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

• Sponsor: Merck KGaA, Darmstadt, Germany (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03164551
• Collaborator: (none)
• Enrollment: 408
• Locations: 17
• Arms: 2
• Actual Duration (Months): 19.2
• Patients Per Site: 24
• Patients Per Site Per Month: 1.3

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Infertility	Device: GERI+ incubator; Device: Conventional incubator	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 408 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Apr 16, 2018
• Actual Primary Completion Date: Nov 20, 2019
• Actual Study Completion Date: Nov 20, 2019

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Clinical Pregnancy Rate With Positive Fetal Heart Beat (FHB) [Gestation Weeks 6 to 8]

   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

1. Utilizable Embryos Rate [Day 3 of embryo culture]

   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.

2. Good Quality Embryos Rate [Day 3 of embryo culture]

   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.

3. Non-viable Embryos Rate [Days 1 to 3 of embryo culture]

   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.

4. Implantation Rate (IR) With Positive Fetal Heart Beat [Gestational Weeks 6 to 8]

   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.

5. Biochemical Pregnancy Rate [From Day 12 of Gestational up to Week 8]

   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.

6. Ongoing Pregnancy Rate [Gestational Weeks 10 to 12]

   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.

7. Multiple Pregnancy Rate [Gestational Weeks 10 to 12]

   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.

8. Ectopic Pregnancy Rate [Gestational Weeks 6 to 8]

   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.

9. Spontaneous Miscarriage Rate [Gestational Weeks 10 to 12]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cambrian Wellness Centre	Calgary		Canada	T3B 4N2
2	Regional Fertility Program	Calgary		Canada
3	Skive Fertility clinic	Skive		Denmark	7800
4	Fertility Clinic Skive Regional Hospital	Skive		Denmark
5	Hopital Antoine Beclere	Clamart		France	92140
6	Krankenhaus Bruneck	Bruneck (BZ)		Italy	I-39031
7	Demetra S.R.L	Firenze		Italy	50141
8	Futura Diagnostica medica PMA SRL	Firenze		Italy	SO129
9	USL Toscana Nordovest	Viareggio		Italy	55043
10	Oslo University Hospital	Oslo		Norway
11	Sykehuset Telemark HF Fertilitetsavdeliningen Sor	Skien		Norway	3710
12	St. Olavs Hospital Hf, Universitetssykehuset i Trondheim	Trodheim		Norway	N-7006
13	Centro Hospitalar e Universitario de Coimbra	Coimbra		Portugal	3000-075
14	Hospital de Cruces	Baracaldo		Spain	48903
15	Nephrology Service Fundacion Puigvert	Barcelona		Spain	8025
16	Hospital Universitario Virgen de las Nieves	Granada		Spain
17	Hosp Univ de Canarias	Santa Cruz de Tenerife		Spain

Sponsors and Collaborators

• Merck KGaA, Darmstadt, Germany

Investigators

• Study Director: Medical Responsible, Merck KGaA, Darmstadt, Germany

Study Documents (Full-Text)

• Study Protocol - Jan 31, 2018
• Statistical Analysis Plan - Jan 14, 2020

More Information

Additional Information:

• Trial Awareness and Transparency website

Publications

None provided.

• Responsible Party: Merck KGaA, Darmstadt, Germany
• ClinicalTrials.gov Identifier: NCT03164551
• Other Study ID Numbers: MS200497_0006
• First Posted: May 23, 2017
• Last Update Posted: Dec 2, 2020
• Last Verified: Nov 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Merck KGaA, Darmstadt, Germany: GERI+; TICON; EEVA; Embryo culture; In Vitro Fertilization; Intracytoplasmic Sperm Injection
• Additional relevant MeSH terms: Infertility

Study Results

Participant Flow

Arm/Group Title	GERI+ Incubator	Conventional Incubator
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	200	208
COMPLETED	171	192
NOT COMPLETED	29	16

Baseline Characteristics

Arm/Group Title	GERI+ Incubator	Conventional Incubator	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	200	208	408
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	33.27 (4.076)	33.23 (3.996)	33.25 (4.030)
Sex: Female, Male (Count of Participants)
Female	200 100%	208 100%	408 100%
Male	0 0%	0 0%	0 0%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Full analysis (FA) dataset included all randomized participants.

Arm/Group Title	GERI+ Incubator	Conventional Incubator
Arm/Group Description	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.	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.
Measure Participants	200	208
Number [Percentage of pregnancy per ET]	39.4	38.9

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GERI+ Incubator	Conventional Incubator
Arm/Group Description	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.	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.
Measure Participants	198	208
Mean (Standard Deviation) [Percentage of embryos]	50.72 (23.379)	50.11 (24.183)

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GERI+ Incubator	Conventional Incubator
Arm/Group Description	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.	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.
Measure Participants	198	208
Mean (Standard Deviation) [Percentage of Good Quality Embryos]	34.85 (25.999)	37.68 (29.115)

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GERI+ Incubator	Conventional Incubator
Arm/Group Description	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.	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.
Measure Participants	198	208
Mean (Standard Deviation) [Percentage of Non-viable Embryos]	29.64 (27.932)	30.67 (29.001)

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

FA dataset included all randomized participants.

Arm/Group Title	GERI+ Incubator	Conventional Incubator
Arm/Group Description	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.	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.
Measure Participants	200	208
Number [Percentage of gestational sacs per ET]	31.2	32.5

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

FA dataset included all randomized participants.

Arm/Group Title	GERI+ Incubator	Conventional Incubator
Arm/Group Description	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.	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.
Measure Participants	200	208
Number [Percentage of Pregnancy per ET]	7.2	4.7

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

FA dataset included all randomized participants.

Arm/Group Title	GERI+ Incubator	Conventional Incubator
Arm/Group Description	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.	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.
Measure Participants	200	208
Number [Percentage of Pregnancy per ET]	35.0	36.3

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

FA dataset included all randomized participants.

Arm/Group Title	GERI+ Incubator	Conventional Incubator
Arm/Group Description	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.	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.
Measure Participants	200	208
Number [Percentage of Multiple Pregnancy]	1.6	11.4

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

FA dataset included all randomized participants.

Arm/Group Title	GERI+ Incubator	Conventional Incubator
Arm/Group Description	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.	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.
Measure Participants	200	208
Number [Percentage of Pregnancy per ET]	1.1	0.5

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

FA dataset included all randomized participants.

Arm/Group Title	GERI+ Incubator	Conventional Incubator
Arm/Group Description	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.	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.
Measure Participants	200	208
Number [Percentage of miscarriages]	9.3	10.1

Adverse Events

Time Frame	Not Applicable (NA)
Adverse Event Reporting Description	This is a fertility device technology study and this study was not designed to monitor all-cause mortality, serious, and other (not Including serious) adverse events. Therefore, all-cause mortality, serious, and other (not Including serious) adverse events data could not be reported.
Arm/Group Title	GERI+ Incubator		Conventional Incubator
Arm/Group Description	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.		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.
All Cause Mortality
	GERI+ Incubator		Conventional Incubator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	GERI+ Incubator		Conventional Incubator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	GERI+ Incubator		Conventional Incubator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.