Effect of Recombinant Follicular Stimulating Hormone (FSH) Dosing Following Cori-follitropin Alfa

NCT ID: NCT03686852

Last Updated: 2019-03-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

261 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-05-01

Study Completion Date

2020-05-01

Brief Summary

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In the trial, women planned to be treated with 150μg corifollitropin alfa followed by rFSH in a fixed GnRH antagonist protocol will be asked to participate and sign the ICF. Corifollitropin alpha treatment will be initiated at D2-D3 of the cycle. Patients who need additional r-FSH following corifollitropin-alfa will be randomized on day 8 of the stimulation into 3 study groups. In group A, B and C, ovarian stimulation with Corifollitropin alfa (Elonva®, MSD) will be used for ovarian stimulation, followed by 50IU (Group A), 150IU (Group B) or 250IU (Group C) of recFSH (Puregon®, MSD).

Detailed Description

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On day 2 or on day 3 of the cycle, blood sampling for estradiol (E2), progesterone (P), follicle stimulating hormone (FSH), luteinising hormone (LH) and human chorionic gonadotropin (hCG) levels, will be per-formed prior to the administration of corifollitropin alfa.

All the blood samples taken during the stimulation for the hormonal profile, starting from day 2, will be performed in a double tube, one for a central assessment and one for the local assessment in order to be used during the monitoring of the cycle. AMH will also be assess on day 2 of the stimulation with a blood sample that will be sent for central assessment.

Administration of the GnRH antagonist ganirelix (Orgalutran®, MSD) will be initiated on day 6 of stimula-tion in all treatment arms at a daily dose of 0.25 mg to prevent a premature LH surge. Suppression with the GnRH antagonist will be continued until the day of final oocyte maturation. Endocrine monitoring and ultrasound scan will be carried out on day 8 of stimulation and repeated every two days until trigger, de-pending on the patients' response. Triggering for final oocyte maturation is performed as soon as 3 follicles of ≥17 mm will be observed.

Cycles will be cancelled if less than 3 follicles of 12 mm are observed on day 8 day of stimulation, nonethe-less, blood test for hormonal evaluation will be performed in any case on day 8.

Oocyte maturation will be triggered with a single subcutaneous injection of hCG (Pregnyl®: 5000UI/sc, MSD, or 10000UI/sc if body weight exceeds 80 kg) as soon as 3 follicles of ≥17 mm will be observed. Ap-proximately 34-36 hours after trigger, oocyte retrieval will be performed. An embryo transfer will be per-formed on day 3 or on day 5 of embryonic development; one or 2 embryos will be replaced.

The luteal phase will be supported by vaginal administration of micronized progesterone 600 mg/day (Utrogestan®) from the day after ovarian puncture until the day of pregnancy test. In case of pregnancy, progesterone administration will be extended until week 7. In case of risk of OHSS, namely the presence of \>18 follicles of 11 mm or more, final oocyte maturation will be triggered with a GnRH agonist (Gonapep-tyl, 0.2 mg) and a freeze-all strategy will be applied (Papanikolaou et al., 2006, Griesinger et al., 2016). A freeze -all strategy will also be applied in case of P\>1.5 ng/mL on the day of hCG and per clinician prefer-ence.

All the patients will be asked to inject CFA and rFSH between 6-10 PM; the antagonist injection (ganirelix) will be performed between 7-11 AM and the endocrine profile measurements, alias blood tests, will be done between 7 and 11 AM.

Conditions

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Infertility

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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group A

The main difference between the groups is due to the different dose of r-FSH which will be given to pa-tients after the 7 days of CFA; namely that patients who need additional r-FSH following corifollitropin-alfa will be randomized on day 8 of the stimulation into 3 study groups. In group A, B and C, ovarian stimula-tion with Corifollitropin alfa (Elonva®, MSD) will be used for ovarian stimulation, followed by 50IU (Group A).

Group Type ACTIVE_COMPARATOR

same medications but different dosages

Intervention Type OTHER

The main difference between the groups is due to the different dose of r-FSH which will be given to pa-tients after the 7 days of CFA; namely that patients who need additional r-FSH following corifollitropin-alfa will be randomized on day 8 of the stimulation into 3 study groups. In group A, B and C, ovarian stimula-tion with Corifollitropin alfa (Elonva®, MSD) will be used for ovarian stimulation, followed by 50IU (Group A), 150IU (Group B) or 250IU (Group C) of recFSH (Puregon®, MSD)

groppo B

The main difference between the groups is due to the different dose of r-FSH which will be given to pa-tients after the 7 days of CFA; namely that patients who need additional r-FSH following corifollitropin-alfa will be randomized on day 8 of the stimulation into 3 study groups. In group A, B and C, ovarian stimula-tion with Corifollitropin alfa (Elonva®, MSD) will be used for ovarian stimulation, followed by 150IU (Group B)

Group Type ACTIVE_COMPARATOR

same medications but different dosages

Intervention Type OTHER

The main difference between the groups is due to the different dose of r-FSH which will be given to pa-tients after the 7 days of CFA; namely that patients who need additional r-FSH following corifollitropin-alfa will be randomized on day 8 of the stimulation into 3 study groups. In group A, B and C, ovarian stimula-tion with Corifollitropin alfa (Elonva®, MSD) will be used for ovarian stimulation, followed by 50IU (Group A), 150IU (Group B) or 250IU (Group C) of recFSH (Puregon®, MSD)

Group C

The main difference between the groups is due to the different dose of r-FSH which will be given to pa-tients after the 7 days of CFA; namely that patients who need additional r-FSH following corifollitropin-alfa will be randomized on day 8 of the stimulation into 3 study groups. In group A, B and C, ovarian stimula-tion with Corifollitropin alfa (Elonva®, MSD) will be used for ovarian stimulation, followed by 250IU (Group C) of recFSH (Puregon®, MSD).

Group Type ACTIVE_COMPARATOR

same medications but different dosages

Intervention Type OTHER

The main difference between the groups is due to the different dose of r-FSH which will be given to pa-tients after the 7 days of CFA; namely that patients who need additional r-FSH following corifollitropin-alfa will be randomized on day 8 of the stimulation into 3 study groups. In group A, B and C, ovarian stimula-tion with Corifollitropin alfa (Elonva®, MSD) will be used for ovarian stimulation, followed by 50IU (Group A), 150IU (Group B) or 250IU (Group C) of recFSH (Puregon®, MSD)

Interventions

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same medications but different dosages

The main difference between the groups is due to the different dose of r-FSH which will be given to pa-tients after the 7 days of CFA; namely that patients who need additional r-FSH following corifollitropin-alfa will be randomized on day 8 of the stimulation into 3 study groups. In group A, B and C, ovarian stimula-tion with Corifollitropin alfa (Elonva®, MSD) will be used for ovarian stimulation, followed by 50IU (Group A), 150IU (Group B) or 250IU (Group C) of recFSH (Puregon®, MSD)

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Female age: \> 18 to \< 38 years
* The patient must have undergone not more than three consecutive unsuccessful IVF/ICSI cycles since the last ongoing pregnancy (whether fresh and/or several frozen ET resulted from these attempts)
* BMI ≤29 Kg /m2
* Patients of ≤ 35 years old, body weight should be ≥ 60kg
* Patients of \>35 years old, body weight should be \> 50 kg
* Regular normo-ovulatory menstrual cycles (26-35 days)
* Basal FSH \<10 IU/l, basal E2 \<60 pg/ml and basal Progesteone (\< 1.5 ng/mL) (normal cycle day-3 basal serum hormone levels), to be measured on cycle day 2 or 3 of the treatment cycle
* Normal ultrasound scan (presence of both ovaries without evidence of abnormality within 6 months)
* AFC \>7 and \< 20
* No pill within the 3 months before treatment
* Signed informed consent

Exclusion Criteria

* Polycystic ovarian syndrome (PCOS) according to the Rotterdam classification (2004)
* Oocyte donors
* Poor responder patients (development of \<4 follicles in previous IVF/ICSI or cancelled cycles)
* Endometriosis ≥ grade 3
* Contraindications to the use of gonadotropins
* Abnormal vaginal bleeding of unknown cause
* History of ovarian hyperstimulation syndrome (OHSS) or a previous ovarian stimulation cycle with more than 30 follicles of 11 mm or higher (as recommended by the Elonva® Summary of Product Characteristics)
* A history of recurrent miscarriage (three or more consecutive miscarriages)
Minimum Eligible Age

18 Years

Maximum Eligible Age

38 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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AZ Jan Palfijn Gent

OTHER

Sponsor Role collaborator

Erasme University Hospital

OTHER

Sponsor Role collaborator

Universitair Ziekenhuis Brussel

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Other Identifiers

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rFSHdosingfinding.2018

Identifier Type: -

Identifier Source: org_study_id