Follow-up Protocol on the Outcome of Frozen-thawed Embryo Transfer Cycles From Clinical Trial P05690 (P05711)

Study Overview
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Brief Summary
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Clinical trial objective is to collect the outcome of Frozen-Thawed Embryo Transfer (FTET) cycles performed after the embryos are cryopreserved in the base study P05690 in order to estimate the cumulative pregnancy rate for each treatment group.

Detailed Description
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This is a follow-up protocol to collect the outcome of FTET cycles, performed after the embryos are cryopreserved in base study P05690 (NCT00702845), to enable estimation of the cumulative pregnancy rate for each treatment group.

Official Title
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Follow-up Protocol to Collect the Outcome of Frozen-thawed Embryo Transfer Cycles After Cryopreservation of Embryos in Clinical Trial 107012

Conditions
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In Vitro Fertilization

Intervention / Treatment
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* Drug: corifollitropin alfa
* Biological: recFSH (follitropin alfa)
* Drug: gonadatropin releasing hormone (GnRH) antagonist ganirelix
* Drug: human chorion gonadatropin (hCG)
* Biological: progesterone
* Drug: placebo-recFSH (follitropin alfa)
* Drug: placebo-corifollitropin alfa
* Biological: open-label recFSH


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants from whom embryos have been cryopreserved in base study P05690, of which at least one embryo is thawed for use in a subsequent FTET cycle; Able and willing to give written informed consent. Exclusion Criteria: None

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 36 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Corifollitropin alfa 100 μg<br>In follow-up study, no medication or investigational product was administered. But in base study P05690 (NCT00702845), participants received single subcutaneous (SC) injection of corifollitropin alfa 100 μg (Org 36286) on Day 2 or 3 of the menstrual cycle and daily placebo-recombinant Follicle Stimulating Hormone (recFSH) injections (7 total) from Stimulation Day 1 up to and including Stimulation Day 7. Participants in base study P05690 also received open-label recFSH (up to 200 IU/day) from Stimulation Day 8 onwards, up to and including Day of Human Chorion Gonadotropin (hCG) administration. Participants also received Gonadotropin Releasing Hormone (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 day of oocyte pick-up (OPU) and continuing for at least 6 weeks or up to menses. | Drug: corifollitropin alfa<br>* Single injection of 100 μg corifollitropin alfa administered under protocol P05690<br>* Other names: Org 36286;Drug: gonadatropin releasing hormone (GnRH) antagonist ganirelix<br>* GnRH antagonist ganirelix administered SC at a dose of 0.25 mg/day under protocol P05690<br>Drug: human chorion gonadatropin (hCG)<br>* hCG 5,000 IU or 10,000 IU administered SC under protocol P05690<br>Biological: progesterone<br>* 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.<br>Drug: placebo-recFSH (follitropin alfa)<br>* Placebo-recFSH at the equivalent volume of 150 IU/day administered under protocol P05690<br>Biological: open-label recFSH<br>* Open-label recFSH up to a maximum dose of 200 IU/day, administered under protocol P0590<br>|
| recFSH 150 IU<br>In this follow-up study, no medication or investigational product was administered. However, in base study P05690 (NCT00702845), participants in the reference group 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 (10,000 or 5,000 IU/USP) 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. 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. | Biological: recFSH (follitropin alfa)<br>* Daily recFSH administered under protocol P05690<br>* Other names: Puregon®/Follistim®;Drug: gonadatropin releasing hormone (GnRH) antagonist ganirelix<br>* GnRH antagonist ganirelix administered SC at a dose of 0.25 mg/day under protocol P05690<br>Drug: human chorion gonadatropin (hCG)<br>* hCG 5,000 IU or 10,000 IU administered SC under protocol P05690<br>Biological: progesterone<br>* 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.<br>Drug: placebo-corifollitropin alfa<br>* Single SC injection of placebo-corifollitropin alfa on Day 2 or 3 of the menstrual cycle, administered under protocol P05690<br>Biological: open-label recFSH<br>* Open-label recFSH up to a maximum dose of 200 IU/day, administered under protocol P0590<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Ongoing Pregnancy (Cumulative Ongoing Pregnancy Rate) | Cumulative ongoing pregnancy rate was defined as 100 times the number of participants with an ongoing pregnancy either immediately after embryo transfer in base study P05690 (NCT00702845) or after one or more FTET cycles in follow up study P05711 following cryopreservation, divided by the total number of subjects that started treatment in base study P05690. | Up to 1 year after embryo transfer in base trial P05690 (NCT00702845), and FTET cycles in follow up study P05711 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants in Follow up Study With a Miscarriage Per Clinical Pregnancy | Miscarriages were calculated per clinical pregnancy, defined as the presence of at least one gestational sac as assessed by USS or Doppler, or confirmed by live birth. | After one or more FTET cycles, assessed at least 10 weeks after embryo transfer (up to 1 year) | 
| Percentage of Participants in Follow up Study With a Miscarriage Per Vital Pregnancy | Miscarriages were calculated per vital pregnancy, defined as the presence of at least one fetus with heart activity as assessed by USS or Doppler, or confirmed by live birth. | After one or more FTET cycles, assessed at least 10 weeks after embryo transfer (up to 1 year) | 
| Percentage of Participants in Follow up Study With an Ecotopic Pregnancy | An ectopic pregnancy is where the embryo implants outside the uterus. Ectopic pregnancies were calculated per total number of participants started in FTET. | After one or more FTET cycles, assessed at least 10 weeks after embryo transfer (up to 1 year) | 
| Percentage of Participants in Follow up Study 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. | After one or more FTET cycles, assessed at least 10 weeks after embryo transfer (up to 1 year) | 
| Percentage of Participants in Follow up Study 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. | After one or more FTET cycles, assessed at least 10 weeks after embryo transfer (up to 1 year) | 
| Percentage of Participants 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. | After one or more FTET, assessed at least 10 weeks after embryo transfer or at live birth (up to 1 year) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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In-vitro fertilization, Controlled Ovarian Stimulation, Cumulative pregnancy data, Follow-up