Polycystic Ovarian Syndrome, Infertility
Conditions
Keywords
pre-menopausal women, PCOS, polycystic ovarian syndrome, infertility, IVF, in vitro fertilization
Brief summary
This multicenter, randomized, open-label exploratory study will be performed in approximately 200 polycystic ovary syndrome (PCOS) but otherwise healthy females undergoing in vitro fertilization (IVF). Each study center will follow its standard practice for in vitro fertilization (IVF) within the study parameters as noted in this protocol. The study centers will use marketed products purchased from Schraft's Pharmacy for all phases of the study (down-regulation, stimulation, ovulation induction, and luteal support). Subjects will be randomly assigned to highly purified menotropin (Menopur®) or follitropin beta (Follistim Pen®) for stimulation and progesterone vaginal insert (Endometrin®) or progesterone in oil for luteal support. Subjects will return to the study center for regular scheduled clinic visits as required per in vitro fertilization (IVF) protocol at the site and at specified times during the cycle (Stimulation Day 6, Day of human chorionic gonadotropin (hCG), and first serum pregnancy test) for estradiol (E2), progesterone (P4) and human chorionic gonadotropin (hCG) labs. All subjects will be required to complete a final study visit at completion of luteal support or negative serum pregnancy test following embryo transfer.
Interventions
DRUGMenotropin
225 IU (up to 450 IU) by subcutaneous injection once per day for up to about 15 days.
DRUGProgesterone vaginal insert
100 mg inserted vaginally 2 or 3 times daily (BID or TID) (start on the day after oocyte retrieval) until 10 weeks gestation or confirmation of negative pregnancy test.
DRUGFollitropin beta
225 IU (up to 450 IU) by subcutaneous injection once per day for up to about 15 days.
50 mg by intramuscular injection once per day, starting on the day after oocyte retrieval until 10 weeks gestation or confirmation of negative pregnancy test.
DRUGleuprolide acetate
Daily administration of 0.5mg of leuprolide acetate (depot formulations were not permitted) began on Day 21 following onset of menses, and then decreased to 0.25 mg when gonadotropin therapy was initiated.
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 42 Years
Healthy volunteers
No
Inclusion criteria
1. Pre-menopausal females between the ages of 18 and 42 years 2. Diagnosed with polycystic ovary syndrome (PCOS), using criteria adopted as the 2003 Rotterdam PCOS Consensus (2 out of 3, excluding other etiologies \[congenital adrenal hyperplasia, androgen-secreting tumors, Cushing's syndrome\]) * Oligo- or anovulation * Clinical and/or biochemical signs of hyperandrogenism * Polycystic ovaries 3. Body mass index (BMI) of 18-39 4. Early follicular phase (Day 3) follicle stimulating hormone (FSH) \< 15 IU/L and estradiol (E2) within normal limits 5. Documented history of infertility (e.g., unable to conceive for at least one year, or for 6 months for women \> 38 years of age, or bilateral tubal occlusion or absence, or male factor but excluding severe male factor requiring invasive or surgical sperm retrieval. Donor sperm may be used.) 6. Transvaginal ultrasound at screening consistent with findings adequate for assisted reproductive technology (ART) with respect to uterus and adnexa 7. Signed informed consent
Exclusion criteria
1. Gestational or surrogate carrier, donor oocyte 2. Presence of any clinically relevant systemic disease (e.g., uncontrolled thyroid or adrenal dysfunction, an organic intracranial lesion such as a pituitary tumor, insulin-dependent diabetes mellitus, uterine cancer) 3. Surgical or medical condition which, in the judgment of the Investigator or Sponsor, may interfere with absorption, distribution, metabolism, or excretion of the drugs to be used 4. Two or more previous failed in vitro fertilization (IVF) cycles or in vitro fertilization (IVF)/assisted reproductive technology (ART) failure due to a poor response to gonadotropins, defined as development of 2 mature follicles 5. History of recurrent pregnancy loss, defined as more than two clinical losses 6. Presence of abnormal uterine bleeding of undetermined origin 7. Current or recent substance abuse, including alcohol or smoking \> 10 cigarettes per day 8. Refusal or inability to comply with the requirements of the Protocol for any reason, including scheduled clinic visits and laboratory tests 9. Participation in any experimental drug study within 30 days prior to Screening 10. Severe male factor requiring invasive or surgical sperm retrieval (e.g., microsurgical epididymal sperm aspiration \[MESA\], testicular sperm extraction \[TESE\]) 11. Prior hypersensitivity to any of the protocol drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Cycle Cancellation Due to Risk of Ovarian Hyperstimulation Syndrome (OHSS) Between Weeks 1 - 3 | weeks 1-3 | A count of participants whose discontinuation was clearly documented on the study completion/termination form as cycle cancellation for risk of ovarian hyperstimulation syndrome (OHSS). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Oocytes Retrieved at Day 18 | approximately day 18 | The mean number of oocytes retrieved approximately 36 hours after hCG (Novarel®) administration and fertilized (by insemination or intra cytoplasmic sperm injection (ICSI)) according to site-specific procedures. |
| Percentage of Oocytes Fertilized of the Total Number of Oocytes Retrieved | approximately day 19 | The fertilization rate for each participant was the percentage of the number of oocytes inseminated of the total number of oocytes retrieved. |
| Number of Embryos Transferred at Three Stages of Development Before Implantation | approximately day 24 | The number of embryos, morulas and blastocysts transferred to the study participant on either day 3 or day 5 following fertilization. Embryos represent the earliest development stage and contain 2-8 cells. Morulas, the next stage, continued cellular cleavage results in a 16-30 cell solid sphere. Morula further develop into blastocyst, which contains 70-100 cells in a hollow spherical shape. |
| Number of Embryos Frozen | approximately day 24 | The number of embryos that were not transferred but instead were frozen for future use. |
| Percentage of Participants With Biochemical Pregnancy at Approximately Day 38 | approximately day 38 (Day 14 post embryo transfer) | Biochemical pregnancy is a positive β-hCG pregnancy test 12-14 days post embryo transfer. |
| Percentage of Participants With Clinical Pregnancy at Week 7 | approximately Day 52 | Clinical pregnancy is the confirmation of the presence of intrauterine gestational sacs on pregnancy ultrasound examination. |
| Number of Follicles Observed at Day 15 | approximately day 15 | The mean number of follicles observed in both ovaries at the last transvaginal ultrasound in the stimulation phase. |
| Estradiol Levels at Day 6 | Day 6 | Estradiol monitoring during fertility therapy assesses follicular growth and is useful in monitoring the treatment. Blood tests sent to a central laboratory to obtain estradiol levels. |
| Human Chorionic Gonadotropin (hCG) Levels at Day 6 | Day 6 | Blood tests were sent to a central laboratory to obtain hCG levels. |
| Progesterone Levels at Human Chorionic Gonadotropin (hCG) Administration | approximately day 16 | Blood tests were sent to a central laboratory to obtain progesterone levels. |
| Number of Live Births Resulting From the In Vitro Fertilization Process | Approximately 10 months | Number of live births resulting from the IVF process |
| Participants With Treatment Emergent Adverse Events | Week 1 to week12 | Number of participants with adverse events (AEs) that started after first treatment. Severity used a three point scale: mild=awareness of signs/symptoms, but no disruption of usual activity moderate=event sufficient to affect usual activity (disturbing) severe=event causes inability to work or perform usual activities (unacceptable) Relatedness to study treatment used a four point scale: unrelated, unlikely, possible, probable. Seriousness refers to death, hospitalization, a life-threatening experience, persistent or significant disability/incapacity, or congenital anomaly. |
| Percentage of Participants With Ongoing Pregnancy at Week 9 | approximately Day 65 | Clinical pregnancy is the confirmation of the presence of intrauterine gestational sacs on pregnancy ultrasound examination. |
Countries
United States
Participant flow
Recruitment details
The original plan was for 200 participants to be enrolled across six (6) women's reproductive study centers across the US.
Pre-assignment details
127 patients were screened. 120 patients were randomized. Of the randomized patients, 10 did not receive treatment. 110 randomized participants started the study on treatment.
Participants by arm
| Arm | Count |
|---|---|
| Menotropin/Progesterone Vaginal Insert Highly purified menotropin (Menopur®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met.
Progesterone vaginal insert (Endometrin®) 100 mg starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained. | 25 |
| Menotropin/Progesterone in Oil Highly purified menotropin (Menopur®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met.
Progesterone in oil 50 mg injections start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained. | 27 |
| Follitropin Beta/Progesterone Vaginal Insert Follitropin beta (Follistim®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met.
Progesterone vaginal insert (Endometrin®) 50 mg injections start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained. | 28 |
| Follitropin Beta/Progesterone in Oil Follitropin beta (Follistim®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met.
Progesterone in oil 50 mg injections start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained. | 30 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Biochemical pregnancy | 0 | 1 | 0 | 0 |
| Overall Study | Chemical pregnancy | 0 | 5 | 3 | 2 |
| Overall Study | Cycle cancellation for risk of OHSS | 1 | 0 | 1 | 0 |
| Overall Study | Cycle cancelled | 0 | 0 | 2 | 0 |
| Overall Study | Ectopic pregnancy | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Overall Study | No positive serum pregnancy | 8 | 7 | 6 | 5 |
| Overall Study | Ovarian hyperstimulation syndrome(OHSS) | 0 | 0 | 0 | 1 |
| Overall Study | Pregnancy loss/miscarriage | 2 | 0 | 0 | 0 |
| Overall Study | Pregnancy not confirmed by ultrasound | 0 | 0 | 0 | 1 |
| Overall Study | Serious Adverse Event-congenital anomaly | 0 | 1 | 0 | 0 |
| Overall Study | Stimulation Failure | 1 | 5 | 2 | 2 |
Baseline characteristics
| Characteristic | Menotropin/Progesterone Vaginal Insert | Menotropin/Progesterone in Oil | Follitropin Beta/Progesterone Vaginal Insert | Follitropin Beta/Progesterone in Oil | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 27 Participants | 28 Participants | 30 Participants | 110 Participants |
| Race/Ethnicity, Customized African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 1 Participants | 4 Participants | 1 Participants | 11 Participants |
| Race/Ethnicity, Customized Caucasian | 18 Participants | 18 Participants | 20 Participants | 25 Participants | 81 Participants |
| Race/Ethnicity, Customized Hispanic | 2 Participants | 7 Participants | 4 Participants | 3 Participants | 16 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 25 Participants | 27 Participants | 28 Participants | 30 Participants | 110 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 25 | 11 / 27 | 15 / 28 | 14 / 30 |
| serious Total, serious adverse events | 0 / 25 | 1 / 27 | 0 / 28 | 0 / 30 |
Outcome results
Primary
Participants With Cycle Cancellation Due to Risk of Ovarian Hyperstimulation Syndrome (OHSS) Between Weeks 1 - 3
A count of participants whose discontinuation was clearly documented on the study completion/termination form as cycle cancellation for risk of ovarian hyperstimulation syndrome (OHSS).
Time frame: weeks 1-3
Population: Intend-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Menotropin/Progesterone Vaginal Insert | Participants With Cycle Cancellation Due to Risk of Ovarian Hyperstimulation Syndrome (OHSS) Between Weeks 1 - 3 | Yes | 1 Participants |
| Menotropin/Progesterone Vaginal Insert | Participants With Cycle Cancellation Due to Risk of Ovarian Hyperstimulation Syndrome (OHSS) Between Weeks 1 - 3 | No | 24 Participants |
| Menotropin/Progesterone in Oil | Participants With Cycle Cancellation Due to Risk of Ovarian Hyperstimulation Syndrome (OHSS) Between Weeks 1 - 3 | No | 27 Participants |
| Menotropin/Progesterone in Oil | Participants With Cycle Cancellation Due to Risk of Ovarian Hyperstimulation Syndrome (OHSS) Between Weeks 1 - 3 | Yes | 0 Participants |
| Follitropin Beta/Progesterone Vaginal Insert | Participants With Cycle Cancellation Due to Risk of Ovarian Hyperstimulation Syndrome (OHSS) Between Weeks 1 - 3 | Yes | 1 Participants |
| Follitropin Beta/Progesterone Vaginal Insert | Participants With Cycle Cancellation Due to Risk of Ovarian Hyperstimulation Syndrome (OHSS) Between Weeks 1 - 3 | No | 27 Participants |
| Follitropin Beta/Progesterone in Oil | Participants With Cycle Cancellation Due to Risk of Ovarian Hyperstimulation Syndrome (OHSS) Between Weeks 1 - 3 | Yes | 0 Participants |
| Follitropin Beta/Progesterone in Oil | Participants With Cycle Cancellation Due to Risk of Ovarian Hyperstimulation Syndrome (OHSS) Between Weeks 1 - 3 | No | 30 Participants |
p-value: 1Fisher Exact
p-value: 1Fisher Exact
Comparison: Comparing Progesterone vaginal insert to Progesterone in oil within the menotropin treatments arms.p-value: 0.481Fisher Exact
Comparison: Comparing Progesterone vaginal insert to Progesterone in oil within the follitropin beta treatment group.p-value: 0.483Fisher Exact
Secondary
Estradiol Levels at Day 6
Estradiol monitoring during fertility therapy assesses follicular growth and is useful in monitoring the treatment. Blood tests sent to a central laboratory to obtain estradiol levels.
Time frame: Day 6
Population: Intend-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Menotropin/Progesterone Vaginal Insert | Estradiol Levels at Day 6 | 354.6 pg/mL | Standard Deviation 331.3 |
| Menotropin/Progesterone in Oil | Estradiol Levels at Day 6 | 268.2 pg/mL | Standard Deviation 260.7 |
| Follitropin Beta/Progesterone Vaginal Insert | Estradiol Levels at Day 6 | 617.5 pg/mL | Standard Deviation 409.6 |
| Follitropin Beta/Progesterone in Oil | Estradiol Levels at Day 6 | 550.5 pg/mL | Standard Deviation 486.9 |
Secondary
Human Chorionic Gonadotropin (hCG) Levels at Day 6
Blood tests were sent to a central laboratory to obtain hCG levels.
Time frame: Day 6
Population: Intend-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Menotropin/Progesterone Vaginal Insert | Human Chorionic Gonadotropin (hCG) Levels at Day 6 | 1.0 mIU/ml | Standard Deviation 0.2 |
| Menotropin/Progesterone in Oil | Human Chorionic Gonadotropin (hCG) Levels at Day 6 | 1.0 mIU/ml | Standard Deviation 0 |
| Follitropin Beta/Progesterone Vaginal Insert | Human Chorionic Gonadotropin (hCG) Levels at Day 6 | 1.0 mIU/ml | Standard Deviation 0 |
| Follitropin Beta/Progesterone in Oil | Human Chorionic Gonadotropin (hCG) Levels at Day 6 | 1.0 mIU/ml | Standard Deviation 0 |
Secondary
Number of Embryos Frozen
The number of embryos that were not transferred but instead were frozen for future use.
Time frame: approximately day 24
Population: Intend-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Menotropin/Progesterone Vaginal Insert | Number of Embryos Frozen | 1.9 Embryos | Standard Deviation 2.3 |
| Menotropin/Progesterone in Oil | Number of Embryos Frozen | 1.9 Embryos | Standard Deviation 2.6 |
Secondary
Number of Embryos Transferred at Three Stages of Development Before Implantation
The number of embryos, morulas and blastocysts transferred to the study participant on either day 3 or day 5 following fertilization. Embryos represent the earliest development stage and contain 2-8 cells. Morulas, the next stage, continued cellular cleavage results in a 16-30 cell solid sphere. Morula further develop into blastocyst, which contains 70-100 cells in a hollow spherical shape.
Time frame: approximately day 24
Population: Intend-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Menotropin/Progesterone Vaginal Insert | Number of Embryos Transferred at Three Stages of Development Before Implantation | Number of embryos transferred | 2.0 Embryos | Standard Deviation 0.7 |
| Menotropin/Progesterone Vaginal Insert | Number of Embryos Transferred at Three Stages of Development Before Implantation | Number of morula transferred | 0.0 Embryos | Standard Deviation 0.1 |
| Menotropin/Progesterone Vaginal Insert | Number of Embryos Transferred at Three Stages of Development Before Implantation | Number of blastocyst transferred | 0.8 Embryos | Standard Deviation 0.9 |
| Menotropin/Progesterone in Oil | Number of Embryos Transferred at Three Stages of Development Before Implantation | Number of embryos transferred | 2.0 Embryos | Standard Deviation 0.5 |
| Menotropin/Progesterone in Oil | Number of Embryos Transferred at Three Stages of Development Before Implantation | Number of morula transferred | 0.1 Embryos | Standard Deviation 0.4 |
| Menotropin/Progesterone in Oil | Number of Embryos Transferred at Three Stages of Development Before Implantation | Number of blastocyst transferred | 1.1 Embryos | Standard Deviation 0.9 |
Secondary
Number of Follicles Observed at Day 15
The mean number of follicles observed in both ovaries at the last transvaginal ultrasound in the stimulation phase.
Time frame: approximately day 15
Population: Intend-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Menotropin/Progesterone Vaginal Insert | Number of Follicles Observed at Day 15 | 27.7 Follicles | Standard Deviation 12.8 |
| Menotropin/Progesterone in Oil | Number of Follicles Observed at Day 15 | 30.5 Follicles | Standard Deviation 16.1 |
Secondary
Number of Live Births Resulting From the In Vitro Fertilization Process
Number of live births resulting from the IVF process
Time frame: Approximately 10 months
Population: Database was locked prior to most participants giving birth.
Secondary
Number of Oocytes Retrieved at Day 18
The mean number of oocytes retrieved approximately 36 hours after hCG (Novarel®) administration and fertilized (by insemination or intra cytoplasmic sperm injection (ICSI)) according to site-specific procedures.
Time frame: approximately day 18
Population: Intend-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Menotropin/Progesterone Vaginal Insert | Number of Oocytes Retrieved at Day 18 | 13.0 Oocytes | Standard Deviation 7.7 |
| Menotropin/Progesterone in Oil | Number of Oocytes Retrieved at Day 18 | 15.6 Oocytes | Standard Deviation 8.6 |
Secondary
Participants With Treatment Emergent Adverse Events
Number of participants with adverse events (AEs) that started after first treatment. Severity used a three point scale: mild=awareness of signs/symptoms, but no disruption of usual activity moderate=event sufficient to affect usual activity (disturbing) severe=event causes inability to work or perform usual activities (unacceptable) Relatedness to study treatment used a four point scale: unrelated, unlikely, possible, probable. Seriousness refers to death, hospitalization, a life-threatening experience, persistent or significant disability/incapacity, or congenital anomaly.
Time frame: Week 1 to week12
Population: Safety population all randomized and treated participants. The safety population is identical intent-to- treat (ITT) population in this study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Menotropin/Progesterone Vaginal Insert | Participants With Treatment Emergent Adverse Events | With at least one adverse event | 9 Participants |
| Menotropin/Progesterone Vaginal Insert | Participants With Treatment Emergent Adverse Events | With at least one mild or moderate adverse event | 9 Participants |
| Menotropin/Progesterone Vaginal Insert | Participants With Treatment Emergent Adverse Events | With at least one severe adverse event | 0 Participants |
| Menotropin/Progesterone Vaginal Insert | Participants With Treatment Emergent Adverse Events | With at least one serious adverse event | 0 Participants |
| Menotropin/Progesterone Vaginal Insert | Participants With Treatment Emergent Adverse Events | With at least one unrelated or unlikely AE | 8 Participants |
| Menotropin/Progesterone Vaginal Insert | Participants With Treatment Emergent Adverse Events | With at least one possibly or probably related AE | 3 Participants |
| Menotropin/Progesterone in Oil | Participants With Treatment Emergent Adverse Events | With at least one possibly or probably related AE | 7 Participants |
| Menotropin/Progesterone in Oil | Participants With Treatment Emergent Adverse Events | With at least one serious adverse event | 1 Participants |
| Menotropin/Progesterone in Oil | Participants With Treatment Emergent Adverse Events | With at least one adverse event | 12 Participants |
| Menotropin/Progesterone in Oil | Participants With Treatment Emergent Adverse Events | With at least one severe adverse event | 2 Participants |
| Menotropin/Progesterone in Oil | Participants With Treatment Emergent Adverse Events | With at least one mild or moderate adverse event | 11 Participants |
| Menotropin/Progesterone in Oil | Participants With Treatment Emergent Adverse Events | With at least one unrelated or unlikely AE | 11 Participants |
| Follitropin Beta/Progesterone Vaginal Insert | Participants With Treatment Emergent Adverse Events | With at least one mild or moderate adverse event | 15 Participants |
| Follitropin Beta/Progesterone Vaginal Insert | Participants With Treatment Emergent Adverse Events | With at least one severe adverse event | 1 Participants |
| Follitropin Beta/Progesterone Vaginal Insert | Participants With Treatment Emergent Adverse Events | With at least one serious adverse event | 0 Participants |
| Follitropin Beta/Progesterone Vaginal Insert | Participants With Treatment Emergent Adverse Events | With at least one possibly or probably related AE | 8 Participants |
| Follitropin Beta/Progesterone Vaginal Insert | Participants With Treatment Emergent Adverse Events | With at least one unrelated or unlikely AE | 12 Participants |
| Follitropin Beta/Progesterone Vaginal Insert | Participants With Treatment Emergent Adverse Events | With at least one adverse event | 15 Participants |
| Follitropin Beta/Progesterone in Oil | Participants With Treatment Emergent Adverse Events | With at least one unrelated or unlikely AE | 13 Participants |
| Follitropin Beta/Progesterone in Oil | Participants With Treatment Emergent Adverse Events | With at least one possibly or probably related AE | 6 Participants |
| Follitropin Beta/Progesterone in Oil | Participants With Treatment Emergent Adverse Events | With at least one mild or moderate adverse event | 14 Participants |
| Follitropin Beta/Progesterone in Oil | Participants With Treatment Emergent Adverse Events | With at least one serious adverse event | 0 Participants |
| Follitropin Beta/Progesterone in Oil | Participants With Treatment Emergent Adverse Events | With at least one adverse event | 14 Participants |
| Follitropin Beta/Progesterone in Oil | Participants With Treatment Emergent Adverse Events | With at least one severe adverse event | 0 Participants |
Secondary
Percentage of Oocytes Fertilized of the Total Number of Oocytes Retrieved
The fertilization rate for each participant was the percentage of the number of oocytes inseminated of the total number of oocytes retrieved.
Time frame: approximately day 19
Population: Intend-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Menotropin/Progesterone Vaginal Insert | Percentage of Oocytes Fertilized of the Total Number of Oocytes Retrieved | 17.1 Percentage of oocytes retrieved |
| Menotropin/Progesterone in Oil | Percentage of Oocytes Fertilized of the Total Number of Oocytes Retrieved | 24.8 Percentage of oocytes retrieved |
Secondary
Percentage of Participants With Biochemical Pregnancy at Approximately Day 38
Biochemical pregnancy is a positive β-hCG pregnancy test 12-14 days post embryo transfer.
Time frame: approximately day 38 (Day 14 post embryo transfer)
Population: Intend-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Menotropin/Progesterone Vaginal Insert | Percentage of Participants With Biochemical Pregnancy at Approximately Day 38 | 60.0 Percentage of participants |
| Menotropin/Progesterone in Oil | Percentage of Participants With Biochemical Pregnancy at Approximately Day 38 | 55.6 Percentage of participants |
| Follitropin Beta/Progesterone Vaginal Insert | Percentage of Participants With Biochemical Pregnancy at Approximately Day 38 | 60.7 Percentage of participants |
| Follitropin Beta/Progesterone in Oil | Percentage of Participants With Biochemical Pregnancy at Approximately Day 38 | 73.3 Percentage of participants |
Secondary
Percentage of Participants With Clinical Pregnancy at Week 7
Clinical pregnancy is the confirmation of the presence of intrauterine gestational sacs on pregnancy ultrasound examination.
Time frame: approximately Day 52
Population: Intend-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Menotropin/Progesterone Vaginal Insert | Percentage of Participants With Clinical Pregnancy at Week 7 | 56.0 Percentage of participants |
| Menotropin/Progesterone in Oil | Percentage of Participants With Clinical Pregnancy at Week 7 | 33.3 Percentage of participants |
| Follitropin Beta/Progesterone Vaginal Insert | Percentage of Participants With Clinical Pregnancy at Week 7 | 46.4 Percentage of participants |
| Follitropin Beta/Progesterone in Oil | Percentage of Participants With Clinical Pregnancy at Week 7 | 66.7 Percentage of participants |
Secondary
Percentage of Participants With Ongoing Pregnancy at Week 9
Clinical pregnancy is the confirmation of the presence of intrauterine gestational sacs on pregnancy ultrasound examination.
Time frame: approximately Day 65
Population: Intend-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Menotropin/Progesterone Vaginal Insert | Percentage of Participants With Ongoing Pregnancy at Week 9 | 48.0 Percentage of participants |
| Menotropin/Progesterone in Oil | Percentage of Participants With Ongoing Pregnancy at Week 9 | 33.3 Percentage of participants |
| Follitropin Beta/Progesterone Vaginal Insert | Percentage of Participants With Ongoing Pregnancy at Week 9 | 46.4 Percentage of participants |
| Follitropin Beta/Progesterone in Oil | Percentage of Participants With Ongoing Pregnancy at Week 9 | 63.3 Percentage of participants |
Secondary
Progesterone Levels at Human Chorionic Gonadotropin (hCG) Administration
Blood tests were sent to a central laboratory to obtain progesterone levels.
Time frame: approximately day 16
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Menotropin/Progesterone Vaginal Insert | Progesterone Levels at Human Chorionic Gonadotropin (hCG) Administration | 1.3 ng/mL | Standard Deviation 0.7 |
| Menotropin/Progesterone in Oil | Progesterone Levels at Human Chorionic Gonadotropin (hCG) Administration | 1.1 ng/mL | Standard Deviation 0.4 |
| Follitropin Beta/Progesterone Vaginal Insert | Progesterone Levels at Human Chorionic Gonadotropin (hCG) Administration | 1.7 ng/mL | Standard Deviation 0.9 |
| Follitropin Beta/Progesterone in Oil | Progesterone Levels at Human Chorionic Gonadotropin (hCG) Administration | 1.3 ng/mL | Standard Deviation 0.6 |