TiLE (Time Lapse Eeva) Clinical Trial (TiLE)

A Phase IV, Prospective, Randomized, Exploratory, Multicenter, Eeva™ Trial (Time Lapse Eeva - TiLE)

The purpose of the study was to explore the added value of adjunctive use of Early Embryo Viability Assessment (Eeva) with morphological grading in identifying optimal embryos for transfer.

Study Overview

• Status: Completed
• Conditions: Fertility
• Intervention / Treatment: Device: Eeva

Detailed Description

This study is a Phase IV, open label, prospective, randomized, exploratory, multicenter study. Subjects were randomized in 2:1 ratio to two treatment groups: in the experimental group, embryos were assessed for embryo transfer (ET) with Eeva and morphological grading, while in the control group embryos were assessed with morphological grading only.

• Study Type: Interventional
• Enrollment (Actual): 976
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Toronto, Canada
    • Mount Sinai Hospital
  • Alberta
    • Calgary, Alberta, Canada
      • Cambrian Wellness Centre
  • Ontario
    • Burlington, Ontario, Canada
      • ONE Fertility
    • Mississauga, Ontario, Canada
      • ISIS Regional Fertility Clinic
• Denmark
  • Copenhagen, Denmark
    • Rigshospitalet
• France
  • Lille Cedex, France
    • CHRU - Hopital Jeanne de Flandres
  • Marseille, France
    • Laboratoire Alphabio & Institut de Médecine de la Reproducti
  • Nantes, France
    • Hôpital Hotel Dieu
• Germany
  • Luebeck, Germany
    • Universitätsklinik Schleswig-Holstein
  • Munich, Germany
    • Kinderwunsch Centrum München
  • Wiesbaden, Germany
    • MVZ Kinderwunschzentrum Wiesbaden GmbH
• Italy
  • Montichiari, Italy
    • Montichiari Università degli studi di Bresca
  • Rozzano, Italy
    • Istituto Clinico Humanitas
  • Torino, Italy
    • Università degli Studi Torino
  • Viareggio, Italy
    • Ospedale Versilia
• Norway
  • Skien, Norway
    • Telemark hospital Porsgrunn
• Spain
  • Alicante, Spain
    • Clinica Vistahermosa
  • Barcelona, Spain
    • Clínica Sagrada Familia
  • Granada, Spain
    • Hospital Universitario Virgen de las Nieves
• Sweden
  • Stockholm, Sweden
    • Fertilitetscentrum Stockholm
• United Kingdom
  • Cambridge, United Kingdom
    • Bourn Hall
  • Edgbaston, United Kingdom
    • Birmingham Women's Health Care NHS Trust
  • London, United Kingdom
    • Homerton University Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• All infertile subjects treated with In vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)
• Subject age less than or equal to (<=) 40 years
• Less than or equal to (<=) 3 failed IVF/ICSI cycles
• At least 4 normally fertilized eggs (2 pronuclei [2PN]) in current cycle
• Normal uterine cavity
• Fertilization using only ejaculated sperm (fresh or frozen)
• Subject must have read and signed the Informed Consent Form

Exclusion Criteria:

• Have clinically significant systemic disease
• Have abnormal, undiagnosed gynecological bleeding
• Have any contraindication to Controlled Ovarian Stimulation (COS) for assisted reproductive technologies (ART) and to gonadotropins to be used in ART
• Egg donor cycle
• Planned "freeze all" cycle (oocytes or embryos)
• Concurrent participation in another clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early Embryo Viability Assessment + Morphological Grading; Embryos of subjects randomized in this group were assessed using Early Embryo Viability Assessment (Eeva) System and morphological grading to identify optimal embryos for transfer.	Device: Eeva; Embryos of subjects randomized in this group were assessed using Eeva System and morphological grading to identify optimal embryos for transfer.
No Intervention: Morphological Grading; Embryos of subjects randomized in this group were assessed only using morphological grading to identify optimal embryos for transfer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Implantation Rate	Implantation rate was calculated by dividing the number of intrauterine gestational sacs by the number of embryos transferred multiplied by 100.	Gestational Weeks 5 to 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Pregnancy Rate	Clinical pregnancy was confirmed by the presence of a gestational sac with heartbeat as assessed by ultrasonography. Clinical pregnancy rate was measured as the number of clinical pregnancies divided by number of embryo transfer (ET) cycles multiplied by 100.	Gestational Weeks 5 to 8
Number of Subjects With Ongoing Pregnancy Status	Ongoing pregnancy was defined as having a positive fetal heart beat (FHB) as assessed by ultrasonography at gestational week 10-12. Number of subjects with ongoing pregnancy status has been reported, where "Yes" indicates participants with positive ongoing pregnancy status and "No" indicates participants with negative ongoing pregnancy status .	Gestational Weeks 10 to 12
Multiple Pregnancy Rate	Multiple pregnancy rate was defined as a clinical pregnancy with greater than equals to (>=) 2 fetal sacs as assessed by ultrasonography. Multiple Pregnancies rate was measured by number of multiple pregnancies divided by number of embryo transfer cycles multiplied by 100.	Gestational Weeks 5 to 8
Utilization Rate	Utilization rate was defined as the sum of number of transferred and frozen embryos divided by number of normally fertilized oocytes multiplied by 100.	Day 3 or Day 5/6 of embryo culture
Spontaneous Miscarriage Rate	Spontaneous miscarriage rate was measured by the number of spontaneous miscarriages as communicated during medical appointment or by telephone contact divided by number of clinical pregnancies multiplied by 100.	Gestational Weeks 10 to 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eeva Conformity in Early Embryo Viability Assessment + Morphological Grading Group for Day 3 Embryo Transfer (ET)	Eeva Conformity was reported as the number of subjects who were compliant to use Eeva in embryo assessment in the "Early Embryo Viability Assessment + morphological grading" group. Eeva-compliance subgroup refers to subjects whose embryos were assessed by embryologists following the recommendation of Eeva system and the instructions for use (IFU) of Eeva. Subgroup analysis revealed a high incidence of Eeva noncompliance in the experimental group, which compromised the quality of this study. Only "Early Embryo Viability Assessment + Morphological Grading" reporting arm was applicable for this outcome measure.	Day 3 of embryo culture
Eeva Conformity in Early Embryo Viability Assessment + Morphological Grading Group for Day 5/6 Embryo Transfer (ET)	Eeva Conformity was reported as the number of subjects who were compliant to use Eeva in embryo assessment in the "Early Embryo Viability Assessment + morphological grading" group. Eeva-compliance subgroup refers to subjects whose embryos were assessed by embryologists following the recommendation of Eeva system and the IFU of Eeva. Subgroup analysis revealed a high incidence of Eeva noncompliance in the experimental group, which compromised the quality of this study. Only "Early Embryo Viability Assessment + Morphological Grading" reporting arm was applicable for this outcome measure.	Day 5/6 of embryo culture

Collaborators and Investigators

• Sponsor: Merck KGaA, Darmstadt, Germany

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2015
• Primary Completion (Actual): February 9, 2017
• Study Completion (Actual): February 9, 2017

Study Registration Dates

• First Submitted: April 10, 2015
• First Submitted That Met QC Criteria: April 10, 2015
• First Posted (Estimate): April 15, 2015

Study Record Updates

• Last Update Posted (Actual): January 30, 2020
• Last Update Submitted That Met QC Criteria: January 29, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Pregnancy; Implantation; TiLE; Embryo Assessment
• Other Study ID Numbers: EMR700623_545