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TICON-Day 3, Time Lapse Versus Conventional Method in Day 3 Embryo Culture and Assessment (TICON)

Primary Purpose

Infertility

Status
Terminated
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
GERI+ incubator
Conventional incubator
Sponsored by
Merck KGaA, Darmstadt, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Infertility focused on measuring GERI+, TICON, EEVA, Embryo culture, In Vitro Fertilization, Intracytoplasmic Sperm Injection

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Sites / Locations

  • Cambrian Wellness Centre
  • Regional Fertility Program
  • Skive Fertility clinic
  • Fertility Clinic Skive Regional Hospital
  • Hopital Antoine Beclere
  • Krankenhaus Bruneck
  • Demetra S.R.L
  • Futura Diagnostica medica PMA SRL
  • USL Toscana Nordovest
  • Oslo University Hospital
  • Sykehuset Telemark HF Fertilitetsavdeliningen Sor
  • St. Olavs Hospital Hf, Universitetssykehuset i Trondheim
  • Centro Hospitalar e Universitario de Coimbra
  • Hospital de Cruces
  • Nephrology Service Fundacion Puigvert
  • Hospital Universitario Virgen de las Nieves
  • Hosp Univ de Canarias

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Other

Arm Label

GERI+ Incubator

Conventional incubator

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
May 22, 2017
Last Updated
November 6, 2020
Sponsor
Merck KGaA, Darmstadt, Germany
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1. Study Identification

Unique Protocol Identification Number
NCT03164551
Brief Title
TICON-Day 3, Time Lapse Versus Conventional Method in Day 3 Embryo Culture and Assessment
Acronym
TICON
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Terminated
Why Stopped
Participant enrollment has remained significantly behind plan despite increased site enrollment activity.
Study Start Date
April 16, 2018 (Actual)
Primary Completion Date
November 20, 2019 (Actual)
Study Completion Date
November 20, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility
Keywords
GERI+, TICON, EEVA, Embryo culture, In Vitro Fertilization, Intracytoplasmic Sperm Injection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
408 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GERI+ Incubator
Arm Type
Active Comparator
Arm Title
Conventional incubator
Arm Type
Other
Intervention Type
Device
Intervention Name(s)
GERI+ incubator
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Conventional incubator
Intervention Description
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.
Primary Outcome Measure Information:
Title
Clinical Pregnancy Rate With Positive Fetal Heart Beat (FHB)
Description
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.
Time Frame
Gestation Weeks 6 to 8
Secondary Outcome Measure Information:
Title
Utilizable Embryos Rate
Description
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.
Time Frame
Day 3 of embryo culture
Title
Good Quality Embryos Rate
Description
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.
Time Frame
Day 3 of embryo culture
Title
Non-viable Embryos Rate
Description
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.
Time Frame
Days 1 to 3 of embryo culture
Title
Implantation Rate (IR) With Positive Fetal Heart Beat
Description
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.
Time Frame
Gestational Weeks 6 to 8
Title
Biochemical Pregnancy Rate
Description
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.
Time Frame
From Day 12 of Gestational up to Week 8
Title
Ongoing Pregnancy Rate
Description
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.
Time Frame
Gestational Weeks 10 to 12
Title
Multiple Pregnancy Rate
Description
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.
Time Frame
Gestational Weeks 10 to 12
Title
Ectopic Pregnancy Rate
Description
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.
Time Frame
Gestational Weeks 6 to 8
Title
Spontaneous Miscarriage Rate
Description
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.
Time Frame
Gestational Weeks 10 to 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
Cambrian Wellness Centre
City
Calgary
ZIP/Postal Code
T3B 4N2
Country
Canada
Facility Name
Regional Fertility Program
City
Calgary
Country
Canada
Facility Name
Skive Fertility clinic
City
Skive
ZIP/Postal Code
7800
Country
Denmark
Facility Name
Fertility Clinic Skive Regional Hospital
City
Skive
Country
Denmark
Facility Name
Hopital Antoine Beclere
City
Clamart
ZIP/Postal Code
92140
Country
France
Facility Name
Krankenhaus Bruneck
City
Bruneck (BZ)
ZIP/Postal Code
I-39031
Country
Italy
Facility Name
Demetra S.R.L
City
Firenze
ZIP/Postal Code
50141
Country
Italy
Facility Name
Futura Diagnostica medica PMA SRL
City
Firenze
ZIP/Postal Code
SO129
Country
Italy
Facility Name
USL Toscana Nordovest
City
Viareggio
ZIP/Postal Code
55043
Country
Italy
Facility Name
Oslo University Hospital
City
Oslo
Country
Norway
Facility Name
Sykehuset Telemark HF Fertilitetsavdeliningen Sor
City
Skien
ZIP/Postal Code
3710
Country
Norway
Facility Name
St. Olavs Hospital Hf, Universitetssykehuset i Trondheim
City
Trodheim
ZIP/Postal Code
N-7006
Country
Norway
Facility Name
Centro Hospitalar e Universitario de Coimbra
City
Coimbra
ZIP/Postal Code
3000-075
Country
Portugal
Facility Name
Hospital de Cruces
City
Baracaldo
ZIP/Postal Code
48903
Country
Spain
Facility Name
Nephrology Service Fundacion Puigvert
City
Barcelona
ZIP/Postal Code
8025
Country
Spain
Facility Name
Hospital Universitario Virgen de las Nieves
City
Granada
Country
Spain
Facility Name
Hosp Univ de Canarias
City
Santa Cruz de Tenerife
Country
Spain

12. IPD Sharing Statement

Links:
URL
https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS200497_0006
Description
Trial Awareness and Transparency website

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TICON-Day 3, Time Lapse Versus Conventional Method in Day 3 Embryo Culture and Assessment

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