InfertilityPhase 4TICONNCT03164551
TICON-Day 3, Time Lapse Versus Conventional Method in Day 3 Embryo Culture and Assessment
A Phase 4 study testing GERI+ incubator and Conventional incubator in people with Infertility, run by Merck KGaA, Darmstadt, Germany at 17 sites in 7 countries.
Trial summary
The main purpose of the study was to evaluate the overall clinical value of GERI+ as an integrated embryo culture and assessment system, providing an undisturbed culture environment, continuous monitoring of embryo development and automated scoring using a predictive algorithm. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Infertility
- What is being tested?
- GERI+ incubator and Conventional incubator
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 408 participants
- Where
- 17 sitesin 7 countries
- Study dates
- 16 Apr 2018to 20 Nov 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Couples with less than or equal to (<= ) two failed fresh In Vitro Fertilization/Intracytoplasmic Sperm Injection (IVF/ICSI) embryo transfer cycles
- Age greater than or equal to (>=) 18 and <= 40 years
- Body mass index (BMI): 18-30 kilogram per meter square (kg/m2)
- Normal uterine cavity under ultrasound
- Participant and her husband/partner must have read and signed the Informed Consent form (ICF)
- At least four normally fertilized oocytes (2Pronuclear stage (PN)) in the current cycle
Who cannot join
- Male with non-ejaculated sperm
- Participants with abnormal, undiagnosed gynecological bleeding or with genitourinary malformations
- Participants with any contraindication to Controlled Ovarian Stimulation (COS) for Assisted Reproductive Technologies (ART) or to gonadotropins
- Planned "freeze all" cycle (oocytes or embryos)
- Planned preimplantation genetic screening (PGS) or Pre-implantation genetic diagnosis (PGD) cycle
- Concurrent participation in another clinical study
Trial locations and contacts
17 sites in 7 countries.
17 sites in 7 countries
Italy4 sites
Krankenhaus Bruneck
Bruneck (BZ), I-39031
Demetra S.R.L
Florence, 50141
Futura Diagnostica medica PMA SRL
Florence, SO129
USL Toscana Nordovest
Viareggio, 55043
Spain4 sites
Hospital de Cruces
Barakaldo, 48903
Nephrology Service Fundacion Puigvert
Barcelona, 8025
Hospital Universitario Virgen de las Nieves
Granada
Hosp Univ de Canarias
Santa Cruz de Tenerife
Norway3 sites
Oslo University Hospital
Oslo
Sykehuset Telemark HF Fertilitetsavdeliningen Sor
Skien, 3710
St. Olavs Hospital Hf, Universitetssykehuset i Trondheim
Trodheim, N-7006
Canada2 sites
Cambrian Wellness Centre
Calgary, T3B 4N2
Regional Fertility Program
Calgary
Denmark2 sites
Skive Fertility clinic
Skive, 7800
Fertility Clinic Skive Regional Hospital
Skive
Portugal1 site
Centro Hospitalar e Universitario de Coimbra
Coimbra, 3000-075
About this study
Official title: A Phase IV, Single-blinded, Prospective, Randomized, Controlled, Multi-center Study to Compare the Clinical Outcomes of Genea Embryo Review Instrument Plus (GERI+) Time Lapse System With a Conventional Embryo Culture and Assessment System
The main purpose of the study was to evaluate the overall clinical value of GERI+ as an integrated embryo culture and assessment system, providing an undisturbed culture environment, continuous monitoring of embryo development and automated scoring using a predictive algorithm.
- Conditions
- Infertility
- Being tested
- GERI+ incubator, Conventional incubator
- Keywords
- GERI+, TICON, EEVA, Embryo culture, In Vitro Fertilization, Intracytoplasmic Sperm Injection
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GERI+ incubatorDevice
The embryo culture of consented participants were carried out in GERI+ incubator for both bright-field and dark-field time lapse monitoring until Day 3 of embryo culture. On Day 3, all embryos were reviewed firstly by GERI Assess software, using bright-field imaging. Finally the embryo(s) with the highest EEVA grade are transferred were followed up until the achievement of implantation and confirmation of pregnancy.
Conventional incubatorDevice
The embryo culture of consented participants were carried out in conventional incubator for culture until Day 3 of embryo culture. On Day 3 of embryo culture, all embryos are assessed using a bench-top microscope. The embryo(s) with optimal cell stage and grade were transferred and were followed up until the achievement of implantation and confirmation of pregnancy.
| Study group | Role | What they receive |
|---|---|---|
| GERI+ Incubator | Active comparator | Not described Receives: Device: GERI+ incubator |
| Conventional incubator | Other | Not described Receives: Device: Conventional incubator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Pregnancy Rate With Positive Fetal Heart Beat (FHB)
Clinical Pregnancy was defined as the pregnancy diagnosed by ultrasonographic or clinical documentation of at least one fetus with heart beat in gestational week 6 to 8. Clinical pregnancy rate with positive FHB was measured as the number of participants with FHB positive clinical pregnancy divided by number of participants with embryo transfer (ET) multiplied by 100. Here, data used for analysis was based on Merck Global Medical Affairs (GMA) interpretation.
Measured: Gestation Weeks 6 to 8
Secondary outcomes (9)
Utilizable Embryos Rate
Utilizable embryos rate is defined as the number of transferred and cryopreserved embryos divided by the number embryos stage zygotes per participant multiply by 100. Here, data used for analysis was based on Merck GMA interpretation.
Measured: Day 3 of embryo culture
Good Quality Embryos Rate
Good Quality Embryos is defined embryos with 7 or more blastomeres, less than (<) 25 % fragmentation, size and symmetry of blastomeres appropriate to the cell number, and no evidence of multinucleation, based on the morphology on Day 3 of embryo culture. Good quality embryos rate was defined as the number of good quality embryos divided by the number of embryos per participant multiplied by 100. Here, data used for analysis was based on Merck GMA interpretation.
Measured: Day 3 of embryo culture
Non-viable Embryos Rate
Non-viable Embryos is defined as the embryos in which development has been arrested for at least 24 hour or in which all the cells have degenerated or lysed. Non-viable embryos rate was defined as the number of non-viable embryos divided by the number of embryos per participant multiplied by 100. Here, data used for analysis was based on Merck GMA interpretation.
Measured: Days 1 to 3 of embryo culture
Implantation Rate (IR) With Positive Fetal Heart Beat
A successful implantation is defined as the presence of one gestational sac with fetal heart beat (FHB) under ultrasonography at gestational weeks 6-8. Implantation rate (IR) was defined as the number of intrauterine gestational sacs with positive FHB under ultrasound scans at gestational weeks 6-8 divided by the total number of embryos transferred (ET) multiplied by 100. Here, data used for analysis was based on Merck GMA interpretation.
Measured: Gestational Weeks 6 to 8
Biochemical Pregnancy Rate
Biochemical Pregnancy defined as a pregnancy diagnosed only by the detection of Human Chorionic Gonadotropin (hCG) in serum or urine and that does not develop into a clinical pregnancy. Biochemical pregnancy rate was defined as the number of participants with biochemical pregnancy divided by the number of participants with embryo transfer (ET) multiplied by 100. Here, data used for analysis was based on Merck GMA interpretation.
Measured: From Day 12 of Gestational up to Week 8
Ongoing Pregnancy Rate
Ongoing pregnancy is defined as the presence of viable fetuses identified by ultrasonography at gestational weeks 10-12. Ongoing pregnancy rate is defined as the number of participants with ongoing pregnancy divided by the number of participants with embryo transfer (ET) multiplied by 100. Here, data used for analysis was based on Merck GMA interpretation.
Measured: Gestational Weeks 10 to 12
Multiple Pregnancy Rate
Multiple pregnancy is defined as a pregnancy with more than one fetus. It is identified by ultrasonography at gestational weeks 10-12. Multiple pregnancy rate was defined as the number of participants with multiple pregnancy divided by the number of participants with ongoing pregnancy multiplied by 100. Here, data used for analysis was based on Merck GMA interpretation.
Measured: Gestational Weeks 10 to 12
Ectopic Pregnancy Rate
Ectopic pregnancy is defined as a pregnancy in which implantation takes place outside the uterine cavity. It is identified by ultrasonography at weeks 6-8. Ectopic Pregnancy Rate was defined as the number of participants with ectopic pregnancy divided by the number of participants with embryo transfer (ET) multiplied by 100. Here, data used for analysis was based on Merck GMA interpretation.
Measured: Gestational Weeks 6 to 8
Spontaneous Miscarriage Rate
Spontaneous miscarriage (SM) is the spontaneous loss of a clinical pregnancy before 20 completed weeks of gestational age (18 weeks after fertilization). In this study, the spontaneous miscarriage was tracked up to 10-12 weeks of gestational age. Spontaneous miscarriage rate was defined as the number of participants with spontaneous miscarriage divided by the number of participants with clinical pregnancy multiplied by 100. Here, data used for analysis was based on Merck GMA interpretation.
Measured: Gestational Weeks 10 to 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2017
- Study start16 Apr 2018
- Primary completion20 Nov 2019
- Study completion20 Nov 2019
Why it stopped: Participant enrollment has remained significantly behind plan despite increased site enrollment activity.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for InfertilityStudies 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 408 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03164551
- Sponsor's protocol ID
- MS200497_0006
- Acronym
- TICON
- Status last verified
- Nov 2020
- First submitted
- 22 May 2017
- Last updated
- 2 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IV, Single-blinded, Prospective, Randomized, Controlled, Multi-center Study to Compare the Clinical Outcomes of Genea Embryo Review Instrument Plus (GERI+) Time Lapse System With a Conventional Embryo Culture and Assessment System
- ClinicalTrials.gov ID
- NCT03164551
- Acronym / sponsor ID
- TICON / MS200497_0006
- Conditions
- Infertility
- Keywords
- GERI+, TICON, EEVA, Embryo culture, In Vitro Fertilization, Intracytoplasmic Sperm Injection
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Participant enrollment has remained significantly behind plan despite increased site enrollment activity.
- Enrolment
- 408 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- 16 Apr 2018 (actual)
- Primary completion
- 20 Nov 2019 (actual)
- Study completion
- 20 Nov 2019 (actual)
- First posted
- 23 May 2017 (actual)
- Results
- Posted 2 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of the study was to evaluate the overall clinical value of GERI+ as an integrated embryo culture and assessment system, providing an undisturbed culture environment, continuous monitoring of embryo development and automated scoring using a predictive algorithm.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GERI+ Incubator | Active comparator | Device: GERI+ incubator |
| Conventional incubator | Other | Device: Conventional incubator |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Couples with less than or equal to (<= ) two failed fresh In Vitro Fertilization/Intracytoplasmic Sperm Injection (IVF/ICSI) embryo transfer cycles
- Age greater than or equal to (>=) 18 and <= 40 years
- Body mass index (BMI): 18-30 kilogram per meter square (kg/m2)
- Normal uterine cavity under ultrasound
- Participant and her husband/partner must have read and signed the Informed Consent form (ICF)
Key exclusion criteria (6 listed)
- Male with non-ejaculated sperm
- Participants with abnormal, undiagnosed gynecological bleeding or with genitourinary malformations
- Participants with any contraindication to Controlled Ovarian Stimulation (COS) for Assisted Reproductive Technologies (ART) or to gonadotropins
- Planned "freeze all" cycle (oocytes or embryos)
- Planned preimplantation genetic screening (PGS) or Pre-implantation genetic diagnosis (PGD) cycle
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 |
|---|---|---|
| GERI+ incubatorThe embryo culture of consented participants were carried out in GERI+ incubator for both bright-field and dark-field time lapse monitoring until Day 3 of embryo culture. On Day 3, all embryos were reviewed firstly by GERI Assess software, using bright-field imaging. Finally the embryo(s) with the highest EEVA grade are transferred were followed up until the achievement of implantation and confirmation of pregnancy. | Device | GERI+ Incubator |
| Conventional incubatorThe embryo culture of consented participants were carried out in conventional incubator for culture until Day 3 of embryo culture. On Day 3 of embryo culture, all embryos are assessed using a bench-top microscope. The embryo(s) with optimal cell stage and grade were transferred and were followed up until the achievement of implantation and confirmation of pregnancy. | Device | Conventional incubator |
Primary outcome
Clinical Pregnancy Rate With Positive Fetal Heart Beat (FHB)
Time frame: Gestation Weeks 6 to 8
Clinical Pregnancy was defined as the pregnancy diagnosed by ultrasonographic or clinical documentation of at least one fetus with heart beat in gestational week 6 to 8. Clinical pregnancy rate with positive FHB was measured as the number of participants with FHB positive clinical pregnancy divided by number of participants with embryo transfer (ET) multiplied by 100. Here, data used for analysis was based on Merck Global Medical Affairs (GMA) interpretation.
9 secondary outcomes
Utilizable Embryos Rate
Time frame: Day 3 of embryo culture
Good Quality Embryos Rate
Time frame: Day 3 of embryo culture
Non-viable Embryos Rate
Time frame: Days 1 to 3 of embryo culture
Implantation Rate (IR) With Positive Fetal Heart Beat
Time frame: Gestational Weeks 6 to 8
Biochemical Pregnancy Rate
Time frame: From Day 12 of Gestational up to Week 8
Ongoing Pregnancy Rate
Time frame: Gestational Weeks 10 to 12
Multiple Pregnancy Rate
Time frame: Gestational Weeks 10 to 12
Ectopic Pregnancy Rate
Time frame: Gestational Weeks 6 to 8
Spontaneous Miscarriage Rate
Time frame: Gestational Weeks 10 to 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Trial Awareness and Transparency websiteLink provided by the sponsor.
- Medical Information Location Map - Med Info ContactsLink provided by the sponsor.
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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.
Medical Responsible study director
Merck KGaA, Darmstadt, Germany
17 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing GERI+ incubator and Conventional incubator in people with Infertility, run by Merck KGaA, Darmstadt, Germany at 17 sites in 7 countries.
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 6 inclusion and 6 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 2 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Italy, Spain, Norway, Canada, Denmark and 2 more countries. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 With Positive Fetal Heart Beat (FHB) (time frame: Gestation Weeks 6 to 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Dec 2020.