Randomized Controlled Trial Comparing EmbryoScope Time-Lapse System With the New Model EmbryoScope+.
Phase: NA
Conditions: Infertility
Sponsor: Weill Medical College of Cornell University

WCMC Protocol #: 1612017837 
Version Date: V2 5.17.2018  
NCT Identifiers:  NCT03522350 
 
 
 
Title: 
Randomized Controlled Trial Comparing EmbryoScope Time-Lapse System with the new model 
EmbryoScope+. 
 
Required Summary: 
The purpose of the study is to compare the current EmbryoScope Time-Lapse System being used 
in IVF which has become standard of care to the new model EmbryoScope+. 
 
Performance Sites 
Weill Medical College of 
Cornell University 
Grants & Contracts 1300 York Avenue, Box 89 New York NY - 
10021 USA 
 
Performing Organization 
Weill Medical College of 
Cornell University 
Grants & Contracts 1300 York Avenue, Box 89 New York NY - 
10021 USA 
 
Investigators 
Person Name Primary Title Directory Title Units Affiliate Training Flag 
Zaninovic, Nikica 
Associate Professor- Clinical  Ph.D. Medicine 
PI - Responsible for Entire Protocol 
 
Co-Investigators: 
Clarke, Robert N., PhD- Associate Professor- Clinical 
Joseph-Sohan, Mitasha- Research Nurse Specialist 
Stubbs, Rodriq E., NP- Research Practice Administrator 
Witzke, Justine D., PhD- Operations Administrator 
Ye, Zhen Staff Associate B.Sc. 
Zhan, Qiansheng, PhD.- Assistant Professor- Research 
 
Protocol Versions and Dates: 
Original Version1 dated  6/19/2017 
Continuing Review and Amendment dated 4/29/2018 
 
 
 
 

Study Summary: 
The purpose of the study is to compare the current EmbryoScope Time-Lapse System being used 
in IVF, which has become standard of care, to the new model EmbryoScope+.  
 
Brief background/rationale for the study: 
During in vitro fertilization, human embryos are evaluated to assess their speed and 
morphological characteristics that allow prediction of their developmental potential and 
probability to achieve pregnancy and implantation.   The advancement of the time-lapse 
technology enable us to understand the embryo development in vitro.  IVF practices is improved 
by selection of the embryos with the highest implantation potential using time-lapse technology. 
Automated recording of embryos provides the opportunity to determine the exact timing of 
embryo cleavages and accurate selection of the viable embryos for transfer. EmbryoScope time-
lapse system is the most used for IVF with over 300,000 patient treatments since 2009. The new 
time-lapse instrument, EmbryoScope+, is the newer model that provides the same result with 3.3 
times greater capacity and a more efficient workflow with the automated registration of the 
EmbryoSlide+ culture dishes. It has been used in Scandinavia in over 500 treatments. We aim to 
compare the current EmbryoScope Time-Lapse System being used in IVF, which has become 
standard of care, to the new model EmbryoScope+ to demonstrate that the EmbryoScope+ is as 
safe and reliable as the EmbryoScope. 
 
Brief study summary including, if applicable: 
o Randomization arms: Standard EmbryoScope Time-Lapse system versus 
EmbryoScope+ on sibling oocytes. 
o Length of time on treatment, length of follow-up: 10 months 
 
Brief Summary:  
o In-vitro Fertilization (IVF) will be completed according to normal clinical 
procedures. Participant’s oocytes will be randomly assigned to one of two 
groups: Standard EmbryoScope versus EmbryoScope+. 
o The best quality embryos are selected for embryo transfer and the 
pregnancy outcome is evaluated.  
o Study participants will not be compensated.  
 
 
Key eligibility:  
Inclusion:  
40 years of age or younger (maternal) 

65 years of age or younger (paternal) 
Fresh or frozen (including donor) sperm can be used 
Fresh or frozen oocytes (including donor), 10 or more oocytes 
ICSI only 
Frozen embryos from this study can be included in the outcome portion of this study. 
Exclusion:  
Patients with less then 10 oocytes 
Co-culture patients 
 
 
Study Design:  
This is a randomized, controlled, single-center study in otherwise healthy infertile female 
subjects undergoing in vitro fertilization (IVF). The subjects recruited for this study will be 
among those patients who have been diagnosed with infertility and are planning to undergo IVF 
at the center where this study is being performed. The subjects will have undergone the usual 
informed consent procedure at the center.  
Subjects will undergo ovarian stimulation, oocyte retrieval, IVF, and Intracytoplasmic Sperm 
Injection (ICSI) procedure following the center's usual procedures. At the time of retrieval, 
participant’s oocytes will be randomly assigned to one of two groups: Standard EmbryoScope 
versus EmbryoScope+. The best quality embryos are selected for embryo transfer and the 
pregnancy outcome is evaluated.  
"Best grade" embryos will be transferred regardless of EmbryoScope use.  The standard 
EmbryoScope as well as the EmbryoScope+ monitor system as assigned during the 
randomization process will be used to observe the embryo development and document timing of 
embryo cleavages and morphology dynamics. Subjects will not be provided with the time- lapse 
images.  
Endpoints will be Day 3 and Day 5/6 embryo development, implantation and pregnancy rate.  
The study is approximately 2 months, the estimated time it takes a physician to perform one IVF-
ART treatment cycle.  If embryos are frozen, the patient may be in the study until the time they 
choose to thaw the embryos or up to 1 year if they become pregnant. We aim to compare the 
current EmbryoScope Time-Lapse System being used in IVF which has become standard of 
care to the new model EmbryoScope+ to demonstrate that the EmbryoScope+ is as safe and 
reliable as the EmbryoScope. 
 
Primary Objective:  
Comparison of embryo development using standard assessments of morphokinetic parameters, 
embryo selection algorithms and standard embryo grading.   

 
Secondary Objective:  
1- Implantation and clinical pregnancy rates 
2- Embryo transfer rate 
3- Morphokinetic data 
4- Frozen embryo transfer outcomes 
 
 
 
Statistical Considerations:  
The primary outcome of the study is the comparison of embryo development between oocytes 
assigned to Standard EmbryoScope versus oocytes assigned to EmbryoScope+.  The proposed 
sample size is 100 subjects and their partner, if applicable.  In order to compare embryo 
development (primary endpoint) and implantation rate (secondary endpoint), as well as resulting 
pregnancy outcome (secondary endpoint), between the two EmbryoScope devices, a sample size 
of 100 subjects (200 including partners) will result in approximately 1000 embryos available for 
randomization.    
Each subject’s oocytes will be randomly divided between the two study arms, resulting in at least 
500 oocytes per study arm.  With a sample size of 500 oocytes per study arm, a 95% confidence 
interval for the proportion of oocytes undergoing adequate embryo development (at day 3 and 
day 5/6) in each study arm can be constructed to be within ± 4.4% of the observed proportion of 
oocytes experiencing adequate embryo development.  This calculation assumes an adequate 
embryo development proportion of 50% to conservatively maximize the width of the obtained 
confidence intervals.  The chi-square test or Fisher’s exact test will be used, as appropriate, to 
compare the adequate embryo development proportion between the Standard EmbryoScope and 
EmbryoScope+ study arms.  Similar analyses will be performed for the secondary endpoints of 
implantation proportion, pregnancy proportion, embryo transfer proportion, and descriptive 
morphokinetic data proportions.  A univariate generalized estimating equations (GEE) model 
will also be used to compare the adequate embryo development proportion between the two 
study arms, correcting for clustering by subject (i.e., multiple oocytes per subject).  Lack of any 
observed statistically significant differences between the two study arms will not constitute 
evidence of equivalence or non-inferiority between the two study arms; rather, estimates of the 
adequate embryo development proportion in each group will serve as preliminary data for further 
investigation (i.e., hypothesis-generating).  All p-values will be two-sided with statistical 
significance evaluated at the 0.05 alpha level.  Ninety-five percent confidence intervals for the 
adequate embryo development proportion, as well as the secondary outcome proportions of 
interest, will be calculated to assess the precision of the obtained estimates.  All analyses will be 
performed in SAS Version 9.4 (SAS Institute, Inc., Cary, NC) and Stata Version 14.0 
(StataCorp, College Station, TX).  Note: The statistical considerations section was written in 

conjunction with Dr. Paul Christos, in the Division of Biostatistics and Epidemiology, 
Department of Healthcare Policy & Research. 
 
Pregnancy Rate will be defined as: 
Biochemical pregnancy - positive beta hcg after embryo transfer 
Clinical pregnancy - identification of fetal sac in ultra sound post embryo transfer 
Ongoing pregnancy - identification of fetal heart in ultra sound post embryo transfer 
Delivery rate - live birth 
Miscarriage rate - positive fetal sac or fetal heart without live birth.