Efficacy and Safety of FE 999049 in Controlled Ovarian Stimulation in Japanese Women

• ClinicalTrials.gov Identifier: NCT03228680
• Recruitment Status: Completed
• First Posted: July 25, 2017
• Results First Posted: March 24, 2021
• Last Update Posted: January 14, 2022
• Sponsor: Ferring Pharmaceuticals
• Information provided by (Responsible Party): Ferring Pharmaceuticals

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Infertility
• Interventions: Drug: Follitropin delta; Drug: Follitropin beta
• Enrollment: 373

Participant Flow

Recruitment Details	A total of 17 investigational sites in Japan randomized participants to the trial between 29 July 2017 to 08 July 2019.
Pre-assignment Details	A total of 373 participants were screened. Of these, 25 were screening failures and 348 participants were randomized: 170 participants were exposed to FE 999049 & 177 participants were exposed to FOLLISTIM. One participant was randomized to FOLLISTIM but not exposed to investigational medicinal product (IMP) was considered a randomization failure.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their anti-Müllerian hormone (AMH) level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Period Title: Overall Study
Started	170	178
Completed	147	143
Not Completed	23	35
Reason Not Completed
Adverse Event	13	18
Randomization failure	0	1
Withdrawal by Subject	1	0
Other	9	16

Baseline Characteristics

Arm/Group Title		FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)	Total
Arm/Group Description		FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	Total of all reporting groups
Overall Number of Baseline Participants		170	177	347
Baseline Analysis Population Description		[Not Specified]
Age, Continuous [1]; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	170 participants	177 participants	347 participants
		34.2 (3.5)	34.0 (3.4)	34.1 (3.5)
		[1] Measure Description: Number analyzed differs from the overall population as one subject in the FOLLISTIM (Follitropin beta) group was randomized but not exposed to treatment.
Sex: Female, Male [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	170 participants	177 participants	347 participants
	Female	170 100.0%	177 100.0%	347 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
		[1] Measure Description: Number analyzed differs from the overall population as one subject in the FOLLISTIM (Follitropin beta) group was randomized but not exposed to treatment.
Ethnicity (NIH/OMB) [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	170 participants	177 participants	347 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%
	Not Hispanic or Latino	170 100.0%	177 100.0%	347 100.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
		[1] Measure Description: Number analyzed differs from the overall population as one subject in the FOLLISTIM (Follitropin beta) group was randomized but not exposed to treatment.
Race (NIH/OMB) [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	170 participants	177 participants	347 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	170 100.0%	177 100.0%	347 100.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%
	White	0 0.0%	0 0.0%	0 0.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
		[1] Measure Description: Number analyzed differs from the overall population as one subject in the FOLLISTIM (Follitropin beta) group was randomized but not exposed to treatment.
Region of Enrollment [1]; Measure Type: Number; Unit of measure: Participants
Japan	Number Analyzed	170 participants	177 participants	347 participants
		170	177	347
		[1] Measure Description: Number analyzed differs from the overall population as one subject in the FOLLISTIM (Follitropin beta) group was randomized but not exposed to treatment.

Outcome Measures

1. Primary Outcome

Title	Number of Oocytes Retrieved
Description	The number of oocytes retrieved was recorded at the oocyte retrieval visit.
Time Frame	36h (± 2h) after triggering of final follicular maturation (On day of oocyte retrieval)

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS) comprised all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Mean (Standard Deviation); Unit of Measure: Oocytes retrieved
	9.3 (5.4)	10.5 (6.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Mean number of oocytes retrieved.
	Type of Statistical Test	Non-Inferiority
	Comments	The pre-specified non-inferiority (NI) margin was -3.0 oocytes. The NI was evaluated based on the two-sided 95% CI from the ANOVA on 'number of oocytes retrieved' with treatment and AMH stratum as fixed factors.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -2.3 to -0.1
	Estimation Comments	If the lower bound of 95% CI was well above pre-specified NI limit of -3.0 oocytes, then NI of FE 999049 to FOLLISTIM with respect to number of oocytes retrieved in women undergoing controlled ovarian stimulation would be demonstrated

2. Secondary Outcome

Title	Clinical Pregnancy Rate
Description	Clinical pregnancy was defined as at least one gestational sac 5-6 weeks after transfer.
Time Frame	5-6 weeks after transfer (up to approximately 3 months after start of stimulation)

Outcome Measure Data

Analysis Population Description

The FAS comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Measure Type: Number; Unit of Measure: percentage of participants
	25.3	23.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Percentage of participants with at least one gestational sac 5-6 weeks after transfer.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 95%; -7.5 to 10.6
	Estimation Comments	The difference (FE 999049-FOLLISTIM) in rates was estimated and a two-sided 95% Cl was constructed using the Mantel-Haenszel method to combine results across AMH strata.

3. Secondary Outcome

Title	Positive Beta Unit of Human Chorionic Gonadotropin (Beta-hCG) Rate
Description	Defined as positive serum beta-hCG test 13-15 days after transfer.
Time Frame	13-15 days after transfer (up to approximately 1.5 months after start of stimulation)

Outcome Measure Data

Analysis Population Description

The FAS comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Measure Type: Number; Unit of Measure: percentage of participants
	29.4	29.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Percentage of participants with positive beta-hCG.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -9.5 to 9.6
	Estimation Comments	The difference (FE 999049-FOLLISTIM) in rates was estimated and a two-sided 95% Cl was constructed using the Mantel-Haenszel method to combine results across AMH strata.

4. Secondary Outcome

Title	Vital Pregnancy Rate
Description	Vital pregnancy was defined as at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after transfer.
Time Frame	5-6 weeks after transfer (up to approximately 3 months after start of stimulation)

Outcome Measure Data

Analysis Population Description

The FAS comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Measure Type: Number; Unit of Measure: percentage of participants
	23.5	21.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Percentage of participants with vital pregnancy.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 95%; -6.7 to 10.8
	Estimation Comments	The difference (FE 999049-FOLLISTIM) in rates was estimated and a two-sided 95% Cl was constructed using the Mantel-Haenszel method to combine results across AMH strata.

5. Secondary Outcome

Title	Implantation Rate
Description	Implantation rate was defined as the number of gestational sacs 5-6 weeks after transfer divided by the number of blastocysts transferred.
Time Frame	5-6 weeks after transfer (up to approximately 3 months after start of stimulation)

Outcome Measure Data

Analysis Population Description

The FAS comprised of all randomized and exposed participants with blastocyst transfer.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Overall Number of Units Analyzed; Type of Units Analyzed: Embryos transferred	135	141
Measure Type: Number; Unit of Measure: % of sacs/blastocysts transferred
	31.9	29.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Percentage of implanted embryos 5-6 weeks after transfer.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	1.9
	Confidence Interval	(2-Sided) 95%; -8.9 to 12.8
	Estimation Comments	The difference (FE 999049-FOLLISTIM) in rates was estimated and a two-sided 95% Cl was constructed using the Mantel-Haenszel method to combine results across AMH strata.

6. Secondary Outcome

Title	Proportion of Participants With Cycle Cancellation Due to Poor or Excessive Ovarian Response
Description	[Not Specified]
Time Frame	End-of-stimulation (up to 20 stimulation days)

Outcome Measure Data

Analysis Population Description

The FAS comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Measure Type: Number; Unit of Measure: percentage of participants
Cycle cancelled due to poor ovarian response	1.2	0.6
Cycle cancelled due to excessive ovarian response	0	1.1

7. Secondary Outcome

Title	Proportion of Participants With Blastocyst Transfer Cancellation Due to Excessive Ovarian Response / OHSS Risk
Description	[Not Specified]
Time Frame	End-of-stimulation (up to 20 stimulation days)

Outcome Measure Data

Analysis Population Description

The FAS comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Measure Type: Number; Unit of Measure: percentage of participants
	7.6	11.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Proportion of participants with blastocyst transfer cancellation.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.244
	Comments	P-value was based on likelihood ratio chi-square test.
	Method	Regression, Logistic
	Comments	The model included treatment and AMH stratum (<15 pmol/L and ≥15 pmol/L) as fixed factors.

8. Secondary Outcome

Title	Proportion of Participants With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved
Description	Defined as proportion of participants grouped according to the number of oocytes retrieved. The proportion of participants with <4 oocytes (low response), 4-7 oocytes (moderate response), 8-14 oocytes (targeted response), 15-19 oocytes (hyperresponse) and ≥20 oocytes (severe hyperresponse) are presented.
Time Frame	On the day of oocyte retrieval (up to 22 days after start of stimulation)

Outcome Measure Data

Analysis Population Description

The FAS comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	169	173
Measure Type: Number; Unit of Measure: percentage of participants
Low response (<4 oocytes)	8.3	5.2
Moderate response (4-7 oocytes)	36.1	26.6
Targeted response (8-14 oocytes)	40.8	42.8
Hyperresponse (15-19 oocytes)	10.1	14.5
Severe hyperresponse (≥ 20 oocytes)	4.7	11.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Proportion of participants with <4 oocytes retrieved (low response).
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.254
	Comments	P-value was based on likelihood ratio chi-square test.
	Method	Regression, Logistic
	Comments	The model included treatment and AMH stratum (<15 pmol/L and ≥15 pmol/L) as fixed factors.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Proportion of participants with 4-7 oocytes retrieved (moderate response).
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.041
	Comments	P-value was based on likelihood ratio test.
	Method	Regression, Logistic
	Comments	The model included treatment and AMH stratum (<15 pmol/L and ≥15 pmol/L) as fixed factors.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Proportion of participants with 8-14 oocytes retrieved (targeted response).
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.705
	Comments	P-value was based on likelihood ratio test.
	Method	Regression, Logistic
	Comments	The model included treatment and AMH stratum (<15 pmol/L and ≥15 pmol/L) as fixed factors.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Proportion of participants with 15-19 oocytes retrieved (hyperresponse).
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.183
	Comments	P-value was based on likelihood ratio test.
	Method	Regression, Logistic
	Comments	The model included treatment and AMH stratum (<15 pmol/L and ≥15 pmol/L) as fixed factors.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Proportion of participants with >= (more than equal to) 20 oocytes retrieved (severe hyperresponse).
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.030
	Comments	P-value was based on likelihood ratio chi-square test.
	Method	Regression, Logistic
	Comments	The model included treatment and AMH stratum (<15 pmol/L and ≥15 pmol/L) as fixed factors.

9. Secondary Outcome

Title	Proportion of Participants With Extreme Ovarian Responses (Defined as <4, ≥15 or ≥20 Oocytes Retrieved) in Risk Population
Description	[Not Specified]
Time Frame	On the day of oocyte retrieval (up to 22 days after start of stimulation)

Outcome Measure Data

Analysis Population Description

The FAS comprised of all randomized and exposed participants.

Arm/Group Title		FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:		FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed		169	173
Measure Type: Number; Unit of Measure: percentage of participants
AMH < 15 pmol/L (<4 oocytes retrieved)	Number Analyzed	69 participants	73 participants
		11.6	12.3
AMH >= 15 pmol/L (>=15 oocytes retrieved)	Number Analyzed	100 participants	100 participants
		22.0	42.0
AMH >= 15 pmol/L (>=20 oocytes retrieved)	Number Analyzed	100 participants	100 participants
		8.0	19.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Proportion of participants with extreme ovarian responses: AMH < 15 pmol/L (<4 oocytes retrieved)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.893
	Comments	P-value was based on likelihood ratio chi-square test.
	Method	Chi-squared
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Proportion of participants with extreme ovarian responses: AMH >= 15 pmol/L (>=15 oocytes retrieved)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.002
	Comments	P-value was based on likelihood ratio chi-square test.
	Method	Chi-squared
	Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Proportion of participants with extreme ovarian responses: AMH >= 15 pmol/L (>=20 oocytes retrieved)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.021
	Comments	P-value based on likelihood ratio chi-square test.
	Method	Chi-squared
	Comments	[Not Specified]

10. Secondary Outcome

Title	Proportion of Participants With Preventive Interventions for Early Ovarian Hyperstimulation Syndrome (OHSS)
Description	[Not Specified]
Time Frame	≤9 days after triggering of final follicular maturation

Outcome Measure Data

Analysis Population Description

The FAS comprised of all participants randomized or exposed.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Measure Type: Number; Unit of Measure: percentage of participants
Cycle cancellation	0	1.1
Triggering with GnRH agonist	1.2	1.1
Administration of dopamine agonist	0.6	1.7

11. Secondary Outcome

Title	Proportions of Participants With Early OHSS (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS
Description	Defined as proportion of participants with early OHSS, early OHSS of moderate or severe grade, preventive interventions for early OHSS, early OHSS and/or preventive interventions for early OHSS, and early OHSS of moderate or severe grade and/or preventive interventions for early OHSS are presented.
Time Frame	Up to 9 days after triggering of final follicular maturation

Outcome Measure Data

Analysis Population Description

The FAS comprised of all participants randomized and exposed.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Measure Type: Number; Unit of Measure: percentage of participants
Early OHSS (any grade)	10.0	18.6
Early OHSS (moderate/severe)	6.5	13.0
Early OHSS (any grade) and/or preventive	10.6	20.9
Early OHSS (moderate/severe) and/or preventive	7.6	16.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Proportions of participants with early OHSS (any grade).
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.017
	Comments	P-value was based on likelihood ratio chi-square test.
	Method	Regression, Logistic
	Comments	The model included treatment and AMH stratum (<15 pmol/L and ≥15 pmol/L) as fixed factors.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Proportion of participants with early OHSS (moderate/severe).
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.035
	Comments	P-value was based on likelihood ratio chi-square test.
	Method	Regression, Logistic
	Comments	The model included treatment and AMH stratum (<15 pmol/L and ≥15 pmol/L) as fixed factors.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Proportion of participants with early OHSS (any grade) and/or preventive interventions.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.006
	Comments	P-value was based on likelihood ratio chi-square test.
	Method	Regression, Logistic
	Comments	The model included treatment and AMH stratum (<15 pmol/L and ≥15 pmol/L) as fixed factors.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Proportion of participants with early OHSS (moderate/severe) and/or preventive interventions.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.009
	Comments	P-value was based on likelihood ratio chi-square test.
	Method	Regression, Logistic
	Comments	The model included treatment and AMH stratum (<15 pmol/L and ≥15 pmol/L) as fixed factors.

12. Secondary Outcome

Title	Proportions of Participants With Late OHSS (Including OHSS of Moderate/Severe Grade)
Description	Defined as proportions of participants with late OHSS (including OHSS of moderate/severe grade). Late OHSS was defined as OHSS with onset >9 days after triggering of final follicular maturation. The proportion of participants with late OHSS, and late OHSS of moderate or severe grade are presented. All OHSS cases were graded as mild, moderate, or severe.
Time Frame	>9 days after triggering of final follicular maturation

Outcome Measure Data

Analysis Population Description

The FAS comprised of all participants randomized or exposed.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Measure Type: Number; Unit of Measure: percentage of participants
Late OHSS (any grade)	1.2	1.1
Late OHSS (moderate/severe)	0.6	1.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Proportions of participants with late OHSS (any grade).
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.968
	Comments	P-value was based on likelihood ratio chi-square test.
	Method	Regression, Logistic
	Comments	The model included treatment and AMH stratum (<15 pmol/L and ≥15 pmol/L) as fixed factors.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Proportions of participants with late OHSS (moderate/severe).
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.582
	Comments	P-value was based on likelihood ratio chi-square test.
	Method	Regression, Logistic
	Comments	The model included treatment and AMH stratum (<15 pmol/L and ≥15 pmol/L) as fixed factors.

13. Secondary Outcome

Title	Number of Follicles on Stimulation Day 6
Description	Defined as the number of follicles observed in both ovaries at the last transvaginal ultrasound (TVUS) in the stimulation phase (on stimulation Day 6).
Time Frame	At Day 6 of stimulation

Outcome Measure Data

Analysis Population Description

The FAS comprised of all randomized or exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Mean (Standard Deviation); Unit of Measure: Follicles
	12.8 (7.2)	13.3 (7.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	The number of follicles on stimulation Day 6 was analyzed.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.198
	Comments	2-sided
	Method	van Elteren test
	Comments	P-value was based on van Elteren test adjusted for AMH strata.

14. Secondary Outcome

Title	Number of Follicles at End-of-stimulation
Description	Defined as the number of follicles observed in both ovaries at the last TVUS in the stimulation phase (end-of-stimulation).
Time Frame	End-of-stimulation (up to 20 stimulation days)

Outcome Measure Data

Analysis Population Description

The FAS comprised of all randomized or exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Mean (Standard Deviation); Unit of Measure: Follicles
	14.9 (8.0)	16.3 (8.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	The number of follicles at end-of-stimulation was analyzed.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.036
	Comments	2-sided
	Method	van Elteren test
	Comments	P-value was based on van Elteren test adjusted for AMH strata.

15. Secondary Outcome

Title	Size of Follicles on Stimulation Day 6
Description	Defined as size characteristics of follicles on stimulation Day 6. Average size of 3 largest follicles has been presented in this endpoint.
Time Frame	At Day 6 of stimulation

Outcome Measure Data

Analysis Population Description

The FAS comprised of all randomized and exposed participants

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Mean (Standard Deviation); Unit of Measure: mm
	12.7 (2.1)	12.8 (2.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	The average size of 3 largest follicles was analyzed.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.592
	Comments	2-sided
	Method	van Elteren test
	Comments	P-value was based on van Elteren test adjusted for AMH strata.

16. Secondary Outcome

Title	Size of Follicles at End-of-Stimulation
Description	Defined as size characteristics of follicles at end-of-stimulation. Average size of 3 largest follicles has been presented in this endpoint.
Time Frame	End-of-stimulation (up to 20 stimulation days)

Outcome Measure Data

Analysis Population Description

The FAS comprised of all randomized and exposed participants

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Mean (Standard Deviation); Unit of Measure: mm
	19.2 (1.5)	19.4 (1.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	The average size of 3 largest follicles was analyzed.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.286
	Comments	2-sided
	Method	van Elteren test
	Comments	P-value was based on van Elteren test adjusted for AMH strata.

17. Secondary Outcome

Title	Fertilization Rate
Description	The fertilization rate was defined as the number of oocytes with 2 pronuclei divided by the number of oocytes retrieved.
Time Frame	Day 1 after oocyte retrieval (up to approximately 22 days after start of stimulation)

Outcome Measure Data

Analysis Population Description

The FAS comprised all randomized and exposed participants

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Mean (Standard Deviation); Unit of Measure: percentage of fertilized oocytes
	54.5 (26.1)	57.1 (23.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	The fertilization rate (number of oocytes with 2 pronuclei divided by the number of oocytes retrieved) was analyzed.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.395
	Comments	2-sided
	Method	van Elteren test
	Comments	P-value was based on van Elteren test adjusted for AMH strata.

18. Secondary Outcome

Title	Number and Quality of Embryos
Description	Number of embryos (total and good-quality) on Day 3 are presented. A good-quality embryo was defined as an embryo with ≥6 blastomeres and fragmentation ≤20% on Day 3.
Time Frame	Day 3 after oocyte retrieval (up to approximately 24 days after start of stimulation)

Outcome Measure Data

Analysis Population Description

The FAS comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Mean (Standard Deviation); Unit of Measure: Embryo
Number of embryo	5.8 (4.2)	7.0 (4.3)
Number of good-quality embryo	3.9 (3.3)	4.6 (3.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	The number of embryos on Day 3 was analyzed.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.001
	Comments	2-sided
	Method	van Elteren test
	Comments	P-value was based on van Elteren test adjusted for AMH strata.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	The number of good-quality embryos on Day 3 was analyzed.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.004
	Comments	2-sided
	Method	van Elteren test
	Comments	P-value was based on van Elteren test adjusted for AMH strata.

19. Secondary Outcome

Title	Number and Quality of Blastocysts
Description	Number of embryos (total and good-quality) on Day 5 are presented. The quality evaluation of blastocysts consisted of assessment of three parameters, as per the Gardner & Schoolcraft system: blastocyst expansion and hatching status (graded: 1-6), inner cell mass (graded: A-D) and trophectoderm (graded: A-D). A good-quality blastocyst was defined as a blastocyst of grade 3BB or higher.
Time Frame	Day 5 after oocyte retrieval (up to approximately 26 days after start of stimulation)

Outcome Measure Data

Analysis Population Description

The FAS comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Mean (Standard Deviation); Unit of Measure: Blastocysts
Number of blastocysts	3.1 (2.7)	4.2 (3.4)
Number of good-quality blastocysts	2.3 (2.3)	3.0 (2.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	The number of blastocysts on Day 5 was analyzed.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.001
	Comments	2-sided
	Method	van Elteren test
	Comments	P-value was based on van Elteren test adjusted for AMH strata.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	The number of good-quality blastocysts on Day 5 was analyzed.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	2-sided
	Method	van Elteren test
	Comments	P-value was based on van Elteren test adjusted for AMH strata.

20. Secondary Outcome

Title	Circulating Levels of Endocrine Parameters (Follicle-stimulating Hormone [FSH], Luteinising Hormone [LH]) on Stimulation Day 6
Description	The median and inter-quartile range (IQR) of FSH and LH levels on stimulation Day 6 are presented.
Time Frame	At Day 6 of stimulation

Outcome Measure Data

Analysis Population Description

The FAS comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	166	175
Median (Inter-Quartile Range); Unit of Measure: IU/L
FSH	15.4; (12.0 to 19.6)	14.7; (12.8 to 17.3)
LH	2.6; (1.5 to 6.2)	2.8; (1.6 to 5.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Circulating levels of FSH on stimulation Day 6.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.228
	Comments	The P-value corresponds to the two-sided F-test of treatment effect.
	Method	ANCOVA
	Comments	The ANCOVA model included treatment and AMH stratum (<15 pmol/L and ≥15 pmol/L) as fixed factors and log-baseline as covariate.
Method of Estimation	Estimation Parameter	Mean ratio
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.98 to 1.09
	Estimation Comments	Mean ratio is equal to FE 999049/FOLLISTIM.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Circulating levels of LH on stimulation Day 6.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.777
	Comments	The P-value corresponds to the two-sided F-test of treatment effect.
	Method	ANCOVA
	Comments	The ANCOVA model included treatment and AMH stratum (<15 pmol/L and ≥15 pmol/L) as fixed factors and log-baseline as covariate.
Method of Estimation	Estimation Parameter	Mean ratio
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.81 to 1.17
	Estimation Comments	Mean ratio is equal to FE 999049/FOLLISTIM.

21. Secondary Outcome

Title	Circulating Levels of Endocrine Parameters (Follicle-stimulating Hormone [FSH], Luteinising Hormone [LH]) at End-of-stimulation
Description	The median and IQR of FSH and LH levels at end-of-stimulation are presented.
Time Frame	End-of-stimulation (up to 20 stimulation days)

Outcome Measure Data

Analysis Population Description

The FAS comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	169	172
Median (Inter-Quartile Range); Unit of Measure: IU/L
FSH	14.3; (11.6 to 19.7)	16.4; (13.5 to 20.4)
LH	1.6; (1.0 to 2.5)	1.4; (0.9 to 2.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Circulating levels of FSH at end-of-stimulation.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The P-value corresponds to the two-sided F-test of treatment effect.
	Method	ANCOVA
	Comments	The ANCOVA model included treatment and AMH stratum (<15 pmol/L and ≥15 pmol/L) as fixed factors and log-baseline as covariate.
Method of Estimation	Estimation Parameter	Mean ratio
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.84 to 0.94
	Estimation Comments	Mean ratio is equal to FE 999049/FOLLISTIM.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Circulating levels of LH at end-of-stimulation.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.057
	Comments	The P-value corresponds to the two-sided F-test of treatment effect.
	Method	ANCOVA
	Comments	The ANCOVA model included treatment and AMH stratum (<15 pmol/L and ≥15 pmol/L) as fixed factors and log-baseline as covariate.
Method of Estimation	Estimation Parameter	Mean ratio
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 95%; 1.00 to 1.39
	Estimation Comments	Mean ratio is equal to FE 999049/FOLLISTIM.

22. Secondary Outcome

Title	Circulating Levels of Endocrine Parameter (Estradiol) on Stimulation Day 6
Description	The median and IQR of estradiol levels on stimulation Day 6 are presented.
Time Frame	At Day 6 of stimulation

Outcome Measure Data

Analysis Population Description

The FAS comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	166	175
Median (Inter-Quartile Range); Unit of Measure: pmol/L
	2277.1; (1479.4 to 3580.1)	2680.0; (1608.8 to 4685.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Circulating levels of estradiol on stimulation Day 6.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.002
	Comments	The P-value corresponds to the two-sided F-test of treatment effect.
	Method	ANCOVA
	Comments	The ANCOVA model included treatment and AMH stratum (<15 pmol/L and ≥15 pmol/L) as fixed factors and log-baseline as covariate.
Method of Estimation	Estimation Parameter	Mean ratio
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.71 to 0.93
	Estimation Comments	Mean ratio is equal to FE 999049/FOLLISTIM.

23. Secondary Outcome

Title	Circulating Levels of Endocrine Parameter (Estradiol) at End-of-stimulation
Description	The median and IQR of estradiol levels at end-of-stimulation are presented.
Time Frame	End-of-stimulation (up to 20 stimulation days)

Outcome Measure Data

Analysis Population Description

The FAS comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	169	172
Median (Inter-Quartile Range); Unit of Measure: pmol/L
	6517.0; (4465.3 to 9033.4)	7438.8; (5363.6 to 10283.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Circulating levels of estradiol at end-of-stimulation.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.003
	Comments	The P-value corresponds to the two-sided F-test of treatment effect.
	Method	ANCOVA
	Comments	The ANCOVA model included treatment and AMH stratum (<15 pmol/L and ≥15 pmol/L) as fixed factors and log-baseline as covariate.
Method of Estimation	Estimation Parameter	Mean ratio
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.76 to 0.95
	Estimation Comments	Mean ratio is equal to FE 999049/FOLLISTIM.

24. Secondary Outcome

Title	Circulating Levels of Endocrine Parameter (Progesterone) on Stimulation Day 6
Description	The median and IQR of progesterone levels on stimulation Day 6 are presented.
Time Frame	At Day 6 of stimulation

Outcome Measure Data

Analysis Population Description

The FAS comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	166	175
Median (Inter-Quartile Range); Unit of Measure: nmol/L
	1.7; (0.8 to 2.4)	1.7; (0.8 to 2.65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Circulating levels of progesterone on stimulation Day 6.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.814
	Comments	The P-value corresponds to the two-sided F-test of treatment effect.
	Method	ANCOVA
	Comments	The ANCOVA model included treatment and AMH stratum (<15 pmol/L and ≥15 pmol/L) as fixed factors and log-baseline as covariate.
Method of Estimation	Estimation Parameter	Mean ratio
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.89 to 1.16
	Estimation Comments	Mean ratio is equal to FE 999049/FOLLISTIM.

25. Secondary Outcome

Title	Circulating Levels of Endocrine Parameter (Progesterone) at End-of-stimulation
Description	The median and IQR of progesterone levels at end-of-stimulation are presented.
Time Frame	End-of-stimulation (up to 20 stimulation days)

Outcome Measure Data

Analysis Population Description

The FAS comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	168	172
Median (Inter-Quartile Range); Unit of Measure: nmol/L
	2.5; (1.9 to 3.5)	3.1; (2.3 to 4.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Circulating levels of progesterone levels at end-of-stimulation.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The P-value corresponds to the two-sided F-test of treatment effect.
	Method	ANCOVA
	Comments	The ANCOVA model included treatment and AMH stratum (<15 pmol/L and ≥15 pmol/L) as fixed factors and log-baseline as covariate.
Method of Estimation	Estimation Parameter	Mean ratio
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 95%; 0.68 to 0.88
	Estimation Comments	Mean ratio is equal to FE 999049/FOLLISTIM.

26. Secondary Outcome

Title	Circulating Levels of Endocrine Parameters (Inhibin A) on Stimulation Day 6
Description	The median and IQR of Inhibin A levels on stimulation Day 6 are presented.
Time Frame	At Day 6 of stimulation

Outcome Measure Data

Analysis Population Description

The FAS comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	166	175
Median (Inter-Quartile Range); Unit of Measure: ng/L
	113.1; (75.1 to 171.9)	129.8; (81.6 to 210.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Circulating levels of Inhibin A on stimulation Day 6.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The P-value corresponds to the two-sided F-test of treatment effect.
	Method	ANCOVA
	Comments	The ANCOVA model included treatment and AMH stratum (<15 pmol/L and ≥15 pmol/L) as fixed factors and log-baseline as covariate.
Method of Estimation	Estimation Parameter	Mean ratio
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 95%; 0.73 to 0.92
	Estimation Comments	Mean ratio is equal to FE 999049/FOLLISTIM.

27. Secondary Outcome

Title	Circulating Levels of Endocrine Parameters (Inhibin A) at End-of-stimulation
Description	The median and IQR of Inhibin A levels at end-of-stimulation are presented.
Time Frame	End-of-stimulation (up to 20 stimulation days)

Outcome Measure Data

Analysis Population Description

The FAS comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	169	172
Median (Inter-Quartile Range); Unit of Measure: ng/L
	323.8; (222.1 to 458.8)	390.3; (301.0 to 551.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Circulating levels of Inhibin A at end-of-stimulation.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The P-value corresponds to the two-sided F-test of treatment effect.
	Method	ANCOVA
	Comments	The ANCOVA model included treatment and AMH stratum (<15 pmol/L and ≥15 pmol/L) as fixed factors and log-baseline as covariate.
Method of Estimation	Estimation Parameter	Mean ratio
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95%; 0.72 to 0.88
	Estimation Comments	Mean ratio is equal to FE 999049/FOLLISTIM.

28. Secondary Outcome

Title	Circulating Levels of Endocrine Parameters (Inhibin B) on Stimulation Day 6
Description	The median and IQR of inhibin B levels on stimulation Day 6 are presented.
Time Frame	At Day 6 of stimulation

Outcome Measure Data

Analysis Population Description

The FAS comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	166	175
Median (Inter-Quartile Range); Unit of Measure: ng/L
	570.5; (396.0 to 853.0)	686.0; (431.0 to 1004.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Circulating levels of Inhibin B on stimulation Day 6.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The P-value corresponds to the two-sided F-test of treatment effect.
	Method	ANCOVA
	Comments	The ANCOVA model included treatment and AMH stratum (<15 pmol/L and ≥15 pmol/L) as fixed factors and log-baseline as covariate.
Method of Estimation	Estimation Parameter	Mean ratio
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95%; 0.75 to 0.93
	Estimation Comments	Mean ratio is equal to FE 999049/FOLLISTIM.

29. Secondary Outcome

Title	Circulating Levels of Endocrine Parameters (Inhibin B) at End-of-stimulation
Description	The median and IQR of inhibin B levels at end-of-stimulation are presented.
Time Frame	End-of-stimulation (up to 20 stimulation days)

Outcome Measure Data

Analysis Population Description

The FAS comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	169	172
Median (Inter-Quartile Range); Unit of Measure: ng/L
	686.0; (461.0 to 1057.0)	734.5; (492.5 to 1120.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	Circulating levels of Inhibin B at end-of-stimulation.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.027
	Comments	The P-value corresponds to the two-sided F-test of treatment effect.
	Method	ANCOVA
	Comments	The ANCOVA model included treatment and AMH stratum (<15 pmol/L and ≥15 pmol/L) as fixed factors and log-baseline as covariate.
Method of Estimation	Estimation Parameter	Mean ratio
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.79 to 0.99
	Estimation Comments	Mean ratio is equal to FE 999049/FOLLISTIM.

30. Secondary Outcome

Title	Number of Stimulation Days
Description	[Not Specified]
Time Frame	End-of-stimulation (up to 20 stimulation days)

Outcome Measure Data

Analysis Population Description

The safety analysis set comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Mean (Standard Deviation); Unit of Measure: Days
	8.9 (1.9)	8.8 (1.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FE 999049 (Follitropin Delta), FOLLISTIM (Follitropin Beta)
	Comments	The number of stimulation days at end-of-stimulation.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.694
	Comments	2-sided
	Method	van Elteren test
	Comments	P-value was based on van Elteren test adjusted for AMH strata.

31. Secondary Outcome

Title	Total Gonadotropin Dose of FE 999049
Description	[Not Specified]
Time Frame	End-of-stimulation (up to 20 stimulation days)

Outcome Measure Data

Analysis Population Description

The safety analysis set comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170
Mean (Standard Deviation); Unit of Measure: μg
	83.5 (28.9)

32. Secondary Outcome

Title	Total Gonadotropin Dose of FOLLISTIM
Description	[Not Specified]
Time Frame	End-of-stimulation (up to 20 stimulation days)

Outcome Measure Data

Analysis Population Description

The safety analysis set comprised of all randomized and exposed participants.

Arm/Group Title	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	177
Mean (Standard Deviation); Unit of Measure: IU
	1499 (514)

33. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) Stratified by Intensity
Description	The frequency of participants with total AEs and AEs by categories of intensity (mild, moderate, severe) are presented. An AE was any untoward medical occurrence in a participants participating in clinical trial. The intensity of AE was classified using the following 3-point scale: mild = awareness of signs or symptoms, but no disruption of usual activity); moderate = event sufficient to affect usual activity (disturbing); or severe = inability to work or perform usual activities (unacceptable).
Time Frame	From signed informed consent up to 5-6 weeks after transfer

Outcome Measure Data

Analysis Population Description

The safety analysis set comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Measure Type: Number; Unit of Measure: Participants
Any AE	73	92
Mild AE	69	86
Moderate AE	8	12
Severe AE	0	1

34. Secondary Outcome

Title	Proportion of Participants Who Had Markedly Abnormal Value Changes From Baseline in Clinical Chemistry Parameters at End-of-stimulation
Description	Defined as number of participants with at least one markedly abnormal finding in clinical chemistry parameters (as assessed by investigator) were reported. The clinical chemistry parameters included: alanine transaminase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), bicarbonate, bilirubin direct, bilirubin total, blood urea nitrogen, calcium, chloride, cholesterol total, creatinine, gamma-glutamyl transpeptidase, glucose, lactate dehydrogenase, phosphorus, potassium, sodium, total protein, uric acid.
Time Frame	End-of-stimulation (up to 20 stimulation days)

Outcome Measure Data

Analysis Population Description

The safety analysis set comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Measure Type: Number; Unit of Measure: participants
ALT (IU/L): Normal to markedly high (>3xULN)	0	1
AST (IU/L): Normal to markedly high (>3xULN)	0	1

35. Secondary Outcome

Title	Proportion of Participants Who Had Markedly Abnormal Value Changes From Baseline in Hematology Parameters at End-of-stimulation
Description	Defined as number of participants with at least one markedly abnormal changes in hematology parameters (as assessed by investigator) were reported. Hematology parameters included: red blood cells, white blood cells, red blood cells morphology, white blood cells morphology, haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, platelets.
Time Frame	End-of-stimulation (up to 20 stimulation days)

Outcome Measure Data

Analysis Population Description

The safety analysis set comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Measure Type: Number; Unit of Measure: participants
	0	0

36. Secondary Outcome

Title	Proportion of Participants Who Had Markedly Abnormal Value Changes From Baseline in Clinical Chemistry Parameters at End-of-trial
Description	Defined as number of participants with at least one markedly abnormal finding in clinical chemistry parameters (as assessed by investigator) were reported. The clinical chemistry parameters included: alanine transaminase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), bicarbonate, bilirubin direct, bilirubin total, blood urea nitrogen, calcium, chloride, cholesterol total, creatinine, gamma-glutamyl transpeptidase, glucose, lactate dehydrogenase, phosphorus, potassium, sodium, total protein, uric acid.
Time Frame	Up to 5-6 weeks after transfer

Outcome Measure Data

Analysis Population Description

The safety analysis set comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Measure Type: Number; Unit of Measure: participants
	0	0

37. Secondary Outcome

Title	Proportion of Participants Who Had Markedly Abnormal Value Changes From Baseline in Hematology Parameters at End-of-trial
Description	Defined as number of participants with at least one markedly abnormal changes in hematology parameters (as assessed by investigator) were reported. Hematology parameters included: red blood cells, white blood cells, red blood cells morphology, white blood cells morphology, haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, platelets.
Time Frame	Up to 5-6 weeks after transfer

Outcome Measure Data

Analysis Population Description

The safety analysis set comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Measure Type: Number; Unit of Measure: participants
Leukocytes (10^9/L) Normal to markedly high (>=16)	0	1
Hemoglobin (g/L) Normal to markedly low	0	1
Hematocrit (ratio) Normal to markedly low (>=0.56)	0	1

38. Secondary Outcome

Title	Frequency and Intensity of Injection Site Reactions
Description	The presence of of injection site reactions (redness, itching, pain, swelling and bruising) immediately, 30 minutes and 24 hours after the injection are presented. The injection site reactions were assessed as none, mild, moderate and severe. The number of injection site reactions (mild, moderate or severe) based on all assessments performed is presented.
Time Frame	End-of-stimulation (up to 20 stimulation days)

Outcome Measure Data

Analysis Population Description

The safety analysis set comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Measure Type: Number; Unit of Measure: events
Any mild injection site reaction	271	719
Any moderate injection site reaction	7	19
Any severe injection site reaction	1	0
Mild redness	140	174
Moderate redness	2	0
Severe redness	0	0
Mild itching	4	5
Moderate itching	1	0
Severe itching	0	0
Mild pain	19	411
Moderate pain	1	16
Severe pain	0	0
Mild swelling	6	10
Moderate swelling	0	0
Severe swelling	0	0
Mild bruising	102	119
Moderate bruising	3	3
Severe bruising	1	0

39. Secondary Outcome

Title	Technical Malfunctions of the Administration Pens
Description	[Not Specified]
Time Frame	End-of-stimulation (up to 20 stimulation days)

Outcome Measure Data

Analysis Population Description

The safety analysis set comprised of all randomized and exposed participants.

Arm/Group Title	FE 999049 (Follitropin Delta)	FOLLISTIM (Follitropin Beta)
Arm/Group Description:	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.	FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
Overall Number of Participants Analyzed	170	177
Measure Type: Number; Unit of Measure: percentage of participants
	0	0

Adverse Events

Time Frame	Adverse events were monitored from the time of obtaining informed consent until the last visit (end-of-trial) (up to approximately 2 years) .
Adverse Event Reporting Description	Adverse events with onset after start of first administration of IMP were considered treatment -emergent and are presented for the safety analysis set.
Arm/Group Title	FE 999049 (Follitropin Delta)		FOLLISTIM (Follitropin Beta)
Arm/Group Description	FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.		FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
All-Cause Mortality
	FE 999049 (Follitropin Delta)		FOLLISTIM (Follitropin Beta)
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/170 (0.00%)		0/177 (0.00%)
Serious Adverse Events
	FE 999049 (Follitropin Delta)		FOLLISTIM (Follitropin Beta)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/170 (0.00%)		2/177 (1.13%)
Reproductive system and breast disorders
Ovarian hyperstimulation syndrome † 1	0/170 (0.00%)	0	2/177 (1.13%)	2
1 Term from vocabulary, MedDRA (20.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2%
	FE 999049 (Follitropin Delta)		FOLLISTIM (Follitropin Beta)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	73/170 (42.94%)		92/177 (51.98%)
Gastrointestinal disorders
Constipation † 1	4/170 (2.35%)	4	5/177 (2.82%)	6
General disorders
Injection site erythema † 1	13/170 (7.65%)	14	15/177 (8.47%)	15
Injection site pruritus † 1	0/170 (0.00%)	0	5/177 (2.82%)	5
Infections and infestations
Viral upper respiratory tract infection † 1	6/170 (3.53%)	6	6/177 (3.39%)	6
Nervous system disorders
Headache † 1	4/170 (2.35%)	4	4/177 (2.26%)	4
Pregnancy, puerperium and perinatal conditions
Biochemical pregnancy † 1	6/170 (3.53%)	6	10/177 (5.65%)	10
Abortion spontenous † 1	3/170 (1.76%)	3	4/177 (2.26%)	4
Haemorrhage in pregnancy † 1	4/170 (2.35%)	4	0/177 (0.00%)	0
Reproductive system and breast disorders
Ovarian hyperstimulation syndrome † 1	19/170 (11.18%)	19	35/177 (19.77%)	35
Ovarian cyst † 1	5/170 (2.94%)	5	7/177 (3.95%)	7
Ovarian enlargement † 1	5/170 (2.94%)	5	5/177 (2.82%)	5
Pelvic fluid collection † 1	4/170 (2.35%)	4	4/177 (2.26%)	4
1 Term from vocabulary, MedDRA (20.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The only disclosure restriction on the PI is that the sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the sponsor. Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow Ferring to seek patent protection of the invention.

Results Point of Contact

• Name/Title: Clinical Development Support
• Organization: Ferring Pharmaceuticals
• EMail: DK0-Disclosure@ferring.com

Publications of Results:

Ishihara O, Arce JC; Japanese Follitropin Delta Phase 3 Trial (STORK) Group. Individualized follitropin delta dosing reduces OHSS risk in Japanese IVF/ICSI patients: a randomized controlled trial. Reprod Biomed Online. 2021 May;42(5):909-918. doi: 10.1016/j.rbmo.2021.01.023. Epub 2021 Feb 9.

Ishihara O, Nelson SM, Arce JC. Comparison of ovarian response to follitropin delta in Japanese and White IVF/ICSI patients. Reprod Biomed Online. 2022 Jan;44(1):177-184. doi: 10.1016/j.rbmo.2021.09.014. Epub 2021 Sep 23.

• Responsible Party: Ferring Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03228680
• Other Study ID Numbers: 000273
• First Submitted: July 13, 2017
• First Posted: July 25, 2017
• Results First Submitted: January 20, 2021
• Results First Posted: March 24, 2021
• Last Update Posted: January 14, 2022