Not Specified]
Time Frame Days 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days])
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all the randomized participants who had received at least 1 dose of Pergoveris® or Gonal-f®. ."N" (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Gonal-f® Plus Pergoveris® Pergoveris®
Hide Arm/Group Description:
Gonal-f® (follitropin alfa) 300 International Unit (IU) was administered subcutaneously once daily from stimulation day 1 (S1) to stimulation day 5 (S5) followed by subsequent daily administration of Pergoveris® (follitropin alfa and lutropin alfa) 300 IU subcutaneously starting from S6 until recombinant human chorionic gonadotropin (r-hCG) (Ovidrel®/Ovitrelle®) administration day (at least 1 follicles greater than or equal to (>=) 18 millimeter [mm]). On r-hCG day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted based upon the participant's ovarian response and according to the site's standard practice.
Pergoveris® (follitropin alfa and lutropin alfa) 300 IU was administered subcutaneously once daily from S1 until r-hCG administration day (at least 1 follicles >= 18 mm). On r-hCG (Ovidrel®/Ovitrelle®) day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted starting from S6 based upon the participant's ovarian response and according to the site's standard practice.
Overall Number of Participants Analyzed 93 99
Mean (Standard Deviation)
Unit of Measure: beats per minute (bpm)
75.7  (10.5) 76.5  (10)
Time Frame Days 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days])
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Gonal-f® Plus Pergoveris® Pergoveris®
Hide Arm/Group Description Gonal-f® (follitropin alfa) 300 International Unit (IU) was administered subcutaneously once daily from stimulation day 1 (S1) to stimulation day 5 (S5) followed by subsequent daily administration of Pergoveris® (follitropin alfa and lutropin alfa) 300 IU subcutaneously starting from S6 until recombinant human chorionic gonadotropin (r-hCG) (Ovidrel®/Ovitrelle®) administration day (at least 1 follicles greater than or equal to (>=) 18 millimeter [mm]). On r-hCG day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted based upon the participant's ovarian response and according to the site's standard practice. Pergoveris® (follitropin alfa and lutropin alfa) 300 IU was administered subcutaneously once daily from S1 until r-hCG administration day (at least 1 follicles >= 18 mm). On r-hCG (Ovidrel®/Ovitrelle®) day, 250 microgram of r-hCG was administered once subcutaneously. The dose of Pergoveris® was adjusted starting from S6 based upon the participant's ovarian response and according to the site's standard practice.
All-Cause Mortality
Gonal-f® Plus Pergoveris® Pergoveris®
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Gonal-f® Plus Pergoveris® Pergoveris®
Affected / at Risk (%) Affected / at Risk (%)
Total   2/99 (2.02%)   0/103 (0.00%) 
Reproductive system and breast disorders     
Ovarian hyperstimulation syndrome * 1  2/99 (2.02%)  0/103 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 15.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Gonal-f® Plus Pergoveris® Pergoveris®
Affected / at Risk (%) Affected / at Risk (%)
Total   31/99 (31.31%)   32/103 (31.07%) 
Cardiac disorders     
Extrasystoles * 1  1/99 (1.01%)  0/103 (0.00%) 
Ear and labyrinth disorders     
Vertigo * 1  0/99 (0.00%)  1/103 (0.97%) 
Eye disorders     
Myopia * 1  1/99 (1.01%)  0/103 (0.00%) 
Gastrointestinal disorders     
Abdominal pain * 1  6/99 (6.06%)  4/103 (3.88%) 
Abdominal distension * 1  2/99 (2.02%)  2/103 (1.94%) 
Abdominal pain lower * 1  2/99 (2.02%)  2/103 (1.94%) 
Nausea * 1  1/99 (1.01%)  3/103 (2.91%) 
Flatulence * 1  1/99 (1.01%)  2/103 (1.94%) 
Diarrhoea * 1  1/99 (1.01%)  1/103 (0.97%) 
Abdominal discomfort * 1  1/99 (1.01%)  0/103 (0.00%) 
Abdominal pain upper * 1  1/99 (1.01%)  0/103 (0.00%) 
Constipation * 1  0/99 (0.00%)  1/103 (0.97%) 
Dental caries * 1  1/99 (1.01%)  0/103 (0.00%) 
Dyspepsia * 1  1/99 (1.01%)  0/103 (0.00%) 
Lip pruritus * 1  1/99 (1.01%)  0/103 (0.00%) 
General disorders     
Fatigue * 1  0/99 (0.00%)  2/103 (1.94%) 
Injection site induration * 1  0/99 (0.00%)  1/103 (0.97%) 
Infections and infestations     
Nasopharyngitis * 1  2/99 (2.02%)  6/103 (5.83%) 
Oral herpes * 1  1/99 (1.01%)  1/103 (0.97%) 
Escherichia vaginitis * 1  1/99 (1.01%)  0/103 (0.00%) 
Eye infection viral * 1  0/99 (0.00%)  1/103 (0.97%) 
Vaginitis bacterial * 1  1/99 (1.01%)  0/103 (0.00%) 
Injury, poisoning and procedural complications     
Procedural pain * 1  1/99 (1.01%)  1/103 (0.97%) 
Investigations     
Waist circumference increased * 1  2/99 (2.02%)  0/103 (0.00%) 
Oestradiol increased * 1  0/99 (0.00%)  1/103 (0.97%) 
Weight increased * 1  0/99 (0.00%)  1/103 (0.97%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  1/99 (1.01%)  1/103 (0.97%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Fibroadenoma of breast * 1  0/99 (0.00%)  1/103 (0.97%) 
Nervous system disorders     
Headache * 1  14/99 (14.14%)  13/103 (12.62%) 
Somnolence * 1  1/99 (1.01%)  2/103 (1.94%) 
Migraine * 1  1/99 (1.01%)  0/103 (0.00%) 
Syncope * 1  0/99 (0.00%)  1/103 (0.97%) 
Pregnancy, puerperium and perinatal conditions     
Abortion missed * 1  1/99 (1.01%)  0/103 (0.00%) 
Abortion spontaneous * 1  0/99 (0.00%)  1/103 (0.97%) 
Renal and urinary disorders     
Renal colic * 1  1/99 (1.01%)  0/103 (0.00%) 
Reproductive system and breast disorders     
Ovarian hyperstimulation syndrome * 1  3/99 (3.03%)  4/103 (3.88%) 
Vaginal haemorrhage * 1  3/99 (3.03%)  3/103 (2.91%) 
Dysmenorrhoea * 1  3/99 (3.03%)  2/103 (1.94%) 
Adnexa uteri pain * 1  2/99 (2.02%)  2/103 (1.94%) 
Breast pain * 1  1/99 (1.01%)  1/103 (0.97%) 
Vulvovaginal burning sensation * 1  2/99 (2.02%)  0/103 (0.00%) 
Vulvovaginal pruritus * 1  2/99 (2.02%)  0/103 (0.00%) 
Breast tenderness * 1  1/99 (1.01%)  0/103 (0.00%) 
Menopausal symptoms * 1  1/99 (1.01%)  0/103 (0.00%) 
Pelvic pain * 1  0/99 (0.00%)  1/103 (0.97%) 
Vulvovaginal pain * 1  0/99 (0.00%)  1/103 (0.97%) 
Respiratory, thoracic and mediastinal disorders     
Oropharyngeal pain * 1  2/99 (2.02%)  1/103 (0.97%) 
Skin and subcutaneous tissue disorders     
Pruritus * 1  1/99 (1.01%)  1/103 (0.97%) 
Dermatitis allergic * 1  0/99 (0.00%)  1/103 (0.97%) 
Dermatitis contact * 1  1/99 (1.01%)  0/103 (0.00%) 
Dry skin * 1  1/99 (1.01%)  0/103 (0.00%) 
Eczema * 1  0/99 (0.00%)  1/103 (0.97%) 
Erythema * 1  1/99 (1.01%)  0/103 (0.00%) 
Rash * 1  1/99 (1.01%)  0/103 (0.00%) 
Xeroderma * 1  0/99 (0.00%)  1/103 (0.97%) 
Vascular disorders     
Hypertension * 1  3/99 (3.03%)  0/103 (0.00%) 
Hot flush * 1  0/99 (0.00%)  1/103 (0.97%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 15.0
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
Publications of Results:
H Behre, C Howles, S Longobardi. Luteinizing hormone supplementation from Day 1 versus 6 of ovarian stimulation in women aged 36-40 years: results from an open-label, randomized, multicentre, multinational trial. Human Reproduction. 2013;28(suppl 1)
Layout table for additonal information
Responsible Party: Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT01297465     History of Changes
Other Study ID Numbers: EMR 200061-504
2010-023534-23 ( EudraCT Number )
First Submitted: February 15, 2011
First Posted: February 16, 2011
Results First Submitted: October 23, 2013
Results First Posted: February 24, 2014
Last Update Posted: February 24, 2014