Neonates, Pregnancy
Conditions
Keywords
Neonatal outcome, Congenital malformations, In-Vitro fertilization, Controlled ovarian stimulation, Follow-up
Brief summary
The objective of this trial was to evaluate whether Corifollitropin Alfa 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) was safe for pregnant participants and their offspring. The primary endpoint was the take-home baby rate calculated as the number of participants with an ongoing pregnancy in Base Trial P05787 (NCT00696800) with at least one live born infant relative to the number of participants in the Base Trial, and to the number of participants in the Base Trial with Embryo Transfer (ET).
Detailed description
This is a follow-up protocol to prospectively monitor pregnancy, delivery, and neonatal outcome of all women who were treated with Corifollitropin Alfa or recFSH and became pregnant during Base Trial P05787 (NCT00696800). For this trial, no study specific assessments are required, but information as obtained in standard practice will be used.
Interventions
DRUGCorifollitropin Alfa 150 μg
In the Base Trial P05787, on the morning of day 2 or 3 of the menstrual cycle (Stimulation Day 1), a single SC injection of 150 μg (0.5 mL) Corifollitropin Alfa was administered in the abdominal wall.
In the Base Trial P05787, daily SC injections with 200 IU fixed dose recFSH were started on Stimulation Day 1 and continued up to and including Stimulation Day 7.
In the Base Trial P05787, on the morning of day 2 or 3 of the menstrual cycle (Stimulation Day 1), a single SC injection from a pre-filled syringe containing an identical solution when compared to Corifollitropin Alfa was administered in the abdominal wall.
In the Base Trial P05787, daily SC injections of an identical ready-for-use solution, but without the active ingredient, supplied in cartridges for SC injection with the Follistim Pen, were started on Stimulation Day 1 and continued up to and including Stimulation Day 7.
In the Base Trial P05787, from Stimulation Day 8 onwards a daily SC dose of 200 IU recFSH was administered up to and including the Day of hCG.
DRUGGanirelix
In the Base Trial P05787, on Stimulation Day 5 a daily SC injection of 0.25 mg was started, which continued up to and including the day of hCG.
BIOLOGICALhCG
In the Base Trial P05787, when 3 follicles \>= 17 mm were observed by USS, a single dose of 10,000 IU/USP hCG was administered; or, for those at risk for Ovarian Hyperstimulation Syndrome (OHSS), a lower dose of 5,000 IU/USP
BIOLOGICALProgesterone
In the Base Trial P05787, on the day of OPU, luteal phase support was started by administering micronized progesterone of at least 600 mg/day vaginally, or at least 50 mg/day intramuscular (IM), which continued for at least 6 weeks, or up to menses.
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 received at least one dose of either Corifollitropin Alfa or Puregon®/Follistim® AQ Cartridge in Base Trial P05787 (NCT00696800); * Ongoing pregnancy confirmed by ultrasound at least 10 weeks after embryo transfer in Base Trial P05787 (NCT00696800); * Able and willing to give written informed consent.
Exclusion criteria
* None
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Mothers in Current Follow Up Trial Experiencing Adverse Events (AEs) | Up to one day following delivery (up to 1 year) | An AE is any untoward medical occurrence in a trial participant administered a pharmaceutical product, and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including laboratory finding), symptom, or disease temporally associated with the use of investigational medicinal product. |
| Number of Mothers in Current Follow Up Trial Experiencing Serious AEs (SAEs) | Up to one day following delivery (up to 1 year) | A SAE is any untoward medical occurrence that at any dose resulted in the following: death, was life threatening, required in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, or was a congenital anomaly/birth defect. |
| Number of Infants Born in Current Follow Up Trial Experiencing AEs | Up to 12 weeks following delivery (up to 1 year) | An AE is any untoward medical occurrence in a trial participant administered a pharmaceutical product, and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including laboratory finding), symptom, or disease temporally associated with the use of investigational medicinal product. |
| Number of Infants in Current Follow Up Trial Experiencing SAEs | Up to 12 weeks following delivery (up to 1 year) | A SAE is any untoward medical occurrence that at any dose resulted in the following: death, was life threatening, required in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, or was a congenital anomaly/birth defect. |
| Percentage of Mothers From the Base Trial P05787 With at Least One Live Born Infant (Take-home Baby Rate) Relative to the Number of Participants in the Base Trial. | At least 10 weeks after embryo transfer in Base Trial P05787 up to birth in current follow up Trial (up to 1 year) | The take-home baby rate is 100 X the number of participants with an ongoing pregnancy in Base Trial P05787 (NCT00696800), from the Intent-to-Treat (ITT) group, with at least one live born infant relative to the number of participants in the Base Trial. |
| Percentage of Mothers From the Base Trial P05787 With at Least One Live Born Infant (Take-home Baby Rate) Relative to the Number of Participants From the Base Trial With Embryo Transfer. | At least 10 weeks after embryo transfer in Base Trial P05787 up to birth in current Follow Up Trial (up to 1 year) | The take-home baby rate is 100 X the number of participants with an ongoing pregnancy in Base Trial P05787 (NCT00696800), from the ITT group, with at least one live born infant relative to the number of participants from the Base Trial with embryo transfer. |
Participant flow
Pre-assignment details
Period one consists of mothers from the Base Trial P05787 (NCT00696800), randomized to treatment groups Corifollitropin Alfa (Org 36286) or recombinant Follicle Stimulating Hormone (recFSH). Period two consists of mothers (N = 541) who enrolled in trial P05712. Period three consists of miscarried/stillborn fetuses and infants born in trial P05712.
Participants by arm
| Arm | Count |
|---|---|
| Mothers Corifollitropin Alfa 150 µg Participants from the Base Trial P05787 (NCT00696800) who received a SC injection of 150 µg Corifollitropin Alfa on day 2 or 3 of the menstrual cycle (Stimulation Day 1); 7 daily SC injections from Stimulation Days 1 to 7 with placebo-recFSH; followed by daily SC injections with 200 IU recFSH up to the day of hCG; multiple daily SC injections of Ganirelix from Stimulation Day 5 to the day of hCG; a single dose of hCG (10,000 or 5,000 IU/USP) was administered when 3 follicles \>= 17 mm were observed; and on the day of OPU daily doses of progesterone were started and continued for up to 6 weeks or menses. Eligible participants from the Base Trial were enrolled in Follow Up Trial P05712, where no study treatments were given, and pregnancy, delivery and neonatal outcome were monitored. | 274 |
| Mothers recFSH 200 IU Participants from the Base Trial P05787 (NCT00696800) who received a single SC injection of placebo Corifollitropin Alfa on day 2 or 3 of the menstrual cycle (Stimulation Day 1); 7 daily SC injections with 200 IU recFSH from Stimulation Days 1 to 7; followed by daily SC injections with 200 IU recFSH up to the day of hCG; multiple daily SC injections of Ganirelix from Stimulation Day 5 to the day of hCG; single dose of hCG (10,000 or 5,000 IU/USP) was administered when 3 follicles \>= 17 mm were observed; and on the day of OPU daily doses of progesterone were started and continued for up to 6 weeks or menses. Eligible participants from the Base Trial were enrolled in Follow Up Trial P05712, where no study treatments were given, and pregnancy, delivery and neonatal outcome were monitored. | 267 |
| Total | 541 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Fetuses/Infants Follow Up Trial P05712 | Did not complete follow up in P05712 | 0 | 0 | 47 | 42 |
| Mothers Follow Up Trial P05712 | Did not complete follow up in P05712 | 33 | 32 | 0 | 0 |
Baseline characteristics
| Characteristic | Mothers Corifollitropin Alfa 150 µg | Mothers recFSH 200 IU | Total |
|---|---|---|---|
| Age, Continuous | 31.4 Years STANDARD_DEVIATION 3.2 | 31.3 Years STANDARD_DEVIATION 3.5 | 31.3 Years STANDARD_DEVIATION 3.3 |
| Sex: Female, Male Female | 274 Participants | 267 Participants | 541 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 | 112 / 274 | 118 / 267 | 37 / 352 | 41 / 326 |
| serious Total, serious adverse events | 129 / 274 | 117 / 267 | 106 / 352 | 94 / 326 |
Outcome results
Primary
Number of Infants Born in Current Follow Up Trial Experiencing AEs
An AE is any untoward medical occurrence in a trial participant administered a pharmaceutical product, and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including laboratory finding), symptom, or disease temporally associated with the use of investigational medicinal product.
Time frame: Up to 12 weeks following delivery (up to 1 year)
Population: Infants born in Follow Up Trial P05712. Mothers were not analyzed in this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mothers Corifollitropin Alfa 150 µg | Number of Infants Born in Current Follow Up Trial Experiencing AEs | 164 Participants |
| Mothers recFSH 200 IU | Number of Infants Born in Current Follow Up Trial Experiencing AEs | 161 Participants |
Primary
Number of Infants in Current Follow Up Trial Experiencing SAEs
A SAE is any untoward medical occurrence that at any dose resulted in the following: death, was life threatening, required in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, or was a congenital anomaly/birth defect.
Time frame: Up to 12 weeks following delivery (up to 1 year)
Population: Infants born in Follow Up Trial P05712. Mothers were not analyzed in this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mothers Corifollitropin Alfa 150 µg | Number of Infants in Current Follow Up Trial Experiencing SAEs | 106 Participants |
| Mothers recFSH 200 IU | Number of Infants in Current Follow Up Trial Experiencing SAEs | 94 Participants |
Primary
Number of Mothers in Current Follow Up Trial Experiencing Adverse Events (AEs)
An AE is any untoward medical occurrence in a trial participant administered a pharmaceutical product, and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including laboratory finding), symptom, or disease temporally associated with the use of investigational medicinal product.
Time frame: Up to one day following delivery (up to 1 year)
Population: Eligible Mothers from the Base Trial P05787 (NCT00696800) who enrolled in the Follow Up Trial P05712. Infants from Follow Up Trial P05712 were not analyzed in this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mothers Corifollitropin Alfa 150 µg | Number of Mothers in Current Follow Up Trial Experiencing Adverse Events (AEs) | 222 Participants |
| Mothers recFSH 200 IU | Number of Mothers in Current Follow Up Trial Experiencing Adverse Events (AEs) | 214 Participants |
Primary
Number of Mothers in Current Follow Up Trial Experiencing Serious AEs (SAEs)
A SAE is any untoward medical occurrence that at any dose resulted in the following: death, was life threatening, required in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, or was a congenital anomaly/birth defect.
Time frame: Up to one day following delivery (up to 1 year)
Population: Eligible Mothers from the Base Trial P05787 (NCT00696800) who enrolled in the Follow Up Trial P05712. Infants from Follow Up Trial P05712 were not analyzed in this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mothers Corifollitropin Alfa 150 µg | Number of Mothers in Current Follow Up Trial Experiencing Serious AEs (SAEs) | 129 Participants |
| Mothers recFSH 200 IU | Number of Mothers in Current Follow Up Trial Experiencing Serious AEs (SAEs) | 117 Participants |
Primary
Percentage of Mothers From the Base Trial P05787 With at Least One Live Born Infant (Take-home Baby Rate) Relative to the Number of Participants From the Base Trial With Embryo Transfer.
The take-home baby rate is 100 X the number of participants with an ongoing pregnancy in Base Trial P05787 (NCT00696800), from the ITT group, with at least one live born infant relative to the number of participants from the Base Trial with embryo transfer.
Time frame: At least 10 weeks after embryo transfer in Base Trial P05787 up to birth in current Follow Up Trial (up to 1 year)
Population: Mothers from the ITT group of the Base Trial P05787 (NCT00696800) who had ET. Infants from Follow Up Trial P05712 were not analyzed in this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mothers Corifollitropin Alfa 150 µg | Percentage of Mothers From the Base Trial P05787 With at Least One Live Born Infant (Take-home Baby Rate) Relative to the Number of Participants From the Base Trial With Embryo Transfer. | 40.0 Percentage of Participants |
| Mothers recFSH 200 IU | Percentage of Mothers From the Base Trial P05787 With at Least One Live Born Infant (Take-home Baby Rate) Relative to the Number of Participants From the Base Trial With Embryo Transfer. | 36.6 Percentage of Participants |
Primary
Percentage of Mothers From the Base Trial P05787 With at Least One Live Born Infant (Take-home Baby Rate) Relative to the Number of Participants in the Base Trial.
The take-home baby rate is 100 X the number of participants with an ongoing pregnancy in Base Trial P05787 (NCT00696800), from the Intent-to-Treat (ITT) group, with at least one live born infant relative to the number of participants in the Base Trial.
Time frame: At least 10 weeks after embryo transfer in Base Trial P05787 up to birth in current follow up Trial (up to 1 year)
Population: Mothers from the ITT group of the Base Trial P05787 (NCT00696800). Infants from Follow Up Trial P05712 were not analyzed in this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mothers Corifollitropin Alfa 150 µg | Percentage of Mothers From the Base Trial P05787 With at Least One Live Born Infant (Take-home Baby Rate) Relative to the Number of Participants in the Base Trial. | 35.6 Percentage of Participants |
| Mothers recFSH 200 IU | Percentage of Mothers From the Base Trial P05787 With at Least One Live Born Infant (Take-home Baby Rate) Relative to the Number of Participants in the Base Trial. | 34.4 Percentage of Participants |