A Benchtop Incubator Prospective Study

NCT ID: NCT04969575

Last Updated: 2023-03-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

50 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-07-15

Study Completion Date

2023-12-31

Brief Summary

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The use of extended embryo culture to the blastocyst stage and preimplantation genetic testing for aneuploidy (PGT-A) has enabled identification and selection of embryos with the best developmental potential and improved in vitro fertilization (IVF) clinical outcomes. While numerous types of commercially available human embryo culture media exist for culture to the blastocyst stage, the impact of culture conditions on blastocyst development and aneuploidy formation is not well understood.

Culture conditions are very important for the success of the IVF cycle, many of the factors involved in the process have been extensively studied, including the use of sequential culture medium vs single step culture medium, humidified incubators vs dry incubators and refreshing the medium on day 3 vs uninterrupted culture till day 5. However, none of the studies investigated the effect on euploid rate in a sibling oocyte design with PGT-A, which requires culture till day 7.

Detailed Description

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It is considered a routine practice to grade the embryos on day 3 of development, which will require disturbing the culture conditions by annotating the embryos using inverted microscopes. Extended culture to day 7 is required in order to perform trophectoderm biopsy required for PGT-A. There are several culture factors that can affect embryo development, such as the pH, which is controlled through the concentration of CO2, and also the osmolality, which is the concentration of solute per liter of solution. Evaporation of the solution due to the exposure to high temperature (37°C) can change the concentrations and hence compromise embryo development.

To reduce the rate of evaporation, culture droplets are covered with a layer of mineral oil. Humidified incubators can also reduce the rate of evaporation. However, in the case of dry incubators, such as benchtop incubators, replenishing the culture medium at least once -by moving the embryos to a new culture dish- during these 7 days of culture might be the solution.

Since single-step medium is designed to sustain embryo development for 5 continuous culture days, while some laboratories culture embryos for 7 days, refreshing the culture medium is inevitable either on day 3 or day 5 of development.

There is no concrete evidence on which of these practices will provide a better environment for embryo development. Moreover, none of the studies investigated the effect of single-step culture medium changeover on day 3 or day 5, on the chromosomal errors (aneuploidy/mosaicism). Investigators aim in this prospective sibling oocyte study, to explore which day of culture medium refreshment (day 3 or day 5) provides a higher rate of euploid blastocysts.

Conditions

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Infertility

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

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day 3 refreshment

All MII oocytes will be inseminated by ICSI 39-41 hours post final oocyte maturation trigger.

Following ICSI, oocytes will be cultured in 2-4 culture dishes placed in 2 separate chambers.

Media refreshment: Zygote scoring on day 1 (18-20hpi). Culture medium refreshment will be done 67-69 hours post insemination (Day3). Embryo grading will not be done day2-5. Culture media preparation and refreshment: 30µL of culture medium (Global total LP is added to each well of the 8 wells of LifeGlobal GPS Dish (EGPS-010) and 50µL to the center 3 drops.

Dishes will be equilibrated overnight in a CO2 incubator. Embryo grading should be done prior to media refreshment. Time out of the incubator during media refreshment will be assessed on day 3 and day 5.

One operator should perform the ICSI. In case of multiple operators, each operator's injected oocytes will be split between the 2 groups.

Insemination and culture

Intervention Type OTHER

All MII oocytes will be inseminated by ICSI 39-41 hours post final oocyte maturation trigger.

Media refreshment Group 1

Intervention Type OTHER

Zygote scoring on day 1 (18-20hpi). Culture medium refreshment will be done 67-69 hours post insemination (Day3).

Culture media preparation and refreshment

Intervention Type OTHER

30µL of culture medium (Global total LP is added to each well of the 8 wells of LifeGlobal GPS Dish (EGPS-010) and 50µL to the center 3 drops.

Dishes will be equilibrated overnight in a CO2 incubator.

Embryo grading

Intervention Type OTHER

Should be done prior to media refreshment. For group 2, embryo grading and media refreshment is done prior to blastocyst biopsy.

day 5 refreshment

All MII oocytes will be inseminated by ICSI 39-41 hours post final oocyte maturation trigger.

Following ICSI, oocytes will be cultured in 2-4 culture dishes placed in 2 separate chambers.

Media refreshment and embryo grading timings: Zygote scoring on day 1 (18-20hpi). Embryo grading and culture media refreshment will be done 114-118 hours post insemination (Day5).

Culture media preparation and refreshment: 30µL of culture medium (Global total LP is added to each well of the 8 wells of LifeGlobal GPS Dish (EGPS-010) and 50µL to the center 3 drops. Dishes will be equilibrated overnight in a CO2 incubator.

Embryo grading and media refreshment is done prior to blastocyst biopsy. Time out of the incubator during media refreshment will be assessed on day 3 and day 5.

One operator should perform the ICSI. In case of multiple operators, each operator's injected oocytes will be split between the 2 groups.

Insemination and culture

Intervention Type OTHER

All MII oocytes will be inseminated by ICSI 39-41 hours post final oocyte maturation trigger.

Culture media preparation and refreshment

Intervention Type OTHER

30µL of culture medium (Global total LP is added to each well of the 8 wells of LifeGlobal GPS Dish (EGPS-010) and 50µL to the center 3 drops.

Dishes will be equilibrated overnight in a CO2 incubator.

Embryo grading

Intervention Type OTHER

Should be done prior to media refreshment. For group 2, embryo grading and media refreshment is done prior to blastocyst biopsy.

Media refreshment Group 2

Intervention Type OTHER

Zygote scoring on day 1 (18-20hpi). Culture media refreshment will be done 114-118 hours post insemination (Day5).

Interventions

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Insemination and culture

All MII oocytes will be inseminated by ICSI 39-41 hours post final oocyte maturation trigger.

Intervention Type OTHER

Media refreshment Group 1

Zygote scoring on day 1 (18-20hpi). Culture medium refreshment will be done 67-69 hours post insemination (Day3).

Intervention Type OTHER

Culture media preparation and refreshment

30µL of culture medium (Global total LP is added to each well of the 8 wells of LifeGlobal GPS Dish (EGPS-010) and 50µL to the center 3 drops.

Dishes will be equilibrated overnight in a CO2 incubator.

Intervention Type OTHER

Embryo grading

Should be done prior to media refreshment. For group 2, embryo grading and media refreshment is done prior to blastocyst biopsy.

Intervention Type OTHER

Media refreshment Group 2

Zygote scoring on day 1 (18-20hpi). Culture media refreshment will be done 114-118 hours post insemination (Day5).

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Patients with a minimum of 8 - 10 follicles during ovarian stimulation
* Patients with a minimum of 8 mature oocytes
* PGT-A
* ICSI
* BMI\<35
* Age 18- 40
* Fresh or frozen ejaculated sperm \>10,000 motile sperm
* Any ovarian stimulation
* Embryos cultured in benchtop incubator

Exclusion Criteria

* PGT-M or PGT-SR
* Previous history of embryo arrest
* Endometriosis
* History of previous treatment which may impact the ovarian reserve (adnexal surgery, chemotherapy, radiation…)
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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ART Fertility Clinics LLC

OTHER

Sponsor Role lead

Responsible Party

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Ibrahim Elkhatib

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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IBRAHIM ELKHATIB

Role: PRINCIPAL_INVESTIGATOR

ART Fertility Clinics LLC

Locations

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ART Fertility Clinics LLC

Abu Dhabi, , United Arab Emirates

Site Status RECRUITING

Countries

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United Arab Emirates

Central Contacts

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BARBARA LAWRENZ, PhD

Role: CONTACT

97126528000 ext. 1108

SHIERYL DIGMA, RN

Role: CONTACT

97126528000 ext. 1061

Facility Contacts

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Barbara Lawrenz, PhD

Role: primary

+97102 652 8000 ext. 1108

Shieryl Digma, RN

Role: backup

+97102 652 8000 ext. 1122

References

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Bavister BD, Poole KA. Duration and temperature of culture medium equilibration affect frequency of blastocyst development. Reprod Biomed Online. 2005 Jan;10(1):124-9. doi: 10.1016/s1472-6483(10)60813-9.

Reference Type BACKGROUND
PMID: 15705308 (View on PubMed)

Costa-Borges N, Belles M, Meseguer M, Galliano D, Ballesteros A, Calderon G. Blastocyst development in single medium with or without renewal on day 3: a prospective cohort study on sibling donor oocytes in a time-lapse incubator. Fertil Steril. 2016 Mar;105(3):707-713. doi: 10.1016/j.fertnstert.2015.11.038. Epub 2015 Dec 12.

Reference Type BACKGROUND
PMID: 26690010 (View on PubMed)

Pena F, Davalos R, Rechkemmer A, Ascenzo A, Gonzales M. Embryo development until blastocyst stage with and without renewal of single medium on day 3. JBRA Assist Reprod. 2018 Mar 1;22(1):49-51. doi: 10.5935/1518-0557.20180012.

Reference Type BACKGROUND
PMID: 29318868 (View on PubMed)

Krasnopolskaya KV, Beketova AN, Sesina NI, capital ES, Cyrillichinchenko NK, Badalyan GV, Sudarikova NM, Bocharova TV, Zakharchenko EO. The effect of short-term disturbance of day 3 embryo culture on the development and implantation. Gynecol Endocrinol. 2019;35(sup1):1-4. doi: 10.1080/09513590.2019.1632083.

Reference Type BACKGROUND
PMID: 31532309 (View on PubMed)

Related Links

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https://doi.org/10.1016/j.fertnstert.2010.07.607

1\. Mori, C., Kuwayama, M., Silber, S., Kagawa, N., Kato, H. Water evaporation and osmolality change of human embryo culture media in humid or in dry culture systems. Fertil. Steril. 2010; 94: s151

Other Identifiers

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2105-ABU-008-IK

Identifier Type: -

Identifier Source: org_study_id

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