CONSORT Randomized Controlled Trial in Assisted Reproductive Technology

• Sponsor: Merck KGaA, Darmstadt, Germany (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00829244
• Collaborator: (none)
• Enrollment: 200
• Location: 1
• Arms: 2
• Duration (Months): 17
• Patients Per Site Per Month: 11.8

Study Details

Study Description

Brief Summary

The overall objective of this trial is to compare the ovarian response in assisted reproductive technology (ART) subjects administered GONAL f® according to the 'Consistency in recombinant follicle stimulating hormone [r-FSH] starting doses for individualized treatment' (CONSORT) calculator versus given a standard GONAL f® dose of 150 International Unit (IU) per day.

Condition or Disease	Intervention/Treatment	Phase
Infertility	Drug: GONAL f® prefilled pen; Drug: GONAL f® prefilled pen	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase IV Prospective, Multicenter, Randomized, Open-label Trial to Assess the Efficacy and Safety of GONAL f® at a Dose Based on Subject Baseline Characteristics Determined According to the CONSORT Calculator Compared With a Standard Dose of GONAL f® 150 IU Per Day for Ovarian Stimulation in Women Undergoing Assisted Reproductive Technology (ART)
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CONSORT Dosing GONAL-f® dose based on subject baseline characteristics determined according to the CONSORT calculator	Drug: GONAL f® prefilled pen; GONAL f® doses starting at minimum of 112.5 IU per day and a maximum of 450 IU per day for 1 cycle only; Other Names: Follitropin alfa Recombinant human follicle stimulating hormone (r-hFSH) GONAL-f® Prefilled Pen
Active Comparator: Standard Dosing GONAL-f® at a standard dose of 150 IU per day	Drug: GONAL f® prefilled pen; GONAL f® standard treatment arm (150 IU of GONAL f® per day) up to Day 5 of stimulation after which the dose can be adjusted based upon the subject's ovarian response and according to the center's standard practice.; Other Names: Follitropin alfa r-hFSH GONAL-f® Prefilled Pen

Outcome Measures

Primary Outcome Measures

1. Number of Oocytes Retrieved Per Participant [34-38 hours post-recombinant human choriogonadotropin (hCG) (OPU)]

   Mean number of oocytes retrieved on the day of ovum pick up (OPU) was calculated. Oocyte retrieval is a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body.

Secondary Outcome Measures

1. Total GONAL-f® Dose [Start of treatment until end of stimulation cycle (approximately 28 days)]

2. Mean GONAL-f® Daily Dose [Start of treatment until end of stimulation cycle (approximately 28 days)]

3. Total Number of GONAL-f® Stimulation Treatment Days [Start of treatment until end of stimulation cycle (approximately 28 days)]

4. Number of Participants With Cancelled Cycles Due to Excessive or Inadequate Response to Treatment [Start of treatment until Day 15-20 post-hCG]

   Number of participants with cancelled cycles due to excessive or inadequate response was evaluated. An excessive response: greater than or equal to 25 oocytes which could put the participant at risk of OHSS; An inadequate response: defined as 3 or less follicles of greater than or equal to 12 millimeter (mm) developing following at least 7 days of GONAL-f® treatment.

5. Percentage of Participants With Biochemical Pregnancies [Start of treatment until Day 15-20 Post-hCG]

   Biochemical pregnancy was defined as a pregnancy diagnosed only by the detection of hCG in serum and that does not develop into a clinical pregnancy.

6. Number of Participants With Fetal Sacs and Fetal Hearts [Day 35-42 Post-hCG]

   Number of participants with fetal sacs and fetal hearts (with activity) as seen on an ultrasound scan to confirm clinical pregnancy.

7. Implantation Rate [Day 35-42 Post-hCG]

   Implantation rate was measured as the number of gestational sacs observed divided by the number of embryos transferred multiplied by 100.

8. Number of Participants With Multiple Pregnancies [Day 35-42 Post-hCG]

   Multiple pregnancy was defined as 2 or more fetal hearts with activity.

9. Serum Progesterone (P4) Levels [End of stimulation cycle (approximately 28 days)]

10. Percentage of Participants With Clinical Pregnancy [Day 35-42 Post-hCG]

    Clinical pregnancy is defined by the number of sacs and hearts with activity per ultrasound scan performed on Day 35-42 post-hCG.

11. Number of Participants With OHSS [Start of treatment until Day 15-20 Post-hCG]

    OHSS is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting.

12. Pregnancy Outcome - Number of Participants With Pregnancy and Their Outcome [up to 9 month (following the end of treatment)]

    Pregnancy outcomes are live outcome (live infant) and non-live outcome (non-live infant) or unknown outcome (subject lost to follow-up).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 34 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Female subjects justifying an in-vitro fertilization (IVF)/embryo transfer (ET) treatment

2. Have a male partner with semen analysis within the past 6 months prior to randomization considered adequate to proceed with regular insemination or intracytoplasmic sperm injection (ICSI) according to the center's standard practice. If these criteria are not met, the subject can only be entered if donor sperm will be used

3. Between her 18th and 35th birthday (35 not included) at the time of the randomization visit

4. Body mass index (BMI) lower than 30 kilogram per square meter (kg/m^2) where the BMI is calculated according to the formula

5. Have a regular spontaneous ovulatory menstrual cycle between 21 and 35 days in length

6. Have an early follicular phase (Day 2-4) serum level of basal FSH lower than or equal to 12 International Unit per Liter (IU/L) measured in the center's local laboratory during the screening period (i.e. within 2 months prior to down-regulation start)

7. Presence of both ovaries

8. Normal uterine cavity, which in the investigator's opinion is compatible with pregnancy

9. Have a negative cervical papanicolaou (PAP) test within the last 6 months prior to randomization

10. Have at least 1 wash-out cycle (defined as greater than or equal to 30 days since the last dose of clomiphene citrate or gonadotrophin treatment) since the last ART cycle and/or clomiphene citrate or gonadotrophin treatment prior to starting gonadotropin releasing hormone (GnRH) agonist therapy

11. Willing and able to comply with the protocol for the duration of the trial

12. Have given written informed consent, prior to any trial-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to her future medical care

Exclusion Criteria:

1. Have greater than or equal to 2 previous ART cycles with a poor response to gonadotrophin stimulation (defined as lower than or equal to 5 mature follicles and/or lower than or equal to 3 oocytes collected) or have greater than or equal to 2 previous ART cycles with a hyper response (defined as greater than or equal to 25 oocytes retrieved)

2. Any medical condition, which in the judgment of the investigator may interfere with the absorption, distribution, metabolism or excretion of the drug. In case of doubt, the subject in question should be discussed with Merck Serono's Medical responsible

3. Have previous severe ovarian hyperstimulation syndrome (OHSS)

4. Polycystic ovary syndrome (PCOS; Rotterdam criteria) to reduce the risk of the occurrence of OHSS

5. Presence of endometriosis requiring treatment

6. Uterine myoma requiring treatment

7. Any contraindication to being pregnant and/or carrying a pregnancy to term

8. Extra-uterine pregnancy within the last 3 months prior to screening

9. History of 3 or more miscarriages (early or late miscarriages) due to any cause

10. Tumors of the hypothalamus and pituitary gland

11. Ovarian enlargement or cyst of unknown etiology

12. Ovarian, uterine or mammary cancer

13. A clinically significant systemic disease

14. Known infection with Human Immunodeficiency Virus (HIV), Hepatitis B or C virus in the trial subject or her male partner,

15. Abnormal gynecological bleeding of undetermined origin

16. Known allergy or hypersensitivity to human gonadotrophin preparations,

17. Any active substance abuse or history of drug medication or alcohol abuse in the past 5 years prior to the screening visit

18. Entered previously into this trial or simultaneous participation in another clinical trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Geneva		Switzerland

Sponsors and Collaborators

• Merck KGaA, Darmstadt, Germany

Investigators

• Study Director: Pablo Arriagada, MD, Merck Serono S.A., Geneva

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck KGaA, Darmstadt, Germany
• ClinicalTrials.gov Identifier: NCT00829244
• Other Study ID Numbers: 28613
• First Posted: Jan 26, 2009
• Last Update Posted: Feb 13, 2014
• Last Verified: Jan 1, 2014

• Keywords provided by Merck KGaA, Darmstadt, Germany: Infertility; Assisted reproductive technology
• Additional relevant MeSH terms: Infertility; Follicle Stimulating Hormone

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at 22 clinical trial centers in 9 European countries and 1 center in Chile. Recruitment period: 29 August 2008 to 21 January 2010.
Pre-assignment Detail	A total of 244 participants gave informed consent and were screened for study entry. Forty-four (44) of these participants were not randomized due to: screening failure (38), failure to down regulate (3), or other reasons (3). A total of 200 participants were randomized to one of the two treatment arms.

Arm/Group Title	GONAL-f ® CONSORT Calculator	GONAL-f ® Standard Treatment
Arm/Group Description	GONAL-f® (follitropin alfa) administered subcutaneously (sc), dose ranging from 112.5 to 450 International Unit (IU) per day based on participant baseline characteristics determined according to the consistency in recombinant follicle stimulating hormone [r-FSH] starting doses for individualized treatment (CONSORT) calculator throughout stimulation cycle.	GONAL-f® (follitropin alfa) administered sc at a standard dose of 150 IU per day up to Day 5 of stimulation (S5) after which the dose was adjusted based upon the participant's ovarian response and according to the center's standard practice.
Period Title: Overall Study
STARTED	96	104
COMPLETED	82	83
NOT COMPLETED	14	21

Baseline Characteristics

Arm/Group Title	GONAL-f ® CONSORT Calculator	GONAL-f ® Standard Treatment	Total
Arm/Group Description	GONAL-f® (follitropin alfa) administered subcutaneously (sc), dose ranging from 112.5 to 450 International Unit (IU) per day based on participant baseline characteristics determined according to the consistency in recombinant follicle stimulating hormone [r-FSH] starting doses for individualized treatment (CONSORT) calculator throughout stimulation cycle.	GONAL-f® (follitropin alfa) administered sc at a standard dose of 150 IU per day up to Day 5 of stimulation (S5) after which the dose was adjusted based upon the participant's ovarian response and according to the center's standard practice.	Total of all reporting groups
Overall Participants	96	104	200
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	96 100%	104 100%	200 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.0 (2.9)	30.6 (2.6)	30.3 (2.8)
Sex: Female, Male (Count of Participants)
Female	96 100%	104 100%	200 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Chile	7 7.3%	8 7.7%	15 7.5%
Denmark	26 27.1%	26 25%	52 26%
France	6 6.3%	5 4.8%	11 5.5%
Germany	13 13.5%	16 15.4%	29 14.5%
Italy	10 10.4%	10 9.6%	20 10%
Netherlands	5 5.2%	6 5.8%	11 5.5%
Spain	4 4.2%	6 5.8%	10 5%
Sweden	8 8.3%	7 6.7%	15 7.5%
Switzerland	11 11.5%	14 13.5%	25 12.5%
United Kingdom	6 6.3%	6 5.8%	12 6%
Serum Anti-Mullerian Hormone (AMH) (nanogram/milliliter (ng/mL)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [nanogram/milliliter (ng/mL)]	2.705 (1.870)	2.399 (1.492)	2.551 (1.692)
Serum Progesterone (P4) (nanomole/liter (nmol/L)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [nanomole/liter (nmol/L)]	2.934 (2.328)	2.803 (2.291)	2.868 (2.303)

Outcome Measures

1. Primary Outcome

Title	Number of Oocytes Retrieved Per Participant
Description	Mean number of oocytes retrieved on the day of ovum pick up (OPU) was calculated. Oocyte retrieval is a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body.
Time Frame	34-38 hours post-recombinant human choriogonadotropin (hCG) (OPU)

Outcome Measure Data

Analysis Population Description

The modified Intention-To-Treat (ITT) population included all participants randomized into trial who received at least 1 dose of GONAL-f®, and who completed primary efficacy assessment (total number of oocytes retrieved per participant following GONAL-f® stimulation and hCG injection). Participants were analyzed based on treatment they received.

Arm/Group Title	GONAL-f ® CONSORT Calculator	GONAL-f ® Standard Treatment
Arm/Group Description	GONAL-f® (follitropin alfa) administered subcutaneously (sc), dose ranging from 112.5 to 450 International Unit (IU) per day based on participant baseline characteristics determined according to the consistency in recombinant follicle stimulating hormone [r-FSH] starting doses for individualized treatment (CONSORT) calculator throughout stimulation cycle.	GONAL-f® (follitropin alfa) administered sc at a standard dose of 150 IU per day up to Day 5 of stimulation (S5) after which the dose was adjusted based upon the participant's ovarian response and according to the center's standard practice.
Measure Participants	86	93
Mean (Standard Deviation) [oocytes]	10.0 (5.6)	11.8 (5.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GONAL-f ® CONSORT Calculator, GONAL-f ® Standard Treatment
	Comments	The null hypothesis was that the difference between the mean number of oocytes [CONSORT calculator dosing - Standard dosing] was less than or equal to [=<] (-3). The alternate hypothesis was that the difference was greater than [>] (-3).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.037
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -3.3 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.8
	Estimation Comments

2. Secondary Outcome

Title	Total GONAL-f® Dose
Time Frame	Start of treatment until end of stimulation cycle (approximately 28 days)

Outcome Measure Data

Analysis Population Description

The modified ITT population included all participants randomized into trial who received at least 1 dose of GONAL-f®, and who completed primary efficacy assessment (total number of oocytes retrieved per participant following GONAL-f® stimulation and hCG injection). Participants were analyzed based on treatment they received.

Arm/Group Title	GONAL-f ® CONSORT Calculator	GONAL-f ® Standard Treatment
Arm/Group Description	GONAL-f® (follitropin alfa) administered subcutaneously (sc), dose ranging from 112.5 to 450 International Unit (IU) per day based on participant baseline characteristics determined according to the consistency in recombinant follicle stimulating hormone [r-FSH] starting doses for individualized treatment (CONSORT) calculator throughout stimulation cycle.	GONAL-f® (follitropin alfa) administered sc at a standard dose of 150 IU per day up to Day 5 of stimulation (S5) after which the dose was adjusted based upon the participant's ovarian response and according to the center's standard practice.
Measure Participants	86	93
Mean (Standard Deviation) [IU]	1288.54 (300.95)	1809.95 (546.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GONAL-f ® CONSORT Calculator, GONAL-f ® Standard Treatment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-511.37
	Confidence Interval	(2-Sided) 95%; -638.78 to -383.96
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 64.52
	Estimation Comments

3. Secondary Outcome

Title	Mean GONAL-f® Daily Dose
Time Frame	Start of treatment until end of stimulation cycle (approximately 28 days)

Outcome Measure Data

Analysis Population Description

The modified ITT population included all participants randomized into trial who received at least 1 dose of GONAL-f®, and who completed primary efficacy assessment (total number of oocytes retrieved per participant following GONAL-f® stimulation and hCG injection). Participants were analyzed based on treatment they received.

Arm/Group Title	GONAL-f ® CONSORT Calculator	GONAL-f ® Standard Treatment
Arm/Group Description	GONAL-f® (follitropin alfa) administered subcutaneously (sc), dose ranging from 112.5 to 450 International Unit (IU) per day based on participant baseline characteristics determined according to the consistency in recombinant follicle stimulating hormone [r-FSH] starting doses for individualized treatment (CONSORT) calculator throughout stimulation cycle.	GONAL-f® (follitropin alfa) administered sc at a standard dose of 150 IU per day up to Day 5 of stimulation (S5) after which the dose was adjusted based upon the participant's ovarian response and according to the center's standard practice.
Measure Participants	86	93
Mean (Standard Deviation) [IU]	121.49 (22.56)	167.43 (30.79)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GONAL-f ® CONSORT Calculator, GONAL-f ® Standard Treatment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-45.60
	Confidence Interval	(2-Sided) 95%; -53.75 to -37.46
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.12
	Estimation Comments

4. Secondary Outcome

Title	Total Number of GONAL-f® Stimulation Treatment Days
Time Frame	Start of treatment until end of stimulation cycle (approximately 28 days)

Outcome Measure Data

Analysis Population Description

The modified ITT population included all participants randomized into trial who received at least 1 dose of GONAL-f®, and who completed primary efficacy assessment (total number of oocytes retrieved per participant following GONAL-f® stimulation and hCG injection). Participants were analyzed based on treatment they received.

Arm/Group Title	GONAL-f ® CONSORT Calculator	GONAL-f ® Standard Treatment
Arm/Group Description	GONAL-f® (follitropin alfa) administered subcutaneously (sc), dose ranging from 112.5 to 450 International Unit (IU) per day based on participant baseline characteristics determined according to the consistency in recombinant follicle stimulating hormone [r-FSH] starting doses for individualized treatment (CONSORT) calculator throughout stimulation cycle.	GONAL-f® (follitropin alfa) administered sc at a standard dose of 150 IU per day up to Day 5 of stimulation (S5) after which the dose was adjusted based upon the participant's ovarian response and according to the center's standard practice.
Measure Participants	86	93
Mean (Standard Deviation) [days]	10.6 (1.7)	10.7 (1.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GONAL-f ® CONSORT Calculator, GONAL-f ® Standard Treatment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.933
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.4 to 0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.2
	Estimation Comments

5. Secondary Outcome

Title	Number of Participants With Cancelled Cycles Due to Excessive or Inadequate Response to Treatment
Description	Number of participants with cancelled cycles due to excessive or inadequate response was evaluated. An excessive response: greater than or equal to 25 oocytes which could put the participant at risk of OHSS; An inadequate response: defined as 3 or less follicles of greater than or equal to 12 millimeter (mm) developing following at least 7 days of GONAL-f® treatment.
Time Frame	Start of treatment until Day 15-20 post-hCG

Outcome Measure Data

Analysis Population Description

All the randomized participants were analyzed for this outcome measure (N=200).

Arm/Group Title	GONAL-f ® CONSORT Calculator	GONAL-f ® Standard Treatment
Arm/Group Description	GONAL-f® (follitropin alfa) administered subcutaneously (sc), dose ranging from 112.5 to 450 International Unit (IU) per day based on participant baseline characteristics determined according to the consistency in recombinant follicle stimulating hormone [r-FSH] starting doses for individualized treatment (CONSORT) calculator throughout stimulation cycle.	GONAL-f® (follitropin alfa) administered sc at a standard dose of 150 IU per day up to Day 5 of stimulation (S5) after which the dose was adjusted based upon the participant's ovarian response and according to the center's standard practice.
Measure Participants	96	104
Inadequate response	9 9.4%	5 4.8%
Excessive response (Risk of OHSS)	1 1%	6 5.8%

6. Secondary Outcome

Title	Percentage of Participants With Biochemical Pregnancies
Description	Biochemical pregnancy was defined as a pregnancy diagnosed only by the detection of hCG in serum and that does not develop into a clinical pregnancy.
Time Frame	Start of treatment until Day 15-20 Post-hCG

Outcome Measure Data

Analysis Population Description

The modified ITT population included all participants randomized into trial who received at least 1 dose of GONAL-f®, and who completed primary efficacy assessment (total number of oocytes retrieved per participant following GONAL-f® stimulation and hCG injection). Participants were analyzed based on treatment they received.

Arm/Group Title	GONAL-f ® CONSORT Calculator	GONAL-f ® Standard Treatment
Arm/Group Description	GONAL-f® (follitropin alfa) administered subcutaneously (sc), dose ranging from 112.5 to 450 International Unit (IU) per day based on participant baseline characteristics determined according to the consistency in recombinant follicle stimulating hormone [r-FSH] starting doses for individualized treatment (CONSORT) calculator throughout stimulation cycle.	GONAL-f® (follitropin alfa) administered sc at a standard dose of 150 IU per day up to Day 5 of stimulation (S5) after which the dose was adjusted based upon the participant's ovarian response and according to the center's standard practice.
Measure Participants	86	93
Number [percentage of participants]	47.7 49.7%	44.1 42.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GONAL-f ® CONSORT Calculator, GONAL-f ® Standard Treatment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percent difference
	Estimated Value	3.6
	Confidence Interval	(2-Sided) 95%; -11.0 to 18.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Number of Participants With Fetal Sacs and Fetal Hearts
Description	Number of participants with fetal sacs and fetal hearts (with activity) as seen on an ultrasound scan to confirm clinical pregnancy.
Time Frame	Day 35-42 Post-hCG

Outcome Measure Data

Analysis Population Description

The modified ITT population included all participants randomized into trial who received at least 1 dose of GONAL-f®, and who completed primary efficacy assessment (total number of oocytes retrieved per participant following GONAL-f® stimulation and hCG injection). Participants were analyzed based on treatment they received.

Arm/Group Title	GONAL-f ® CONSORT Calculator	GONAL-f ® Standard Treatment
Arm/Group Description	GONAL-f® (follitropin alfa) administered subcutaneously (sc), dose ranging from 112.5 to 450 International Unit (IU) per day based on participant baseline characteristics determined according to the consistency in recombinant follicle stimulating hormone [r-FSH] starting doses for individualized treatment (CONSORT) calculator throughout stimulation cycle.	GONAL-f® (follitropin alfa) administered sc at a standard dose of 150 IU per day up to Day 5 of stimulation (S5) after which the dose was adjusted based upon the participant's ovarian response and according to the center's standard practice.
Measure Participants	86	93
Missing (fetal sacs and fetal hearts)	47 49%	57 54.8%
0 (fetal sacs)	6 6.3%	1 1%
1 (fetal sacs)	27 28.1%	25 24%
2 (fetal sacs)	5 5.2%	10 9.6%
3 (fetal sacs)	1 1%	0 0%
0 (fetal hearts)	8 8.3%	3 2.9%
1 (fetal hearts)	25 26%	24 23.1%
2 (fetal hearts)	5 5.2%	9 8.7%
3 (fetal hearts)	1 1%	0 0%

8. Secondary Outcome

Title	Implantation Rate
Description	Implantation rate was measured as the number of gestational sacs observed divided by the number of embryos transferred multiplied by 100.
Time Frame	Day 35-42 Post-hCG

Outcome Measure Data

Analysis Population Description

The modified ITT population included all participants randomized into trial who received at least 1 dose of GONAL-f®, and who completed primary efficacy assessment (total number of oocytes retrieved per participant following GONAL-f® stimulation and hCG injection). Participants were analyzed based on treatment they received.

Arm/Group Title	GONAL-f ® CONSORT Calculator	GONAL-f ® Standard Treatment
Arm/Group Description	GONAL-f® (follitropin alfa) administered subcutaneously (sc), dose ranging from 112.5 to 450 International Unit (IU) per day based on participant baseline characteristics determined according to the consistency in recombinant follicle stimulating hormone [r-FSH] starting doses for individualized treatment (CONSORT) calculator throughout stimulation cycle.	GONAL-f® (follitropin alfa) administered sc at a standard dose of 150 IU per day up to Day 5 of stimulation (S5) after which the dose was adjusted based upon the participant's ovarian response and according to the center's standard practice.
Measure Participants	86	93
Mean (Standard Deviation) [percent sacs per embryo]	31.1 (41.3)	31.2 (40.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GONAL-f ® CONSORT Calculator, GONAL-f ® Standard Treatment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.926
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -12.3 to 13.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.6
	Estimation Comments

9. Secondary Outcome

Title	Number of Participants With Multiple Pregnancies
Description	Multiple pregnancy was defined as 2 or more fetal hearts with activity.
Time Frame	Day 35-42 Post-hCG

Outcome Measure Data

Analysis Population Description

The modified ITT population. Number of participants analyzed (N) signifies those participants who were evaluated for this outcome measure.

Arm/Group Title	GONAL-f ® CONSORT Calculator	GONAL-f ® Standard Treatment
Arm/Group Description	GONAL-f® (follitropin alfa) administered subcutaneously (sc), dose ranging from 112.5 to 450 International Unit (IU) per day based on participant baseline characteristics determined according to the consistency in recombinant follicle stimulating hormone [r-FSH] starting doses for individualized treatment (CONSORT) calculator throughout stimulation cycle.	GONAL-f® (follitropin alfa) administered sc at a standard dose of 150 IU per day up to Day 5 of stimulation (S5) after which the dose was adjusted based upon the participant's ovarian response and according to the center's standard practice.
Measure Participants	39	36
Number [participants]	6 6.3%	9 8.7%

10. Secondary Outcome

Title	Serum Progesterone (P4) Levels
Time Frame	End of stimulation cycle (approximately 28 days)

Outcome Measure Data

Analysis Population Description

The modified ITT population included all participants randomized into trial who received at least 1 dose of GONAL-f®, and who completed primary efficacy assessment (total number of oocytes retrieved per participant following GONAL-f® stimulation and hCG injection). Participants were analyzed based on treatment they received.

Arm/Group Title	GONAL-f ® CONSORT Calculator	GONAL-f ® Standard Treatment
Arm/Group Description	GONAL-f® (follitropin alfa) administered subcutaneously (sc), dose ranging from 112.5 to 450 International Unit (IU) per day based on participant baseline characteristics determined according to the consistency in recombinant follicle stimulating hormone [r-FSH] starting doses for individualized treatment (CONSORT) calculator throughout stimulation cycle.	GONAL-f® (follitropin alfa) administered sc at a standard dose of 150 IU per day up to Day 5 of stimulation (S5) after which the dose was adjusted based upon the participant's ovarian response and according to the center's standard practice.
Measure Participants	86	93
Mean (Standard Deviation) [nmol/L]	5.41 (7.57)	4.88 (2.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GONAL-f ® CONSORT Calculator, GONAL-f ® Standard Treatment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.235
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; -0.61 to 2.47
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.78
	Estimation Comments

11. Secondary Outcome

Title	Percentage of Participants With Clinical Pregnancy
Description	Clinical pregnancy is defined by the number of sacs and hearts with activity per ultrasound scan performed on Day 35-42 post-hCG.
Time Frame	Day 35-42 Post-hCG

Outcome Measure Data

Analysis Population Description

The modified ITT population included all participants randomized into trial who received at least 1 dose of GONAL-f®, and who completed primary efficacy assessment (total number of oocytes retrieved per participant following GONAL-f® stimulation and hCG injection). Participants were analyzed based on treatment they received.

Arm/Group Title	GONAL-f ® CONSORT Calculator	GONAL-f ® Standard Treatment
Arm/Group Description	GONAL-f® (follitropin alfa) administered subcutaneously (sc), dose ranging from 112.5 to 450 International Unit (IU) per day based on participant baseline characteristics determined according to the consistency in recombinant follicle stimulating hormone [r-FSH] starting doses for individualized treatment (CONSORT) calculator throughout stimulation cycle.	GONAL-f® (follitropin alfa) administered sc at a standard dose of 150 IU per day up to Day 5 of stimulation (S5) after which the dose was adjusted based upon the participant's ovarian response and according to the center's standard practice.
Measure Participants	86	93
Number [percentage of participants]	36.0 37.5%	35.5 34.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GONAL-f ® CONSORT Calculator, GONAL-f ® Standard Treatment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percent difference
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -13.5 to 14.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Number of Participants With OHSS
Description	OHSS is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting.
Time Frame	Start of treatment until Day 15-20 Post-hCG

Outcome Measure Data

Analysis Population Description

Safety population included all the participants who were randomized.

Arm/Group Title	GONAL-f ® CONSORT Calculator	GONAL-f ® Standard Treatment
Arm/Group Description	GONAL-f® (follitropin alfa) administered subcutaneously (sc), dose ranging from 112.5 to 450 International Unit (IU) per day based on participant baseline characteristics determined according to the consistency in recombinant follicle stimulating hormone [r-FSH] starting doses for individualized treatment (CONSORT) calculator throughout stimulation cycle.	GONAL-f® (follitropin alfa) administered sc at a standard dose of 150 IU per day up to Day 5 of stimulation (S5) after which the dose was adjusted based upon the participant's ovarian response and according to the center's standard practice.
Measure Participants	96	104
Number [participants]	6 6.3%	13 12.5%

13. Secondary Outcome

Title	Pregnancy Outcome - Number of Participants With Pregnancy and Their Outcome
Description	Pregnancy outcomes are live outcome (live infant) and non-live outcome (non-live infant) or unknown outcome (subject lost to follow-up).
Time Frame	up to 9 month (following the end of treatment)

Outcome Measure Data

Analysis Population Description

The modified ITT population included all participants randomized into trial who received at least 1 dose of GONAL-f®, and who completed primary efficacy assessment (total number of oocytes retrieved per participant following GONAL-f® stimulation and hCG injection). Participants were analyzed based on treatment they received.

Arm/Group Title	GONAL-f ® CONSORT Calculator	GONAL-f ® Standard Treatment
Arm/Group Description	GONAL-f® (follitropin alfa) administered subcutaneously (sc), dose ranging from 112.5 to 450 International Unit (IU) per day based on participant baseline characteristics determined according to the consistency in recombinant follicle stimulating hormone [r-FSH] starting doses for individualized treatment (CONSORT) calculator throughout stimulation cycle.	GONAL-f® (follitropin alfa) administered sc at a standard dose of 150 IU per day up to Day 5 of stimulation (S5) after which the dose was adjusted based upon the participant's ovarian response and according to the center's standard practice.
Measure Participants	31	33
Live outcomes	24 25%	25 24%
Non-live outcomes	2 2.1%	3 2.9%
Unknown outcomes	5 5.2%	5 4.8%

Adverse Events

Time Frame	Adverse Events (AEs) were collected on an ongoing basis from day of written informed consent. All new AEs must be recorded until the final treatment examination, on Day 15-20 of the post-treatment assessment period
Adverse Event Reporting Description	Pre-Treatment:Medical conditions present at the initial study visit that did not worsen in severity or frequency during the study; Treatment-Emergent: If the onset date of the AE was on or after the first dose date of the study medication.
Arm/Group Title	GONAL-f ® CONSORT Calculator		GONAL-f ® Standard Treatment
Arm/Group Description	GONAL-f® (follitropin alfa) administered subcutaneously (sc), dose ranging from 112.5 to 450 International Unit (IU) per day based on participant baseline characteristics determined according to the consistency in recombinant follicle stimulating hormone [r-FSH] starting doses for individualized treatment (CONSORT) calculator throughout stimulation cycle.		GONAL-f® (follitropin alfa) administered sc at a standard dose of 150 IU per day up to Day 5 of stimulation (S5) after which the dose was adjusted based upon the participant's ovarian response and according to the center's standard practice.
All Cause Mortality
	GONAL-f ® CONSORT Calculator		GONAL-f ® Standard Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	GONAL-f ® CONSORT Calculator		GONAL-f ® Standard Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/96 (4.2%)		3/104 (2.9%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/96 (1%)	1	0/104 (0%)	0
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy	1/96 (1%)	1	0/104 (0%)	0
Reproductive system and breast disorders
Ovarian hyperstimulation syndrome	2/96 (2.1%)	2	2/104 (1.9%)	2
Skin and subcutaneous tissue disorders
Urticaria	0/96 (0%)	0	1/104 (1%)	1
Other (Not Including Serious) Adverse Events
	GONAL-f ® CONSORT Calculator		GONAL-f ® Standard Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/96 (41.7%)		48/104 (46.2%)
Gastrointestinal disorders
Nausea	8/96 (8.3%)	9	9/104 (8.7%)	11
Abdominal distension	8/96 (8.3%)	8	3/104 (2.9%)	5
Injury, poisoning and procedural complications
Procedural pain	9/96 (9.4%)	9	5/104 (4.8%)	5
Nervous system disorders
Headache	18/96 (18.8%)	30	25/104 (24%)	40
Reproductive system and breast disorders
Adnexa uteri pain	9/96 (9.4%)	10	8/104 (7.7%)	9
Ovarian hyperstimulation syndrome	5/96 (5.2%)	5	11/104 (10.6%)	12

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The PI shall submit any results communication to the sponsor for review and comment at least 30 business days prior to submission. The sponsor shall have the right to request the PI to delete or modify any of sponsor's proprietary information contained therein. If the PI does not agree to the deletion or appropriate modification of such information, it shall postpone submission for publication or presentation for 60 days from the date the PI notifies the sponsor.