Controlled Ovarian StimulationNCT03697031
Impact of Blastocyst Morphological Development and Blastocoele Re-expansion on Pregnancy Outcome After Using REKOVELLE®
An observational study of Controlled Ovarian Stimulation, run by Ferring Pharmaceuticals at 1 site in Denmark.
Trial summary
The purpose of this observational study is to examine the development and appearance of embryos before and after freezing following a single controlled ovarian stimulation cycle using REKOVELLE® (follitropin delta) as the recombinant follicular stimulating hormone (rFSH) for controlled ovarian stimulation. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Controlled Ovarian Stimulation
- What is being tested?
- Follitropin Delta
- Type of treatment
- Injection or infusion
- How many people
- 362 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Sep 2018to 31 Dec 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Study population: The study aims to enroll between 1200 and 1500 cycles which is estimated to be sufficient for observing 616 single frozen-thawed blastocyst transfers. Patients can contribute data from one or more frozen-thawed blastocyst transfers. Further, the patient cohort will be recruited among the patient population of 8-10 public and private in vitro fertilization (IVF) clinics in Denmark.
Who may be able to join
- Patients undergoing elective single embryo transfer (e-SET) in a frozen embryo replacement (FER) treatment where the frozen blastocyst was obtained from an IVF or intracytoplasmic sperm injection (ICSI) cycle following controlled ovarian stimulation with REKOVELLE® .
- Women are prescribed REKOVELLE® for their IVF or ICSI according to the approved label.
- Morphological measurements and clinical outcomes are available for the fresh embryos obtained from the IVF or ICSI cycle.
- Willing and able to understand Danish or English patient information.
- Willingness and ability to provide written informed consent.
Who cannot join
- Patients with any contraindication for treatment with REKOVELLE® for controlled ovarian stimulation.
- Patients with contraindication for undergoing assisted reproductive technologies (ART) such as an IVF or ICSI cycle.
- Oocyte donors.
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Ciconia, VivaNeo (there may be other sites in this country)
Højbjerg
About this study
Official title: The Impact of Frozen - Thawed Blastocyst Morphological Development and Blastocoele Re-expansion on Clinical Pregnancy Outcome After One Controlled Ovarian Stimulation Cycle Using REKOVELLE®
The purpose of this observational study is to examine the development and appearance of embryos before and after freezing following a single controlled ovarian stimulation cycle using REKOVELLE® (follitropin delta) as the recombinant follicular stimulating hormone (rFSH) for controlled ovarian stimulation. The primary objective of the study is to examine how specific factors of embryo development or appearance are related to the chance of becoming pregnant.
The ovarian stimulation protocol with REKOVELLE®, a new rFSH prescribed for ovarian stimulation, is individualised with a dosing regimen that is based on two parameters: the body weight and the level of a hormone, the anti-Müllerian hormone, (AMH), a parameter used to predict how the ovaries will respond to the ovarian stimulation.
- Conditions
- Controlled Ovarian Stimulation
- Being tested
- Follitropin Delta
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Follitropin DeltaDrug
The Intervention (solution for injection) is delivered with an injection pen. For women with AMH <15 pmol/L the daily dose is 12 micrograms, irrespective of body weight. For women with AMH ≥15 pmol/L the daily dose decreases from 0.19 to 0.10 micrograms/kg by increasing AMH concentration. The maximum daily dose for the first treatment cycle is 12 micrograms.
For subsequent treatment cycles, the daily dose of REKOVELLE® should be maintained or modified according to the patient's ovarian response in the previous cycle. Based on the ovarian hypo/hyper-response in the previous cycle, the daily dose in the subsequent cycle should be increased (by 25% or 50%) or decreased (by 20% or 33%). The maximum daily dose is 24 micrograms.
| Study group | Role | What they receive |
|---|---|---|
| REKOVELLE® | Follitropin Delta Receives: Drug: Follitropin Delta |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical pregnancy rate
Clinical pregnancy is defined as at least one intrauterine gestational sac with fetal heart beat at week 7, from frozen thawed blastocysts. The correlation between morphological parameters (blastocyst score, timelapse score, blastocoele re-expansion) and clinical pregnancy rate will be assessed.
Measured: 7 weeks after each embryo transfer
Secondary outcomes (8)
Cumulative clinical pregnancy rate
The cumulative clinical pregnancy rate will be calculated based on all participants included in the study and all clinical pregnancies recorded from fresh and frozen-thawed blastocyst transfers as the fraction of participants with at least one positive clinical pregnancy. The cumulative pregnancy rate will be plotted versus transfer number and versus time from start of REKOVELLE® treatment.
Measured: Up to 24 months
Positive βhCG result (blood or urinary pregnancy test)
Measured: Up to 24 months
Use of the algorithm-based individualized dosing regimen with REKOVELLE®
Use of the Ferring developed dosing app for the daily dose calculation. The daily dose is calculated with body weight in kilograms or pounds and AMH serum level in pmoL/L or ng/ml to define the daily dose of REKOVELLE® in micrograms.
Measured: At the day of the consultation visit where the daily dose of REKOVELLE® is decided
Daily dose of REKOVELLE® administered
Daily dose of REKOVELLE® in micrograms is recorded.
Measured: From day 1 up to day 20 of REKOVELLE® stimulation
Number of days of treatment with REKOVELLE®
Measured: From day 1 up to day 20 of REKOVELLE® stimulation
Day of REKOVELLE® stimulation start
The time point of the start of the stimulation is decided at the discretion of the investigator.
Measured: At the day of the first REKOVELLE® injection during the ovarian stimulation treatment
Day of REKOVELLE® stimulation end
The time point of the end of the stimulation is decided at the discretion of the investigator.
Measured: At the day of the last REKOVELLE® injection during the ovarian stimulation treatment
Any deviation in REKOVELLE® administration
REKOVELLE® should be used according to the approved label, any possible deviations such as different starting dose or dose adjustment during stimulation will be recorded and analyzed.
Measured: From day 1 up to day 20 of REKOVELLE® stimulation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2018
- Study start1 Sep 2018
- Primary completion31 Dec 2020
- Study completion31 Dec 2020
Why it stopped: Permanently terminated due to halt of recruitment due to COVID-19 pandemic
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Controlled Ovarian StimulationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 362 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ferring Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Global Clinical Compliance, Study director, Ferring Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03697031
- Sponsor's protocol ID
- 000317
- Status last verified
- Oct 2021
- First submitted
- 14 Sep 2018
- Last updated
- 12 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Gabrielsen A, Iversen LH, Fedder J, Eskildsen TV, Englund AL, Hansen SR, Pinton P. Pre-Vitrification and Post-Warming Variables of Vitrified-Warmed Blastocysts That Are Predictable for Implantation. J Clin Med. 2023 Oct 6;12(19):6389. doi: 10.3390/jcm12196389.
PubMed 37835035
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Frozen - Thawed Blastocyst Morphological Development and Blastocoele Re-expansion on Clinical Pregnancy Outcome After One Controlled Ovarian Stimulation Cycle Using REKOVELLE®
- ClinicalTrials.gov ID
- NCT03697031
- Acronym / sponsor ID
- 000317
- Conditions
- Controlled Ovarian Stimulation
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Permanently terminated due to halt of recruitment due to COVID-19 pandemic
- Enrolment
- 362 participants (actual)
- Lead sponsor
- Ferring PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 1 Sep 2018 (actual)
- Primary completion
- 31 Dec 2020 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 5 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this observational study is to examine the development and appearance of embryos before and after freezing following a single controlled ovarian stimulation cycle using REKOVELLE® (follitropin delta) as the recombinant follicular stimulating hormone (rFSH) for controlled ovarian stimulation. The primary objective of the study is to examine how specific factors of embryo development or appearance are related to the chance of becoming pregnant.
The ovarian stimulation protocol with REKOVELLE®, a new rFSH prescribed for ovarian stimulation, is individualised with a dosing regimen that is based on two parameters: the body weight and the level of a hormone, the anti-Müllerian hormone, (AMH), a parameter used to predict how the ovaries will respond to the ovarian stimulation.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| REKOVELLE® | – | Drug: Follitropin DeltaFollitropin Delta |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- The study aims to enroll between 1200 and 1500 cycles which is estimated to be sufficient for observing 616 single frozen-thawed blastocyst transfers. Patients can contribute data from one or more frozen-thawed blastocyst transfers. Further, the patient cohort will be recruited among the patient population of 8-10 public and private in vitro fertilization (IVF) clinics in Denmark.
Key inclusion criteria (5 listed)
- Patients undergoing elective single embryo transfer (e-SET) in a frozen embryo replacement (FER) treatment where the frozen blastocyst was obtained from an IVF or intracytoplasmic sperm injection (ICSI) cycle following controlled ovarian stimulation with REKOVELLE® .
- Women are prescribed REKOVELLE® for their IVF or ICSI according to the approved label.
- Morphological measurements and clinical outcomes are available for the fresh embryos obtained from the IVF or ICSI cycle.
- Willing and able to understand Danish or English patient information.
- Willingness and ability to provide written informed consent.
Key exclusion criteria (3 listed)
- Patients with any contraindication for treatment with REKOVELLE® for controlled ovarian stimulation.
- Patients with contraindication for undergoing assisted reproductive technologies (ART) such as an IVF or ICSI cycle.
- Oocyte donors.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Follitropin DeltaThe Intervention (solution for injection) is delivered with an injection pen. For women with AMH <15 pmol/L the daily dose is 12 micrograms, irrespective of body weight. For women with AMH ≥15 pmol/L the daily dose decreases from 0.19 to 0.10 micrograms/kg by increasing AMH concentration. The maximum daily dose for the first treatment cycle is 12 micrograms. For subsequent treatment cycles, the daily dose of REKOVELLE® should be maintained or modified according to the patient's ovarian response in the previous cycle. Based on the ovarian hypo/hyper-response in the previous cycle, the daily dose in the subsequent cycle should be increased (by 25% or 50%) or decreased (by 20% or 33%). The maximum daily dose is 24 micrograms. | Drug | REKOVELLE® |
Primary outcome
Clinical pregnancy rate
Time frame: 7 weeks after each embryo transfer
Clinical pregnancy is defined as at least one intrauterine gestational sac with fetal heart beat at week 7, from frozen thawed blastocysts. The correlation between morphological parameters (blastocyst score, timelapse score, blastocoele re-expansion) and clinical pregnancy rate will be assessed.
8 secondary outcomes
Cumulative clinical pregnancy rate
Time frame: Up to 24 months
Positive βhCG result (blood or urinary pregnancy test)
Time frame: Up to 24 months
Use of the algorithm-based individualized dosing regimen with REKOVELLE®
Time frame: At the day of the consultation visit where the daily dose of REKOVELLE® is decided
Daily dose of REKOVELLE® administered
Time frame: From day 1 up to day 20 of REKOVELLE® stimulation
Number of days of treatment with REKOVELLE®
Time frame: From day 1 up to day 20 of REKOVELLE® stimulation
Day of REKOVELLE® stimulation start
Time frame: At the day of the first REKOVELLE® injection during the ovarian stimulation treatment
Day of REKOVELLE® stimulation end
Time frame: At the day of the last REKOVELLE® injection during the ovarian stimulation treatment
Any deviation in REKOVELLE® administration
Time frame: From day 1 up to day 20 of REKOVELLE® stimulation
Results and safety
The study was stopped early (reason given: Permanently terminated due to halt of recruitment due to COVID-19 pandemic). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2023.
- Results publication: PubMed 37835035Gabrielsen A, Iversen LH, Fedder J, Eskildsen TV, Englund AL, Hansen SR, Pinton P. Pre-Vitrification and Post-Warming Variables of Vitrified-Warmed Blastocysts That Are Predictable for Implantation. J Clin Med. 2023 Oct 6;12(19):6389. doi: 10.3390/jcm12196389.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Global Clinical Compliance study director
Ferring Pharmaceuticals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Controlled Ovarian Stimulation, run by Ferring Pharmaceuticals at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Permanently terminated due to halt of recruitment due to COVID-19 pandemic). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical pregnancy rate (time frame: 7 weeks after each embryo transfer). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03697031, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2023.