Neonates, Pregnancy
Conditions
Keywords
Neonatal outcome, Congenital malformations, In-Vitro fertilization, Controlled ovarian stimulation, Follow-up
Brief summary
The objective of this follow-up study is to evaluate whether corifollitropin alfa (Org 36286) treatment for the induction of multifollicular growth in women undergoing controlled ovarian stimulation (COS) prior to in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) is safe for pregnant participants and their offspring.
Detailed description
This is a follow-up protocol to prospectively monitor pregnancy, delivery, and neonatal outcome of women who were treated with corifollitropin alfa or recFSH and became pregnant during the base study P05690 (NCT00702845). For this trial no study specific assessments are required, but information as obtained in standard practice will be used.
Interventions
DRUGCorifollitropin alfa
Single injection of 100 μg corifollitropin alfa administered under protocol P05690
BIOLOGICALrecFSH (follitropin beta)
Daily recFSH administered under protocol P05690
GnRH antagonist ganirelix administered SC at a dose of 0.25 mg/day under protocol P05690
BIOLOGICALhuman chorion gonadotropin (hCG)
hCG 5,000 IU/USP or 10,000 IU/USP administered under protocol P05690
BIOLOGICALprogesterone
Under protocol P05690, 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.
DRUGplacebo-recFSH (follitropin beta)
Placebo-recFSH at the equivalent volume of 150 IU/day administered under protocol P05690
Single SC injection of placebo-corifollitropin alfa on Day 2 or 3 of the menstrual cycle, administered under protocol P05690
BIOLOGICALopen-label recFSH (follitropin beta)
Open-label recFSH up to a maximum dose of 200 IU/day, administered under protocol P05690
Sponsors
Organon and Co
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 36 Years
Healthy volunteers
No
Inclusion criteria
* Participants who participated in base study P05690 (NCT00702845) and received at least one dose of either corifollitropin alfa (Org 36286) or recFSH in base study P05690; * Ongoing pregnancy confirmed by ultrasound at least 10 weeks after embryo transfer in base study P05690; * Able and willing to give written informed consent.
Exclusion criteria
* None
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Women With ≥1 Live Born Infant During Follow-up (Take-Home Baby Rate) | From approximately 10 weeks after ET in base study P05690 up to birth of infant (up to approximately 6 months) | The Take-Home Baby Rate was defined as the number of participants with an ongoing pregnancy in base study P05690 with at least one live born infant during follow up relative to the number of participants treated in base study. |
| Number of Expectant Mothers Experiencing Adverse Events (AEs) | From approximately 10 weeks after ET in base study P05690 up to birth of infant (up to approximately 6 months) | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. |
| Number of Expectant Mothers Experiencing Serious AEs (SAEs) | From approximately 10 weeks after ET in base study P05690 up to birth of infant (up to approximately 6 months) | An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect. |
| Number of Infants Experiencing AEs | Up to 12 weeks after birth | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. |
| Number of Infants Experiencing SAEs | Up to 12 weeks after birth | An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Corifollitropin Alfa 100 μg Expectant Mothers Participants in base study P05690 received single SC injection of corifollitropin alfa 100 μg (Org 36286) on Day 2 or 3 of menstrual cycle and daily placebo recFSH injections (7 total) from Stimulation Day 1 up to and including Stimulation Day 7. Participants 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 Day of hCG (10,000 or 5,000 IU/USP); and progesterone (at least 600 mg/day vaginally or 50 mg/day IM), starting on day of OPU and continuing at least 6 weeks or up to menses. Eligible participants from base study were enrolled in follow up study P05710, but no study treatments were given. | 68 |
| recFSH 150 IU Expectant Mothers Participants in the reference group in base study P05690 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 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 (10,000 or 5,000 IU/USP). 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. Eligible participants from the base study were enrolled in follow up study P05710, but no study treatments were given. | 45 |
| Total | 113 |
Baseline characteristics
| Characteristic | Corifollitropin Alfa 100 μg Expectant Mothers | recFSH 150 IU Expectant Mothers | Total |
|---|---|---|---|
| Age, Continuous | 30.5 Years STANDARD_DEVIATION 3.3 | 31.3 Years STANDARD_DEVIATION 3.1 | 30.8 Years STANDARD_DEVIATION 3.2 |
| Sex: Female, Male Female | 68 Participants | 45 Participants | 113 Participants |
| Sex: Female, Male Male | 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 | 13 / 68 | 17 / 45 | 9 / 88 | 5 / 55 |
| serious Total, serious adverse events | 38 / 68 | 21 / 45 | 31 / 88 | 16 / 55 |
Outcome results
Primary
Number of Expectant Mothers Experiencing Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time frame: From approximately 10 weeks after ET in base study P05690 up to birth of infant (up to approximately 6 months)
Population: Follow-up safety analysis was performed on expectant mothers who received corifollitropin alfa or recFSH on base study P05690 (NCT00702845) and who enrolled on the follow-up study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Corifollitropin Alfa 100 μg Women | Number of Expectant Mothers Experiencing Adverse Events (AEs) | 48 Participants |
| recFSH 150 IU Women | Number of Expectant Mothers Experiencing Adverse Events (AEs) | 35 Participants |
Primary
Number of Expectant Mothers Experiencing Serious AEs (SAEs)
An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect.
Time frame: From approximately 10 weeks after ET in base study P05690 up to birth of infant (up to approximately 6 months)
Population: Follow-up safety analysis was performed on expectant mothers who received corifollitropin alfa or recFSH on base study P05690 (NCT00702845) and who enrolled on the follow-up study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Corifollitropin Alfa 100 μg Women | Number of Expectant Mothers Experiencing Serious AEs (SAEs) | 38 Participants |
| recFSH 150 IU Women | Number of Expectant Mothers Experiencing Serious AEs (SAEs) | 21 Participants |
Primary
Number of Infants Experiencing AEs
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time frame: Up to 12 weeks after birth
Population: Follow-up safety analysis was performed on live born infants delivered by expectant mothers who received corifollitropin alfa or recFSH on base study P05690 (NCT00702845) and who enrolled on the follow-up study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Corifollitropin Alfa 100 μg Women | Number of Infants Experiencing AEs | 37 Live born infants |
| recFSH 150 IU Women | Number of Infants Experiencing AEs | 27 Live born infants |
Primary
Number of Infants Experiencing SAEs
An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect.
Time frame: Up to 12 weeks after birth
Population: Follow-up safety analysis was performed on live born infants delivered by expectant mothers who received corifollitropin alfa or recFSH on base study P05690 (NCT00702845) and who enrolled on the follow-up study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Corifollitropin Alfa 100 μg Women | Number of Infants Experiencing SAEs | 30 Live born infants |
| recFSH 150 IU Women | Number of Infants Experiencing SAEs | 16 Live born infants |
Primary
Percentage of Women With ≥1 Live Born Infant During Follow-up (Take-Home Baby Rate)
The Take-Home Baby Rate was defined as the number of participants with an ongoing pregnancy in base study P05690 with at least one live born infant during follow up relative to the number of participants treated in base study.
Time frame: From approximately 10 weeks after ET in base study P05690 up to birth of infant (up to approximately 6 months)
Population: Intent-to-Treat (ITT) group from base study P05690 (NCT00702845), which consisted of randomized participants who were treated with corifollitropin alfa or recFSH.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Corifollitropin Alfa 100 μg Women | Percentage of Women With ≥1 Live Born Infant During Follow-up (Take-Home Baby Rate) | 23.5 Percentage of participants |
| recFSH 150 IU Women | Percentage of Women With ≥1 Live Born Infant During Follow-up (Take-Home Baby Rate) | 34.4 Percentage of participants |