Infertility
Conditions
Keywords
In vitro fertilization, Pharmacological effects of drugs, Hormones, Hormone Substitutes and Hormone Antagonists, Pharmacological Actions, Randomized, Multi-center, Multi-national, Double-blind, Active-controlled, Equivalence
Brief summary
Clinical trial objectives are to investigate the efficacy and safety of a single injection of 100 μg Org 36286 in women weighing 60 kg or less to induce multifollicular development for controlled ovarian stimulation (COS), using daily recFSH as a reference.
Detailed description
This is a randomized, double-blind, active-controlled, equivalence clinical trial investigating the efficacy and safety of a new treatment regimen with Org 36286, a recombinant gonadotropin applied to initiate and sustain follicular stimulation in COS for Assisted Reproductive Technology (ART). For this regimen, patients receive a single injection of Org 36286 and one week later, treatment is continued with daily recFSH up to the day of triggering final oocyte maturation. In the reference group patients receive daily injections of recFSH up to the day of triggering final oocyte maturation. Equivalence between the two treatment groups in the number of oocytes retrieved is the primary objective of this trial.
Interventions
DRUGcorifollitropin alfa (Org 36286)
100 µg corifollitropin alfa subcutaneous (SC) injection
150 IU recFSH SC injection
DRUGgonadatropin releasing hormone (GnRH) antagonist (ganirelix)
GnRH antagonist (ganirelix) administered SC at a dose of 0.25 mg/day
hCG 5,000 IU or 10,000 IU administered SC
BIOLOGICALprogesterone
Progesterone was started on the day of oocyte pick-up (OPU) and continued for at least 6 weeks or up to menses. Participants received at least 600 mg/day vaginally or 50 mg/day IM.
Placebo-recFSH administered at the equivalent volume of 150 IU/day.
Single SC injection of placebo-corifollitropin alfa administered on Day 2 or 3 of the menstrual cycle.
BIOLOGICALopen-label recFSH
Open-label recFSH administered up to a maximum dose of 200 IU/day.
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 36 Years
Healthy volunteers
No
Inclusion criteria
* Females of couples with an indication for COS and IVF or ICSI; * \>=18 and \<= 36 years of age at the time of signing informed consent; * Body weight \<= 60 kg and BMI \>= 18 and \<= 32 kg/m\^2; * Normal menstrual cycle length: 24-35 days; * Availability of ejaculatory sperm (use of donated and/or cryopreserved sperm is allowed); * Willing and able to sign informed consent.
Exclusion criteria
* History of/or any current (treated) endocrine abnormality; * History of ovarian hyper-response or ovarian hyperstimulation syndrome (OHSS); * History of/or current polycystic ovary syndrome (PCOS); * More than 20 basal antral follicles \<11 mm (both ovaries combined) as measured on USS in the early follicular phase (menstrual cycle day 2-5); * Less than 2 ovaries or any other ovarian abnormality (including endometrioma \> 10 mm; visible on USS); * Presence of unilateral or bilateral hydrosalphinx (visible on USS); * Presence of any clinically relevant pathology affecting the uterine cavity or fibroids \>= 5 cm; * More than three unsuccessful IVF cycles since the last established ongoing pregnancy (if applicable); * History of non- or low ovarian response to FSH/hMG treatment; * History of recurrent miscarriage (3 or more, even when unexplained); * FSH \> 12 IU/L or LH \> 12 IU/L as measured by the local laboratory (sample taken during the early follicular phase: menstrual cycle day 2-5); * Any clinically relevant abnormal laboratory value based on a sample taken during the screening phase; * Contraindications for the use of gonadotropins (e.g. tumors, pregnancy/lactation, undiagnosed vaginal bleeding, hypersensitivity, ovarian cysts); * Recent history of/or current epilepsy, HIV infection, diabetes, cardiovascular, gastro-intestinal, hepatic, renal or pulmonary disease; * Abnormal karyotyping of the patient or her partner (if karyotyping is performed); * Smoking more than 5 cigarettes per day; * History or presence of alcohol or drug abuse within 12 months prior to signing informed consent; * Previous use of Org 36286; * Use of hormonal preparations within 1 month prior to randomization; * Hypersensitivity to any of the concomitant medication prescribed as part of the treatment regimen in this protocol; * Administration of investigational drugs within three months prior to signing informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Cumulus-oocyte-complexes Retrieved, Per Attempt | One COS cycle with cumulus-oocyte-complex retrieval (up to a maximum total duration of 21 days) | The primary efficacy parameter was defined as the number of cumulus-oocyte-complexes retrieved from participants in a controlled ovarian stimulation (COS) cycle for in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI). For participants who did not have cumulus-oocyte-complex retrieval, the number retrieved was set to zero. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Dose of recFSH Administered From Day 8 Onwards | Stimulation Day 8 of COS cycle up to day of hCG administration (up to a maximum total duration of 19 stimulation days) | Total dose of recFSH (IU) needed from Stimulation Day 8 onwards to reach the criterion for administration of hCG (at least 3 follicles \>=17mm). |
| Number of Days Treated With recFSH | One COS cycle (up to a maximum total duration of 19 stimulation days) | Numbers of days treated with recFSH was defined as the total number of days participants received recFSH (excluding coasting days) until they reached the criterion for administration of hCG (at least 3 follicles \>=17mm). |
| Total Duration of Stimulation (Days) | One COS cycle (up to a maximum total duration of 19 stimulation days) | Total duration of stimulation was defined as the number of days from first drug administration up to and including the Day of hCG administration. |
| Serum Follicle Stimulating Hormone (FSH) Levels (Restricted to Participants With hCG Injection) | Predose up to 2 weeks after ET (up to maximum of 6 weeks) | Blood samples for assessment of serum FSH were taken prior to injection on Stimulation Day 1, Day 3, Day 5, Day 8, Day of hCG, Day of ET, at the visit two weeks after ET. |
| Serum Lutenizing Hormone (LH) Levels (Restricted to Participants With hCG Injection) | Predose up to 2 weeks after ET (up to maximum of 6 weeks) | Blood samples for assessment of serum LH were taken prior to injection on Stimulation Day 1, Day 3, Day 5, Day 8, Day of hCG, Day of ET, at the visit two weeks after ET. |
| Serum Estradiol (E2) Levels (Restricted to Participants With hCG Injection) | Predose up to 2 weeks after ET (up to maximum of 6 weeks) | Blood samples for assessment of serum E2 were taken prior to injection on Stimulation Day 1, Day 3, Day 5, Day 8, Day of hCG, Day of ET, at the visit two weeks after ET. |
| Serum Progesterone (P) Levels (Restricted to Participants With hCG Injection) | Predose up to 2 weeks after ET (up to maximum of 6 weeks) | Blood samples for assessment of serum P were taken prior to injection on Stimulation Day 1, Day 3, Day 5, Day 8, Day of hCG, Day of ET, at the visit two weeks after ET. |
| Total Dose of recFSH Administered | One COS cycle (up to a maximum total duration of 19 stimulation days) | Total dose of recFSH (IU) administered was defined as the total amount of recFSH needed by participants to reach the criterion for administration of hCG (at least 3 follicles \>=17mm). |
| Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Predose up to day of hCG administration (up to a maximum total duration of 19 stimulation days, including day of hCG administration) | For each participant, the number of follicles ≥11 mm, ≥15 mm, and ≥17 mm, documented by ultrasonography on defined days during the treatment cycle, was calculated. |
| Number and Quality of Oocytes Assessed Prior to ICSI (Restricted to Participants With ICSI Only) | Up to 36 hours after administration of hCG | The number of oocytes used for ICSI was assessed and categorized based on their quality (i.e., metaphase I oocytes, metaphase II oocytes, and germinal vesicles stage oocytes). |
| Fertilization Rate | Up to 10 weeks after ET | Fertilization rate, defined as 100 times the ratio of the number of fertilized 2 pronuclei (PN) oocytes obtained and the number of oocytes incubated, was tabulated for each treatment group. |
| Number and Quality of Embryos Obtained at Day 3 (Restricted to Participants With IVF and/or ICSI) | Post fertilization Day 3 (up to a maximum of 2 days after hCG administration) | Embryo quality was rated Grade 1, 2, 3, or other. Grade 1 represented excellent quality; Grade 2 good quality; Grade 3 fair quality. Other grade embryos were those that did not qualify as Grade 1, 2, or 3. |
| Implantation Rate for Participants With ET | Up to 6 weeks after ET within a treatment cycle (up to a maximum 10 weeks) | The implantation rate was defined as 100 times the maximum number of gestational sacs as assessed by any ultrasound scan (USS) after ET divided by the number of embryos transferred (per participant), maximized to 100%. |
| Number of Participants With Miscarriages | Up to 10 weeks after ET (up to a maximum of 14 weeks) | A miscarriage, also known as a spontaneous abortion, was defined as the loss of a fetus without induction or instrumentation. |
| Number of Participants With Pregnancies | Up to 10 weeks after ET (up to a maximum of 14 weeks) | A Biochemical Pregnancy was defined as a pregnancy proven by a biochemical pregnancy test. (Participants not having a positive biochemical pregnancy test result, but with an ultrasound showing at least one gestational sac were counted as having a biochemical pregnancy.) A Clinical Pregnancy was defined as the presence of at least one gestational sac as assessed by an USS scan. A Vital Pregnancy was considered the presence of at least one fetus with heart activity as assessed by USS. An Ongoing Pregnancy was defined as the presence of at least one fetus with heart activity at least 10 weeks after ET as assessed by USS or Doppler, or confirmed by live birth. |
| Serum Inhibin-B Levels (Restricted to Participants With hCG Injection) | Predose up to 2 weeks after ET (up to maximum of 6 weeks) | Blood samples for assessment of serum inhibin-B were taken prior to injection on Stimulation Day 1, Day 3, Day 5, Day 8, Day of hCG, Day of ET, at the visit two weeks after ET. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 100 μg Corifollitropin Alfa Participants received a single SC injection of corifollitropin alfa 100 μg (Org 36286) on Day 2 or 3 of the menstrual cycle and daily placebo-recFSH injections (7 total) from Stimulation Day 1 up to and including Stimulation Day 7. Participants also received open-label recFSH (up to 200 IU/day) from Stimulation Day 8 onwards, up to and including Day of hCG administration. Participants also received GnRH antagonist ganirelix (0.25 mg) once daily SC starting on Stimulation Day 5 up to and including the Day of hCG (10,000 or 5,000 IU/USP). Participants also received progesterone (at least 600 mg/day vaginally or 50 mg/day IM), starting on day of OPU and continuing for at least 6 weeks or up to menses. | 268 |
| 150 IU recFSH Participants received a single SC injection of placebo-corifollitropin alfa administered on Day 2 or 3 of the menstrual cycle and daily SC recFSH 150 IU injections (7 total) from Stimulation Day 1 up to and including Stimulation Day 7. Participants also received open-label recFSH (up to 200 IU/day) from Stimulation Day 8 onwards, up to and including the day of hCG (10,000 or 5,000 IU/USP) administration. Participants also received the GnRH antagonist ganirelix (0.25 mg) once daily SC starting on Stimulation Day 5 up to and including the Day of hCG. Participants also received progesterone (at least 600 mg/day vaginally or 50 mg/day IM), starting on the day of OPU and continuing for at least 6 weeks or up to menses. | 128 |
| Total | 396 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Insufficient ovarian response | 1 | 0 |
| Overall Study | No or abnormal fertilization | 4 | 2 |
| Overall Study | No/too few/bad quality embryos retrieved | 7 | 1 |
| Overall Study | No/too few/bad quality oocytes retrieved | 2 | 2 |
| Overall Study | Not randomized | 0 | 1 |
| Overall Study | Patient's decision | 2 | 1 |
| Overall Study | Risk of ovarian hyperstimulation synd. | 1 | 0 |
| Overall Study | Too high ovarian response | 5 | 1 |
Baseline characteristics
| Characteristic | 100 μg Corifollitropin Alfa | 150 IU recFSH | Total |
|---|---|---|---|
| Age, Continuous | 30.9 Years STANDARD_DEVIATION 3.2 | 31.1 Years STANDARD_DEVIATION 3 | 31.0 Years STANDARD_DEVIATION 3.1 |
| Sex: Female, Male Female | 268 Participants | 128 Participants | 396 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 | — / — | — / — |
| other Total, other adverse events | 107 / 268 | 55 / 129 |
| serious Total, serious adverse events | 20 / 268 | 9 / 129 |
Outcome results
Primary
Number of Cumulus-oocyte-complexes Retrieved, Per Attempt
The primary efficacy parameter was defined as the number of cumulus-oocyte-complexes retrieved from participants in a controlled ovarian stimulation (COS) cycle for in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI). For participants who did not have cumulus-oocyte-complex retrieval, the number retrieved was set to zero.
Time frame: One COS cycle with cumulus-oocyte-complex retrieval (up to a maximum total duration of 21 days)
Population: Intent-to-Treat (ITT) Group, which consisted of all randomized participants who received corifollitropin alfa or recFSH.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 100 μg Corifollitropin Alfa | Number of Cumulus-oocyte-complexes Retrieved, Per Attempt | 13.3 Number of cumulus-oocyte-complexes | Standard Deviation 7.3 |
| 150 IU recFSH | Number of Cumulus-oocyte-complexes Retrieved, Per Attempt | 10.6 Number of cumulus-oocyte-complexes | Standard Deviation 5.9 |
p-value: <0.00195% CI: [1.2, 3.9]ANOVA
Secondary
Fertilization Rate
Fertilization rate, defined as 100 times the ratio of the number of fertilized 2 pronuclei (PN) oocytes obtained and the number of oocytes incubated, was tabulated for each treatment group.
Time frame: Up to 10 weeks after ET
Population: Participants from the ITT Group (consisting of all randomized participants who received corifollitropin alfa or recFSH) who received fertilized oocytes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 100 μg Corifollitropin Alfa | Fertilization Rate | 67.6 Percentage | Standard Deviation 22.5 |
| 150 IU recFSH | Fertilization Rate | 67.7 Percentage | Standard Deviation 25.4 |
Secondary
Implantation Rate for Participants With ET
The implantation rate was defined as 100 times the maximum number of gestational sacs as assessed by any ultrasound scan (USS) after ET divided by the number of embryos transferred (per participant), maximized to 100%.
Time frame: Up to 6 weeks after ET within a treatment cycle (up to a maximum 10 weeks)
Population: Participants from the ITT Group (consisting of all randomized participants who received corifollitropin alfa or recFSH) who underwent ET.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 100 μg Corifollitropin Alfa | Implantation Rate for Participants With ET | 23.6 Percentage | Standard Deviation 37.4 |
| 150 IU recFSH | Implantation Rate for Participants With ET | 28.5 Percentage | Standard Deviation 38.6 |
Secondary
Number and Quality of Embryos Obtained at Day 3 (Restricted to Participants With IVF and/or ICSI)
Embryo quality was rated Grade 1, 2, 3, or other. Grade 1 represented excellent quality; Grade 2 good quality; Grade 3 fair quality. Other grade embryos were those that did not qualify as Grade 1, 2, or 3.
Time frame: Post fertilization Day 3 (up to a maximum of 2 days after hCG administration)
Population: Participants from the ITT Group (consisting of all randomized participants who received corifollitropin alfa or recFSH) who underwent IVF and/or ICSI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 100 μg Corifollitropin Alfa | Number and Quality of Embryos Obtained at Day 3 (Restricted to Participants With IVF and/or ICSI) | Total (n=259,123) | 7.2 Number of embryos | Standard Deviation 4.1 |
| 100 μg Corifollitropin Alfa | Number and Quality of Embryos Obtained at Day 3 (Restricted to Participants With IVF and/or ICSI) | Good quality | 3.4 Number of embryos | Standard Deviation 3 |
| 100 μg Corifollitropin Alfa | Number and Quality of Embryos Obtained at Day 3 (Restricted to Participants With IVF and/or ICSI) | Grade 1 | 1.7 Number of embryos | Standard Deviation 2.3 |
| 100 μg Corifollitropin Alfa | Number and Quality of Embryos Obtained at Day 3 (Restricted to Participants With IVF and/or ICSI) | Grade 2 | 1.8 Number of embryos | Standard Deviation 1.9 |
| 100 μg Corifollitropin Alfa | Number and Quality of Embryos Obtained at Day 3 (Restricted to Participants With IVF and/or ICSI) | Grade 3 | 2.8 Number of embryos | Standard Deviation 2.8 |
| 100 μg Corifollitropin Alfa | Number and Quality of Embryos Obtained at Day 3 (Restricted to Participants With IVF and/or ICSI) | Other | 1.0 Number of embryos | Standard Deviation 1.6 |
| 150 IU recFSH | Number and Quality of Embryos Obtained at Day 3 (Restricted to Participants With IVF and/or ICSI) | Grade 3 | 2.4 Number of embryos | Standard Deviation 2.4 |
| 150 IU recFSH | Number and Quality of Embryos Obtained at Day 3 (Restricted to Participants With IVF and/or ICSI) | Total (n=259,123) | 6.2 Number of embryos | Standard Deviation 4 |
| 150 IU recFSH | Number and Quality of Embryos Obtained at Day 3 (Restricted to Participants With IVF and/or ICSI) | Grade 2 | 1.6 Number of embryos | Standard Deviation 1.9 |
| 150 IU recFSH | Number and Quality of Embryos Obtained at Day 3 (Restricted to Participants With IVF and/or ICSI) | Good quality | 3.0 Number of embryos | Standard Deviation 3 |
| 150 IU recFSH | Number and Quality of Embryos Obtained at Day 3 (Restricted to Participants With IVF and/or ICSI) | Other | 0.7 Number of embryos | Standard Deviation 1.7 |
| 150 IU recFSH | Number and Quality of Embryos Obtained at Day 3 (Restricted to Participants With IVF and/or ICSI) | Grade 1 | 1.4 Number of embryos | Standard Deviation 2.1 |
Secondary
Number and Quality of Oocytes Assessed Prior to ICSI (Restricted to Participants With ICSI Only)
The number of oocytes used for ICSI was assessed and categorized based on their quality (i.e., metaphase I oocytes, metaphase II oocytes, and germinal vesicles stage oocytes).
Time frame: Up to 36 hours after administration of hCG
Population: Participants from the ITT Group (consisting of all randomized participants who received corifollitropin alfa or recFSH) who underwent ICSI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 100 μg Corifollitropin Alfa | Number and Quality of Oocytes Assessed Prior to ICSI (Restricted to Participants With ICSI Only) | Oocytes assessed prior to ICSI | 12.7 Number of oocytes | Standard Deviation 6.8 |
| 100 μg Corifollitropin Alfa | Number and Quality of Oocytes Assessed Prior to ICSI (Restricted to Participants With ICSI Only) | Metaphase I oocytes | 0.8 Number of oocytes | Standard Deviation 1.2 |
| 100 μg Corifollitropin Alfa | Number and Quality of Oocytes Assessed Prior to ICSI (Restricted to Participants With ICSI Only) | Metaphase II oocytes | 10.7 Number of oocytes | Standard Deviation 6.4 |
| 100 μg Corifollitropin Alfa | Number and Quality of Oocytes Assessed Prior to ICSI (Restricted to Participants With ICSI Only) | Germinal vesicles stage oocytes | 1.1 Number of oocytes | Standard Deviation 1.6 |
| 150 IU recFSH | Number and Quality of Oocytes Assessed Prior to ICSI (Restricted to Participants With ICSI Only) | Germinal vesicles stage oocytes | 1.3 Number of oocytes | Standard Deviation 2.1 |
| 150 IU recFSH | Number and Quality of Oocytes Assessed Prior to ICSI (Restricted to Participants With ICSI Only) | Oocytes assessed prior to ICSI | 9.9 Number of oocytes | Standard Deviation 5.4 |
| 150 IU recFSH | Number and Quality of Oocytes Assessed Prior to ICSI (Restricted to Participants With ICSI Only) | Metaphase II oocytes | 7.8 Number of oocytes | Standard Deviation 4.8 |
| 150 IU recFSH | Number and Quality of Oocytes Assessed Prior to ICSI (Restricted to Participants With ICSI Only) | Metaphase I oocytes | 0.7 Number of oocytes | Standard Deviation 1.2 |
Secondary
Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration
For each participant, the number of follicles ≥11 mm, ≥15 mm, and ≥17 mm, documented by ultrasonography on defined days during the treatment cycle, was calculated.
Time frame: Predose up to day of hCG administration (up to a maximum total duration of 19 stimulation days, including day of hCG administration)
Population: Participants from the ITT Group (consisting of all randomized participants who received corifollitropin alfa or recFSH) who received hCG.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 15, >=11mm (n=1,1) | 7.0 Follicles | Standard Deviation 0 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 5, >=15mm (n=267,128) | 0.3 Follicles | Standard Deviation 0.7 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 15, >=15mm (n=1,1) | 4.0 Follicles | Standard Deviation 0 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 7, >=15mm (n=30,12) | 4.5 Follicles | Standard Deviation 4.7 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 15, >=17mm (n=1,1) | 2.0 Follicles | Standard Deviation 0 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 3, >=11mm (n=268,128) | 0.6 Follicles | Standard Deviation 1.7 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Day of hCG administration, >=11mm (n=266,127) | 14.9 Follicles | Standard Deviation 6.6 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 7, >=17mm (n=30,12) | 1.8 Follicles | Standard Deviation 2.8 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Day of hCG administration, >=15mm (n=266,127) | 9.4 Follicles | Standard Deviation 4.9 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 5, >=17mm (n=267,128) | 0.0 Follicles | Standard Deviation 0.2 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Day of hCG administration, >=17mm (n=266,127) | 5.3 Follicles | Standard Deviation 3 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 8, >=11mm (n=259,121) | 11.8 Follicles | Standard Deviation 6.1 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 1, >=11mm (n=266,124) | 0.0 Follicles | Standard Deviation 0.1 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 3, >=17mm (n=268,128) | 0.0 Follicles | Standard Deviation 0 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 1, >=15mm (n=266,124) | 0.0 Follicles | Standard Deviation 0.1 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 8, >=15mm (n=259,121) | 5.0 Follicles | Standard Deviation 4.6 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 9, >=11mm (n=185,76) | 13.4 Follicles | Standard Deviation 6.5 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 6, >=11mm (n=9,5) | 7.6 Follicles | Standard Deviation 5.2 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 9, >=15mm (n=185,76) | 6.9 Follicles | Standard Deviation 4.7 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 8, >=17mm (n=259,121) | 2.0 Follicles | Standard Deviation 3 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 9, >=17mm (n=185,76) | 2.6 Follicles | Standard Deviation 2.5 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 1, >=17mm (n=266,124) | 0.0 Follicles | Standard Deviation 0.1 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 10, >=11mm (n=101,40) | 13.9 Follicles | Standard Deviation 6.7 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 13, >=15mm (n=5,4) | 10.6 Follicles | Standard Deviation 8.6 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 10, >=15mm (n=101,40) | 7.4 Follicles | Standard Deviation 4.9 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 6, >=15mm (n=9,5) | 1.8 Follicles | Standard Deviation 3 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 10, >=17mm (n=101,40) | 3.6 Follicles | Standard Deviation 3.5 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 13, >=17mm (n=5,4) | 4.4 Follicles | Standard Deviation 6.2 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 11, >=11mm (n=38,14) | 13.9 Follicles | Standard Deviation 6.7 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 5, >=11mm (n=267,128) | 4.7 Follicles | Standard Deviation 3.6 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 11, >=15mm (n=38,14) | 7.7 Follicles | Standard Deviation 5.7 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 14, >=11mm (n=2,1) | 13.5 Follicles | Standard Deviation 12 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 11, >=17mm (n=38,14) | 3.9 Follicles | Standard Deviation 3.8 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 6, >=17mm (n=9,5) | 0.7 Follicles | Standard Deviation 1.3 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 12, >=11mm (n=17,6) | 12.7 Follicles | Standard Deviation 5.4 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 3, >=15mm (n=268,128) | 0.0 Follicles | Standard Deviation 0.1 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 12, >=15mm (n=17,6) | 6.8 Follicles | Standard Deviation 3.5 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 14, >=17mm (n=2,1) | 6.0 Follicles | Standard Deviation 5.7 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 12, >=17mm (n=17,6) | 3.5 Follicles | Standard Deviation 2.8 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 7, >=11mm (n=30,12) | 11.9 Follicles | Standard Deviation 6.8 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 13, >=11mm (n=5,4) | 17.0 Follicles | Standard Deviation 9.5 |
| 100 μg Corifollitropin Alfa | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 14, >=15mm (n=2,1) | 10.5 Follicles | Standard Deviation 12 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 11, >=15mm (n=38,14) | 7.1 Follicles | Standard Deviation 4.6 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 1, >=17mm (n=266,124) | 0.0 Follicles | Standard Deviation 0 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 3, >=11mm (n=268,128) | 0.5 Follicles | Standard Deviation 0.9 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 3, >=15mm (n=268,128) | 0.0 Follicles | Standard Deviation 0 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 3, >=17mm (n=268,128) | 0.0 Follicles | Standard Deviation 0 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 5, >=11mm (n=267,128) | 4.1 Follicles | Standard Deviation 3.2 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 5, >=15mm (n=267,128) | 0.3 Follicles | Standard Deviation 0.9 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 5, >=17mm (n=267,128) | 0.0 Follicles | Standard Deviation 0.1 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 6, >=11mm (n=9,5) | 8.6 Follicles | Standard Deviation 6.3 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 6, >=15mm (n=9,5) | 4.0 Follicles | Standard Deviation 3.8 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 6, >=17mm (n=9,5) | 1.8 Follicles | Standard Deviation 2 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 7, >=11mm (n=30,12) | 9.2 Follicles | Standard Deviation 4.4 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 7, >=15mm (n=30,12) | 3.3 Follicles | Standard Deviation 2.8 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 7, >=17mm (n=30,12) | 1.1 Follicles | Standard Deviation 1.3 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 8, >=11mm (n=259,121) | 10.6 Follicles | Standard Deviation 5.3 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 8, >=15mm (n=259,121) | 5.1 Follicles | Standard Deviation 4.5 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 13, >=11mm (n=5,4) | 10.3 Follicles | Standard Deviation 5.4 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 13, >=15mm (n=5,4) | 6.3 Follicles | Standard Deviation 4.5 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 13, >=17mm (n=5,4) | 4.0 Follicles | Standard Deviation 3.4 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 14, >=11mm (n=2,1) | 3.0 Follicles | Standard Deviation 0 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 14, >=15mm (n=2,1) | 0.0 Follicles | Standard Deviation 0 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 14, >=17mm (n=2,1) | 0.0 Follicles | Standard Deviation 0 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 15, >=11mm (n=1,1) | 4.0 Follicles | Standard Deviation 0 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 15, >=15mm (n=1,1) | 4.0 Follicles | Standard Deviation 0 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 15, >=17mm (n=1,1) | 3.0 Follicles | Standard Deviation 0 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Day of hCG administration, >=11mm (n=266,127) | 12.9 Follicles | Standard Deviation 5.8 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Day of hCG administration, >=15mm (n=266,127) | 8.5 Follicles | Standard Deviation 4.4 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Day of hCG administration, >=17mm (n=266,127) | 5.1 Follicles | Standard Deviation 3 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 1, >=11mm (n=266,124) | 0.0 Follicles | Standard Deviation 0.2 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 8, >=17mm (n=259,121) | 2.4 Follicles | Standard Deviation 3.1 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 9, >=11mm (n=185,76) | 11.1 Follicles | Standard Deviation 5 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 9, >=15mm (n=185,76) | 6.0 Follicles | Standard Deviation 4.5 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 9, >=17mm (n=185,76) | 2.6 Follicles | Standard Deviation 2.5 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 10, >=11mm (n=101,40) | 13.0 Follicles | Standard Deviation 6.4 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 10, >=15mm (n=101,40) | 7.5 Follicles | Standard Deviation 5.3 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 10, >=17mm (n=101,40) | 4.0 Follicles | Standard Deviation 4 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 11, >=11mm (n=38,14) | 11.6 Follicles | Standard Deviation 7.1 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 1, >=15mm (n=266,124) | 0.0 Follicles | Standard Deviation 0 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 11, >=17mm (n=38,14) | 3.8 Follicles | Standard Deviation 3.5 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 12, >=11mm (n=17,6) | 9.3 Follicles | Standard Deviation 4 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 12, >=15mm (n=17,6) | 5.2 Follicles | Standard Deviation 2.9 |
| 150 IU recFSH | Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration | Stimulation Day 12, >=17mm (n=17,6) | 2.7 Follicles | Standard Deviation 2.1 |
Secondary
Number of Days Treated With recFSH
Numbers of days treated with recFSH was defined as the total number of days participants received recFSH (excluding coasting days) until they reached the criterion for administration of hCG (at least 3 follicles \>=17mm).
Time frame: One COS cycle (up to a maximum total duration of 19 stimulation days)
Population: Participants from the ITT Group (consisting of all randomized participants who received corifollitropin alfa or recFSH) who received hCG.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 100 μg Corifollitropin Alfa | Number of Days Treated With recFSH | 2.0 Days |
| 150 IU recFSH | Number of Days Treated With recFSH | 9.0 Days |
Secondary
Number of Participants With Miscarriages
A miscarriage, also known as a spontaneous abortion, was defined as the loss of a fetus without induction or instrumentation.
Time frame: Up to 10 weeks after ET (up to a maximum of 14 weeks)
Population: Participants from the ITT Group (consisting of all randomized participants who received corifollitropin alfa or recFSH) who had a biological pregnancy.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| 100 μg Corifollitropin Alfa | Number of Participants With Miscarriages | Per clinical pregnancy (n=78,48) | 10 Participants | 12.8 |
| 100 μg Corifollitropin Alfa | Number of Participants With Miscarriages | Per vital pregnancy (n=69,45) | 1 Participants | — |
| 150 IU recFSH | Number of Participants With Miscarriages | Per clinical pregnancy (n=78,48) | 4 Participants | 8.3 |
| 150 IU recFSH | Number of Participants With Miscarriages | Per vital pregnancy (n=69,45) | 1 Participants | — |
Secondary
Number of Participants With Pregnancies
A Biochemical Pregnancy was defined as a pregnancy proven by a biochemical pregnancy test. (Participants not having a positive biochemical pregnancy test result, but with an ultrasound showing at least one gestational sac were counted as having a biochemical pregnancy.) A Clinical Pregnancy was defined as the presence of at least one gestational sac as assessed by an USS scan. A Vital Pregnancy was considered the presence of at least one fetus with heart activity as assessed by USS. An Ongoing Pregnancy was defined as the presence of at least one fetus with heart activity at least 10 weeks after ET as assessed by USS or Doppler, or confirmed by live birth.
Time frame: Up to 10 weeks after ET (up to a maximum of 14 weeks)
Population: ITT Group, which consisted of all randomized participants who received corifollitropin alfa or recFSH.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 100 μg Corifollitropin Alfa | Number of Participants With Pregnancies | Ongoing pregnancy, per attempt (n=268,128) | 68 Participants |
| 100 μg Corifollitropin Alfa | Number of Participants With Pregnancies | Clinical pregnancy, per attempt (n=268,128) | 78 Participants |
| 100 μg Corifollitropin Alfa | Number of Participants With Pregnancies | Biochemical pregnancy, per attempt (n=268,128) | 101 Participants |
| 100 μg Corifollitropin Alfa | Number of Participants With Pregnancies | Clinical pregnancy, per ET (n=246,121) | 78 Participants |
| 100 μg Corifollitropin Alfa | Number of Participants With Pregnancies | Ongoing pregnancy, per ET (n=246,121) | 68 Participants |
| 100 μg Corifollitropin Alfa | Number of Participants With Pregnancies | Vital pregnancy, per attempt (n=268,128) | 69 Participants |
| 100 μg Corifollitropin Alfa | Number of Participants With Pregnancies | Biochemical pregnancy, per ET (n=246,121) | 101 Participants |
| 100 μg Corifollitropin Alfa | Number of Participants With Pregnancies | Vital pregnancy, per ET (n=246,121) | 69 Participants |
| 150 IU recFSH | Number of Participants With Pregnancies | Biochemical pregnancy, per ET (n=246,121) | 58 Participants |
| 150 IU recFSH | Number of Participants With Pregnancies | Ongoing pregnancy, per attempt (n=268,128) | 44 Participants |
| 150 IU recFSH | Number of Participants With Pregnancies | Ongoing pregnancy, per ET (n=246,121) | 44 Participants |
| 150 IU recFSH | Number of Participants With Pregnancies | Biochemical pregnancy, per attempt (n=268,128) | 58 Participants |
| 150 IU recFSH | Number of Participants With Pregnancies | Vital pregnancy, per ET (n=246,121) | 45 Participants |
| 150 IU recFSH | Number of Participants With Pregnancies | Clinical pregnancy, per attempt (n=268,128) | 48 Participants |
| 150 IU recFSH | Number of Participants With Pregnancies | Clinical pregnancy, per ET (n=246,121) | 48 Participants |
| 150 IU recFSH | Number of Participants With Pregnancies | Vital pregnancy, per attempt (n=268,128) | 45 Participants |
Secondary
Serum Estradiol (E2) Levels (Restricted to Participants With hCG Injection)
Blood samples for assessment of serum E2 were taken prior to injection on Stimulation Day 1, Day 3, Day 5, Day 8, Day of hCG, Day of ET, at the visit two weeks after ET.
Time frame: Predose up to 2 weeks after ET (up to maximum of 6 weeks)
Population: Participants from the ITT Group (consisting of all randomized participants who received corifollitropin alfa or recFSH) who received hCG.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| 100 μg Corifollitropin Alfa | Serum Estradiol (E2) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 5 (n=265,127) | 1901.06 pmol/L | Full Range 1490.48 |
| 100 μg Corifollitropin Alfa | Serum Estradiol (E2) Levels (Restricted to Participants With hCG Injection) | Day of hCG injection (n=262,126) | 4440.70 pmol/L | Full Range 3355.95 |
| 100 μg Corifollitropin Alfa | Serum Estradiol (E2) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 3 (n=265,127) | 803.73 pmol/L | Full Range 553.18 |
| 100 μg Corifollitropin Alfa | Serum Estradiol (E2) Levels (Restricted to Participants With hCG Injection) | Day of ET (n=242,121) | 3475.49 pmol/L | Full Range 2640.49 |
| 100 μg Corifollitropin Alfa | Serum Estradiol (E2) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 8 (n=255,121) | 2899.30 pmol/L | Full Range 2632.83 |
| 100 μg Corifollitropin Alfa | Serum Estradiol (E2) Levels (Restricted to Participants With hCG Injection) | 2 weeks after ET (n=245,121) | 168.45 pmol/L | Full Range 3002.09 |
| 100 μg Corifollitropin Alfa | Serum Estradiol (E2) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 1 (pre-dose) (n=265,122) | 118.17 pmol/L | Full Range 53.18 |
| 150 IU recFSH | Serum Estradiol (E2) Levels (Restricted to Participants With hCG Injection) | 2 weeks after ET (n=245,121) | 392.69 pmol/L | Full Range 2889.61 |
| 150 IU recFSH | Serum Estradiol (E2) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 1 (pre-dose) (n=265,122) | 120.38 pmol/L | Full Range 71.07 |
| 150 IU recFSH | Serum Estradiol (E2) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 3 (n=265,127) | 506.46 pmol/L | Full Range 369.66 |
| 150 IU recFSH | Serum Estradiol (E2) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 5 (n=265,127) | 1295.51 pmol/L | Full Range 1015.75 |
| 150 IU recFSH | Serum Estradiol (E2) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 8 (n=255,121) | 3167.21 pmol/L | Full Range 2710.16 |
| 150 IU recFSH | Serum Estradiol (E2) Levels (Restricted to Participants With hCG Injection) | Day of hCG injection (n=262,126) | 4440.70 pmol/L | Full Range 3114.93 |
| 150 IU recFSH | Serum Estradiol (E2) Levels (Restricted to Participants With hCG Injection) | Day of ET (n=242,121) | 3670.00 pmol/L | Full Range 2946.26 |
Secondary
Serum Follicle Stimulating Hormone (FSH) Levels (Restricted to Participants With hCG Injection)
Blood samples for assessment of serum FSH were taken prior to injection on Stimulation Day 1, Day 3, Day 5, Day 8, Day of hCG, Day of ET, at the visit two weeks after ET.
Time frame: Predose up to 2 weeks after ET (up to maximum of 6 weeks)
Population: Participants from the ITT Group (consisting of all randomized participants who received corifollitropin alfa or recFSH) who received hCG.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| 100 μg Corifollitropin Alfa | Serum Follicle Stimulating Hormone (FSH) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 1 (pre-dose) (n=265,122) | 6.46 IU/L | Full Range 1.84 |
| 100 μg Corifollitropin Alfa | Serum Follicle Stimulating Hormone (FSH) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 5 (n=265,127) | 19.50 IU/L | Full Range 4.52 |
| 100 μg Corifollitropin Alfa | Serum Follicle Stimulating Hormone (FSH) Levels (Restricted to Participants With hCG Injection) | 2 weeks after ET (n=245,121) | 4.46 IU/L | Full Range 3.53 |
| 100 μg Corifollitropin Alfa | Serum Follicle Stimulating Hormone (FSH) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 8 (n=255,121) | 10.10 IU/L | Full Range 2.12 |
| 100 μg Corifollitropin Alfa | Serum Follicle Stimulating Hormone (FSH) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 3 (n=265,127) | 26.30 IU/L | Full Range 7.14 |
| 100 μg Corifollitropin Alfa | Serum Follicle Stimulating Hormone (FSH) Levels (Restricted to Participants With hCG Injection) | Day of hCG injection (n=262,126) | 11.50 IU/L | Full Range 2.65 |
| 100 μg Corifollitropin Alfa | Serum Follicle Stimulating Hormone (FSH) Levels (Restricted to Participants With hCG Injection) | Day of ET (n=242,121) | 2.52 IU/L | Full Range 1.05 |
| 150 IU recFSH | Serum Follicle Stimulating Hormone (FSH) Levels (Restricted to Participants With hCG Injection) | Day of hCG injection (n=262,126) | 10.65 IU/L | Full Range 3.57 |
| 150 IU recFSH | Serum Follicle Stimulating Hormone (FSH) Levels (Restricted to Participants With hCG Injection) | Day of ET (n=242,121) | 1.32 IU/L | Full Range 1.02 |
| 150 IU recFSH | Serum Follicle Stimulating Hormone (FSH) Levels (Restricted to Participants With hCG Injection) | 2 weeks after ET (n=245,121) | 1.90 IU/L | — |
| 150 IU recFSH | Serum Follicle Stimulating Hormone (FSH) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 1 (pre-dose) (n=265,122) | 6.51 IU/L | Full Range 1.89 |
| 150 IU recFSH | Serum Follicle Stimulating Hormone (FSH) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 3 (n=265,127) | 9.18 IU/L | Full Range 2.48 |
| 150 IU recFSH | Serum Follicle Stimulating Hormone (FSH) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 5 (n=265,127) | 10.20 IU/L | Full Range 2.98 |
| 150 IU recFSH | Serum Follicle Stimulating Hormone (FSH) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 8 (n=255,121) | 10.30 IU/L | Full Range 2.26 |
Secondary
Serum Inhibin-B Levels (Restricted to Participants With hCG Injection)
Blood samples for assessment of serum inhibin-B were taken prior to injection on Stimulation Day 1, Day 3, Day 5, Day 8, Day of hCG, Day of ET, at the visit two weeks after ET.
Time frame: Predose up to 2 weeks after ET (up to maximum of 6 weeks)
Population: Participants from the ITT Group (consisting of all randomized participants who received corifollitropin alfa or recFSH) who received hCG.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| 100 μg Corifollitropin Alfa | Serum Inhibin-B Levels (Restricted to Participants With hCG Injection) | Stimulation Day 5 (n=264,127) | 598.00 pg/mL | Full Range 527.96 |
| 100 μg Corifollitropin Alfa | Serum Inhibin-B Levels (Restricted to Participants With hCG Injection) | Day of hCG injection (n=262,126) | 729.50 pg/mL | Full Range 721.2 |
| 100 μg Corifollitropin Alfa | Serum Inhibin-B Levels (Restricted to Participants With hCG Injection) | Stimulation Day 3 (n=265,127) | 351.00 pg/mL | Full Range 216.79 |
| 100 μg Corifollitropin Alfa | Serum Inhibin-B Levels (Restricted to Participants With hCG Injection) | Day of ET (n=242,121) | 18.20 pg/mL | Full Range 25.49 |
| 100 μg Corifollitropin Alfa | Serum Inhibin-B Levels (Restricted to Participants With hCG Injection) | Stimulation Day 8 (n=255,121) | 619.00 pg/mL | Full Range 643.76 |
| 100 μg Corifollitropin Alfa | Serum Inhibin-B Levels (Restricted to Participants With hCG Injection) | 2 weeks after ET (n=245,121) | 17.50 pg/mL | — |
| 100 μg Corifollitropin Alfa | Serum Inhibin-B Levels (Restricted to Participants With hCG Injection) | Stimulation Day 1 (pre-dose) (n=265,123) | 54.20 pg/mL | Full Range 26.4 |
| 150 IU recFSH | Serum Inhibin-B Levels (Restricted to Participants With hCG Injection) | 2 weeks after ET (n=245,121) | NA pg/mL | — |
| 150 IU recFSH | Serum Inhibin-B Levels (Restricted to Participants With hCG Injection) | Stimulation Day 1 (pre-dose) (n=265,123) | 57.80 pg/mL | Full Range 168.69 |
| 150 IU recFSH | Serum Inhibin-B Levels (Restricted to Participants With hCG Injection) | Stimulation Day 3 (n=265,127) | 259.00 pg/mL | Full Range 143.21 |
| 150 IU recFSH | Serum Inhibin-B Levels (Restricted to Participants With hCG Injection) | Stimulation Day 5 (n=264,127) | 489.00 pg/mL | Full Range 348.64 |
| 150 IU recFSH | Serum Inhibin-B Levels (Restricted to Participants With hCG Injection) | Stimulation Day 8 (n=255,121) | 650.00 pg/mL | Full Range 536.39 |
| 150 IU recFSH | Serum Inhibin-B Levels (Restricted to Participants With hCG Injection) | Day of hCG injection (n=262,126) | 615.50 pg/mL | Full Range 571.49 |
| 150 IU recFSH | Serum Inhibin-B Levels (Restricted to Participants With hCG Injection) | Day of ET (n=242,121) | 17.00 pg/mL | Full Range 29.36 |
Secondary
Serum Lutenizing Hormone (LH) Levels (Restricted to Participants With hCG Injection)
Blood samples for assessment of serum LH were taken prior to injection on Stimulation Day 1, Day 3, Day 5, Day 8, Day of hCG, Day of ET, at the visit two weeks after ET.
Time frame: Predose up to 2 weeks after ET (up to maximum of 6 weeks)
Population: Participants from the ITT Group (consisting of all randomized participants who received corifollitropin alfa or recFSH) who received hCG.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| 100 μg Corifollitropin Alfa | Serum Lutenizing Hormone (LH) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 1 (pre-dose) (n=265,122) | 4.46 IU/L | Full Range 1.81 |
| 100 μg Corifollitropin Alfa | Serum Lutenizing Hormone (LH) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 3 (n=265,127) | 1.18 IU/L | Full Range 0.8 |
| 100 μg Corifollitropin Alfa | Serum Lutenizing Hormone (LH) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 5 (n=264,127) | 1.91 IU/L | Full Range 3.7 |
| 100 μg Corifollitropin Alfa | Serum Lutenizing Hormone (LH) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 8 (n=255,121) | 0.82 IU/L | — |
| 100 μg Corifollitropin Alfa | Serum Lutenizing Hormone (LH) Levels (Restricted to Participants With hCG Injection) | Day of hCG injection (n=262,126) | 0.88 IU/L | — |
| 100 μg Corifollitropin Alfa | Serum Lutenizing Hormone (LH) Levels (Restricted to Participants With hCG Injection) | Day of ET (n=242,121) | NA IU/L | — |
| 100 μg Corifollitropin Alfa | Serum Lutenizing Hormone (LH) Levels (Restricted to Participants With hCG Injection) | 2 weeks after ET (n=245,121) | 2.38 IU/L | — |
| 150 IU recFSH | Serum Lutenizing Hormone (LH) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 1 (pre-dose) (n=265,122) | 4.12 IU/L | Full Range 1.94 |
| 150 IU recFSH | Serum Lutenizing Hormone (LH) Levels (Restricted to Participants With hCG Injection) | Day of hCG injection (n=262,126) | 1.30 IU/L | Full Range 2.06 |
| 150 IU recFSH | Serum Lutenizing Hormone (LH) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 3 (n=265,127) | 1.46 IU/L | Full Range 1 |
| 150 IU recFSH | Serum Lutenizing Hormone (LH) Levels (Restricted to Participants With hCG Injection) | 2 weeks after ET (n=245,121) | 1.02 IU/L | — |
| 150 IU recFSH | Serum Lutenizing Hormone (LH) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 5 (n=264,127) | 1.49 IU/L | Full Range 7.26 |
| 150 IU recFSH | Serum Lutenizing Hormone (LH) Levels (Restricted to Participants With hCG Injection) | Day of ET (n=242,121) | NA IU/L | — |
| 150 IU recFSH | Serum Lutenizing Hormone (LH) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 8 (n=255,121) | 1.60 IU/L | Full Range 2.35 |
Secondary
Serum Progesterone (P) Levels (Restricted to Participants With hCG Injection)
Blood samples for assessment of serum P were taken prior to injection on Stimulation Day 1, Day 3, Day 5, Day 8, Day of hCG, Day of ET, at the visit two weeks after ET.
Time frame: Predose up to 2 weeks after ET (up to maximum of 6 weeks)
Population: Participants from the ITT Group (consisting of all randomized participants who received corifollitropin alfa or recFSH) who received hCG.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| 100 μg Corifollitropin Alfa | Serum Progesterone (P) Levels (Restricted to Participants With hCG Injection) | Day of ET (n=242,121) | 421.35 nmol/L | Full Range 223.93 |
| 100 μg Corifollitropin Alfa | Serum Progesterone (P) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 8 (n=255,121) | 1.39 nmol/L | Full Range 0.64 |
| 100 μg Corifollitropin Alfa | Serum Progesterone (P) Levels (Restricted to Participants With hCG Injection) | Day of hCG injection (n=262,126) | 2.10 nmol/L | Full Range 1.34 |
| 100 μg Corifollitropin Alfa | Serum Progesterone (P) Levels (Restricted to Participants With hCG Injection) | 2 weeks after ET (n=244,120) | 38.64 nmol/L | Full Range 263.88 |
| 100 μg Corifollitropin Alfa | Serum Progesterone (P) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 1 (pre-dose) (n=264,120) | 1.36 nmol/L | Full Range 2.9 |
| 100 μg Corifollitropin Alfa | Serum Progesterone (P) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 3 (n=263,126) | 1.23 nmol/L | — |
| 100 μg Corifollitropin Alfa | Serum Progesterone (P) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 5 (n=265,127) | 1.65 nmol/L | Full Range 3.27 |
| 150 IU recFSH | Serum Progesterone (P) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 1 (pre-dose) (n=264,120) | 1.40 nmol/L | Full Range 0.97 |
| 150 IU recFSH | Serum Progesterone (P) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 5 (n=265,127) | 1.28 nmol/L | — |
| 150 IU recFSH | Serum Progesterone (P) Levels (Restricted to Participants With hCG Injection) | 2 weeks after ET (n=244,120) | 51.99 nmol/L | Full Range 236.91 |
| 150 IU recFSH | Serum Progesterone (P) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 8 (n=255,121) | 2.03 nmol/L | Full Range 1.11 |
| 150 IU recFSH | Serum Progesterone (P) Levels (Restricted to Participants With hCG Injection) | Stimulation Day 3 (n=263,126) | NA nmol/L | — |
| 150 IU recFSH | Serum Progesterone (P) Levels (Restricted to Participants With hCG Injection) | Day of hCG injection (n=262,126) | 2.39 nmol/L | Full Range 1.78 |
| 150 IU recFSH | Serum Progesterone (P) Levels (Restricted to Participants With hCG Injection) | Day of ET (n=242,121) | 333.90 nmol/L | Full Range 157.38 |
Secondary
Total Dose of recFSH Administered
Total dose of recFSH (IU) administered was defined as the total amount of recFSH needed by participants to reach the criterion for administration of hCG (at least 3 follicles \>=17mm).
Time frame: One COS cycle (up to a maximum total duration of 19 stimulation days)
Population: Participants from the ITT Group (consisting of all randomized participants who received corifollitropin alfa or recFSH) who received hCG.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 100 μg Corifollitropin Alfa | Total Dose of recFSH Administered | 300.0 International Unit (IU) |
| 150 IU recFSH | Total Dose of recFSH Administered | 1350.0 International Unit (IU) |
Secondary
Total Dose of recFSH Administered From Day 8 Onwards
Total dose of recFSH (IU) needed from Stimulation Day 8 onwards to reach the criterion for administration of hCG (at least 3 follicles \>=17mm).
Time frame: Stimulation Day 8 of COS cycle up to day of hCG administration (up to a maximum total duration of 19 stimulation days)
Population: Participants from the ITT Group (consisting of all randomized participants who received corifollitropin alfa or recFSH) who received hCG.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 100 μg Corifollitropin Alfa | Total Dose of recFSH Administered From Day 8 Onwards | 300.0 International Unit (IU) |
| 150 IU recFSH | Total Dose of recFSH Administered From Day 8 Onwards | 275.0 International Unit (IU) |
Secondary
Total Duration of Stimulation (Days)
Total duration of stimulation was defined as the number of days from first drug administration up to and including the Day of hCG administration.
Time frame: One COS cycle (up to a maximum total duration of 19 stimulation days)
Population: Participants from the ITT Group (consisting of all randomized participants who received corifollitropin alfa or recFSH) who received hCG.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 100 μg Corifollitropin Alfa | Total Duration of Stimulation (Days) | 9.0 Days |
| 150 IU recFSH | Total Duration of Stimulation (Days) | 9.0 Days |