In Vitro Fertilization
Conditions
Keywords
In-vitro fertilization, Controlled Ovarian Stimulation, Cumulative pregnancy data, Follow-up
Brief summary
To collect the outcome of frozen-thawed embryo transfer cycles after the embryos are cryopreserved up to at least 1 year in Trial P05787 (NCT00696800), in order to estimate the cumulative pregnancy rate for each treatment group.
Detailed description
This is a follow-up protocol to collect the outcome of frozen-thawed embryo transfer cycles, performed after the embryos are cryopreserved up to at least 1 year in Trial P05787 (NCT00696800), to enable estimation of the cumulative pregnancy rate for each treatment group.
Interventions
DRUG150 µg Corifollitropin Alfa
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.
Daily SC injections with 200 IU fixed dose recFSH were started on Stimulation Day 1 and continued up to and including Stimulation Day 7.
Pre-filled syringe containing an identical solution when compared to Corifollitropin Alfa. On the morning of day 2 or 3 of the menstrual cycle (Stimulation Day 1), a single SC injection was administered in the abdominal wall.
Identical ready-for-use solution, but without the active ingredient, supplied in cartridges for SC injection with the Follistim Pen. Daily SC injections were started on Stimulation Day 1 and continued up to and including Stimulation Day 7.
From Stimulation Day 8 onwards a daily SC dose of 200 IU recFSH was administered up to and including the Day of hCG.
DRUGGanirelix
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
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
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 from whom embryos have been cryopreserved in Base Trial P05787 (NCT00696800), of which at least one embryo is thawed for use in a subsequent FTET cycle; * Able and willing to give informed consent.
Exclusion criteria
* None
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an Ongoing Pregnancy (Cumulative Ongoing Pregnancy Rate) | Up to 1 year after embryo transfer in base trial P05787 (NCT00696800), and FTET cycles in follow up trial | An ongoing pregnancy is the presence of at least one fetus with heart activity at least 10 weeks after embryo transfer or confirmed by live birth.The cumulative ongoing pregnancy rate is 100 times the number of participants with an ongoing pregnancy either immediately after embryo transfer in base Trial P05787 (NCT00696800), or after one or more FTET cycles in follow-up Trial P05716 following cryopreservation, divided by the total number of participants that started treatment in base Trial P05787 (NCT00696800). Participants who did not have cryopreserved embryos, or embryo transfers in the FTET cycle(s), were considered 'not pregnant'. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in Follow up Trial With a Miscarriage Per Vital Pregnancy | After one or more FTET cycles, up to day of miscarriage (up to 1 year) | Miscarriages were calculated per vital pregnancy, meaning the presence of at least one fetus with heart activity. |
| Percentage of Participants in Follow up Trial With an Ectopic Pregnancy | After one or more FTET cycles, assessed at least 10 weeks after embryo transfer (up to 1 year) | An ectopic pregnancy is where the embryo implants outside the uterus. Ectopic pregnancies were calculated per total number of participants started in FTET. |
| Percentage of Participants in Follow up Trial With a Miscarriage Per Clinical Pregnancy | After one or more FTET cycles, up to day of miscarriage (up to 1 year) | Miscarriages were calculated per clinical pregnancy, meaning the presence of at least one gestational sac or confirmed by live birth. |
| Percentage of Participants in Follow up Trial With a Vital Pregnancy | After one or more FTET cycles, assessed at least 10 weeks after embryo transfer (up to 1 year) | A vital pregnancy is the presence of at least one fetus with heart activity. Vital pregnancies were calculated per attempt, meaning if any stage of IVF treatment was not achieved, zero values were imputed. |
| Percentage of Participants in Follow up Trial With an Ongoing Pregnancy | After one or more FTET, assessed at least 10 weeks after embryo transfer or at live birth (up to 1 year) | An ongoing pregnancy is the presence of at least one fetus with heart activity at least 10 weeks after embryo transfer or confirmed at live birth. Ongoing pregnancies were calculated per attempt, meaning if any stage of IVF treatment was not achieved, zero values were imputed. |
| Percentage of Participants in Follow up Trial With a Clinical Pregnancy | After one or more FTET cycles, assessed at least 10 weeks after embryo transfer (up to 1 year) | A clinical pregnancy is the presence of at least gestational sac or confirmed by live birth. Clinical pregnancies were calculated per attempt, meaning if any stage of in vitro fertilization (IVF) treatment was not achieved, zero values were imputed. |
Participant flow
Pre-assignment details
Period one consists of participants from the base study P05787 (NCT00696800), randomized to treatment groups Corifollitropin Alfa (Cori Alfa) (Org 36286) or recombinant Follicle Stimulating Hormone (recFSH). Period two consists of eligible participants (N = 344) from the base study who enrolled in the follow up study P05716.
Participants by arm
| Arm | Count |
|---|---|
| 150 µg Corifollitropin Alfa Participants from the base study P05787 (NCT00696800), received a single subcutaneous (SC) injection of 150 µg Corifollitropin Alfa on menstrual cycle Day 2/3 (Day 1); 7 daily SC injections from Days 1 to 7 with placebo-recFSH); followed by daily SC injections with 200 IU recFSH up to the day of human chorionogonadotropin (hCG). Daily SC injections of Ganirelix were given from Day 5 to the day of hCG; at which time a single dose of hCG was given when 3 follicles \>= 17 mm. On the day of oocyte pick up (OPU) daily doses of progesterone were started, for up to 6 weeks or menses. Eligible participants from the base study were enrolled in follow up study P05716, where no study treatments were given, and embryos obtained in the base study underwent FTET cycles. | 168 |
| 200 IU RecFSH Participants from the base study P05787 (NCT00696800), received a single SC injection of placebo Corifollitropin Alfa on menstrual cycle day 2/3 (Day 1); 7 daily SC injections with 200 IU recFSH from 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 were given from Day 5 to the day of hCG; at which time a single dose of hCG was given when 3 follicles \>= 17 mm. 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 study were enrolled in follow up study P05716, where no study treatments were given, and embryos obtained in the base study underwent FTET cycles. | 176 |
| Total | 344 |
Baseline characteristics
| Characteristic | 150 µg Corifollitropin Alfa | 200 IU RecFSH | Total |
|---|---|---|---|
| Age, Continuous | 31.1 Years STANDARD_DEVIATION 3.8 | 31.3 Years STANDARD_DEVIATION 3 | 31.2 Years STANDARD_DEVIATION 3.4 |
| Sex: Female, Male Female | 168 Participants | 176 Participants | 344 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 | 0 / 168 | 0 / 176 |
| serious Total, serious adverse events | 1 / 168 | 0 / 176 |
Outcome results
Primary
Percentage of Participants With an Ongoing Pregnancy (Cumulative Ongoing Pregnancy Rate)
An ongoing pregnancy is the presence of at least one fetus with heart activity at least 10 weeks after embryo transfer or confirmed by live birth.The cumulative ongoing pregnancy rate is 100 times the number of participants with an ongoing pregnancy either immediately after embryo transfer in base Trial P05787 (NCT00696800), or after one or more FTET cycles in follow-up Trial P05716 following cryopreservation, divided by the total number of participants that started treatment in base Trial P05787 (NCT00696800). Participants who did not have cryopreserved embryos, or embryo transfers in the FTET cycle(s), were considered 'not pregnant'.
Time frame: Up to 1 year after embryo transfer in base trial P05787 (NCT00696800), and FTET cycles in follow up trial
Population: ITT group from base trial P05787, consisting of randomized participants who were treated with Corifollitropin Alfa or recFSH.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 150 µg Corifollitropin Alfa | Percentage of Participants With an Ongoing Pregnancy (Cumulative Ongoing Pregnancy Rate) | 47.2 Percentage of participants |
| 200 IU RecFSH | Percentage of Participants With an Ongoing Pregnancy (Cumulative Ongoing Pregnancy Rate) | 44.9 Percentage of participants |
Comparison: Treatment groups were compared with a generalized linear model including covariates treatment group, age class and region.95% CI: [-2.6, 7.4]
Secondary
Percentage of Participants in Follow up Trial With a Clinical Pregnancy
A clinical pregnancy is the presence of at least gestational sac or confirmed by live birth. Clinical pregnancies were calculated per attempt, meaning if any stage of in vitro fertilization (IVF) treatment was not achieved, zero values were imputed.
Time frame: After one or more FTET cycles, assessed at least 10 weeks after embryo transfer (up to 1 year)
Population: Participants enrolled in P05716 Follow Up study, that had an embryo transfer in the respective cycle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 150 µg Corifollitropin Alfa | Percentage of Participants in Follow up Trial With a Clinical Pregnancy | 43.5 Percentage of participants |
| 200 IU RecFSH | Percentage of Participants in Follow up Trial With a Clinical Pregnancy | 38.6 Percentage of participants |
Secondary
Percentage of Participants in Follow up Trial With a Miscarriage Per Clinical Pregnancy
Miscarriages were calculated per clinical pregnancy, meaning the presence of at least one gestational sac or confirmed by live birth.
Time frame: After one or more FTET cycles, up to day of miscarriage (up to 1 year)
Population: Participants enrolled in P05716 Follow Up study that had a clinical pregnancy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 150 µg Corifollitropin Alfa | Percentage of Participants in Follow up Trial With a Miscarriage Per Clinical Pregnancy | 8.2 Percentage of participants |
| 200 IU RecFSH | Percentage of Participants in Follow up Trial With a Miscarriage Per Clinical Pregnancy | 17.6 Percentage of participants |
Secondary
Percentage of Participants in Follow up Trial With a Miscarriage Per Vital Pregnancy
Miscarriages were calculated per vital pregnancy, meaning the presence of at least one fetus with heart activity.
Time frame: After one or more FTET cycles, up to day of miscarriage (up to 1 year)
Population: Participants enrolled in P05716 Follow Up study that had a vital pregnancy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 150 µg Corifollitropin Alfa | Percentage of Participants in Follow up Trial With a Miscarriage Per Vital Pregnancy | 0 Percentage of participants |
| 200 IU RecFSH | Percentage of Participants in Follow up Trial With a Miscarriage Per Vital Pregnancy | 0 Percentage of participants |
Secondary
Percentage of Participants in Follow up Trial With an Ectopic Pregnancy
An ectopic pregnancy is where the embryo implants outside the uterus. Ectopic pregnancies were calculated per total number of participants started in FTET.
Time frame: After one or more FTET cycles, assessed at least 10 weeks after embryo transfer (up to 1 year)
Population: Participants enrolled in P05716 Follow Up study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 150 µg Corifollitropin Alfa | Percentage of Participants in Follow up Trial With an Ectopic Pregnancy | 1.2 Percentage of participants |
| 200 IU RecFSH | Percentage of Participants in Follow up Trial With an Ectopic Pregnancy | 0.6 Percentage of participants |
Secondary
Percentage of Participants in Follow up Trial With an Ongoing Pregnancy
An ongoing pregnancy is the presence of at least one fetus with heart activity at least 10 weeks after embryo transfer or confirmed at live birth. Ongoing pregnancies were calculated per attempt, meaning if any stage of IVF treatment was not achieved, zero values were imputed.
Time frame: After one or more FTET, assessed at least 10 weeks after embryo transfer or at live birth (up to 1 year)
Population: Participants enrolled in P05716 Follow Up study, that had an embryo transfer in the respective cycle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 150 µg Corifollitropin Alfa | Percentage of Participants in Follow up Trial With an Ongoing Pregnancy | 38.7 Percentage of participants |
| 200 IU RecFSH | Percentage of Participants in Follow up Trial With an Ongoing Pregnancy | 30.7 Percentage of participants |
Secondary
Percentage of Participants in Follow up Trial With a Vital Pregnancy
A vital pregnancy is the presence of at least one fetus with heart activity. Vital pregnancies were calculated per attempt, meaning if any stage of IVF treatment was not achieved, zero values were imputed.
Time frame: After one or more FTET cycles, assessed at least 10 weeks after embryo transfer (up to 1 year)
Population: Participants enrolled in P05716 Follow Up study, that had an embryo transfer in the respective cycle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 150 µg Corifollitropin Alfa | Percentage of Participants in Follow up Trial With a Vital Pregnancy | 39.9 Percentage of participants |
| 200 IU RecFSH | Percentage of Participants in Follow up Trial With a Vital Pregnancy | 31.8 Percentage of participants |