Pregnancy and Neonatal Follow-up of Ongoing Pregnancies Established in Clinical Trial P05787 (P05712)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Pregnancy and Neonatal Follow-up of Ongoing Pregnancies Established After Controlled Ovarian Stimulation in Clinical Trial 38819 for Org 36286 (Corifollitropin Alfa)

Conditions
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Pregnancy, Neonates

Intervention / Treatment
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* Drug: Corifollitropin Alfa 150 μg
* Biological: 200 IU RecFSH/Follitropin beta (Days 1 to 7)
* Drug: Placebo for Corifollitropin Alfa
* Drug: Placebo for RecFSH/Follitropin beta
* Biological: 200 IU RecFSH/Follitropin beta (Days 8 to hCG)
* Drug: Ganirelix
* Biological: hCG
* Biological: Progesterone


Participation Criteria
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Eligibility Criteria
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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

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 |
| --- | --- |
| Mothers Corifollitropin Alfa 150 µg<br>Participants from the Base Trial P05787 who received a single subcutaneous (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-recombinant Follicle Stimulating Hormone (recFSH); followed by daily SC injections with 200 IU recFSH up to the day of human chorionogonadotropin (hCG); multiple daily SC injections of Ganirelix from Stimulation Day 5 to the day of hCG; a single dose of hCG (5000 or 10,000 IU/USP) was administered when 3 follicles >= 17 mm were observed; and on the day of oocyte pick up (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. | Drug: Corifollitropin Alfa 150 μg<br>* 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.<br>Drug: Placebo for RecFSH/Follitropin beta<br>* 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.<br>Biological: 200 IU RecFSH/Follitropin beta (Days 8 to hCG)<br>* 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.<br>Drug: Ganirelix<br>* 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.<br>Biological: hCG<br>* 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<br>Biological: Progesterone<br>* 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.<br>|
| Mothers recFSH 200 IU<br>Participants from the Base Trial P05787 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; a single dose of hCG (5000 or 10,000 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. | Biological: 200 IU RecFSH/Follitropin beta (Days 1 to 7)<br>* 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.<br>* Other names: Follistim®;Drug: Placebo for Corifollitropin Alfa<br>* 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.<br>Biological: 200 IU RecFSH/Follitropin beta (Days 8 to hCG)<br>* 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.<br>Drug: Ganirelix<br>* 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.<br>Biological: hCG<br>* 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<br>Biological: Progesterone<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to one day following delivery (up to 1 year) | 
| 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. | Up to one day following delivery (up to 1 year) | 
| 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. | Up to 12 weeks following delivery (up to 1 year) | 
| 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. | Up to 12 weeks following delivery (up to 1 year) | 
| 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. | At least 10 weeks after embryo transfer in Base Trial P05787 up to birth in current follow up Trial (up to 1 year) | 
| 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. | At least 10 weeks after embryo transfer in Base Trial P05787 up to birth in current Follow Up Trial (up to 1 year) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neonatal outcome, Congenital malformations, In-Vitro fertilization, Controlled ovarian stimulation, Follow-up