Trial Outcomes & Findings for Progesterone Serum Levels in Subfertile Female Patients Undergoing in Vitro Fertilisation (IVF) (NCT NCT01225835)

Last Updated: 2014-03-14

Results Overview

Ovulation induction was performed by administration of hCG once three follicles \>=17 mm diameter as shown by pelvic ultrasound examination. This outcome compares the serum progesterone level the morning prior to hCG administration across treatment arm, and also by age stratum (\<39 years and \>=39 years).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

124 participants

Primary outcome timeframe

approximately day 10

Results posted on

2014-03-14

Participant Flow

One hundred seventy patients were screened.

Participant milestones

Participant milestones
Measure	Menotrophin Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Follitrophin Alpha Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Overall Study STARTED	62	62
Overall Study Per Protocol Population	48	58
Overall Study COMPLETED	55	59
Overall Study NOT COMPLETED	7	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Menotrophin Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Follitrophin Alpha Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Overall Study Completed protocol	2	1
Overall Study Did not meet hCG criterion	2	0
Overall Study Adverse Event	2	1
Overall Study Other	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Menotrophin n=62 Participants Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Follitrophin Alpha n=62 Participants Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Total n=124 Participants Total of all reporting groups
Age, Continuous	36.5 years STANDARD_DEVIATION 2.4 • n=5 Participants	36.7 years STANDARD_DEVIATION 2.3 • n=7 Participants	36.6 years STANDARD_DEVIATION 2.4 • n=5 Participants
Age, Customized < 39 years	50 participants n=5 Participants	49 participants n=7 Participants	99 participants n=5 Participants
Age, Customized >=39 years	12 participants n=5 Participants	13 participants n=7 Participants	25 participants n=5 Participants
Sex: Female, Male Female	62 Participants n=5 Participants	62 Participants n=7 Participants	124 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Weight	64.3 kg STANDARD_DEVIATION 8.2 • n=5 Participants	63.5 kg STANDARD_DEVIATION 8.7 • n=7 Participants	63.9 kg STANDARD_DEVIATION 8.4 • n=5 Participants
Duration of Infertility	45.7 months STANDARD_DEVIATION 35.0 • n=5 Participants	40.6 months STANDARD_DEVIATION 25.6 • n=7 Participants	43.2 months STANDARD_DEVIATION 30.7 • n=5 Participants
Menstrual Cycle Regular	62 participants n=5 Participants	62 participants n=7 Participants	124 participants n=5 Participants
Menstrual Cycle Irregular	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Length of Menstrual Cycle	28.3 days STANDARD_DEVIATION 1.7 • n=5 Participants	28.2 days STANDARD_DEVIATION 1.5 • n=7 Participants	28.2 days STANDARD_DEVIATION 1.6 • n=5 Participants
Former Treatment for Infertility No	24 participants n=5 Participants	24 participants n=7 Participants	48 participants n=5 Participants
Former Treatment for Infertility Yes	38 participants n=5 Participants	38 participants n=7 Participants	76 participants n=5 Participants
Participants with Gonadotrophin Stimulated Assisted Reproductive Technology (ART) Cycle No	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Participants with Gonadotrophin Stimulated Assisted Reproductive Technology (ART) Cycle Yes	13 participants n=5 Participants	18 participants n=7 Participants	31 participants n=5 Participants
Participants with Gonadotrophin Stimulated Assisted Reproductive Technology (ART) Cycle Missing Values	49 participants n=5 Participants	44 participants n=7 Participants	93 participants n=5 Participants
Aetiology of Infertility Tubal factor	20 participants n=5 Participants	18 participants n=7 Participants	38 participants n=5 Participants
Aetiology of Infertility Endometriosis	4 participants n=5 Participants	3 participants n=7 Participants	7 participants n=5 Participants
Aetiology of Infertility Idiopathic	36 participants n=5 Participants	33 participants n=7 Participants	69 participants n=5 Participants
Aetiology of Infertility Other	1 participants n=5 Participants	8 participants n=7 Participants	9 participants n=5 Participants
Aetiology of Infertility Missing values	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants

PRIMARY outcome

Timeframe: approximately day 10

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Menotrophin n=62 Participants Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Menotrophin: Stratum Age <39 Yrs n=50 Participants The subset of participants in the menotrophin treatment arm who were \< 39 years old.	Menotrophin: Stratum Age >=39 Yrs n=12 Participants The subset of participants in the menotrophin treatment arm who were \>= 39 years old.	Follitrophin Alpha n=62 Participants Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Follitrophin Alpha: Stratum Age <39 Yrs n=49 Participants The subset of participants in the follitrophin alpha treatment arm who were \< 39 years old.	Follitrophin Alpha: Stratum Age >=39 Yrs n=13 Participants The subset of participants in the follitrophin alpha treatment arm who were \>= 39 years old.
Serum Progesterone (P4) Level in the Morning of the Day of Human Chorionic Gonadotrophin (hCG) Administration	0.69 ng/ml Standard Deviation 0.34	0.72 ng/ml Standard Deviation 0.35	0.54 ng/ml Standard Deviation 0.25	0.89 ng/ml Standard Deviation 0.41	0.92 ng/ml Standard Deviation 0.43	0.80 ng/ml Standard Deviation 0.28

SECONDARY outcome

Timeframe: Day 7, approximately Day 10 (hCG Administration)

Population: Full analysis set

The influence of the progesterone level on the ongoing pregnancy rate (in relation to all randomized patients) was determined by means of the receiver operating characteristic (ROC) curve. Youden's Index (sensitivity + specificity -1) has a range of 0-1, with 0.5 indicating a random effect.

Outcome measures

Outcome measures
Measure	Menotrophin n=124 Participants Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Menotrophin: Stratum Age <39 Yrs The subset of participants in the menotrophin treatment arm who were \< 39 years old.	Menotrophin: Stratum Age >=39 Yrs The subset of participants in the menotrophin treatment arm who were \>= 39 years old.	Follitrophin Alpha Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Follitrophin Alpha: Stratum Age <39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \< 39 years old.	Follitrophin Alpha: Stratum Age >=39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \>= 39 years old.
Receiver Operating Characteristic (ROC) Analysis of Progesterone as Predictor for Ongoing Pregnancy Rate at Day 7 and Day of hCG Administration Day 7	0.5189 Youden's index	—	—	—	—	—
Receiver Operating Characteristic (ROC) Analysis of Progesterone as Predictor for Ongoing Pregnancy Rate at Day 7 and Day of hCG Administration Day of hCG Administration (approx Day 10)	0.4944 Youden's index	—	—	—	—	—

SECONDARY outcome

Timeframe: approximately 3.5 months from study start (at least 9 weeks after first positive pregnancy test)

Population: The per-protocol (PP) set -- defined as participants of the full analysis set without any major protocol violation (i.e., any deviation which was likely to bias the assessment of the primary endpoint).

Ongoing pregnancy is defined as having a positive foetal heart action nine or more weeks after the first positive pregnancy test.

Outcome measures

Outcome measures
Measure	Menotrophin n=48 Participants Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Menotrophin: Stratum Age <39 Yrs n=58 Participants The subset of participants in the menotrophin treatment arm who were \< 39 years old.	Menotrophin: Stratum Age >=39 Yrs The subset of participants in the menotrophin treatment arm who were \>= 39 years old.	Follitrophin Alpha Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Follitrophin Alpha: Stratum Age <39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \< 39 years old.	Follitrophin Alpha: Stratum Age >=39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \>= 39 years old.
Percentage of Participants With Ongoing Pregnancy	29.2 percentage of participants	31.0 percentage of participants	—	—	—	—

SECONDARY outcome

Timeframe: approximately day 10

Population: The per-protocol (PP) set of participants with non-missing values. PP set is defined as participants of the full analysis set without any major protocol violation (i.e., any deviation which was likely to bias the assessment of the primary endpoint).

Number of follicles \>=17 mm diameter detected by pelvic ultrasound examination at day of hCG administration.

Outcome measures

Outcome measures
Measure	Menotrophin n=48 Participants Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Menotrophin: Stratum Age <39 Yrs n=57 Participants The subset of participants in the menotrophin treatment arm who were \< 39 years old.	Menotrophin: Stratum Age >=39 Yrs The subset of participants in the menotrophin treatment arm who were \>= 39 years old.	Follitrophin Alpha Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Follitrophin Alpha: Stratum Age <39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \< 39 years old.	Follitrophin Alpha: Stratum Age >=39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \>= 39 years old.
Number of Follicles at hCG Administration	8.7 follicles Standard Deviation 4.7	10.5 follicles Standard Deviation 4.1	—	—	—	—

SECONDARY outcome

Timeframe: approximately day 10

Population: The per-protocol (PP) set of participants with non-missing values.

Outcome measures

Outcome measures
Measure	Menotrophin n=48 Participants Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Menotrophin: Stratum Age <39 Yrs n=57 Participants The subset of participants in the menotrophin treatment arm who were \< 39 years old.	Menotrophin: Stratum Age >=39 Yrs The subset of participants in the menotrophin treatment arm who were \>= 39 years old.	Follitrophin Alpha Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Follitrophin Alpha: Stratum Age <39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \< 39 years old.	Follitrophin Alpha: Stratum Age >=39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \>= 39 years old.
Average Follicle Diameter at hCG Administration	17.6 mm Standard Deviation 1.8	18.1 mm Standard Deviation 1.2	—	—	—	—

SECONDARY outcome

Timeframe: approximately day 12 after study start

Population: The per-protocol (PP) set of participants with non-missing values.

Cumulus-oocyte complexes are oocytes with surrounding cumulus cells.

Outcome measures

Outcome measures
Measure	Menotrophin n=48 Participants Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Menotrophin: Stratum Age <39 Yrs n=57 Participants The subset of participants in the menotrophin treatment arm who were \< 39 years old.	Menotrophin: Stratum Age >=39 Yrs The subset of participants in the menotrophin treatment arm who were \>= 39 years old.	Follitrophin Alpha Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Follitrophin Alpha: Stratum Age <39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \< 39 years old.	Follitrophin Alpha: Stratum Age >=39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \>= 39 years old.
Number of Cumulus-oocyte Complexes Retrieved	6.8 oocytes Standard Deviation 4.2	10.0 oocytes Standard Deviation 4.6	—	—	—	—

SECONDARY outcome

Timeframe: approximately day 13 after study start

Population: The per-protocol (PP) set of participants with non-missing values.

Pronuclear oocytes are fertilized oocytes.

Outcome measures

Outcome measures
Measure	Menotrophin n=48 Participants Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Menotrophin: Stratum Age <39 Yrs n=57 Participants The subset of participants in the menotrophin treatment arm who were \< 39 years old.	Menotrophin: Stratum Age >=39 Yrs The subset of participants in the menotrophin treatment arm who were \>= 39 years old.	Follitrophin Alpha Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Follitrophin Alpha: Stratum Age <39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \< 39 years old.	Follitrophin Alpha: Stratum Age >=39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \>= 39 years old.
Number of Pronuclear Oocytes	3.7 oocytes Standard Deviation 2.8	5.9 oocytes Standard Deviation 3.7	—	—	—	—

SECONDARY outcome

Timeframe: approximately day 13

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

Outcome measures

Outcome measures
Measure	Menotrophin n=48 Participants Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Menotrophin: Stratum Age <39 Yrs n=58 Participants The subset of participants in the menotrophin treatment arm who were \< 39 years old.	Menotrophin: Stratum Age >=39 Yrs The subset of participants in the menotrophin treatment arm who were \>= 39 years old.	Follitrophin Alpha Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Follitrophin Alpha: Stratum Age <39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \< 39 years old.	Follitrophin Alpha: Stratum Age >=39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \>= 39 years old.
Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade Grade 0A	11 participants	17 participants	—	—	—	—
Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade Grade 0B	15 participants	23 participants	—	—	—	—
Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade Grade 1	33 participants	40 participants	—	—	—	—
Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade Grade 2	15 participants	25 participants	—	—	—	—
Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade Grade 3	8 participants	24 participants	—	—	—	—
Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade Grade 4	2 participants	11 participants	—	—	—	—
Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade Grade 5	11 participants	23 participants	—	—	—	—

SECONDARY outcome

Timeframe: approximately day 14

Population: The per-protocol (PP) set who had embryos transferred. PP set is defined as participants of the full analysis set without any major protocol violation (i.e., any deviation which was likely to bias the assessment of the primary endpoint).

Mean number of embryos transferred 2-3 days following oocyte retrieval.

Outcome measures

Outcome measures
Measure	Menotrophin n=46 Participants Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Menotrophin: Stratum Age <39 Yrs n=54 Participants The subset of participants in the menotrophin treatment arm who were \< 39 years old.	Menotrophin: Stratum Age >=39 Yrs The subset of participants in the menotrophin treatment arm who were \>= 39 years old.	Follitrophin Alpha Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Follitrophin Alpha: Stratum Age <39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \< 39 years old.	Follitrophin Alpha: Stratum Age >=39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \>= 39 years old.
Number of Embryos Transferred	2.0 embryos Standard Deviation 0.5	2.0 embryos Standard Deviation 0.4	—	—	—	—

SECONDARY outcome

Timeframe: approximately day 14

Population: Per protocol set of participants who had embryos transferred

Embryo quality was measured by the following grades: * Grade 1: Evenly sized cells, regular cleavage, no fragmentation * Grade 2: Regular or slightly irregular cleavage, \<=20% fragmentation * Grade 2.5: Regular or slightly irregular cleavage, \>20%and \<=50% fragmentation * Grade 3: Irregular cleavage, \>50% fragmentation, \>1 intact cell * Grade 4: Extensive fragmentation, only 1 cell intact * Grade 5: Totally fragmented, no viable cells. Grade 1 represents the healthiest embryos and Grade 5 embryos are not viable.

Outcome measures

Outcome measures
Measure	Menotrophin n=46 Participants Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Menotrophin: Stratum Age <39 Yrs n=54 Participants The subset of participants in the menotrophin treatment arm who were \< 39 years old.	Menotrophin: Stratum Age >=39 Yrs The subset of participants in the menotrophin treatment arm who were \>= 39 years old.	Follitrophin Alpha Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Follitrophin Alpha: Stratum Age <39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \< 39 years old.	Follitrophin Alpha: Stratum Age >=39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \>= 39 years old.
Best Quality of an Embryo Transferred Grade 1	22 participants	26 participants	—	—	—	—
Best Quality of an Embryo Transferred Grade 2	18 participants	22 participants	—	—	—	—
Best Quality of an Embryo Transferred Grade >2	6 participants	6 participants	—	—	—	—

SECONDARY outcome

Timeframe: approximately day 14

Population: Per protocol set of participants who had embryos transferred

No more than three normally developed embryos were transferred 2-3 days after oocyte retrieval. Other normally developed embryos were frozen.

Outcome measures

Outcome measures
Measure	Menotrophin n=46 Participants Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Menotrophin: Stratum Age <39 Yrs n=54 Participants The subset of participants in the menotrophin treatment arm who were \< 39 years old.	Menotrophin: Stratum Age >=39 Yrs The subset of participants in the menotrophin treatment arm who were \>= 39 years old.	Follitrophin Alpha Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Follitrophin Alpha: Stratum Age <39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \< 39 years old.	Follitrophin Alpha: Stratum Age >=39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \>= 39 years old.
Number of Frozen Oocytes at Pronuclear Stage	1.0 oocytes Standard Deviation 2.2	2.7 oocytes Standard Deviation 2.9	—	—	—	—

SECONDARY outcome

Timeframe: approximately day 10

Population: Per protocol set of participants. One participant in the Follitrophin Alpha arm was missing a measurement.

Endometrial thickness was assessed by pelvic ultrasound on the day of hCG administration.

Outcome measures

Outcome measures
Measure	Menotrophin n=48 Participants Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Menotrophin: Stratum Age <39 Yrs n=57 Participants The subset of participants in the menotrophin treatment arm who were \< 39 years old.	Menotrophin: Stratum Age >=39 Yrs The subset of participants in the menotrophin treatment arm who were \>= 39 years old.	Follitrophin Alpha Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Follitrophin Alpha: Stratum Age <39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \< 39 years old.	Follitrophin Alpha: Stratum Age >=39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \>= 39 years old.
Endometrial Thickness on Day of hCG Administration	10.8 mm Standard Deviation 2.1	11.0 mm Standard Deviation 2.2	—	—	—	—

SECONDARY outcome

Timeframe: approximately day 10

Population: Per protocol set. Five participants from each treatment arm were missing blood samples.

Outcome measures

Outcome measures
Measure	Menotrophin n=43 Participants Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Menotrophin: Stratum Age <39 Yrs n=53 Participants The subset of participants in the menotrophin treatment arm who were \< 39 years old.	Menotrophin: Stratum Age >=39 Yrs The subset of participants in the menotrophin treatment arm who were \>= 39 years old.	Follitrophin Alpha Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Follitrophin Alpha: Stratum Age <39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \< 39 years old.	Follitrophin Alpha: Stratum Age >=39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \>= 39 years old.
Estradiol (E2) Levels on Day of hCG Administration	1.81 ng/ml Standard Deviation 1.21	1.65 ng/ml Standard Deviation 0.87	—	—	—	—

SECONDARY outcome

Timeframe: approximately day 18

Population: Per protocol set

Outcome measures

Outcome measures
Measure	Menotrophin n=48 Participants Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Menotrophin: Stratum Age <39 Yrs n=58 Participants The subset of participants in the menotrophin treatment arm who were \< 39 years old.	Menotrophin: Stratum Age >=39 Yrs The subset of participants in the menotrophin treatment arm who were \>= 39 years old.	Follitrophin Alpha Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Follitrophin Alpha: Stratum Age <39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \< 39 years old.	Follitrophin Alpha: Stratum Age >=39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \>= 39 years old.
Percentage of Participants With Successful Embryo Transfer No	4.2 percentage of participants	6.9 percentage of participants	—	—	—	—
Percentage of Participants With Successful Embryo Transfer Yes	95.8 percentage of participants	93.1 percentage of participants	—	—	—	—

SECONDARY outcome

Timeframe: Day 1 up to Day 12

Population: Per protocol set

Number of days in which gonadotrophins were administered until hCG criteria were met. If hCG criteria were not met by day 13, the participant was withdrawn from the study.

Outcome measures

Outcome measures
Measure	Menotrophin n=48 Participants Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Menotrophin: Stratum Age <39 Yrs n=58 Participants The subset of participants in the menotrophin treatment arm who were \< 39 years old.	Menotrophin: Stratum Age >=39 Yrs The subset of participants in the menotrophin treatment arm who were \>= 39 years old.	Follitrophin Alpha Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Follitrophin Alpha: Stratum Age <39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \< 39 years old.	Follitrophin Alpha: Stratum Age >=39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \>= 39 years old.
Number of Days Stimulated With Gonadotrophins	8.7 days Standard Deviation 1.9	9.1 days Standard Deviation 1.6	—	—	—	—

SECONDARY outcome

Timeframe: Day 1 up to Day 12

Population: Per protocol set

Number of ampoules of gonadotrophins used with the goal of reaching hCG criteria. Each ampoule contained 75 IU of either menotrophin or follitrophin alpha.

Outcome measures

Outcome measures
Measure	Menotrophin n=48 Participants Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Menotrophin: Stratum Age <39 Yrs n=58 Participants The subset of participants in the menotrophin treatment arm who were \< 39 years old.	Menotrophin: Stratum Age >=39 Yrs The subset of participants in the menotrophin treatment arm who were \>= 39 years old.	Follitrophin Alpha Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Follitrophin Alpha: Stratum Age <39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \< 39 years old.	Follitrophin Alpha: Stratum Age >=39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \>= 39 years old.
Number of Ampoules of Gonadotrophins Used	20.8 ampoules Standard Deviation 7.5	21.5 ampoules Standard Deviation 6.8	—	—	—	—

SECONDARY outcome

Timeframe: approximately 2.5 months from start of study, 6 weeks after first positive pregnancy test

Population: Per protocol set

A pelvic ultrasound scan was performed approximately 6 weeks after the first positive pregnancy test and the presence of an active foetal heart action indicated a clinical pregnancy.

Outcome measures

Outcome measures
Measure	Menotrophin n=48 Participants Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Menotrophin: Stratum Age <39 Yrs n=58 Participants The subset of participants in the menotrophin treatment arm who were \< 39 years old.	Menotrophin: Stratum Age >=39 Yrs The subset of participants in the menotrophin treatment arm who were \>= 39 years old.	Follitrophin Alpha Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Follitrophin Alpha: Stratum Age <39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \< 39 years old.	Follitrophin Alpha: Stratum Age >=39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \>= 39 years old.
Percentage of Participants With Clinical Pregnancy 6 Weeks After the First Positive Pregnancy Test	29.2 percentage of participants	31.0 percentage of participants	—	—	—	—

SECONDARY outcome

Timeframe: up to 10 months

Population: Per protocol set of participants who reported information during the optional long-term follow up visit.

Pregnancy outcomes were reported at the optional long-term follow up visit.

Outcome measures

Outcome measures
Measure	Menotrophin n=14 Participants Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Menotrophin: Stratum Age <39 Yrs n=16 Participants The subset of participants in the menotrophin treatment arm who were \< 39 years old.	Menotrophin: Stratum Age >=39 Yrs The subset of participants in the menotrophin treatment arm who were \>= 39 years old.	Follitrophin Alpha Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Follitrophin Alpha: Stratum Age <39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \< 39 years old.	Follitrophin Alpha: Stratum Age >=39 Yrs The subset of participants in the follitrophin alpha treatment arm who were \>= 39 years old.
Summary of Pregnancy Outcome Live birth	13 participants	16 participants	—	—	—	—
Summary of Pregnancy Outcome Ectopic pregnancy	1 participants	0 participants	—	—	—	—
Summary of Pregnancy Outcome Congenial abnormality	0 participants	1 participants	—	—	—	—

Adverse Events

Menotrophin

Serious events: 2 serious events

Other events: 43 other events

Deaths: 0 deaths

Follitrophin Alpha

Serious events: 0 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Menotrophin n=62 participants at risk Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 13 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.	Follitrophin Alpha n=62 participants at risk Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 13 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Cardiac disorders Tachycardia	1.6% 1/62 • -Menotrophin: Day 1 up to Day 23. Treatment with investigational product (up to Day 12), plus residual drug effect-10.5 days -Follitropin: Day 1 up to Day 17. Treatment with comparator product (up to Day 12), plus residual drug effort-5 days.	0.00% 0/62 • -Menotrophin: Day 1 up to Day 23. Treatment with investigational product (up to Day 12), plus residual drug effect-10.5 days -Follitropin: Day 1 up to Day 17. Treatment with comparator product (up to Day 12), plus residual drug effort-5 days.
Gastrointestinal disorders Abdominal rigidity	1.6% 1/62 • -Menotrophin: Day 1 up to Day 23. Treatment with investigational product (up to Day 12), plus residual drug effect-10.5 days -Follitropin: Day 1 up to Day 17. Treatment with comparator product (up to Day 12), plus residual drug effort-5 days.	0.00% 0/62 • -Menotrophin: Day 1 up to Day 23. Treatment with investigational product (up to Day 12), plus residual drug effect-10.5 days -Follitropin: Day 1 up to Day 17. Treatment with comparator product (up to Day 12), plus residual drug effort-5 days.
General disorders Thirst	1.6% 1/62 • -Menotrophin: Day 1 up to Day 23. Treatment with investigational product (up to Day 12), plus residual drug effect-10.5 days -Follitropin: Day 1 up to Day 17. Treatment with comparator product (up to Day 12), plus residual drug effort-5 days.	0.00% 0/62 • -Menotrophin: Day 1 up to Day 23. Treatment with investigational product (up to Day 12), plus residual drug effect-10.5 days -Follitropin: Day 1 up to Day 17. Treatment with comparator product (up to Day 12), plus residual drug effort-5 days.
Immune system disorders Drug hypersensitivity	1.6% 1/62 • -Menotrophin: Day 1 up to Day 23. Treatment with investigational product (up to Day 12), plus residual drug effect-10.5 days -Follitropin: Day 1 up to Day 17. Treatment with comparator product (up to Day 12), plus residual drug effort-5 days.	0.00% 0/62 • -Menotrophin: Day 1 up to Day 23. Treatment with investigational product (up to Day 12), plus residual drug effect-10.5 days -Follitropin: Day 1 up to Day 17. Treatment with comparator product (up to Day 12), plus residual drug effort-5 days.
Nervous system disorders Dizziness	1.6% 1/62 • -Menotrophin: Day 1 up to Day 23. Treatment with investigational product (up to Day 12), plus residual drug effect-10.5 days -Follitropin: Day 1 up to Day 17. Treatment with comparator product (up to Day 12), plus residual drug effort-5 days.	0.00% 0/62 • -Menotrophin: Day 1 up to Day 23. Treatment with investigational product (up to Day 12), plus residual drug effect-10.5 days -Follitropin: Day 1 up to Day 17. Treatment with comparator product (up to Day 12), plus residual drug effort-5 days.
Renal and urinary disorders Pollakiuria	1.6% 1/62 • -Menotrophin: Day 1 up to Day 23. Treatment with investigational product (up to Day 12), plus residual drug effect-10.5 days -Follitropin: Day 1 up to Day 17. Treatment with comparator product (up to Day 12), plus residual drug effort-5 days.	0.00% 0/62 • -Menotrophin: Day 1 up to Day 23. Treatment with investigational product (up to Day 12), plus residual drug effect-10.5 days -Follitropin: Day 1 up to Day 17. Treatment with comparator product (up to Day 12), plus residual drug effort-5 days.
Reproductive system and breast disorders Ovarian hyperstimulation syndrome	1.6% 1/62 • -Menotrophin: Day 1 up to Day 23. Treatment with investigational product (up to Day 12), plus residual drug effect-10.5 days -Follitropin: Day 1 up to Day 17. Treatment with comparator product (up to Day 12), plus residual drug effort-5 days.	0.00% 0/62 • -Menotrophin: Day 1 up to Day 23. Treatment with investigational product (up to Day 12), plus residual drug effect-10.5 days -Follitropin: Day 1 up to Day 17. Treatment with comparator product (up to Day 12), plus residual drug effort-5 days.

Other adverse events

Additional Information

Clinical Development Support

Ferring Pharmaceuticals

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Principal investigator is a sponsor employee 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.
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