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Progesterone Serum Levels in Subfertile Female Patients Undergoing in Vitro Fertilisation (IVF) (PREDICT)

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ClinicalTrials.gov Identifier: NCT01225835
Recruitment Status : Completed
First Posted : October 21, 2010
Results First Posted : February 11, 2014
Last Update Posted : March 14, 2014
Sponsor:
Collaborator:
Ferring Arzneimittel GmbH
Information provided by (Responsible Party):
Ferring Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Infertility
Interventions Drug: Menotrophin
Drug: Follitrophin alpha
Drug: Cetrorelix
Drug: Choriongonadotropin
Drug: Progesterone
Enrollment 124
Recruitment Details  
Pre-assignment Details One hundred seventy patients were screened.
Arm/Group Title Menotrophin Follitrophin Alpha
Hide Arm/Group Description Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms. Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Period Title: Overall Study
Started 62 62
Per Protocol Population 48 58
Completed 55 [1] 59 [1]
Not Completed 7 3
Reason Not Completed
Completed protocol             2             1
Did not meet hCG criterion             2             0
Adverse Event             2             1
not specified             1             1
[1]
hCG criterion met
Arm/Group Title Menotrophin Follitrophin Alpha Total
Hide Arm/Group Description Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms. Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms. Total of all reporting groups
Overall Number of Baseline Participants 62 62 124
Hide Baseline Analysis Population Description
Safety
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 62 participants 62 participants 124 participants
36.5  (2.4) 36.7  (2.3) 36.6  (2.4)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 62 participants 62 participants 124 participants
< 39 years 50 49 99
>=39 years 12 13 25
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 62 participants 62 participants 124 participants
Female
62
 100.0%
62
 100.0%
124
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 62 participants 62 participants 124 participants
64.3  (8.2) 63.5  (8.7) 63.9  (8.4)
Duration of Infertility  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 62 participants 62 participants 124 participants
45.7  (35.0) 40.6  (25.6) 43.2  (30.7)
Menstrual Cycle  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 62 participants 62 participants 124 participants
Regular 62 62 124
Irregular 0 0 0
Length of Menstrual Cycle  
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 62 participants 62 participants 124 participants
28.3  (1.7) 28.2  (1.5) 28.2  (1.6)
Former Treatment for Infertility  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 62 participants 62 participants 124 participants
No 24 24 48
Yes 38 38 76
Participants with Gonadotrophin Stimulated Assisted Reproductive Technology (ART) Cycle  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 62 participants 62 participants 124 participants
No 0 0 0
Yes 13 18 31
Missing Values 49 44 93
Aetiology of Infertility  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 62 participants 62 participants 124 participants
Tubal factor 20 18 38
Endometriosis 4 3 7
Idiopathic 36 33 69
Other 1 8 9
Missing values 1 0 1
1.Primary Outcome
Title Serum Progesterone (P4) Level in the Morning of the Day of Human Chorionic Gonadotrophin (hCG) Administration
Hide Description Ovulation induction was performed by administration of hCG once three follicles >=17 mm diameter as shown by pelvic ultrasound examination. This outcome compares the serum progesterone level the morning prior to hCG administration across treatment arm, and also by age stratum (<39 years and >=39 years).
Time Frame approximately day 10
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Menotrophin Menotrophin: Stratum Age <39 Yrs Menotrophin: Stratum Age >=39 Yrs Follitrophin Alpha Follitrophin Alpha: Stratum Age <39 Yrs Follitrophin Alpha: Stratum Age >=39 Yrs
Hide Arm/Group Description:
Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
The subset of participants in the menotrophin treatment arm who were < 39 years old.
The subset of participants in the menotrophin treatment arm who were >= 39 years old.
Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
The subset of participants in the follitrophin alpha treatment arm who were < 39 years old.
The subset of participants in the follitrophin alpha treatment arm who were >= 39 years old.
Overall Number of Participants Analyzed 62 50 12 62 49 13
Mean (Standard Deviation)
Unit of Measure: ng/ml
0.69  (0.34) 0.72  (0.35) 0.54  (0.25) 0.89  (0.41) 0.92  (0.43) 0.80  (0.28)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Menotrophin, Follitrophin Alpha
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments The significance level is 0.05.
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Menotrophin: Stratum Age <39 Yrs, Follitrophin Alpha: Stratum Age <39 Yrs
Comments Age < 39 years
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments The significance level is 0.05.
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Menotrophin: Stratum Age >=39 Yrs, Follitrophin Alpha: Stratum Age >=39 Yrs
Comments Age >= 39 years
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.027
Comments The significance level is 0.05.
Method t-test, 2 sided
Comments [Not Specified]
2.Secondary Outcome
Title Receiver Operating Characteristic (ROC) Analysis of Progesterone as Predictor for Ongoing Pregnancy Rate at Day 7 and Day of hCG Administration
Hide Description The influence of the progesterone level on the ongoing pregnancy rate (in relation to all randomized patients) was determined by means of the receiver operating characteristic (ROC) curve. Youden's Index (sensitivity + specificity -1) has a range of 0-1, with 0.5 indicating a random effect.
Time Frame Day 7, approximately Day 10 (hCG Administration)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title All Participants
Hide Arm/Group Description:
The analysis of whether progesterone level is a predictor for ongoing pregnancy used all participants.
Overall Number of Participants Analyzed 124
Measure Type: Number
Unit of Measure: Youden's index
Day 7 0.5189
Day of hCG Administration (approx Day 10) 0.4944
3.Secondary Outcome
Title Percentage of Participants With Ongoing Pregnancy
Hide Description Ongoing pregnancy is defined as having a positive foetal heart action nine or more weeks after the first positive pregnancy test.
Time Frame approximately 3.5 months from study start (at least 9 weeks after first positive pregnancy test)
Hide Outcome Measure Data
Hide Analysis Population Description
The per-protocol (PP) set -- defined as participants of the full analysis set without any major protocol violation (i.e., any deviation which was likely to bias the assessment of the primary endpoint).
Arm/Group Title Menotrophin Follitrophin Alpha
Hide Arm/Group Description:
Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Overall Number of Participants Analyzed 48 58
Measure Type: Number
Unit of Measure: percentage of participants
29.2 31.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Menotrophin, Follitrophin Alpha
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments The significance level is 0.05.
Method Fisher Exact
Comments [Not Specified]
4.Secondary Outcome
Title Number of Follicles at hCG Administration
Hide Description Number of follicles >=17 mm diameter detected by pelvic ultrasound examination at day of hCG administration.
Time Frame approximately day 10
Hide Outcome Measure Data
Hide Analysis Population Description
The per-protocol (PP) set of participants with non-missing values. PP set is defined as participants of the full analysis set without any major protocol violation (i.e., any deviation which was likely to bias the assessment of the primary endpoint).
Arm/Group Title Menotrophin Follitrophin Alpha
Hide Arm/Group Description:
Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Overall Number of Participants Analyzed 48 57
Mean (Standard Deviation)
Unit of Measure: follicles
8.7  (4.7) 10.5  (4.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Menotrophin, Follitrophin Alpha
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments The significance level is 0.05. P-values are not adjusted for multiple tests and have to be interpreted exploratively.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
5.Secondary Outcome
Title Average Follicle Diameter at hCG Administration
Hide Description [Not Specified]
Time Frame approximately day 10
Hide Outcome Measure Data
Hide Analysis Population Description
The per-protocol (PP) set of participants with non-missing values.
Arm/Group Title Menotrophin Follitrophin Alpha
Hide Arm/Group Description:
Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Overall Number of Participants Analyzed 48 57
Mean (Standard Deviation)
Unit of Measure: mm
17.6  (1.8) 18.1  (1.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Menotrophin, Follitrophin Alpha
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.121
Comments The significance level is 0.05.
Method t-test, 2 sided
Comments [Not Specified]
6.Secondary Outcome
Title Number of Cumulus-oocyte Complexes Retrieved
Hide Description Cumulus-oocyte complexes are oocytes with surrounding cumulus cells.
Time Frame approximately day 12 after study start
Hide Outcome Measure Data
Hide Analysis Population Description
The per-protocol (PP) set of participants with non-missing values.
Arm/Group Title Menotrophin Follitrophin Alpha
Hide Arm/Group Description:
Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Overall Number of Participants Analyzed 48 57
Mean (Standard Deviation)
Unit of Measure: oocytes
6.8  (4.2) 10.0  (4.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Menotrophin, Follitrophin Alpha
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Level of significance is 0.05.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
7.Secondary Outcome
Title Number of Pronuclear Oocytes
Hide Description Pronuclear oocytes are fertilized oocytes.
Time Frame approximately day 13 after study start
Hide Outcome Measure Data
Hide Analysis Population Description
The per-protocol (PP) set of participants with non-missing values.
Arm/Group Title Menotrophin Follitrophin Alpha
Hide Arm/Group Description:
Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Overall Number of Participants Analyzed 48 57
Mean (Standard Deviation)
Unit of Measure: oocytes
3.7  (2.8) 5.9  (3.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Menotrophin, Follitrophin Alpha
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The significance level is 0.05. P-values are not adjusted for multiple tests and have to be interpreted exploratively.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
8.Secondary Outcome
Title Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade
Hide Description

The count of participants with different quality grades of pronuclear stage oocytes is offered. Pronuclear stage oocytes are categorized into seven grades (0A, 0B, 1-5) representing different patterns of pronuclear morphology, according to the German Pronuclear Morphology Study Group. 0A is the highest quality oocyte and grade 5 is the lowest quality.

Participants can have pronuclear stage oocytes of different grades and therefore are counted more than once.

Time Frame approximately day 13
Hide Outcome Measure Data
Hide Analysis Population Description
The per-protocol (PP) set -- defined as participants of the full analysis set without any major protocol violation (i.e., any deviation which was likely to bias the assessment of the primary endpoint).
Arm/Group Title Menotrophin Follitrophin Alpha
Hide Arm/Group Description:
Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Overall Number of Participants Analyzed 48 58
Measure Type: Number
Unit of Measure: participants
Grade 0A 11 17
Grade 0B 15 23
Grade 1 33 40
Grade 2 15 25
Grade 3 8 24
Grade 4 2 11
Grade 5 11 23
9.Secondary Outcome
Title Number of Embryos Transferred
Hide Description Mean number of embryos transferred 2-3 days following oocyte retrieval.
Time Frame approximately day 14
Hide Outcome Measure Data
Hide Analysis Population Description
The per-protocol (PP) set who had embryos transferred. PP set is defined as participants of the full analysis set without any major protocol violation (i.e., any deviation which was likely to bias the assessment of the primary endpoint).
Arm/Group Title Menotrophin Follitrophin Alpha
Hide Arm/Group Description:
Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Overall Number of Participants Analyzed 46 54
Mean (Standard Deviation)
Unit of Measure: embryos
2.0  (0.5) 2.0  (0.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Menotrophin, Follitrophin Alpha
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.482
Comments The significance level is 0.05. P-values are not adjusted for multiple tests and have to be interpreted exploratively.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
10.Secondary Outcome
Title Best Quality of an Embryo Transferred
Hide Description

Embryo quality was measured by the following grades:

  • Grade 1: Evenly sized cells, regular cleavage, no fragmentation
  • Grade 2: Regular or slightly irregular cleavage, <=20% fragmentation
  • Grade 2.5: Regular or slightly irregular cleavage, >20%and <=50% fragmentation
  • Grade 3: Irregular cleavage, >50% fragmentation, >1 intact cell
  • Grade 4: Extensive fragmentation, only 1 cell intact
  • Grade 5: Totally fragmented, no viable cells.

Grade 1 represents the healthiest embryos and Grade 5 embryos are not viable.

Time Frame approximately day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol set of participants who had embryos transferred
Arm/Group Title Menotrophin Follitrophin Alpha
Hide Arm/Group Description:
Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Overall Number of Participants Analyzed 46 54
Measure Type: Number
Unit of Measure: participants
Grade 1 22 26
Grade 2 18 22
Grade >2 6 6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Menotrophin, Follitrophin Alpha
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.871
Comments The significance level is 0.05. P-values are not adjusted for multiple tests and have to be interpreted exploratively.
Method Chi-squared
Comments [Not Specified]
11.Secondary Outcome
Title Number of Frozen Oocytes at Pronuclear Stage
Hide Description No more than three normally developed embryos were transferred 2-3 days after oocyte retrieval. Other normally developed embryos were frozen.
Time Frame approximately day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol set of participants who had embryos transferred
Arm/Group Title Menotrophin Follitrophin Alpha
Hide Arm/Group Description:
Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Overall Number of Participants Analyzed 46 54
Mean (Standard Deviation)
Unit of Measure: oocytes
1.0  (2.2) 2.7  (2.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Menotrophin, Follitrophin Alpha
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The significance level is 0.05. P-values are not adjusted for multiple tests and have to be interpreted exploratively.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
12.Secondary Outcome
Title Endometrial Thickness on Day of hCG Administration
Hide Description Endometrial thickness was assessed by pelvic ultrasound on the day of hCG administration.
Time Frame approximately day 10
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol set of participants. One participant in the Follitrophin Alpha arm was missing a measurement.
Arm/Group Title Menotrophin Follitrophin Alpha
Hide Arm/Group Description:
Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Overall Number of Participants Analyzed 48 57
Mean (Standard Deviation)
Unit of Measure: mm
10.8  (2.1) 11.0  (2.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Menotrophin, Follitrophin Alpha
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.620
Comments The significance level is 0.05. P-values are not adjusted for multiple tests and have to be interpreted exploratively.
Method t-test, 2 sided
Comments [Not Specified]
13.Secondary Outcome
Title Estradiol (E2) Levels on Day of hCG Administration
Hide Description [Not Specified]
Time Frame approximately day 10
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol set. Five participants from each treatment arm were missing blood samples.
Arm/Group Title Menotrophin Follitrophin Alpha
Hide Arm/Group Description:
Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Overall Number of Participants Analyzed 43 53
Mean (Standard Deviation)
Unit of Measure: ng/ml
1.81  (1.21) 1.65  (0.87)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Menotrophin, Follitrophin Alpha
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.478
Comments The significance level is 0.05. P-values are not adjusted for multiple tests and have to be interpreted exploratively.
Method t-test, 2 sided
Comments [Not Specified]
14.Secondary Outcome
Title Percentage of Participants With Successful Embryo Transfer
Hide Description [Not Specified]
Time Frame approximately day 18
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol set
Arm/Group Title Menotrophin Follitrophin Alpha
Hide Arm/Group Description:
Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Overall Number of Participants Analyzed 48 58
Measure Type: Number
Unit of Measure: percentage of participants
No 4.2 6.9
Yes 95.8 93.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Menotrophin, Follitrophin Alpha
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.69
Comments The significance level is 0.05. P-values are not adjusted for multiple tests and have to be interpreted exploratively.
Method Fisher Exact
Comments [Not Specified]
15.Secondary Outcome
Title Number of Days Stimulated With Gonadotrophins
Hide Description Number of days in which gonadotrophins were administered until hCG criteria were met. If hCG criteria were not met by day 13, the participant was withdrawn from the study.
Time Frame Day 1 up to Day 12
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol set
Arm/Group Title Menotrophin Follitrophin Alpha
Hide Arm/Group Description:
Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Overall Number of Participants Analyzed 48 58
Mean (Standard Deviation)
Unit of Measure: days
8.7  (1.9) 9.1  (1.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Menotrophin, Follitrophin Alpha
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.295
Comments The significance level is 0.05. P-values are not adjusted for multiple tests and have to be interpreted exploratively.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
16.Secondary Outcome
Title Number of Ampoules of Gonadotrophins Used
Hide Description Number of ampoules of gonadotrophins used with the goal of reaching hCG criteria. Each ampoule contained 75 IU of either menotrophin or follitrophin alpha.
Time Frame Day 1 up to Day 12
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Hide Analysis Population Description
Per protocol set
Arm/Group Title Menotrophin Follitrophin Alpha
Hide Arm/Group Description:
Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Overall Number of Participants Analyzed 48 58
Mean (Standard Deviation)
Unit of Measure: ampoules
20.8  (7.5) 21.5  (6.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Menotrophin, Follitrophin Alpha
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.405
Comments The significance level is 0.05. P-values are not adjusted for multiple tests and have to be interpreted exploratively.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
17.Secondary Outcome
Title Percentage of Participants With Clinical Pregnancy 6 Weeks After the First Positive Pregnancy Test
Hide Description A pelvic ultrasound scan was performed approximately 6 weeks after the first positive pregnancy test and the presence of an active foetal heart action indicated a clinical pregnancy.
Time Frame approximately 2.5 months from start of study, 6 weeks after first positive pregnancy test
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Hide Analysis Population Description
Per protocol set
Arm/Group Title Menotrophin Follitrophin Alpha
Hide Arm/Group Description:
Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Overall Number of Participants Analyzed 48 58
Measure Type: Number
Unit of Measure: percentage of participants
29.2 31.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Menotrophin, Follitrophin Alpha
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments The significance level is 0.05. P-values are not adjusted for multiple tests and have to be interpreted exploratively.
Method Fisher Exact
Comments [Not Specified]
18.Secondary Outcome
Title Summary of Pregnancy Outcome
Hide Description Pregnancy outcomes were reported at the optional long-term follow up visit.
Time Frame up to 10 months
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Hide Analysis Population Description
Per protocol set of participants who reported information during the optional long-term follow up visit.
Arm/Group Title Menotrophin Follitrophin Alpha
Hide Arm/Group Description:
Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Overall Number of Participants Analyzed 14 16
Measure Type: Number
Unit of Measure: participants
Live birth 13 16
Ectopic pregnancy 1 0
Congenial abnormality 0 1
Time Frame -Menotrophin: Day 1 up to Day 23. Treatment with investigational product (up to Day 12), plus residual drug effect-10.5 days -Follitropin: Day 1 up to Day 17. Treatment with comparator product (up to Day 12), plus residual drug effort-5 days.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Menotrophin Follitrophin Alpha
Hide Arm/Group Description Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 13 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms. Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 13 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
All-Cause Mortality
Menotrophin Follitrophin Alpha
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Menotrophin Follitrophin Alpha
Affected / at Risk (%) Affected / at Risk (%)
Total   2/62 (3.23%)   0/62 (0.00%) 
Cardiac disorders     
Tachycardia  1  1/62 (1.61%)  0/62 (0.00%) 
Gastrointestinal disorders     
Abdominal rigidity  1  1/62 (1.61%)  0/62 (0.00%) 
General disorders     
Thirst  1  1/62 (1.61%)  0/62 (0.00%) 
Immune system disorders     
Drug hypersensitivity  1  1/62 (1.61%)  0/62 (0.00%) 
Nervous system disorders     
Dizziness  1  1/62 (1.61%)  0/62 (0.00%) 
Renal and urinary disorders     
Pollakiuria  1  1/62 (1.61%)  0/62 (0.00%) 
Reproductive system and breast disorders     
Ovarian hyperstimulation syndrome  1  1/62 (1.61%)  0/62 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Menotrophin Follitrophin Alpha
Affected / at Risk (%) Affected / at Risk (%)
Total   43/62 (69.35%)   45/62 (72.58%) 
Cardiac disorders     
Tachycardia  1  0/62 (0.00%)  1/62 (1.61%) 
Endocrine disorders     
Hypothyroidism  1  1/62 (1.61%)  0/62 (0.00%) 
Eye disorders     
Eye pruritus  1  0/62 (0.00%)  1/62 (1.61%) 
Gastrointestinal disorders     
Abdominal pain  1  9/62 (14.52%)  12/62 (19.35%) 
Nausea  1  4/62 (6.45%)  5/62 (8.06%) 
Diarrhoea  1  3/62 (4.84%)  5/62 (8.06%) 
Abdominal distension  1  4/62 (6.45%)  3/62 (4.84%) 
Vomiting  1  0/62 (0.00%)  4/62 (6.45%) 
Abdominal discomfort  1  2/62 (3.23%)  1/62 (1.61%) 
Constipation  1  3/62 (4.84%)  0/62 (0.00%) 
Flatulence  1  1/62 (1.61%)  2/62 (3.23%) 
Toothache  1  0/62 (0.00%)  2/62 (3.23%) 
Abdominal pain upper  1  1/62 (1.61%)  0/62 (0.00%) 
Dental caries  1  0/62 (0.00%)  1/62 (1.61%) 
Proctalgia  1  0/62 (0.00%)  1/62 (1.61%) 
General disorders     
Injection site erythema  1  10/62 (16.13%)  7/62 (11.29%) 
Injection site pruritus  1  9/62 (14.52%)  7/62 (11.29%) 
Injection site pain  1  7/62 (11.29%)  5/62 (8.06%) 
Injection site reaction  1  5/62 (8.06%)  4/62 (6.45%) 
Injection site swelling  1  4/62 (6.45%)  5/62 (8.06%) 
Fatigue  1  3/62 (4.84%)  2/62 (3.23%) 
Injection site rash  1  2/62 (3.23%)  2/62 (3.23%) 
Injection site haemorrhage  1  1/62 (1.61%)  1/62 (1.61%) 
Injection site inflammation  1  0/62 (0.00%)  2/62 (3.23%) 
Chills  1  1/62 (1.61%)  0/62 (0.00%) 
Injection site warmth  1  0/62 (0.00%)  1/62 (1.61%) 
Pyrexia  1  1/62 (1.61%)  0/62 (0.00%) 
Infections and infestations     
Nasopharyngitis  1  2/62 (3.23%)  1/62 (1.61%) 
Pharyngitis  1  1/62 (1.61%)  0/62 (0.00%) 
Rhinitis  1  1/62 (1.61%)  0/62 (0.00%) 
Vaginal infection  1  1/62 (1.61%)  0/62 (0.00%) 
Injury, poisoning and procedural complications     
Procedural pain  1  2/62 (3.23%)  4/62 (6.45%) 
Post procedural haemorrhage  1  0/62 (0.00%)  1/62 (1.61%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  1/62 (1.61%)  1/62 (1.61%) 
Musculoskeletal pain  1  1/62 (1.61%)  0/62 (0.00%) 
Pain in extremity  1  1/62 (1.61%)  0/62 (0.00%) 
Nervous system disorders     
Headache  1  11/62 (17.74%)  13/62 (20.97%) 
Dizziness  1  2/62 (3.23%)  3/62 (4.84%) 
Migraine  1  1/62 (1.61%)  0/62 (0.00%) 
Paraesthesia  1  0/62 (0.00%)  1/62 (1.61%) 
Psychiatric disorders     
Mood swings  1  2/62 (3.23%)  0/62 (0.00%) 
Sleep disorder  1  0/62 (0.00%)  1/62 (1.61%) 
Reproductive system and breast disorders     
Breast pain  1  1/62 (1.61%)  2/62 (3.23%) 
Adnexa uteri pain  1  1/62 (1.61%)  1/62 (1.61%) 
Breast discomfort  1  1/62 (1.61%)  1/62 (1.61%) 
Ovarian hyperstimulation syndrome  1  1/62 (1.61%)  1/62 (1.61%) 
Pelvic discomfort  1  1/62 (1.61%)  1/62 (1.61%) 
Vaginal haemorrhage  1  0/62 (0.00%)  2/62 (3.23%) 
Nipple pain  1  1/62 (1.61%)  0/62 (0.00%) 
Pelvic pain  1  1/62 (1.61%)  0/62 (0.00%) 
Premature ovulation  1  1/62 (1.61%)  0/62 (0.00%) 
Vulvovaginal swelling  1  1/62 (1.61%)  0/62 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Oropharyngeal pain  1  2/62 (3.23%)  0/62 (0.00%) 
Skin and subcutaneous tissue disorders     
Pruritus  1  1/62 (1.61%)  1/62 (1.61%) 
Dry skin  1  1/62 (1.61%)  0/62 (0.00%) 
Vascular disorders     
Flushing  1  0/62 (0.00%)  1/62 (1.61%) 
Hot flush  1  1/62 (1.61%)  0/62 (0.00%) 
Hypotension  1  1/62 (1.61%)  0/62 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.1)
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 only disclosure restriction on the PI is that the sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the sponsor.

Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow Ferring to seek patent protection of the invention.

Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Development Support
Organization: Ferring Pharmaceuticals
EMail: DK0-Disclosure@ferring.com
Layout table for additonal information
Responsible Party: Ferring Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01225835     History of Changes
Other Study ID Numbers: FE999906 CS11
2010-019411-37 ( EudraCT Number )
First Submitted: October 7, 2010
First Posted: October 21, 2010
Results First Submitted: December 19, 2013
Results First Posted: February 11, 2014
Last Update Posted: March 14, 2014