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

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.

Study Overview

• Status: Terminated
• Conditions: Infertility
• Intervention / Treatment: Device: GERI+ incubator; Device: Conventional incubator

• Study Type: Interventional
• Enrollment (Actual): 408
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Calgary, Canada, T3B 4N2
    • Cambrian Wellness Centre
  • Calgary, Canada
    • Regional Fertility Program
• Denmark
  • Skive, Denmark, 7800
    • Skive Fertility clinic
  • Skive, Denmark
    • Fertility Clinic Skive regional Hospital
• France
  • Clamart, France, 92140
    • Hôpital Antoine Béclère
• Italy
  • Bruneck (BZ), Italy, I-39031
    • Krankenhaus Bruneck
  • Firenze, Italy, 50141
    • Demetra S.R.L
  • Firenze, Italy, SO129
    • Futura Diagnostica medica PMA SRL
  • Viareggio, Italy, 55043
    • USL Toscana Nordovest
• Norway
  • Oslo, Norway
    • Oslo University Hospital
  • Skien, Norway, 3710
    • Sykehuset Telemark HF Fertilitetsavdeliningen Sor
  • Trodheim, Norway, N-7006
    • St. Olavs Hospital Hf, Universitetssykehuset i Trondheim
• Portugal
  • Coimbra, Portugal, 3000-075
    • Centro Hospitalar e Universitário de Coimbra
• Spain
  • Baracaldo, Spain, 48903
    • Hospital de Cruces
  • Barcelona, Spain, 8025
    • Nephrology Service Fundacion Puigvert
  • Granada, Spain
    • Hospital Universitario Virgen de las Nieves
  • Santa Cruz de Tenerife, Spain
    • Hosp Univ de Canarias

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: GERI+ Incubator	Device: GERI+ incubator; 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.
Other: Conventional incubator	Device: Conventional incubator; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Gestation Weeks 6 to 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	Gestational Weeks 10 to 12

Collaborators and Investigators

• Sponsor: Merck KGaA, Darmstadt, Germany

Publications and helpful links

Helpful Links

• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2018
• Primary Completion (Actual): November 20, 2019
• Study Completion (Actual): November 20, 2019

Study Registration Dates

• First Submitted: May 22, 2017
• First Submitted That Met QC Criteria: May 22, 2017
• First Posted (Actual): May 23, 2017

Study Record Updates

• Last Update Posted (Actual): December 2, 2020
• Last Update Submitted That Met QC Criteria: November 6, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: In Vitro Fertilization; Embryo culture; Intracytoplasmic Sperm Injection; GERI+; TICON; EEVA
• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: MS200497_0006

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No