Infertility
Conditions
Keywords
Controlled Ovarian Stimulation, Assisted Reproductive Technology
Brief summary
Development of multiple follicles and pregnancy in ovulatory women undergoing controlled ovarian stimulation as part of an assisted reproductive technology (ART) cycle.
Interventions
DRUGMENOPUR solution for injection in pre-filled pen, 1200 IU/1.92 mL
Solution for injection in pre-filled pen, subcutaneous administration
DRUGMENOPUR powder and solvent for solution for injection, 75 IU
Solution for injection in vials (powder and diluent), subcutaneous administration
OTHERPlacebo (for MENOPUR solution for injection in pre-filled pen)
Solution for injection in pre-filled pen, subcutaneous administration
OTHERPlacebo (for MENOPUR powder and solvent for solution for injection)
Solution for injection in vials (powder and diluent); subcutaneous administration
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 42 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consents, prior to any trial-related procedure. * Females between the ages of 18 and 42 years. The participants must be at least 18 years (including the 18th birthday) when they sign the informed consent and no more than 42 years (up to the day before the 43rd birthday) at the time of randomization who desire pregnancy. * Body mass index (BMI) between 17.5 and 38.0 kg/m\^2 (both inclusive) at screening. * Regular menstrual cycles of 24 to 35 days, presumed to be ovulatory. * Documented history of infertility for at least 12 months before randomization for women ≤35 years or for at least 6 months for women ≥36 years. Women with documented bilateral tubal occlusion or male factor infertility requiring the use of donor sperm established as a cause of infertility are eligible at diagnosis. * Early follicular phase (cycle day 2-4) serum FSH level between 1 and 12 IU/L (results obtained within 3 months prior to randomization). * Male partner with semen analysis that is at least adequate for intracytoplasmic sperm injection (ICSI) at screening or within 6 months prior to the screening date. Partners with severe male factors requiring invasive or surgical sperm retrieval may not be used. Use of donor sperm is allowed. * At least 1 cycle with no fertility medication immediately prior to screening. * Hysterosalpingography, hysteroscopy, or saline hysterosonogram documenting uterine anatomy appropriate for ART at screening or within 12 months prior to screening. * Transvaginal ultrasound documenting presence and adequate visualization of both ovaries, without evidence of clinically significant abnormality (e.g., endometrioma ≥3 cm, no dermoid cysts) and normal adnexa (e.g., no hydrosalpinx) at screening. Both ovaries must be accessible for oocyte retrieval.
Exclusion criteria
* More than two previous controlled ovarian stimulation cycles for in vitro fertilization (IVF)/ICSI * Known stage III-IV endometriosis (American Society for Reproductive Medicine, 2012). * Oocyte donor or embryo recipient; gestational or surrogate carrier. * Known history of recurrent miscarriage (defined as three consecutive losses after ultrasound confirmation of pregnancy \[excluding ectopic pregnancy\] and before week 24 of pregnancy). * Participant's male partner, with obvious leukospermia (\>2 million white blood cells/mL) or signs of infection in semen sample within 6 months of the participant's screening. If either of these conditions exists, the male should be treated with antibiotics and retested prior to the participant's randomization. * Active arterial or venous thromboembolism or severe thrombophlebitis, or a history of these events. * Any known endocrine (total testosterone, prolactin and TSH) or metabolic abnormalities (pituitary, adrenal, pancreas, liver or kidney) with the exception of controlled thyroid function disease. * Known tumors of the ovary, breast, uterus, adrenal gland, pituitary or hypothalamus which would contraindicate the use of gonadotrophins. * Any abnormal finding of clinical chemistry, hematology and vital signs at screening, which is judged clinically significant by the investigator. * Pregnancy (negative urine pregnancy test must be documented at screening and prior to the first investigational medicinal product \[IMP\] administration), or contraindication to pregnancy. * Hypersensitivity to any active ingredient or excipients in the medicinal products used in this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Fertilized (2 Pronuclei [2PN]) Oocytes | On Day 1 after oocyte retrieval (up to 23 days after start of stimulation) | Fertilized oocytes with 2PN were regarded as correctly fertilized. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Positive Beta Human Chorionic Gonadotropin (βhCG) Rate | 10-14 days after blastocyst transfer (up to approximately 6 weeks after start of stimulation) | A blood serum βhCG test was obtained 10-14 days after blastocyst transfer. If the test was positive according to the local laboratory's reference ranges, this confirmed a positive βhCG. |
| Clinical Pregnancy Rate | 5-6 weeks after blastocyst transfer (up to approximately 10 weeks after start of stimulation) | Clinical pregnancy was based on detection of at least 1 intrauterine gestational sac with fetal heart beat on transvaginal ultrasound. |
| Ongoing Pregnancy Rate | 8-9 weeks after blastocyst transfer (up to approximately 13 weeks after start of stimulation) | Ongoing pregnancy was based on detection of at least 1 intrauterine viable fetus by transvaginal or abdominal ultrasound |
| Early Pregnancy Loss | 8-9 weeks after blastocyst transfer (up to approximately 13 weeks after start of stimulation) | Number of participants with early pregnancy loss defined as a positive βhCG tests but no ongoing pregnancy. |
| Follicular Development on Stimulation Day 6 | At stimulation Day 6 | The total number of follicles and the number of follicles per size category were reported. |
| Follicular Development on Last Day of Stimulation | At last day of stimulation (up to 20 stimulation days) | The total number of follicles and the number of follicles per size category were reported. |
| Serum Follicle-stimulating Hormone (FSH) Concentration | At Day 6, last day of stimulation (up to 20 stimulation days) and at oocyte retrieval (up to 22 days after start of stimulation) | The concentration of serum FSH was measured. The median and IQR of FSH levels on stimulation day 6, End of stimulation and Oocyte Retrieval visit are presented. |
| Serum Anti-Müllerian Hormone (AMH) Concentration | At the last day of stimulation (up to 20 stimulation days) and at end-of-trial (up to approximately 6 months from the start of screening) | The concentration of serum AMH was measured. The median and IQR of AMH levels on End of stimulation and End of Trial are presented. |
| Human Chorionic Gonadotropin (hCG) Concentration | At Day 6 and last day of stimulation (up to 20 stimulation days) | The concentration of hCG was measured. The median and IQR of hCG levels on stimulation day 6 and End of stimulation are presented. |
| Luteinizing Hormone (LH) Concentration | At Day 6 and last day of stimulation (up to 20 stimulation days) | The concentration of LH was measured. The median and IQR of LH levels on stimulation day 6 and End of stimulation are presented. |
| Progesterone (P4) Concentration | At Day 6 and last day of stimulation (up to 20 stimulation days) | The concentration of P4 was measured. The median and IQR of P4 levels on stimulation day 6 and End of stimulation are presented. |
| Estradiol (E2) Concentration | At stimulation Day 6 and last day of stimulation (up to 20 stimulation days) | The concentration of E2 was measured. The median and IQR of E2 levels on stimulation day 6 and End of stimulation are presented. |
| Number of Oocytes Retrieved | On day of oocyte retrieval (up to 22 days after start of stimulation) | The number of oocytes retrieved was recorded at the oocyte retrieval visit. |
| Number of Metaphase II (MII) Oocytes | On day of oocyte retrieval (up to 22 days after start of stimulation) | Maturity stage was assessed prior to undergoing ICSI. Maturity stage was categorized as germinal vesicle, metaphase I, metaphase II, degenerated or other. |
| Number of Blastocysts and Number of Good-Quality Blastocysts 5 Days After Oocyte Retrieval | On Day 5 after oocyte retrieval (up to 27 days after start of stimulation) | The number of blastocysts (total and good-quality) was reported. Blastocyst quality was assessed by blastocyst expansion and hatching status, blastocyst inner cell mass grading, and trophectoderm grading. The scoring was based on the classification system by Gardner and Schoolcraft, with additional categories for inner cell mass (degenerative or no inner cell mass) and trophectoderm (degenerative or very large cells) |
| Total Gonadotropin Dose | Up to 20 stimulation days | The gonadotropin starting dose was 225 IU for the first 5 days, followed by individual adjustments according to the participant's follicular response. Dose adjustment should be 75 IU per adjustment. Gonadotropin was to be initiated within 3 days of confirmed downregulation. |
| Number of Stimulation Days | Up to 20 stimulation days | Calculated by start dates and end dates. |
| Proportion of Participants With Ovarian Hyperstimulation Syndrome (OHSS) | ≤9 days after triggering of final follicular maturation (early OHSS), >9 days after triggering of final follicular maturation until 21-28 days after last IMP dose or up to ongoing pregnancy 8-9 weeks after transfer in pregnant participants (late OHSS) | OHSS was defined as the total of early OHSS with onset ≤9 days after triggering of final follicular maturation, and late OHSS with onset \>9 days after triggering of final follicular maturation. |
| Frequency of Adverse Events (AEs) | From the time of signed informed consent for participation in the trial until the end-of-trial visit (up to approximately 6 months) | Any AE occurring after start of IMP and before the end-of-trial visit, or a pre-treatment AE or pre-existing medical condition that worsens in intensity after start of IMP and before the end-of-trial visit was considered treatment-emergent, and is presented for this endpoint. |
| Intensity of AEs | From the start of screening until the end-of-trial (up to approximately 6 months) | The intensity of an 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). Severe = Inability to work or perform usual activities (unacceptable). |
| Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Alanine Aminotransferase | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of clinical chemistry parameters. |
| Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Aspartate Aminotransferase | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of clinical chemistry parameters. |
| Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Blood Urea Nitrogen | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of clinical chemistry parameters. |
| Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Calcium | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of clinical chemistry parameters. |
| Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Chloride | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of clinical chemistry parameters. |
| Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Creatinine | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of clinical chemistry parameters. |
| Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Gamma Glutamyl Transferase | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of clinical chemistry parameters. |
| Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Glucose | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of clinical chemistry parameters. |
| Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Potassium | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of clinical chemistry parameters. |
| Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Sodium | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of clinical chemistry parameters. |
| Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Egfr African American | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of clinical chemistry parameters. |
| Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Egfr Non-afr. American | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of clinical chemistry parameters. |
| Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Erythrocytes | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of haematology parameters. |
| Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Leukocytes | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of haematology parameters. |
| Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Hemoglobin | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of haematology parameters. |
| Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Hematocrit | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of haematology parameters. |
| Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Platelets | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of haematology parameters. |
| Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Basophils | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of haematology parameters. |
| Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Basophils/Leukocytes | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of haematology parameters. |
| Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Eosinophils | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of haematology parameters. |
| Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Eosinophils/Leukocytes | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of haematology parameters. |
| Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Lymphocytes | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of haematology parameters. |
| Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Lymphocytes/Leukocytes | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of haematology parameters. |
| Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Monocytes | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of haematology parameters. |
| Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Monocytes/Leukocytes | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of haematology parameters. |
| Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Neutrophils | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of haematology parameters. |
| Fertilization Rate | On Day 1 after oocyte retrieval (up to 23 days after start of stimulation) | Fertilization rate(%) is the number of 2PN oocytes divided by the number of oocytes retrieved. |
| Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters | From the start of screening until the end-of-trial (up to approximately 6 months) | The table represents the percentage of participants in each group with normal baseline values and markedly abnormal end-of-stimulation or end-of-trial visit values. It is only parameters with markedly abnormal values at end of stimulation or end of trial visit which are represented. Parameters with normal baseline values and normal end of stimulation and end of trial values are not represented. |
| Proportion of Participants With Treatment-induced Anti-MENOPUR Antibodies. Overall as Well as With Neutralizing Capacity | Up to 28 days after end of the stimulation period (simulation period up to 20 days) | Measured by presence of anti-MENOPUR antibodies. 95% Clopper-Pearson confidence interval has been reported in this endpoint. |
| Number of Participants With Potential Technical Malfunctions of the Administration Pen | Up to 20 stimulation days | Number of participants With Potential Technical malfunctions of the Administration Pen were recorded. |
| Frequency of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Participant During the Stimulation Period | Up to 20 stimulation days | Assessed by the participant during the stimulation period. Participants assessed the injection site reactions (redness, pain, itching, swelling and bruising) three times daily: immediately after the injection, 30 minutes after the injection and 24 hours after the injection. Total Number of events include all categories None, Mild, Moderate and Severe. Percentage of events with injection site reactions as a sum of the categories Mild, Moderate and Severe is presented. |
| Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Participant During the Stimulation Period | Up to 20 stimulation days | Assessed by the participant during the stimulation period as mild, moderate or severe. Participants assessed the injection site reactions (redness, pain, itching, swelling and bruising) three times daily: immediately after the injection, 30 minutes after the injection and 24 hours after the injection. |
| Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Neutrophils/Leukocytes | From the start of screening until the end-of-trial (up to approximately 6 months) | Blood samples were collected for the analysis of haematology parameters. |
Countries
United States
Participant flow
Recruitment details
The trial was performed in 19 investigational sites in US between Oct 2019 and Jul 2021.
Pre-assignment details
In total, 691 participants were screened. Of these, 97 participants were rescreened after the trial hold was lifted, leading to a total of 788 screening events. Of these, 383 were screening event failures while 405 screening events resulted in randomization. 401 participants were exposed to IMP: 202 participants exposed to MENOPUR liquid and 199 participants were exposed to MENOPUR powder.
Participants by arm
| Arm | Count |
|---|---|
| MENOPUR Liquid MENOPUR liquid (including placebo to MENOPUR powder) initiated at a fixed dose of 225 international units (IU) for first five stimulation days. From stimulation Day 6, dosing could be adjusted as needed every second day by 75 IU per adjustment based on the participant's follicular response. The maximum dose was 450 IU/day and the minimum dose was 75 IU/day. The dosing could continue for a maximum of 20 days.
MENOPUR solution for injection in pre-filled pen, 1200 IU/1.92 mL: Solution for injection in pre-filled pen, subcutaneous administration
Placebo (for MENOPUR powder and solvent for solution for injection): Solution for injection in vials (powder and diluent); subcutaneous administration | 202 |
| MENOPUR Powder MENOPUR powder (including placebo to MENOPUR liquid) initiated at a fixed dose of 225 IU for first five stimulation days. From stimulation Day 6, dosing could be adjusted as needed every second day by 75 IU per adjustment based on the participant's follicular response. The maximum dose was 450 IU/day and the minimum dose was 75 IU/day. The dosing could continue for a maximum of 20 days.
MENOPUR powder and solvent for solution for injection, 75 IU: Solution for injection in vials (powder and diluent), subcutaneous administration
Placebo (for MENOPUR solution for injection in pre-filled pen): Solution for injection in pre-filled pen, subcutaneous administration | 199 |
| Total | 401 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 8 |
| Overall Study | Due to COVID-19 pandemic | 4 | 2 |
| Overall Study | Other | 4 | 2 |
| Overall Study | Participant withdrew consent | 2 | 3 |
| Overall Study | Protocol Deviation | 7 | 13 |
| Overall Study | Randomization failure | 2 | 2 |
Baseline characteristics
| Characteristic | MENOPUR Liquid | MENOPUR Powder | Total |
|---|---|---|---|
| Age, Continuous | 33.9 Years STANDARD_DEVIATION 3.9 | 34.0 Years STANDARD_DEVIATION 4.3 | 34.0 Years STANDARD_DEVIATION 4.1 |
| Age, Customized Age <35 years | 111 Participants | 107 Participants | 218 Participants |
| Age, Customized Age >=35 years | 91 Participants | 92 Participants | 183 Participants |
| Body Mass Index (BMI) | 26.1 kg/m^2 STANDARD_DEVIATION 4.6 | 25.9 kg/m^2 STANDARD_DEVIATION 4.7 | 26.0 kg/m^2 STANDARD_DEVIATION 4.7 |
| Duration of infertility | 46.1 Months STANDARD_DEVIATION 36.8 | 44.5 Months STANDARD_DEVIATION 31.4 | 45.3 Months STANDARD_DEVIATION 34.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 34 Participants | 26 Participants | 60 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 168 Participants | 173 Participants | 341 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Primary Infertility No | 100 Participants | 97 Participants | 197 Participants |
| Primary Infertility Yes | 102 Participants | 102 Participants | 204 Participants |
| Primary reason for infertility Endometriosis stage I/II | 9 Participants | 4 Participants | 13 Participants |
| Primary reason for infertility Mild male factor | 17 Participants | 27 Participants | 44 Participants |
| Primary reason for infertility Moderate male factor | 24 Participants | 24 Participants | 48 Participants |
| Primary reason for infertility Other | 0 Participants | 1 Participants | 1 Participants |
| Primary reason for infertility Severe male factor | 21 Participants | 25 Participants | 46 Participants |
| Primary reason for infertility Tubal infertility | 40 Participants | 39 Participants | 79 Participants |
| Primary reason for infertility Unexplained infertility | 91 Participants | 79 Participants | 170 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 17 Participants | 16 Participants | 33 Participants |
| Race (NIH/OMB) Black or African American | 23 Participants | 19 Participants | 42 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 158 Participants | 160 Participants | 318 Participants |
| Region of Enrollment United States | 202 participants | 199 participants | 401 participants |
| Sex: Female, Male Female | 202 Participants | 199 Participants | 401 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 202 | 0 / 199 |
| other Total, other adverse events | 101 / 202 | 104 / 199 |
| serious Total, serious adverse events | 4 / 202 | 2 / 199 |
Outcome results
Primary
Number of Fertilized (2 Pronuclei [2PN]) Oocytes
Fertilized oocytes with 2PN were regarded as correctly fertilized.
Time frame: On Day 1 after oocyte retrieval (up to 23 days after start of stimulation)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Number of Fertilized (2 Pronuclei [2PN]) Oocytes | 8.3 Fertilized oocytes | Standard Deviation 5.5 |
| MENOPUR Powder | Number of Fertilized (2 Pronuclei [2PN]) Oocytes | 6.7 Fertilized oocytes | Standard Deviation 4.2 |
Secondary
Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Alanine Aminotransferase
Blood samples were collected for the analysis of clinical chemistry parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Alanine Aminotransferase | 0.4 IU/L | Standard Deviation 14.2 |
| MENOPUR Powder | Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Alanine Aminotransferase | -1.0 IU/L | Standard Deviation 12.4 |
Secondary
Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Aspartate Aminotransferase
Blood samples were collected for the analysis of clinical chemistry parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Aspartate Aminotransferase | -0.9 IU/L | Standard Deviation 8.8 |
| MENOPUR Powder | Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Aspartate Aminotransferase | -2.1 IU/L | Standard Deviation 21.1 |
Secondary
Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Blood Urea Nitrogen
Blood samples were collected for the analysis of clinical chemistry parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Blood Urea Nitrogen | -0.7 mmol/L | Standard Deviation 1.2 |
| MENOPUR Powder | Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Blood Urea Nitrogen | -0.7 mmol/L | Standard Deviation 1.3 |
Secondary
Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Calcium
Blood samples were collected for the analysis of clinical chemistry parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Calcium | -0.03 mmol/L | Standard Deviation 0.1 |
| MENOPUR Powder | Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Calcium | -0.03 mmol/L | Standard Deviation 0.08 |
Secondary
Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Chloride
Blood samples were collected for the analysis of clinical chemistry parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Chloride | 0.4 mmol/L | Standard Deviation 2.3 |
| MENOPUR Powder | Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Chloride | 0.3 mmol/L | Standard Deviation 2.2 |
Secondary
Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Creatinine
Blood samples were collected for the analysis of clinical chemistry parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Creatinine | -5.498 umol/L | Standard Deviation 10.896 |
| MENOPUR Powder | Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Creatinine | -5.032 umol/L | Standard Deviation 8.849 |
Secondary
Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Egfr African American
Blood samples were collected for the analysis of clinical chemistry parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Egfr African American | 7.7 mL/min/1.73m2 | Standard Deviation 14.9 |
| MENOPUR Powder | Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Egfr African American | 2.4 mL/min/1.73m2 | Standard Deviation 13.7 |
Secondary
Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Egfr Non-afr. American
Blood samples were collected for the analysis of clinical chemistry parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Egfr Non-afr. American | 6.3 mL/min/1.73m2 | Standard Deviation 13.1 |
| MENOPUR Powder | Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Egfr Non-afr. American | 5.9 mL/min/1.73m2 | Standard Deviation 11.6 |
Secondary
Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Gamma Glutamyl Transferase
Blood samples were collected for the analysis of clinical chemistry parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Gamma Glutamyl Transferase | -0.6 IU/L | Standard Deviation 5.6 |
| MENOPUR Powder | Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Gamma Glutamyl Transferase | -1.6 IU/L | Standard Deviation 8.9 |
Secondary
Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Glucose
Blood samples were collected for the analysis of clinical chemistry parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Glucose | 0.0 mmol/L | Standard Deviation 0.8 |
| MENOPUR Powder | Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Glucose | -0.1 mmol/L | Standard Deviation 0.9 |
Secondary
Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Potassium
Blood samples were collected for the analysis of clinical chemistry parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Potassium | -0.04 mmol/L | Standard Deviation 0.38 |
| MENOPUR Powder | Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Potassium | -0.05 mmol/L | Standard Deviation 0.4 |
Secondary
Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Sodium
Blood samples were collected for the analysis of clinical chemistry parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Sodium | -1.0 mmol/L | Standard Deviation 3 |
| MENOPUR Powder | Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Sodium | -0.8 mmol/L | Standard Deviation 3.1 |
Secondary
Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Basophils
Blood samples were collected for the analysis of haematology parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Basophils | 1.7 cells/uL | Standard Deviation 54 |
| MENOPUR Powder | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Basophils | -0.1 cells/uL | Standard Deviation 60.6 |
Secondary
Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Basophils/Leukocytes
Blood samples were collected for the analysis of haematology parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Basophils/Leukocytes | -0.1 Basophils/leukocytes in Percentage | Standard Deviation 0.8 |
| MENOPUR Powder | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Basophils/Leukocytes | -0.2 Basophils/leukocytes in Percentage | Standard Deviation 1 |
Secondary
Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Eosinophils
Blood samples were collected for the analysis of haematology parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Eosinophils | -10.6 cells/uL | Standard Deviation 100.5 |
| MENOPUR Powder | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Eosinophils | 4.2 cells/uL | Standard Deviation 68.6 |
Secondary
Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Eosinophils/Leukocytes
Blood samples were collected for the analysis of haematology parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Eosinophils/Leukocytes | -0.4 Eosinophils/leukocytes in percentage | Standard Deviation 1.6 |
| MENOPUR Powder | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Eosinophils/Leukocytes | -0.1 Eosinophils/leukocytes in percentage | Standard Deviation 1.2 |
Secondary
Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Erythrocytes
Blood samples were collected for the analysis of haematology parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Erythrocytes | -0.169 10^12 cells/L | Standard Deviation 0.293 |
| MENOPUR Powder | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Erythrocytes | -0.199 10^12 cells/L | Standard Deviation 0.256 |
Secondary
Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Hematocrit
Blood samples were collected for the analysis of haematology parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Hematocrit | -0.02 RATIO | Standard Deviation 0.03 |
| MENOPUR Powder | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Hematocrit | -0.02 RATIO | Standard Deviation 0.03 |
Secondary
Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Hemoglobin
Blood samples were collected for the analysis of haematology parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Hemoglobin | -4.40 g/L | Standard Deviation 9.87 |
| MENOPUR Powder | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Hemoglobin | -5.76 g/L | Standard Deviation 8.02 |
Secondary
Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Leukocytes
Blood samples were collected for the analysis of haematology parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Leukocytes | 1.17 10^9 cells/L | Standard Deviation 2.25 |
| MENOPUR Powder | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Leukocytes | 1.11 10^9 cells/L | Standard Deviation 2.09 |
Secondary
Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Lymphocytes
Blood samples were collected for the analysis of haematology parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Lymphocytes | -53.2 cells/uL | Standard Deviation 414.9 |
| MENOPUR Powder | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Lymphocytes | -4.0 cells/uL | Standard Deviation 442.5 |
Secondary
Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Lymphocytes/Leukocytes
Blood samples were collected for the analysis of haematology parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Lymphocytes/Leukocytes | -4.5 Lymphocytes/leukocytes in percentage | Standard Deviation 9.6 |
| MENOPUR Powder | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Lymphocytes/Leukocytes | -3.4 Lymphocytes/leukocytes in percentage | Standard Deviation 9.5 |
Secondary
Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Monocytes
Blood samples were collected for the analysis of haematology parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Monocytes | 21.5 cells/uL | Standard Deviation 161.8 |
| MENOPUR Powder | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Monocytes | 36.7 cells/uL | Standard Deviation 148.9 |
Secondary
Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Monocytes/Leukocytes
Blood samples were collected for the analysis of haematology parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Monocytes/Leukocytes | -0.8 Monocytes/leukocytes in percentage | Standard Deviation 1.7 |
| MENOPUR Powder | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Monocytes/Leukocytes | -0.5 Monocytes/leukocytes in percentage | Standard Deviation 1.6 |
Secondary
Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Neutrophils
Blood samples were collected for the analysis of haematology parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Neutrophils | 1206.4 cells/uL | Standard Deviation 2096.6 |
| MENOPUR Powder | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Neutrophils | 1069.0 cells/uL | Standard Deviation 1966 |
Secondary
Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Neutrophils/Leukocytes
Blood samples were collected for the analysis of haematology parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Neutrophils/Leukocytes | 5.7 Neutrophils/leukocytes in percentage | Standard Deviation 11.2 |
| MENOPUR Powder | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Neutrophils/Leukocytes | 4.2 Neutrophils/leukocytes in percentage | Standard Deviation 10.6 |
Secondary
Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Platelets
Blood samples were collected for the analysis of haematology parameters.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Platelets | 22.6 10^9 cells/L | Standard Deviation 38.6 |
| MENOPUR Powder | Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Platelets | 23.7 10^9 cells/L | Standard Deviation 43.2 |
Secondary
Clinical Pregnancy Rate
Clinical pregnancy was based on detection of at least 1 intrauterine gestational sac with fetal heart beat on transvaginal ultrasound.
Time frame: 5-6 weeks after blastocyst transfer (up to approximately 10 weeks after start of stimulation)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MENOPUR Liquid | Clinical Pregnancy Rate | 94 Participants |
| MENOPUR Powder | Clinical Pregnancy Rate | 88 Participants |
Secondary
Early Pregnancy Loss
Number of participants with early pregnancy loss defined as a positive βhCG tests but no ongoing pregnancy.
Time frame: 8-9 weeks after blastocyst transfer (up to approximately 13 weeks after start of stimulation)
Population: Only participants who had a positive βhCG test were eligible.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MENOPUR Liquid | Early Pregnancy Loss | 22 Participants |
| MENOPUR Powder | Early Pregnancy Loss | 25 Participants |
Secondary
Estradiol (E2) Concentration
The concentration of E2 was measured. The median and IQR of E2 levels on stimulation day 6 and End of stimulation are presented.
Time frame: At stimulation Day 6 and last day of stimulation (up to 20 stimulation days)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MENOPUR Liquid | Estradiol (E2) Concentration | Stimulation Day 6 | 518.1 pg/mL |
| MENOPUR Liquid | Estradiol (E2) Concentration | End of stimulation | 2720.0 pg/mL |
| MENOPUR Powder | Estradiol (E2) Concentration | Stimulation Day 6 | 336.4 pg/mL |
| MENOPUR Powder | Estradiol (E2) Concentration | End of stimulation | 2292.0 pg/mL |
Secondary
Fertilization Rate
Fertilization rate(%) is the number of 2PN oocytes divided by the number of oocytes retrieved.
Time frame: On Day 1 after oocyte retrieval (up to 23 days after start of stimulation)
Population: Only participants with Oocytes retrieved were eligible.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Fertilization Rate | 57.8 Percentage | Standard Deviation 19.9 |
| MENOPUR Powder | Fertilization Rate | 60.0 Percentage | Standard Deviation 20.9 |
Secondary
Follicular Development on Last Day of Stimulation
The total number of follicles and the number of follicles per size category were reported.
Time frame: At last day of stimulation (up to 20 stimulation days)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MENOPUR Liquid | Follicular Development on Last Day of Stimulation | Total number of follicles | 19.9 Follicles | Standard Deviation 9.8 |
| MENOPUR Liquid | Follicular Development on Last Day of Stimulation | Follicles >= 12 mm | 13.1 Follicles | Standard Deviation 5.2 |
| MENOPUR Liquid | Follicular Development on Last Day of Stimulation | Follicles >= 15 mm | 8.5 Follicles | Standard Deviation 3.1 |
| MENOPUR Liquid | Follicular Development on Last Day of Stimulation | Follicles >= 17 mm | 5.4 Follicles | Standard Deviation 2.3 |
| MENOPUR Powder | Follicular Development on Last Day of Stimulation | Follicles >= 17 mm | 5.2 Follicles | Standard Deviation 2.2 |
| MENOPUR Powder | Follicular Development on Last Day of Stimulation | Total number of follicles | 19.2 Follicles | Standard Deviation 10.1 |
| MENOPUR Powder | Follicular Development on Last Day of Stimulation | Follicles >= 15 mm | 8.1 Follicles | Standard Deviation 3.2 |
| MENOPUR Powder | Follicular Development on Last Day of Stimulation | Follicles >= 12 mm | 12.0 Follicles | Standard Deviation 5.1 |
Secondary
Follicular Development on Stimulation Day 6
The total number of follicles and the number of follicles per size category were reported.
Time frame: At stimulation Day 6
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MENOPUR Liquid | Follicular Development on Stimulation Day 6 | Total number of follicles | 17.0 Follicles | Standard Deviation 9.4 |
| MENOPUR Liquid | Follicular Development on Stimulation Day 6 | Follicles >= 12 mm | 1.8 Follicles | Standard Deviation 2.3 |
| MENOPUR Liquid | Follicular Development on Stimulation Day 6 | Follicles >= 15 mm | 0.2 Follicles | Standard Deviation 0.6 |
| MENOPUR Liquid | Follicular Development on Stimulation Day 6 | Follicles >= 17 mm | 0.0 Follicles | Standard Deviation 0.2 |
| MENOPUR Powder | Follicular Development on Stimulation Day 6 | Follicles >= 17 mm | 0.0 Follicles | Standard Deviation 0.1 |
| MENOPUR Powder | Follicular Development on Stimulation Day 6 | Total number of follicles | 16.5 Follicles | Standard Deviation 8.3 |
| MENOPUR Powder | Follicular Development on Stimulation Day 6 | Follicles >= 15 mm | 0.2 Follicles | Standard Deviation 0.6 |
| MENOPUR Powder | Follicular Development on Stimulation Day 6 | Follicles >= 12 mm | 1.5 Follicles | Standard Deviation 2 |
Secondary
Frequency of Adverse Events (AEs)
Any AE occurring after start of IMP and before the end-of-trial visit, or a pre-treatment AE or pre-existing medical condition that worsens in intensity after start of IMP and before the end-of-trial visit was considered treatment-emergent, and is presented for this endpoint.
Time frame: From the time of signed informed consent for participation in the trial until the end-of-trial visit (up to approximately 6 months)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MENOPUR Liquid | Frequency of Adverse Events (AEs) | 50.0 Percentage of participants |
| MENOPUR Powder | Frequency of Adverse Events (AEs) | 52.3 Percentage of participants |
Secondary
Frequency of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Participant During the Stimulation Period
Assessed by the participant during the stimulation period. Participants assessed the injection site reactions (redness, pain, itching, swelling and bruising) three times daily: immediately after the injection, 30 minutes after the injection and 24 hours after the injection. Total Number of events include all categories None, Mild, Moderate and Severe. Percentage of events with injection site reactions as a sum of the categories Mild, Moderate and Severe is presented.
Time frame: Up to 20 stimulation days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MENOPUR Liquid | Frequency of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Participant During the Stimulation Period | 6.3 Percentage of events |
| MENOPUR Powder | Frequency of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Participant During the Stimulation Period | 14.5 Percentage of events |
Secondary
Human Chorionic Gonadotropin (hCG) Concentration
The concentration of hCG was measured. The median and IQR of hCG levels on stimulation day 6 and End of stimulation are presented.
Time frame: At Day 6 and last day of stimulation (up to 20 stimulation days)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MENOPUR Liquid | Human Chorionic Gonadotropin (hCG) Concentration | Stimulation Day 6 | 2.5 IU/L |
| MENOPUR Liquid | Human Chorionic Gonadotropin (hCG) Concentration | End of stimulation | 2.7 IU/L |
| MENOPUR Powder | Human Chorionic Gonadotropin (hCG) Concentration | Stimulation Day 6 | 2.4 IU/L |
| MENOPUR Powder | Human Chorionic Gonadotropin (hCG) Concentration | End of stimulation | 2.7 IU/L |
Secondary
Intensity of AEs
The intensity of an 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). Severe = Inability to work or perform usual activities (unacceptable).
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MENOPUR Liquid | Intensity of AEs | Mild AEs | 42.1 Percentage of participants |
| MENOPUR Liquid | Intensity of AEs | Moderate AEs | 23.8 Percentage of participants |
| MENOPUR Liquid | Intensity of AEs | Severe AEs | 0.5 Percentage of participants |
| MENOPUR Powder | Intensity of AEs | Mild AEs | 40.7 Percentage of participants |
| MENOPUR Powder | Intensity of AEs | Moderate AEs | 20.6 Percentage of participants |
| MENOPUR Powder | Intensity of AEs | Severe AEs | 2.0 Percentage of participants |
Secondary
Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Participant During the Stimulation Period
Assessed by the participant during the stimulation period as mild, moderate or severe. Participants assessed the injection site reactions (redness, pain, itching, swelling and bruising) three times daily: immediately after the injection, 30 minutes after the injection and 24 hours after the injection.
Time frame: Up to 20 stimulation days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MENOPUR Liquid | Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Participant During the Stimulation Period | Mild injection site reaction | 6.1 Percentage of events |
| MENOPUR Liquid | Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Participant During the Stimulation Period | Moderate injection site reaction | 0.2 Percentage of events |
| MENOPUR Liquid | Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Participant During the Stimulation Period | Severe injection site reaction | 0.0069 Percentage of events |
| MENOPUR Powder | Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Participant During the Stimulation Period | Mild injection site reaction | 12.9 Percentage of events |
| MENOPUR Powder | Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Participant During the Stimulation Period | Moderate injection site reaction | 1.4 Percentage of events |
| MENOPUR Powder | Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Participant During the Stimulation Period | Severe injection site reaction | 0.2 Percentage of events |
Secondary
Luteinizing Hormone (LH) Concentration
The concentration of LH was measured. The median and IQR of LH levels on stimulation day 6 and End of stimulation are presented.
Time frame: At Day 6 and last day of stimulation (up to 20 stimulation days)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MENOPUR Liquid | Luteinizing Hormone (LH) Concentration | Stimulation Day 6 | 1.8 IU/L |
| MENOPUR Liquid | Luteinizing Hormone (LH) Concentration | End of stimulation | 3.3 IU/L |
| MENOPUR Powder | Luteinizing Hormone (LH) Concentration | Stimulation Day 6 | 1.8 IU/L |
| MENOPUR Powder | Luteinizing Hormone (LH) Concentration | End of stimulation | 3.1 IU/L |
Secondary
Number of Blastocysts and Number of Good-Quality Blastocysts 5 Days After Oocyte Retrieval
The number of blastocysts (total and good-quality) was reported. Blastocyst quality was assessed by blastocyst expansion and hatching status, blastocyst inner cell mass grading, and trophectoderm grading. The scoring was based on the classification system by Gardner and Schoolcraft, with additional categories for inner cell mass (degenerative or no inner cell mass) and trophectoderm (degenerative or very large cells)
Time frame: On Day 5 after oocyte retrieval (up to 27 days after start of stimulation)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MENOPUR Liquid | Number of Blastocysts and Number of Good-Quality Blastocysts 5 Days After Oocyte Retrieval | Number of Blastocysts on Day 5 | 4.8 Blastocysts | Standard Deviation 3.8 |
| MENOPUR Liquid | Number of Blastocysts and Number of Good-Quality Blastocysts 5 Days After Oocyte Retrieval | Number of Good-quality blastocysts on Day 5 | 3.0 Blastocysts | Standard Deviation 3 |
| MENOPUR Powder | Number of Blastocysts and Number of Good-Quality Blastocysts 5 Days After Oocyte Retrieval | Number of Blastocysts on Day 5 | 3.9 Blastocysts | Standard Deviation 3 |
| MENOPUR Powder | Number of Blastocysts and Number of Good-Quality Blastocysts 5 Days After Oocyte Retrieval | Number of Good-quality blastocysts on Day 5 | 2.6 Blastocysts | Standard Deviation 2.6 |
Secondary
Number of Metaphase II (MII) Oocytes
Maturity stage was assessed prior to undergoing ICSI. Maturity stage was categorized as germinal vesicle, metaphase I, metaphase II, degenerated or other.
Time frame: On day of oocyte retrieval (up to 22 days after start of stimulation)
Population: Only participants with Oocytes retrieved were eligible.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Number of Metaphase II (MII) Oocytes | 10.6 MII Oocytes | Standard Deviation 6.1 |
| MENOPUR Powder | Number of Metaphase II (MII) Oocytes | 8.9 MII Oocytes | Standard Deviation 4.8 |
Secondary
Number of Oocytes Retrieved
The number of oocytes retrieved was recorded at the oocyte retrieval visit.
Time frame: On day of oocyte retrieval (up to 22 days after start of stimulation)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Number of Oocytes Retrieved | 14.3 Oocytes | Standard Deviation 8.1 |
| MENOPUR Powder | Number of Oocytes Retrieved | 11.4 Oocytes | Standard Deviation 6.3 |
Secondary
Number of Participants With Potential Technical Malfunctions of the Administration Pen
Number of participants With Potential Technical malfunctions of the Administration Pen were recorded.
Time frame: Up to 20 stimulation days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MENOPUR Liquid | Number of Participants With Potential Technical Malfunctions of the Administration Pen | 1 Participants |
| MENOPUR Powder | Number of Participants With Potential Technical Malfunctions of the Administration Pen | 1 Participants |
Secondary
Number of Stimulation Days
Calculated by start dates and end dates.
Time frame: Up to 20 stimulation days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Number of Stimulation Days | 9.6 Days | Standard Deviation 1.7 |
| MENOPUR Powder | Number of Stimulation Days | 9.9 Days | Standard Deviation 1.8 |
Secondary
Ongoing Pregnancy Rate
Ongoing pregnancy was based on detection of at least 1 intrauterine viable fetus by transvaginal or abdominal ultrasound
Time frame: 8-9 weeks after blastocyst transfer (up to approximately 13 weeks after start of stimulation)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MENOPUR Liquid | Ongoing Pregnancy Rate | 91 Participants |
| MENOPUR Powder | Ongoing Pregnancy Rate | 85 Participants |
Secondary
Positive Beta Human Chorionic Gonadotropin (βhCG) Rate
A blood serum βhCG test was obtained 10-14 days after blastocyst transfer. If the test was positive according to the local laboratory's reference ranges, this confirmed a positive βhCG.
Time frame: 10-14 days after blastocyst transfer (up to approximately 6 weeks after start of stimulation)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MENOPUR Liquid | Positive Beta Human Chorionic Gonadotropin (βhCG) Rate | 113 Participants |
| MENOPUR Powder | Positive Beta Human Chorionic Gonadotropin (βhCG) Rate | 110 Participants |
Secondary
Progesterone (P4) Concentration
The concentration of P4 was measured. The median and IQR of P4 levels on stimulation day 6 and End of stimulation are presented.
Time frame: At Day 6 and last day of stimulation (up to 20 stimulation days)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MENOPUR Liquid | Progesterone (P4) Concentration | Stimulation Day 6 | 0.3 ng/mL |
| MENOPUR Liquid | Progesterone (P4) Concentration | End of stimulation | 0.8 ng/mL |
| MENOPUR Powder | Progesterone (P4) Concentration | Stimulation Day 6 | 0.3 ng/mL |
| MENOPUR Powder | Progesterone (P4) Concentration | End of stimulation | 0.6 ng/mL |
Secondary
Proportion of Participants With Ovarian Hyperstimulation Syndrome (OHSS)
OHSS was defined as the total of early OHSS with onset ≤9 days after triggering of final follicular maturation, and late OHSS with onset \>9 days after triggering of final follicular maturation.
Time frame: ≤9 days after triggering of final follicular maturation (early OHSS), >9 days after triggering of final follicular maturation until 21-28 days after last IMP dose or up to ongoing pregnancy 8-9 weeks after transfer in pregnant participants (late OHSS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MENOPUR Liquid | Proportion of Participants With Ovarian Hyperstimulation Syndrome (OHSS) | Early OHSS | 3.5 Percentage of participants |
| MENOPUR Liquid | Proportion of Participants With Ovarian Hyperstimulation Syndrome (OHSS) | Late OHSS | 4.0 Percentage of participants |
| MENOPUR Powder | Proportion of Participants With Ovarian Hyperstimulation Syndrome (OHSS) | Early OHSS | 3.5 Percentage of participants |
| MENOPUR Powder | Proportion of Participants With Ovarian Hyperstimulation Syndrome (OHSS) | Late OHSS | 1.5 Percentage of participants |
Secondary
Proportion of Participants With Treatment-induced Anti-MENOPUR Antibodies. Overall as Well as With Neutralizing Capacity
Measured by presence of anti-MENOPUR antibodies. 95% Clopper-Pearson confidence interval has been reported in this endpoint.
Time frame: Up to 28 days after end of the stimulation period (simulation period up to 20 days)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MENOPUR Liquid | Proportion of Participants With Treatment-induced Anti-MENOPUR Antibodies. Overall as Well as With Neutralizing Capacity | Treatment-induced anti-MENOPUR antibodies (overall) | 1.5 Percentage of participants |
| MENOPUR Liquid | Proportion of Participants With Treatment-induced Anti-MENOPUR Antibodies. Overall as Well as With Neutralizing Capacity | Treatment-induced anti-MENOPUR antibodies with neutralizing capacity | 0 Percentage of participants |
| MENOPUR Powder | Proportion of Participants With Treatment-induced Anti-MENOPUR Antibodies. Overall as Well as With Neutralizing Capacity | Treatment-induced anti-MENOPUR antibodies (overall) | 1.5 Percentage of participants |
| MENOPUR Powder | Proportion of Participants With Treatment-induced Anti-MENOPUR Antibodies. Overall as Well as With Neutralizing Capacity | Treatment-induced anti-MENOPUR antibodies with neutralizing capacity | 0 Percentage of participants |
Secondary
Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters
The table represents the percentage of participants in each group with normal baseline values and markedly abnormal end-of-stimulation or end-of-trial visit values. It is only parameters with markedly abnormal values at end of stimulation or end of trial visit which are represented. Parameters with normal baseline values and normal end of stimulation and end of trial values are not represented.
Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure. Participants who were evaluable had normal baseline values and markedly abnormal end-of-stimulation or end-of-trial visit values.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MENOPUR Liquid | Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters | Leukocytes (10^9 cells/L) (End of stimulation) | 2 Participants |
| MENOPUR Liquid | Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters | Platelets (10^9 cells/L) (End of stimulation) | 1 Participants |
| MENOPUR Liquid | Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters | Erythrocytes (10^12 cells/L) (End of stimulation) | 2 Participants |
| MENOPUR Liquid | Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters | Basophils/leukocytes ratio (%) (End of stimulation) | 1 Participants |
| MENOPUR Liquid | Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters | Hemoglobin (g/L) (End of stimulation) | 2 Participants |
| MENOPUR Liquid | Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters | Lymphocytes/leukocytes ratio (%) (End of stimulation) | 2 Participants |
| MENOPUR Liquid | Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters | Glucose (mmol/L) (End of stimulation) | 1 Participants |
| MENOPUR Liquid | Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters | Alanine Aminotransferase (IU/L) (End of trial) | 1 Participants |
| MENOPUR Liquid | Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters | Hematocrit (RATIO) (End of stimulation) | 2 Participants |
| MENOPUR Liquid | Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters | Leukocytes (10^9 cells/L) (End of trial) | 1 Participants |
| MENOPUR Liquid | Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters | Calcium (mmol/L) (End of stimulation) | 1 Participants |
| MENOPUR Powder | Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters | Leukocytes (10^9 cells/L) (End of trial) | 1 Participants |
| MENOPUR Powder | Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters | Calcium (mmol/L) (End of stimulation) | 0 Participants |
| MENOPUR Powder | Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters | Glucose (mmol/L) (End of stimulation) | 0 Participants |
| MENOPUR Powder | Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters | Erythrocytes (10^12 cells/L) (End of stimulation) | 0 Participants |
| MENOPUR Powder | Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters | Leukocytes (10^9 cells/L) (End of stimulation) | 0 Participants |
| MENOPUR Powder | Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters | Hemoglobin (g/L) (End of stimulation) | 0 Participants |
| MENOPUR Powder | Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters | Hematocrit (RATIO) (End of stimulation) | 0 Participants |
| MENOPUR Powder | Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters | Platelets (10^9 cells/L) (End of stimulation) | 0 Participants |
| MENOPUR Powder | Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters | Basophils/leukocytes ratio (%) (End of stimulation) | 0 Participants |
| MENOPUR Powder | Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters | Lymphocytes/leukocytes ratio (%) (End of stimulation) | 0 Participants |
| MENOPUR Powder | Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters | Alanine Aminotransferase (IU/L) (End of trial) | 0 Participants |
Secondary
Serum Anti-Müllerian Hormone (AMH) Concentration
The concentration of serum AMH was measured. The median and IQR of AMH levels on End of stimulation and End of Trial are presented.
Time frame: At the last day of stimulation (up to 20 stimulation days) and at end-of-trial (up to approximately 6 months from the start of screening)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MENOPUR Liquid | Serum Anti-Müllerian Hormone (AMH) Concentration | End of stimulation | 7.6 pmol/L |
| MENOPUR Liquid | Serum Anti-Müllerian Hormone (AMH) Concentration | End of trial | 16.5 pmol/L |
| MENOPUR Powder | Serum Anti-Müllerian Hormone (AMH) Concentration | End of stimulation | 8.7 pmol/L |
| MENOPUR Powder | Serum Anti-Müllerian Hormone (AMH) Concentration | End of trial | 15.5 pmol/L |
Secondary
Serum Follicle-stimulating Hormone (FSH) Concentration
The concentration of serum FSH was measured. The median and IQR of FSH levels on stimulation day 6, End of stimulation and Oocyte Retrieval visit are presented.
Time frame: At Day 6, last day of stimulation (up to 20 stimulation days) and at oocyte retrieval (up to 22 days after start of stimulation)
Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MENOPUR Liquid | Serum Follicle-stimulating Hormone (FSH) Concentration | Stimulation Day 6 | 16.7 IU/L |
| MENOPUR Liquid | Serum Follicle-stimulating Hormone (FSH) Concentration | End of stimulation | 17.6 IU/L |
| MENOPUR Liquid | Serum Follicle-stimulating Hormone (FSH) Concentration | Oocyte retrieval | 8.8 IU/L |
| MENOPUR Powder | Serum Follicle-stimulating Hormone (FSH) Concentration | Stimulation Day 6 | 14.9 IU/L |
| MENOPUR Powder | Serum Follicle-stimulating Hormone (FSH) Concentration | End of stimulation | 16.5 IU/L |
| MENOPUR Powder | Serum Follicle-stimulating Hormone (FSH) Concentration | Oocyte retrieval | 8.4 IU/L |
Secondary
Total Gonadotropin Dose
The gonadotropin starting dose was 225 IU for the first 5 days, followed by individual adjustments according to the participant's follicular response. Dose adjustment should be 75 IU per adjustment. Gonadotropin was to be initiated within 3 days of confirmed downregulation.
Time frame: Up to 20 stimulation days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MENOPUR Liquid | Total Gonadotropin Dose | 2265.6 IU | Standard Deviation 710.2 |
| MENOPUR Powder | Total Gonadotropin Dose | 2466.7 IU | Standard Deviation 863.5 |