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Phase III Study Comparing Efficacy and Safety of AFOLIA vs Gonal-f® RFF in Women (35 to 42) Undergoing IVF

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ClinicalTrials.gov Identifier: NCT01687712
Recruitment Status : Completed
First Posted : September 19, 2012
Results First Posted : October 18, 2017
Last Update Posted : December 5, 2017
Sponsor:
Information provided by (Responsible Party):
Fertility Biotech AG

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Infertility
Interventions Drug: AFOLIA
Drug: Gonal-f® RFF
Enrollment 1100
Recruitment Details 1548 subjects were enrolled, 1101 subjects were randomized and 1100 received Investigational Medicinal Product (IMP) at 22 investigational sites in the United States.
Pre-assignment Details After the informed consent was signed, each subject received a subject identification number and underwent the down-regulation procedure. After a successful downregulation, subjects were centrally randomized in a 1:1 ratio to one of the treatment groups, AFOLIA or Gonal-f®RFF.
Arm/Group Title AFOLIA Gonal-f® RFF
Hide Arm/Group Description One subcutaneous injection of 225IU AFOLIA (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU. One subcutaneous injection of 225IU Gonal-f® RFF (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
Period Title: Cycle 1
Started 549 551
Received hCG 516 520
Oocyte/Ovum Pick Up 513 517
Fertilization Performed 508 512
Embryo Transfer 466 483
Biochemical Pregnancy 163 203
Clinical Pregnancy [1] 114 138
Completed [2] 101 122
Not Completed 448 429
Reason Not Completed
Not Biochemically Pregnant             386             348
Early Pregnancy Loss             43             60
Ectopic Pregnancy             5             5
Heterotropic Pregnancy             1             0
Miscarriage/Spontaneous Abortion             9             14
Abortion             3             0
Intrauterine Fetal Death             0             1
Lost to Follow-up             1             1
[1]
Ascertained via an ultrasound scan.
[2]
A subject is listed as Completed if they delivered at least one live neonate.
Period Title: Cycle 2
Started 109 120
Received hCG 107 119
Oocyte/Ovum Pick Up 107 119
Fertilization Performed 106 119
Embryo Transfer 101 117
Biochemical Pregnancy 35 43
Clinical Pregnancy [1] 17 26
Completed [2] 16 25
Not Completed 93 95
Reason Not Completed
Not Biochemically Pregnant             74             77
Early Pregnancy Loss             18             16
Ectopic Pregnancy             0             1
Still Birth             1             0
Miscarriage/Spontaneous Abortion             0             1
[1]
Ascertained via an ultrasound scan.
[2]
A subject is listed as Completed if they delivered at least one live neonate.
Period Title: Cycle 3
Started 28 24
Received hCG 27 24
Ooctye/Ovum Pick-Up 27 24
Fertilization Performed 27 24
Embryo Transfer 26 24
Biochemically Pregnant 7 2
Clinical Pregnancy [1] 5 0
Completed [2] 4 0
Not Completed 24 24
Reason Not Completed
Not Biochemically Pregnant             21             22
Early Pregnancy Loss             1             2
Ectopic Pregnancy             1             0
Miscarriage/Spontaneous Abortion             1             0
[1]
Ascertained via an ultrasound scan.
[2]
A subject is listed as Completed if they delivered at least one live neonate.
Arm/Group Title AFOLIA Gonal-f® RFF Total
Hide Arm/Group Description One subcutaneous injection of 225IU AFOLIA (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU. One subcutaneous injection of 225IU Gonal-f® RFF (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU. Total of all reporting groups
Overall Number of Baseline Participants 549 551 1100
Hide Baseline Analysis Population Description
Intention to treat population, defined as all randomized subjects who received at least one dose of the study treatment, based on their randomization.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 549 participants 551 participants 1100 participants
37.7  (2.16) 37.8  (2.18) 37.8  (2.17)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 549 participants 551 participants 1100 participants
35-37
275
  50.1%
276
  50.1%
551
  50.1%
38-40
201
  36.6%
194
  35.2%
395
  35.9%
41-42
73
  13.3%
81
  14.7%
154
  14.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 549 participants 551 participants 1100 participants
Female
549
 100.0%
551
 100.0%
1100
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 549 participants 551 participants 1100 participants
Hispanic or Latino
96
  17.5%
78
  14.2%
174
  15.8%
Not Hispanic or Latino
452
  82.3%
473
  85.8%
925
  84.1%
Unknown or Not Reported
1
   0.2%
0
   0.0%
1
   0.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 549 participants 551 participants 1100 participants
American Indian or Alaska Native
3
   0.5%
1
   0.2%
4
   0.4%
Asian
40
   7.3%
48
   8.7%
88
   8.0%
Native Hawaiian or Other Pacific Islander
2
   0.4%
1
   0.2%
3
   0.3%
Black or African American
61
  11.1%
57
  10.3%
118
  10.7%
White
435
  79.2%
440
  79.9%
875
  79.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
8
   1.5%
4
   0.7%
12
   1.1%
Height (m)   [1] 
Mean (Standard Deviation)
Unit of measure:  Meters
Number Analyzed 549 participants 550 participants 1099 participants
1.643  (0.0660) 1.642  (0.0684) 1.642  (0.0672)
[1]
Measure Analysis Population Description: Number of subjects analysed is less than the number of subjects in the ITT population due to missing data.
Weight (kg)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilograms
Number Analyzed 541 participants 546 participants 1087 participants
70.01  (13.803) 71.12  (13.844) 70.57  (13.828)
[1]
Measure Analysis Population Description: Number of subjects analysed is less than the number of subjects in the ITT population due to missing data.
BMI (kg/m^2)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 541 participants 545 participants 1086 participants
25.92  (4.738) 26.38  (4.784) 26.15  (4.765)
[1]
Measure Analysis Population Description: Number of subjects analysed is less than the number of subjects in the ITT population due to missing data.
BMI Category (kg/m^2)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 549 participants 551 participants 1100 participants
>=18 to <25
279
  50.8%
245
  44.5%
524
  47.6%
>=25 to <30
150
  27.3%
184
  33.4%
334
  30.4%
>=30 to <=38
109
  19.9%
112
  20.3%
221
  20.1%
>38
3
   0.5%
4
   0.7%
7
   0.6%
Unknown or Not Reported
8
   1.5%
6
   1.1%
14
   1.3%
Primary Cause of Infertility   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Unexplained Infertility Number Analyzed 549 participants 551 participants 1100 participants
225
  41.0%
206
  37.4%
431
  39.2%
Male Factor Number Analyzed 549 participants 551 participants 1100 participants
189
  34.4%
178
  32.3%
367
  33.4%
Tubal Factor Number Analyzed 549 participants 551 participants 1100 participants
138
  25.1%
169
  30.7%
307
  27.9%
Mild Endometriosis Number Analyzed 549 participants 551 participants 1100 participants
59
  10.7%
45
   8.2%
104
   9.5%
Other Number Analyzed 549 participants 551 participants 1100 participants
28
   5.1%
41
   7.4%
69
   6.3%
[1]
Measure Description: Subjects can have more than one factor that causes infertility, therefore percentages may add up to more than 100.
Infertility Duration   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 548 participants 550 participants 1098 participants
4.1  (4.61) 4.2  (4.54) 4.1  (4.58)
[1]
Measure Analysis Population Description: Number of subjects analysed is less than the number of subjects in the ITT population due to missing data.
Number of previous fresh ART cycles [N(%)]   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 549 participants 551 participants 1100 participants
0
441
  80.3%
440
  79.9%
881
  80.1%
1
81
  14.8%
77
  14.0%
158
  14.4%
2
20
   3.6%
30
   5.4%
50
   4.5%
≥3
7
   1.3%
4
   0.7%
11
   1.0%
[1]
Measure Description: Number of previous Assisted Reproductive Technology (ART) cycles a subject had prior to starting Cycle 1.
FSH at screening   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  International units (IU)
Number Analyzed 548 participants 550 participants 1098 participants
7.98  (4.636) 7.76  (2.433) 7.87  (3.700)
[1]
Measure Description: Measure of Follicle Stimulating Hormone (FSH) at screening.
[2]
Measure Analysis Population Description: Number of subjects analysed is less than the number of subjects in the ITT population due to missing data.
LH at screening   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  International units (IU)
Number Analyzed 377 participants 385 participants 762 participants
5.77  (3.36) 5.74  (2.44) 5.76  (2.93)
[1]
Measure Description: Measure of Luteinizing Hormone (LH) at screening.
[2]
Measure Analysis Population Description: Number of subjects analysed is less than the number of subjects in the ITT population due to missing data.
1.Primary Outcome
Title Clinical Pregnancy Rate After One Cycle of Treatment - ITT Population
Hide Description Clinical pregnancy was defined as presence of at least one intrauterine gestational sac and fetal heart activity as demonstrated by vaginal ultrasound at six weeks (42 +/- 1 day) post ET (Visit 11). The clinical pregnancy rate is the proportion of subjects who achieve clinical pregnancy, relative to the number of patients in the ITT population of the respective treatment arm.
Time Frame Six weeks post embryo transfer
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention to treat population, defined as all randomized subjects who received at least one dose of study treatment, based on their randomization.
Arm/Group Title AFOLIA Gonal-f® RFF
Hide Arm/Group Description:
One subcutaneous injection of 225IU AFOLIA (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
One subcutaneous injection of 225IU Gonal-f® RFF (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
Overall Number of Participants Analyzed 549 551
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
114
  20.8%
138
  25.0%
No
435
  79.2%
413
  75.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AFOLIA, Gonal-f® RFF
Comments

The null and alternative hypotheses are as follows:

H0: p2– p1 > ∆ and H1: p2– p1 ≤ ∆,

where p1 is the clinical pregnancy rate in the AFOLIA treatment group, p2 is the clinical pregnancy rate in the Gonal f® treatment group, and Δ is the non-inferiority margin of 8%.

Type of Statistical Test Non-Inferiority
Comments Non-inferiority was demonstrated if the upper limit of the two-sided 95% CI of the difference in pregnancy rates (Gonal-f® RFF – AFOLIA) did not exceed 8% (i.e. a one-sided hypothesis test at the 2.5% level of significance). The difference in rates (& Wald CI) was estimated using a logistic regression model with binomial distribution and identity link, with treatment and site as factors.
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 3.7
Confidence Interval (2-Sided) 95%
-1.3 to 8.7
Estimation Comments Note that "risk" in this context is the risk of clinical pregnancy. The difference is in the direction Gonal-f® RFF – AFOLIA.
2.Primary Outcome
Title Clinical Pregnancy Rate After One Cycle of Treatment - PP Population
Hide Description Clinical pregnancy was defined as presence of at least one intrauterine gestational sac and fetal heart activity as demonstrated by vaginal ultrasound at six weeks (42 +/- 1 day) post ET (Visit 11). The clinical pregnancy rate is the proportion of subjects who achieve clinical pregnancy, relative to the number of patients in the PP population of the respective treatment arm.
Time Frame Six weeks post embryo transfer
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Per-protocol population, defined as a subset of the ITT population composed of all patients without any major protocol deviation (i.e. one which would affect the primary efficacy endpoint assessment).
Arm/Group Title AFOLIA Gonal-f® RFF
Hide Arm/Group Description:
One subcutaneous injection of 225IU AFOLIA (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
One subcutaneous injection of 225IU Gonal-f® RFF (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
Overall Number of Participants Analyzed 486 494
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
108
  22.2%
125
  25.3%
No
378
  77.8%
369
  74.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AFOLIA, Gonal-f® RFF
Comments

The null and alternative hypotheses are as follows:

H0: p2– p1 > ∆ and H1: p2– p1 ≤ ∆,

where p1 is the clinical pregnancy rate in the AFOLIA treatment group, p2 is the clinical pregnancy rate in the Gonal f® treatment group, and Δ is the non-inferiority margin of 8%.

Type of Statistical Test Non-Inferiority
Comments Non-inferiority was demonstrated if the upper limit of the two-sided 95% CI of the difference in pregnancy rates (Gonal-f® RFF - AFOLIA) did not exceed 8% (i.e. a one-sided hypothesis test at the 2.5% level of significance). The difference in rates (& Wald CI) was estimated using a logistic regression model with binomial distribution and identity link, with treatment and site as factors.
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 2.8
Confidence Interval (2-Sided) 95%
-2.5 to 8.1
Estimation Comments Note that "risk" in this context is the risk of clinical pregnancy. The difference is in the direction Gonal-f® RFF – AFOLIA.
3.Secondary Outcome
Title Exposure to r-hFSH Injections: Days of r-hFSH Stimulation - Cycle 1
Hide Description The number of days of r-hFSH stimulation a subject received during Cycle 1.
Time Frame Measured at discretionary visits between Days 9 and 15 after FSH starts
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention to treat population, defined as all randomized subjects who received at least one dose of study treatment, based on their randomization.
Arm/Group Title AFOLIA Gonal-f® RFF
Hide Arm/Group Description:
One subcutaneous injection of 225IU AFOLIA (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
One subcutaneous injection of 225IU Gonal-f® RFF (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
Overall Number of Participants Analyzed 549 551
Mean (Standard Deviation)
Unit of Measure: days
10.8  (1.72) 11.0  (1.67)
4.Secondary Outcome
Title Exposure to r-hFSH Injections: Total Dose of r-hFSH (IU) - Cycle 1
Hide Description The total dose of r-hFSH that subjects received during Cycle 1.
Time Frame Measured at discretionary visits between Days 9 and 15 after FSH starts.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention to treat population, defined as all randomized subjects who received at least one dose of study treatment, based on their randomization.
Arm/Group Title AFOLIA Gonal-f® RFF
Hide Arm/Group Description:
One subcutaneous injection of 225IU AFOLIA (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
One subcutaneous injection of 225IU Gonal-f® RFF (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
Overall Number of Participants Analyzed 549 551
Mean (Standard Deviation)
Unit of Measure: international unit (IU)
3209.2  (1008.05) 3343.6  (1005.08)
5.Secondary Outcome
Title Exposure to r-hFSH Injections: Daily Dose of r-hFSH (IU) - Cycle 1
Hide Description The mean dose of r-hFSH that subjects received in a day during Cycle 1.
Time Frame Measured at discretionary visits between Days 9 and 15 after FSH starts.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention to treat population, defined as all randomized subjects who received at least one dose of study treatment, based on their randomization.
Arm/Group Title AFOLIA Gonal-f® RFF
Hide Arm/Group Description:
One subcutaneous injection of 225IU AFOLIA (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
One subcutaneous injection of 225IU Gonal-f® RFF (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
Overall Number of Participants Analyzed 549 551
Mean (Standard Deviation)
Unit of Measure: international unit (IU)
292.1  (57.90) 297.5  (56.97)
6.Secondary Outcome
Title Number of Oocytes Retrieved - Cycle 1
Hide Description The number of oocytes retrieved per subject, following hCG administration in Cycle 1.
Time Frame Visit 8, 34-36 hours after hCG administration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention to treat population, defined as all randomized subjects who received at least one dose of study treatment, based on their randomization.
Arm/Group Title AFOLIA Gonal-f® RFF
Hide Arm/Group Description:
One subcutaneous injection of 225IU AFOLIA (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
One subcutaneous injection of 225IU Gonal-f® RFF (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
Overall Number of Participants Analyzed 513 517
Mean (Standard Deviation)
Unit of Measure: Oocytes retrieved
11.3  (6.76) 11.2  (6.63)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AFOLIA, Gonal-f® RFF
Comments

The null and alternative hypotheses are as follows:

H0: p2– p1 = 0 and H1: p2– p1 ≠0,

where p1 is the least squares adjusted mean number of oocytes retrieved in the AFOLIA treatment group and p2 is the least squares adjusted mean number of oocytes retrieved in the Gonal f® treatment group.

Type of Statistical Test Superiority
Comments Comparisons were tested against a null of zero at the two-side 5% significance level.
Statistical Test of Hypothesis P-Value 0.612
Comments P-values are based upon Type III sums of squares.
Method ANCOVA
Comments Treatment group and Site are included as factors.
7.Secondary Outcome
Title Local and Systemic Adverse Events: Dermal Response to Injection - Cycle 1
Hide Description Number of subjects reporting at least one dermal response to r-hFSH injection and number of subjects reporting no dermal responses.
Time Frame Measure recorded in the Patient Diary which is maintained through entire FSH treatment, from FSH Start through to Day 16 after start of FSH (16 days).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population, defined as all randomized subjects who received at least one dose of study treatment, based on their randomization.
Arm/Group Title AFOLIA Gonal-f® RFF
Hide Arm/Group Description:
One subcutaneous injection of 225IU AFOLIA (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
One subcutaneous injection of 225IU Gonal-f® RFF (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
Overall Number of Participants Analyzed 549 551
Measure Type: Count of Participants
Unit of Measure: Participants
Subjects who reported at least one dermal response
37
   6.7%
42
   7.6%
Subjects who reported no dermal responses
512
  93.3%
509
  92.4%
8.Secondary Outcome
Title Local and Systemic Adverse Events: Dermal Response to Injection by Severity - Cycle 1
Hide Description Dermal response to r-hFSH injection as assessed by the investigator and categorized according to severity of reaction
Time Frame Measure recorded in the Patient Diary which is maintained through entire FSH treatment, from FSH through to Day 16 after start of FSH (16 days).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population, defined as all randomized subjects who received at least one dose of study treatment, based on their randomization.
Arm/Group Title AFOLIA Gonal-f® RFF
Hide Arm/Group Description:
One subcutaneous injection of 225IU AFOLIA (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
One subcutaneous injection of 225IU Gonal-f® RFF (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
Overall Number of Participants Analyzed 549 551
Measure Type: Count of Participants
Unit of Measure: Participants
No evidence of irritation
28
   5.1%
25
   4.5%
Minimal erythema, barely perceptible
2
   0.4%
7
   1.3%
Definited Erythema, readily visible; minimal edema
0
   0.0%
1
   0.2%
Definite Edema
1
   0.2%
0
   0.0%
9.Secondary Outcome
Title Overall Summary of Adverse Events (AEs) - Cycle 1
Hide Description

Summary of AEs, including the number of subjects experiencing to following during Cycle 1:

At least one AE At least one treatment related AE At least one serious AE At least one AE leading to discontinuation of study drug At least one AE due to pregnancy complication

Time Frame Measured from the start of FSH treatment through to either the end FSH treatment + 30 days (up to 46 days) or to the last Telephone Follow-up / Live Birth Questionnaire on pregnancy outcome (if applicable) (up to 10 months).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population, defined as all randomized subjects who received at least one dose of study treatment, based on their randomization.
Arm/Group Title AFOLIA Gonal-f® RFF
Hide Arm/Group Description:
One subcutaneous injection of 225IU AFOLIA (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
One subcutaneous injection of 225IU Gonal-f® RFF (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
Overall Number of Participants Analyzed 549 551
Measure Type: Count of Participants
Unit of Measure: Participants
At least one AE
403
  73.4%
391
  71.0%
At least one treatment related AE
202
  36.8%
197
  35.8%
At least one serious adverse event
32
   5.8%
31
   5.6%
At least one AE leading to discontinuation
2
   0.4%
1
   0.2%
At least one AE due to pregnancy complication
29
   5.3%
30
   5.4%
10.Secondary Outcome
Title Adverse Events of Special Interest: Ovarian Hyperstimulation Syndrome (OHSS) - Cycle 1
Hide Description Summary of the number of subjects with mild, moderate and severe OHSS. The total number of subjects with OHSS is also included.
Time Frame Measured either 3 days after ooctye pick up (Visit 9) or 18 +/- 1 days after oocyte pick up (Visit 10).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population, defined as all randomized subjects who received at least one dose of study treatment, based on their randomization.
Arm/Group Title AFOLIA Gonal-f® RFF
Hide Arm/Group Description:
One subcutaneous injection of 225IU AFOLIA (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
One subcutaneous injection of 225IU Gonal-f® RFF (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
Overall Number of Participants Analyzed 549 551
Measure Type: Count of Participants
Unit of Measure: Participants
Total Number of Subjects with OHSS
13
   2.4%
12
   2.2%
Number of Subjects with Mild OHSS
6
   1.1%
4
   0.7%
Number of Subjects with Moderate OHSS
5
   0.9%
6
   1.1%
Number of Subjects with Severe OHSS
2
   0.4%
2
   0.4%
11.Secondary Outcome
Title Adverse Events of Special Interest: Ovarian Hyperstimulation Syndrome (OHSS) - Cycle 2
Hide Description Summary of the number of subjects with mild, moderate and severe OHSS. The total number of subjects with OHSS is also included.
Time Frame Measured either 3 days after ooctye pick up (Visit 9) or 18 +/- 1 days after oocyte pick up (Visit 10).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population, defined as all randomized subjects who received at least one dose of study treatment, based on their randomization.
Arm/Group Title AFOLIA Gonal-f® RFF
Hide Arm/Group Description:
One subcutaneous injection of 225IU AFOLIA (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
One subcutaneous injection of 225IU Gonal-f® RFF (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
Overall Number of Participants Analyzed 109 120
Measure Type: Count of Participants
Unit of Measure: Participants
Total Number of Subjects with OHSS
1
   0.9%
3
   2.5%
Number of Subjects with Mild OHSS
1
   0.9%
1
   0.8%
Number of Subjects with Moderate OHSS
0
   0.0%
2
   1.7%
Number of Subjects with Severe OHSS
0
   0.0%
0
   0.0%
12.Secondary Outcome
Title Adverse Events of Special Interest: Ovarian Hyperstimulation Syndrome (OHSS) - Cycle 3
Hide Description Summary of the number of subjects with mild, moderate and severe OHSS. The total number of subjects with OHSS is also included.
Time Frame Measured either 3 days after ooctye pick up (Visit 9) or 18 +/- 1 days after oocyte pick up (Visit 10).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population, defined as all randomized subjects who received at least one dose of study treatment, based on their randomization.
Arm/Group Title AFOLIA Gonal-f® RFF
Hide Arm/Group Description:
One subcutaneous injection of 225IU AFOLIA (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
One subcutaneous injection of 225IU Gonal-f® RFF (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
Overall Number of Participants Analyzed 28 24
Measure Type: Count of Participants
Unit of Measure: Participants
Total Number of Subjects with OHSS
0
   0.0%
0
   0.0%
Number of Subjects with Mild OHSS
0
   0.0%
0
   0.0%
Number of Subjects with Moderate OHSS
0
   0.0%
0
   0.0%
Number of Subjects with Severe OHSS
0
   0.0%
0
   0.0%
13.Secondary Outcome
Title Number of Subjects With Detectable Specific Serum Binding to FSH by Surface Plasmon Resonance - Cycle 1
Hide Description Measurement of the number of subjects with detectable specific serum binding to FSH by surface Plasmon resonance during Cycle 1.
Time Frame Immunogenicity samples were taken at baseline, Visit 5 (8 days after start of treatment), Visit 9 (5 days after the end of FSH treatment), Visit 10 (18 +/- 1 days after oocyte retrieval), and Visit 11 (42 +/- 1 days after embryo transfer).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population, defined as all randomized subjects who received at least one dose of study treatment, based on their randomization. Percentages are based on the number of subjects in the safety population with data at the respective visit.
Arm/Group Title AFOLIA Gonal-f® RFF
Hide Arm/Group Description:
One subcutaneous injection of 225IU AFOLIA (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
One subcutaneous injection of 225IU Gonal-f® RFF (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
Overall Number of Participants Analyzed 549 551
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline Number Analyzed 549 participants 551 participants
1
   0.2%
1
   0.2%
Visit 5 Number Analyzed 543 participants 541 participants
1
   0.2%
1
   0.2%
Visit 9 Number Analyzed 463 participants 478 participants
1
   0.2%
1
   0.2%
Visit 10 Number Analyzed 449 participants 471 participants
1
   0.2%
1
   0.2%
Visit 11 Number Analyzed 134 participants 165 participants
0
   0.0%
1
   0.6%
14.Secondary Outcome
Title Number of Subjects With Detectable Specific Serum Binding to FSH by Surface Plasmon Resonance - Cycle 2
Hide Description Measurement of the number of subjects with detectable specific serum binding to FSH by surface Plasmon resonance during Cycle 2.
Time Frame Immunogenicity samples were taken at baseline, Visit 5 (8 days after start of treatment), Visit 9 (5 days after the end of FSH treatment), Visit 10 (18 +/- 1 days after oocyte retrieval), and Visit 11 (42 +/- 1 days after embryo transfer).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population, defined as all randomized subjects who received at least one dose of study treatment, based on their randomization. Percentages are based on the number of subjects in the safety population with data at the respective visit.
Arm/Group Title AFOLIA Gonal-f® RFF
Hide Arm/Group Description:
One subcutaneous injection of 225IU AFOLIA (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
One subcutaneous injection of 225IU Gonal-f® RFF (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
Overall Number of Participants Analyzed 109 120
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline Number Analyzed 107 participants 120 participants
0
   0.0%
0
   0.0%
Visit 5 Number Analyzed 108 participants 120 participants
0
   0.0%
0
   0.0%
Visit 9 Number Analyzed 101 participants 115 participants
0
   0.0%
0
   0.0%
Visit 10 Number Analyzed 101 participants 114 participants
0
   0.0%
0
   0.0%
Visit 11 Number Analyzed 19 participants 32 participants
0
   0.0%
0
   0.0%
15.Secondary Outcome
Title Number of Subjects With Detectable Specific Serum Binding to FSH by Surface Plasmon Resonance - Cycle 3
Hide Description Measurement of the number of subjects with detectable specific serum binding to FSH by surface Plasmon resonance during Cycle 3.
Time Frame Immunogenicity samples were taken at baseline, Visit 5 (8 days after start of treatment), Visit 9 (5 days after the end of FSH treatment), Visit 10 (18 +/- 1 days after oocyte retrieval), and Visit 11 (42 +/- 1 days after embryo transfer).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population, defined as all randomized subjects who received at least one dose of study treatment, based on their randomization. Percentages are based on the number of subjects in the safety population with data at the respective visit.
Arm/Group Title AFOLIA Gonal-f® RFF
Hide Arm/Group Description:
One subcutaneous injection of 225IU AFOLIA (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
One subcutaneous injection of 225IU Gonal-f® RFF (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
Overall Number of Participants Analyzed 28 24
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline Number Analyzed 28 participants 24 participants
0
   0.0%
0
   0.0%
Visit 5 Number Analyzed 28 participants 23 participants
0
   0.0%
0
   0.0%
Visit 9 Number Analyzed 26 participants 24 participants
0
   0.0%
0
   0.0%
Visit 10 Number Analyzed 25 participants 24 participants
0
   0.0%
0
   0.0%
Visit 11 Number Analyzed 5 participants 0 participants
0
   0.0%
0
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title AFOLIA - Cycle 1 Gonal-f® RFF - Cycle 1 AFOLIA - Cycle 2 Gonal-f® RFF - Cycle 2 AFOLIA - Cycle 3 Gonal-f® RFF - Cycle 3
Hide Arm/Group Description Enrolled subjects in Cycle 1 were randomized to one subcutaneous injection of 225IU AFOLIA (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU. Enrolled subjects in Cycle 1 were randomized to one subcutaneous injection of 225IU Gonal-f (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU. Enrolled subjects in Cycle 2 were randomized to one subcutaneous injection of 225IU AFOLIA (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU. Enrolled subjects in Cycle 2 were randomized to one subcutaneous injection of 225IU Gonal-f (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU. Enrolled subjects in Cycle 3 were randomized to one subcutaneous injection of 225IU AFOLIA (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU. Enrolled subjects in Cycle 3 were randomized to one subcutaneous injection of 225IU Gonal-f (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
All-Cause Mortality
AFOLIA - Cycle 1 Gonal-f® RFF - Cycle 1 AFOLIA - Cycle 2 Gonal-f® RFF - Cycle 2 AFOLIA - Cycle 3 Gonal-f® RFF - Cycle 3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/549 (0.00%)   1/551 (0.18%)   0/109 (0.00%)   0/120 (0.00%)   0/28 (0.00%)   0/24 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
AFOLIA - Cycle 1 Gonal-f® RFF - Cycle 1 AFOLIA - Cycle 2 Gonal-f® RFF - Cycle 2 AFOLIA - Cycle 3 Gonal-f® RFF - Cycle 3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   32/549 (5.83%)   31/551 (5.63%)   2/109 (1.83%)   6/120 (5.00%)   3/28 (10.71%)   0/24 (0.00%) 
Cardiac disorders             
Foetal heart rate deceleration  0/549 (0.00%)  2/551 (0.36%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Congenital, familial and genetic disorders             
Accessory auricle  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Cardiac septal defect  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Cleft palate  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Congenital skin dimples  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Cytogenetic abnormality  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Foetal chromosome abnormality  1/549 (0.18%)  3/551 (0.54%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Hypospadias  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Mosaicism  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Patent ductus arteriosus  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Polydactyly  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Trisomy 13  2/549 (0.36%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Trisomy 15  1/549 (0.18%)  2/551 (0.36%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Trisomy 17  0/549 (0.00%)  0/551 (0.00%)  0/109 (0.00%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
Trisomy 21  2/549 (0.36%)  0/551 (0.00%)  0/109 (0.00%)  2/120 (1.67%)  0/28 (0.00%)  0/24 (0.00%) 
Trisomy 22  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Trisomy 9  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Turner's syndrome  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  1/28 (3.57%)  0/24 (0.00%) 
Gastrointestinal disorders             
Gastritis  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Peritoneal haemorrhage  0/549 (0.00%)  0/551 (0.00%)  0/109 (0.00%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
General disorders             
Death neonatal  1/549 (0.18%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Pyrexia  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Hepatobiliary disorders             
Acute fatty liver of pregnancy  0/549 (0.00%)  0/551 (0.00%)  1/109 (0.92%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Cholestasis  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Injury, poisoning and procedural complications             
Fall  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Post procedural haematuria  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Procedural pain  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Road traffic accident  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Musculoskeletal and connective tissue disorders             
Back pain  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Pregnancy, puerperium and perinatal conditions             
Abortion spontaneous  2/549 (0.36%)  5/551 (0.91%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Cervical incompetence  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Ectopic pregnancy  2/549 (0.36%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Foetal death  0/549 (0.00%)  1/551 (0.18%)  1/109 (0.92%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Foetal growth restriction  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
Gestational hypertension  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Heterotopic pregnancy  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Hyperemesis gravidarum  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Postpartum haemorrhage  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Pre-eclampsia  1/549 (0.18%)  2/551 (0.36%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Premature baby  1/549 (0.18%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  1/28 (3.57%)  0/24 (0.00%) 
Premature labour  3/549 (0.55%)  2/551 (0.36%)  1/109 (0.92%)  1/120 (0.83%)  1/28 (3.57%)  0/24 (0.00%) 
Premature rupture of membranes  4/549 (0.73%)  2/551 (0.36%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Prolonged labour  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Transverse presentation  0/549 (0.00%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  1/28 (3.57%)  0/24 (0.00%) 
Umbilical cord abnormality  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Vanishing twin syndrome  0/549 (0.00%)  0/551 (0.00%)  0/109 (0.00%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
Reproductive system and breast disorders             
Ovarian hyperstimulation syndrome [1]  0/549 (0.00%)  2/551 (0.36%)  0/109 (0.00%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
Uterine haemorrhage  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Surgical and medical procedures             
Abortion induced  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Vascular disorders             
Hypertension  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
[1]
Note: This includes subjects who were at risk of OHSS as well those who had actual OHSS.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
AFOLIA - Cycle 1 Gonal-f® RFF - Cycle 1 AFOLIA - Cycle 2 Gonal-f® RFF - Cycle 2 AFOLIA - Cycle 3 Gonal-f® RFF - Cycle 3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   403/549 (73.41%)   391/551 (70.96%)   69/109 (63.30%)   66/120 (55.00%)   13/28 (46.43%)   12/24 (50.00%) 
Blood and lymphatic system disorders             
Anaemia  0/549 (0.00%)  2/551 (0.36%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Cardiac disorders             
Palpitations  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Ear and labyrinth disorders             
Ear discomfort  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Ear pain  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Vertigo  1/549 (0.18%)  1/551 (0.18%)  1/109 (0.92%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Endocrine disorders             
Hypothyroidism  2/549 (0.36%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Eye disorders             
Asthenopia  0/549 (0.00%)  2/551 (0.36%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Conjunctivitis  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Dry eye  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Eye irritation  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Vision blurred  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Gastrointestinal disorders             
Abdominal discomfort  5/549 (0.91%)  10/551 (1.81%)  2/109 (1.83%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
Abdominal distension  49/549 (8.93%)  42/551 (7.62%)  7/109 (6.42%)  4/120 (3.33%)  0/28 (0.00%)  1/24 (4.17%) 
Abdominal pain  46/549 (8.38%)  54/551 (9.80%)  7/109 (6.42%)  6/120 (5.00%)  0/28 (0.00%)  2/24 (8.33%) 
Abdominal pain lower  4/549 (0.73%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Abdominal pain upper  3/549 (0.55%)  4/551 (0.73%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Abdominal tenderness  7/549 (1.28%)  5/551 (0.91%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Ascites  4/549 (0.73%)  3/551 (0.54%)  1/109 (0.92%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Constipation  16/549 (2.91%)  15/551 (2.72%)  4/109 (3.67%)  3/120 (2.50%)  1/28 (3.57%)  0/24 (0.00%) 
Dental caries  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Diarrhoea  13/549 (2.37%)  10/551 (1.81%)  4/109 (3.67%)  1/120 (0.83%)  0/28 (0.00%)  1/24 (4.17%) 
Dry mouth  0/549 (0.00%)  2/551 (0.36%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Dyspepsia  8/549 (1.46%)  9/551 (1.63%)  1/109 (0.92%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Flatulence  3/549 (0.55%)  11/551 (2.00%)  0/109 (0.00%)  0/120 (0.00%)  1/28 (3.57%)  0/24 (0.00%) 
Gingival bleeding  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Gingival pain  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Glossodynia  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Haemorrhoids  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Hypoaesthesia oral  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Lip pain  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Localised intraabdominal fluid collection  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Nausea  53/549 (9.65%)  55/551 (9.98%)  8/109 (7.34%)  11/120 (9.17%)  0/28 (0.00%)  2/24 (8.33%) 
Vomiting  11/549 (2.00%)  14/551 (2.54%)  1/109 (0.92%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
General disorders             
Adverse drug reaction  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Asthenia  0/549 (0.00%)  0/551 (0.00%)  0/109 (0.00%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
Chest discomfort  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Chills  1/549 (0.18%)  3/551 (0.54%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Crying  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Discomfort  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Fatigue  13/549 (2.37%)  14/551 (2.54%)  2/109 (1.83%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Feeling hot  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Inflammation  0/549 (0.00%)  0/551 (0.00%)  1/109 (0.92%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Injection site bruising  6/549 (1.09%)  8/551 (1.45%)  1/109 (0.92%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
Injection site erythema  82/549 (14.94%)  76/551 (13.79%)  11/109 (10.09%)  5/120 (4.17%)  2/28 (7.14%)  0/24 (0.00%) 
Injection site haematoma  3/549 (0.55%)  2/551 (0.36%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Injection site haemorrhage  0/549 (0.00%)  2/551 (0.36%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Injection site inflammation  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Injection site pain  1/549 (0.18%)  2/551 (0.36%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Injection site pruritus  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Injection site reaction  7/549 (1.28%)  7/551 (1.27%)  1/109 (0.92%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Injection site scab  2/549 (0.36%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Injection site swelling  8/549 (1.46%)  4/551 (0.73%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Injection site vesicles  3/549 (0.55%)  4/551 (0.73%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Irritability  2/549 (0.36%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Local swelling  2/549 (0.36%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Malaise  2/549 (0.36%)  2/551 (0.36%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Non-cardiac chest pain  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Pain  0/549 (0.00%)  4/551 (0.73%)  0/109 (0.00%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
Pyrexia  2/549 (0.36%)  2/551 (0.36%)  1/109 (0.92%)  1/120 (0.83%)  0/28 (0.00%)  1/24 (4.17%) 
Vessel puncture site pain  0/549 (0.00%)  2/551 (0.36%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Immune system disorders             
Drug hypersensitivity  1/549 (0.18%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Seasonal allergy  3/549 (0.55%)  2/551 (0.36%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Infections and infestations             
Body tinea  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Ear infection  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Folliculitis  0/549 (0.00%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  1/28 (3.57%)  0/24 (0.00%) 
Fungal infection  1/549 (0.18%)  2/551 (0.36%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Gastroenteritis viral  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Genital herpes  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Herpes simplex  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Infected bites  0/549 (0.00%)  0/551 (0.00%)  0/109 (0.00%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
Influenza  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Nasopharyngitis  9/549 (1.64%)  6/551 (1.09%)  1/109 (0.92%)  1/120 (0.83%)  1/28 (3.57%)  0/24 (0.00%) 
Oral herpes  0/549 (0.00%)  2/551 (0.36%)  1/109 (0.92%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Pharyngitis streptococcal  0/549 (0.00%)  1/551 (0.18%)  1/109 (0.92%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Salpingitis  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Sinusitis  2/549 (0.36%)  4/551 (0.73%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Upper respiratory tract infection  3/549 (0.55%)  3/551 (0.54%)  1/109 (0.92%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
Urinary tract infection  4/549 (0.73%)  3/551 (0.54%)  1/109 (0.92%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
Vaginitis bacterial  0/549 (0.00%)  0/551 (0.00%)  1/109 (0.92%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Vulvovaginal mycotic infection  2/549 (0.36%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Injury, poisoning and procedural complications             
Arthropod bite  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Contusion  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Ligament sprain  2/549 (0.36%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Limb injury  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Muscle strain  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Post procedural complication  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Post procedural discomfort  39/549 (7.10%)  36/551 (6.53%)  8/109 (7.34%)  12/120 (10.00%)  3/28 (10.71%)  3/24 (12.50%) 
Post procedural haematuria  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Post procedural haemorrhage  4/549 (0.73%)  3/551 (0.54%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Procedural hypertension  2/549 (0.36%)  2/551 (0.36%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Procedural nausea  15/549 (2.73%)  15/551 (2.72%)  2/109 (1.83%)  2/120 (1.67%)  0/28 (0.00%)  0/24 (0.00%) 
Procedural pain  105/549 (19.13%)  89/551 (16.15%)  13/109 (11.93%)  11/120 (9.17%)  3/28 (10.71%)  2/24 (8.33%) 
Procedural vomiting  2/549 (0.36%)  3/551 (0.54%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Investigations             
Blood oestrogen increased  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Blood pressure increased  2/549 (0.36%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Blood urine present  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Body temperature increased  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Haemoglobin decreased  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Heart rate increased  0/549 (0.00%)  0/551 (0.00%)  0/109 (0.00%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
Hepatic enzyme increased  0/549 (0.00%)  2/551 (0.36%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Infertility tests  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Weight decreased  0/549 (0.00%)  0/551 (0.00%)  0/109 (0.00%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
Weight increased  0/549 (0.00%)  2/551 (0.36%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Metabolism and nutrition disorders             
Decreased appetite  1/549 (0.18%)  2/551 (0.36%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Hypoglycaemia  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Musculoskeletal and connective tissue disorders             
Arthralgia  2/549 (0.36%)  2/551 (0.36%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Back pain  9/549 (1.64%)  21/551 (3.81%)  1/109 (0.92%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Bone pain  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Flank pain  2/549 (0.36%)  2/551 (0.36%)  1/109 (0.92%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Joint swelling  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Limb discomfort  1/549 (0.18%)  0/551 (0.00%)  1/109 (0.92%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Muscle spasms  9/549 (1.64%)  16/551 (2.90%)  0/109 (0.00%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
Muscle tightness  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Musculoskeletal discomfort  2/549 (0.36%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Musculoskeletal pain  1/549 (0.18%)  0/551 (0.00%)  1/109 (0.92%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
Myalgia  4/549 (0.73%)  4/551 (0.73%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Neck pain  2/549 (0.36%)  3/551 (0.54%)  1/109 (0.92%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
Pain in extremity  2/549 (0.36%)  1/551 (0.18%)  0/109 (0.00%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Leiomyoma  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Uterine leiomyoma  2/549 (0.36%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Nervous system disorders             
Aphonia  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Dizziness  10/549 (1.82%)  7/551 (1.27%)  2/109 (1.83%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
Dysgeusia  2/549 (0.36%)  3/551 (0.54%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Headache  145/549 (26.41%)  127/551 (23.05%)  14/109 (12.84%)  16/120 (13.33%)  2/28 (7.14%)  5/24 (20.83%) 
Hyperaesthesia  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Lethargy  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
Migraine  0/549 (0.00%)  7/551 (1.27%)  1/109 (0.92%)  1/120 (0.83%)  1/28 (3.57%)  0/24 (0.00%) 
Migraine with aura  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Nerve compression  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Paraesthesia  3/549 (0.55%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Poor quality sleep  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Presyncope  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Retinal migraine  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Sciatica  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Sinus headache  4/549 (0.73%)  2/551 (0.36%)  1/109 (0.92%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
Somnolence  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Syncope  1/549 (0.18%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Tension headache  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Pregnancy, puerperium and perinatal conditions             
Abortion early  43/549 (7.83%)  60/551 (10.89%)  18/109 (16.51%)  16/120 (13.33%)  1/28 (3.57%)  2/24 (8.33%) 
Abortion spontaneous  7/549 (1.28%)  9/551 (1.63%)  0/109 (0.00%)  1/120 (0.83%)  1/28 (3.57%)  0/24 (0.00%) 
Cervical incompetence  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  1/28 (3.57%)  0/24 (0.00%) 
Ectopic pregnancy  3/549 (0.55%)  4/551 (0.73%)  0/109 (0.00%)  1/120 (0.83%)  1/28 (3.57%)  0/24 (0.00%) 
Gestational diabetes  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Haemorrhage in pregnancy  2/549 (0.36%)  4/551 (0.73%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Hyperemesis gravidarum  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Placenta praevia  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Premature rupture of membranes  0/549 (0.00%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  1/28 (3.57%)  0/24 (0.00%) 
Retained placenta or membranes  0/549 (0.00%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  1/28 (3.57%)  0/24 (0.00%) 
Subchorionic haematoma  2/549 (0.36%)  5/551 (0.91%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Subchorionic haemorrhage  3/549 (0.55%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Vanishing twin syndrome  1/549 (0.18%)  6/551 (1.09%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Vomiting in pregnancy  2/549 (0.36%)  3/551 (0.54%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Psychiatric disorders             
Anxiety  4/549 (0.73%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Depressed mood  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Depression  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Emotional disorder  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Insomnia  7/549 (1.28%)  4/551 (0.73%)  1/109 (0.92%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Mood altered  2/549 (0.36%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Mood swings  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Nightmare  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Restlessness  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Renal and urinary disorders             
Dysuria  4/549 (0.73%)  3/551 (0.54%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Haematuria  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Micturition urgency  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Pollakiuria  3/549 (0.55%)  2/551 (0.36%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Urinary retention  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Reproductive system and breast disorders             
Adnexa uteri pain  7/549 (1.28%)  3/551 (0.54%)  1/109 (0.92%)  0/120 (0.00%)  1/28 (3.57%)  0/24 (0.00%) 
Breast mass  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Breast pain  2/549 (0.36%)  0/551 (0.00%)  1/109 (0.92%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Breast tenderness  12/549 (2.19%)  8/551 (1.45%)  0/109 (0.00%)  2/120 (1.67%)  0/28 (0.00%)  0/24 (0.00%) 
Cervical discharge  2/549 (0.36%)  0/551 (0.00%)  0/109 (0.00%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
Cervical polyp  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Coital bleeding  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Dysmenorrhoea  4/549 (0.73%)  3/551 (0.54%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Fallopian tube cyst  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Hypomenorrhoea  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Menorrhagia  1/549 (0.18%)  2/551 (0.36%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Nipple pain  1/549 (0.18%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Ovarian cyst  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Ovarian enlargement  3/549 (0.55%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Ovarian hyperstimulation syndrome [1]  16/549 (2.91%)  12/551 (2.18%)  3/109 (2.75%)  2/120 (1.67%)  0/28 (0.00%)  0/24 (0.00%) 
Pelvic discomfort  8/549 (1.46%)  10/551 (1.81%)  1/109 (0.92%)  0/120 (0.00%)  1/28 (3.57%)  0/24 (0.00%) 
Pelvic pain  2/549 (0.36%)  6/551 (1.09%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Uterine cervix stenosis  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Uterine haemorrhage  2/549 (0.36%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Uterine pain  1/549 (0.18%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Uterine polyp  1/549 (0.18%)  1/551 (0.18%)  1/109 (0.92%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Uterine spasm  8/549 (1.46%)  9/551 (1.63%)  2/109 (1.83%)  2/120 (1.67%)  0/28 (0.00%)  0/24 (0.00%) 
Vaginal discharge  2/549 (0.36%)  4/551 (0.73%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Vaginal haemorrhage  14/549 (2.55%)  19/551 (3.45%)  1/109 (0.92%)  2/120 (1.67%)  1/28 (3.57%)  0/24 (0.00%) 
Vaginal odour  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Vulvovaginal discomfort  1/549 (0.18%)  4/551 (0.73%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Vulvovaginal pruritus  1/549 (0.18%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Cough  2/549 (0.36%)  3/551 (0.54%)  0/109 (0.00%)  2/120 (1.67%)  0/28 (0.00%)  1/24 (4.17%) 
Dry throat  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Dysphonia  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Dyspnoea  3/549 (0.55%)  1/551 (0.18%)  0/109 (0.00%)  1/120 (0.83%)  0/28 (0.00%)  0/24 (0.00%) 
Haemoptysis  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Nasal congestion  11/549 (2.00%)  10/551 (1.81%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  1/24 (4.17%) 
Oropharyngeal pain  10/549 (1.82%)  15/551 (2.72%)  2/109 (1.83%)  0/120 (0.00%)  0/28 (0.00%)  1/24 (4.17%) 
Paranasal sinus discomfort  0/549 (0.00%)  0/551 (0.00%)  1/109 (0.92%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Respiratory tract congestion  0/549 (0.00%)  2/551 (0.36%)  1/109 (0.92%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Rhinorrhoea  3/549 (0.55%)  6/551 (1.09%)  2/109 (1.83%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Sinus congestion  2/549 (0.36%)  4/551 (0.73%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Sneezing  3/549 (0.55%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Throat irritation  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Skin and subcutaneous tissue disorders             
Acne  1/549 (0.18%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Alopecia  0/549 (0.00%)  2/551 (0.36%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Blood blister  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Dry skin  1/549 (0.18%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Ingrowing nail  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Miliaria  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Night sweats  2/549 (0.36%)  0/551 (0.00%)  1/109 (0.92%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Pruritus  0/549 (0.00%)  2/551 (0.36%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Rash  3/549 (0.55%)  4/551 (0.73%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Rash maculo-papular  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Rash papular  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Rash pruritic  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Skin discolouration  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Skin disorder  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Skin reaction  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Swelling face  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Urticaria  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Surgical and medical procedures             
Abortion induced  2/549 (0.36%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Sinus operation  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Tooth extraction  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Uterine dilation and curettage  0/549 (0.00%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  1/28 (3.57%)  0/24 (0.00%) 
Vascular disorders             
Diastolic hypotension  0/549 (0.00%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Flushing  1/549 (0.18%)  1/551 (0.18%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Hot flush  11/549 (2.00%)  8/551 (1.45%)  1/109 (0.92%)  3/120 (2.50%)  0/28 (0.00%)  0/24 (0.00%) 
Hypertension  1/549 (0.18%)  0/551 (0.00%)  0/109 (0.00%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
Hypotension  0/549 (0.00%)  0/551 (0.00%)  1/109 (0.92%)  0/120 (0.00%)  0/28 (0.00%)  0/24 (0.00%) 
[1]
Note: This includes subjects who were at risk of OHSS as well those who had actual OHSS.
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.
Contract agreement. Results may not be published or referred to, in whole or in part, without the prior express written consent of the Sponsor.
Results Point of Contact
Name/Title: Executive VP of Regulatory Affairs
Organization: Fertility Biotech AG
Responsible Party: Fertility Biotech AG
ClinicalTrials.gov Identifier: NCT01687712     History of Changes
Other Study ID Numbers: FIN3002
First Submitted: September 3, 2012
First Posted: September 19, 2012
Results First Submitted: September 20, 2017
Results First Posted: October 18, 2017
Last Update Posted: December 5, 2017