Trial Outcomes & Findings for TICON-Day 3, Time Lapse Versus Conventional Method in Day 3 Embryo Culture and Assessment (NCT NCT03164551)

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

408 participants

Primary outcome timeframe

Gestation Weeks 6 to 8

Results posted on

2020-12-02

Participant Flow

Participant milestones

Participant milestones
Measure	GERI+ Incubator The embryo culture of consented participants carried out in Genea Embryo Review Instrument Plus (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 were transferred and were followed up until the achievement of implantation and confirmation of pregnancy.	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 were 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.
Overall Study STARTED	200	208
Overall Study COMPLETED	171	192
Overall Study NOT COMPLETED	29	16

Reasons for withdrawal

Reasons for withdrawal
Measure	GERI+ Incubator The embryo culture of consented participants carried out in Genea Embryo Review Instrument Plus (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 were transferred and were followed up until the achievement of implantation and confirmation of pregnancy.	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 were 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.
Overall Study Imaging discontinued prior completion	8	0
Overall Study Participant was non-compliant	1	0
Overall Study Cancellation of Fresh Embryo Transfer	12	14
Overall Study Other	8	2

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GERI+ Incubator n=200 Participants The embryo culture of consented participants carried out in Genea Embryo Review Instrument Plus (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 were transferred and were followed up until the achievement of implantation and confirmation of pregnancy.	Conventional Incubator n=208 Participants 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 were 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.	Total n=408 Participants Total of all reporting groups
Age, Continuous	33.27 Years STANDARD_DEVIATION 4.076 • n=200 Participants	33.23 Years STANDARD_DEVIATION 3.996 • n=208 Participants	33.25 Years STANDARD_DEVIATION 4.030 • n=408 Participants
Sex: Female, Male Female	200 Participants n=200 Participants	208 Participants n=208 Participants	408 Participants n=408 Participants
Sex: Female, Male Male	0 Participants n=200 Participants	0 Participants n=208 Participants	0 Participants n=408 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: Gestation Weeks 6 to 8

Population: Full analysis (FA) dataset included all randomized participants.

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.

Outcome measures

Outcome measures
Measure	GERI+ Incubator n=200 Participants The embryo culture of consented participants carried out in Genea Embryo Review Instrument Plus (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 were transferred and were followed up until the achievement of implantation and confirmation of pregnancy.	Conventional Incubator n=208 Participants 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 were 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.
Clinical Pregnancy Rate With Positive Fetal Heart Beat (FHB)	39.4 Percentage of pregnancy per ET	38.9 Percentage of pregnancy per ET

SECONDARY outcome

Timeframe: Day 3 of embryo culture

Population: FA dataset included all randomized participants. Here, "Number of participants analyzed" signifies participants who were evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	GERI+ Incubator n=198 Participants The embryo culture of consented participants carried out in Genea Embryo Review Instrument Plus (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 were transferred and were followed up until the achievement of implantation and confirmation of pregnancy.	Conventional Incubator n=208 Participants 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 were 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.
Utilizable Embryos Rate	50.72 Percentage of embryos Standard Deviation 23.379	50.11 Percentage of embryos Standard Deviation 24.183

SECONDARY outcome

Timeframe: Day 3 of embryo culture

Population: FA dataset included all randomized participants. Here, "Number of participants analyzed" signifies participants who were evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	GERI+ Incubator n=198 Participants The embryo culture of consented participants carried out in Genea Embryo Review Instrument Plus (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 were transferred and were followed up until the achievement of implantation and confirmation of pregnancy.	Conventional Incubator n=208 Participants 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 were 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.
Good Quality Embryos Rate	34.85 Percentage of Good Quality Embryos Standard Deviation 25.999	37.68 Percentage of Good Quality Embryos Standard Deviation 29.115

SECONDARY outcome

Timeframe: Days 1 to 3 of embryo culture

Population: FA dataset included all randomized participants. Here, "Number of participants analyzed" signifies participants who were evaluable for this outcome measure.

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.