Pregnancy, Neonates
Conditions
Keywords
Neonatal outcome, Congenital malformations, In-Vitro fertilization, Controlled ovarian stimulation, Follow-up
Brief summary
The objective of this trial 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. In addition, a primary efficacy variable, live birth rate, was evaluated.
Detailed description
This is a follow-up protocol to prospectively monitor pregnancy, delivery, and neonatal outcomes of women who were treated with corifollitropin alfa and became pregnant after fresh embryo transfer during the base study P05714 (NCT00696878). For this trial, no study specific assessments are required, but information as obtained in standard practice will be used.
Interventions
BIOLOGICALCorifollitropin alfa
Subcutaneous (SC) administration of corifollitropin alfa at a dose of 150 μg in base study P05714 (NCT00696878). In this follow-up study P05715, no study medications were administered.
BIOLOGICALGnRH antagonist
SC administration of a GnRH antagonist at a dose of 0.25 mg/day in base study P05714 (NCT00696878). In this follow-up study P05715, no study medications were administered.
BIOLOGICAL(rec)hCG
SC administration of (rec)hCG at a dose of 5,000-10,000 IU/250 µg in base study P05714 (NCT00696878). In this follow-up study P05715, no study medications were administered.
BIOLOGICALFSH
SC administration of FSH at a dose not to exceed 225 IU/day in base study P05714 (NCT00696878). In this follow-up study P05715, no study medications were administered.
DRUGProgesterone
Vaginal administration of progesterone at a dose of at least 600 mg/day in base study P05714 (NCT00696878). In this follow-up study P05715, no study medications were administered.
Sponsors
Organon and Co
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 39 Years
Healthy volunteers
No
Inclusion criteria
* Participants who participated in base study P05714 (NCT00696878) and received at least one dose of corifollitropin alfa in base study P05714; * Ongoing pregnancy confirmed by ultrasound at least 10 weeks after a fresh embryo transfer in base study P05714; * Able and willing to give written informed consent.
Exclusion criteria
* None
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Women With Ongoing Pregnancy After a Corifollitropin Alfa COS Cycle in Base Study and ≥1 Live Born Infant During Follow-up (Live Birth Rate) | Up to approximately 32 months after first dose of corifollitropin alfa in base study P05714 (NCT00696878) | The live birth rate was defined as the number of participants who had an ongoing pregnancy after a corifollitropin alfa COS cycle in base study P05714 (NCT00696878) and who had at least one live born infant during follow-up, divided by the number of participants treated in the base study. For this analysis, it was assumed that any participants with ongoing pregnancy after a COS cycle in base study who did not enroll in follow-up study P05715 had no live born infants. |
| Number of Expectant Mothers Experiencing Adverse Events (AEs) | From approximately 10 weeks after fresh ET in base study P05714 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 fresh ET in base study P05714 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 Live Born 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 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 Live Born 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
Recruitment details
Of 272 participants with ongoing pregnancy at 10 weeks after fresh embryo transfer (ET) in base study P05714 (NCT00696878), 268 enrolled in this follow-up study P05715. A participant could enter follow-up study without meeting formal definition for Completion of base study.
Pre-assignment details
To complete base study P05714 (NCT00696878), a participant must have embryo transfer in the 3rd Controlled Ovarian Stimulation (COS) cycle (Treatment Cycle 3). For this follow-up trial P05715, study completion for participant (expectant mother) or live born infant was defined as completion of infant follow-up visit at 4-12 weeks after delivery.
Participants by arm
| Arm | Count |
|---|---|
| Expectant Mothers - Corifollitropin Alfa 150 µg In base study P05714 (NCT00696878), up to 3 COS cycles were performed, each including the following treatments: A single injection of 150 µg corifollitropin alfa was administered on Day 2 or 3 of the menstrual cycle (Stimulation Day 1). Administration of GnRH antagonist (0.25 mg/day) started on Stimulation Day 5 or 6 and continued through day of administration of (rec)hCG (5,000-10,000 IU/250 µg). Daily dosing with FSH (not to exceed 225 IU/day) began on Stimulation Day 8 and continued up to day of (rec)hCG administration. Progesterone was administered for luteal phase support. After COS cycles 1 and 2, Frozen-Thawed Embryo Transfer cycles (up to 3 after each COS cycle) could occur. Participants with confirmed pregnancy at least 10 weeks after fresh ET in the base study were eligible for this follow-up study. In this follow-up study P05715, no study drugs were administered. | 268 |
| Total | 268 |
Baseline characteristics
| Characteristic | Expectant Mothers - Corifollitropin Alfa 150 µg |
|---|---|
| Age, Continuous | 32.8 years STANDARD_DEVIATION 3.3 |
| Sex: Female, Male Female | 268 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 268 | 0 / 315 |
| serious Total, serious adverse events | 145 / 268 | 84 / 315 |
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 fresh ET in base study P05714 up to birth of infant (up to approximately 6 months)
Population: Follow-up safety analysis was performed on expectant mothers who received corifollitropin alfa in base study P05714 (NCT00696878) and who enrolled in the follow-up study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Women - Corifollitropin Alfa 150 µg | Number of Expectant Mothers Experiencing Adverse Events (AEs) | 203 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 fresh ET in base study P05714 up to birth of infant (up to approximately 6 months)
Population: Follow-up safety analysis was performed on expectant mothers who received corifollitropin alfa in base study P05714 (NCT00696878) and who enrolled in the follow-up study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Women - Corifollitropin Alfa 150 µg | Number of Expectant Mothers Experiencing Serious AEs (SAEs) | 145 participants |
Primary
Number of Live Born 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 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: 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 in base study P05714 (NCT00696878) and who enrolled in the follow-up study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Women - Corifollitropin Alfa 150 µg | Number of Live Born Infants Experiencing AEs | 99 participants |
Primary
Number of Live Born 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 in base study P05714 (NCT00696878) and who enrolled in the follow-up study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Women - Corifollitropin Alfa 150 µg | Number of Live Born Infants Experiencing SAEs | 79 participants |
Primary
Percentage of Women With Ongoing Pregnancy After a Corifollitropin Alfa COS Cycle in Base Study and ≥1 Live Born Infant During Follow-up (Live Birth Rate)
The live birth rate was defined as the number of participants who had an ongoing pregnancy after a corifollitropin alfa COS cycle in base study P05714 (NCT00696878) and who had at least one live born infant during follow-up, divided by the number of participants treated in the base study. For this analysis, it was assumed that any participants with ongoing pregnancy after a COS cycle in base study who did not enroll in follow-up study P05715 had no live born infants.
Time frame: Up to approximately 32 months after first dose of corifollitropin alfa in base study P05714 (NCT00696878)
Population: Participants administered corifollitropin alfa in base study P05714 (NCT00696878)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Women - Corifollitropin Alfa 150 µg | Percentage of Women With Ongoing Pregnancy After a Corifollitropin Alfa COS Cycle in Base Study and ≥1 Live Born Infant During Follow-up (Live Birth Rate) | 37.8 percentage of participants |