Quality of Human Embryos in IVF, Culturing in Differentiated Oxygen

NCT ID: NCT05737381

Last Updated: 2023-02-27

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

RECRUITING

Clinical Phase

NA

Total Enrollment

350 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-09-15

Study Completion Date

2025-12-31

Brief Summary

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The goal of this clinical trial is to evaluate the importance of differential O2 tension to the developing embryos. As a secondary aim, we investigate the levels of reactive oxygen species (ROS) in spent media from the developing blastocysts.

This is a prospective, interventional multicenter study using sibling embryos.

Woman (age 18-41 and normal weight) undergoing assisted reproductive technology (ART) can be included in the study.

Patients included in the project will follow standard IVF protocol and treatment.

By retrieving ≥ 8 oocytes after pickup and upon prior acceptance by the patient, she/the couple can be included in the study.

According to standard treatment, both groups of oocytes will be placed in an incubator with 5% O2.After 3 days of cultivation, the dishes with the study-embryos will be transferred to an incubator with 2% O2. The control embryos will remain in the conventional 5% O2 incubator.

On the fifth day, the embryos will be evaluated, and the blastocyst with expected greatest implantation potential will be transferred to the patients uterus. Surplus embryos with expected implantation potential will be cryopreserved. After transfer or cryopreservation, the media from the wells with used blastocysts will be collected and stored for ROS analysis.

Value for public Health:

If our hypothesis is confirmed, we will be able to optimize the developmental conditions and decreased ROS levels for the embryo in vitro. From a clinical perspective, this could affect the implantation rate of the blastocyst and thus the success of pregnancies for infertile couples while reducing the number of treatments to obtain a viable pregnancy.

Detailed Description

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The goal of this clinical trial is to evaluate the importance of differential O2 tension to the developing embryos. As a secondary aim, we investigate the levels of reactive oxygen species (ROS) in spent media from the developing blastocysts.

This is a prospective, interventional multicenter study using sibling embryos.

Woman (age 18-41 and normal weight) undergoing assisted reproductive technology (ART), with planned IVF or intracytoplasmic sperm injection (ICSI) cycles can be included in the study.

Patients included in the project will follow standard IVF protocol and treatment including hormonal injections, oocyte pick-up, embryo transfer and blastocyst cryopreservation. No further examinations or deviation from standard treatment is necessary in order to participate in the project.

By retrieving ≥ 8 oocytes after pickup and upon prior acceptance by the patient, she/the couple can be included in the study. The minimum number of 8 oocytes has been determined to ensure an average of two blastocysts. The oocytes, will be divided into 2 groups. The first part of the collected oocytes will be included as controls, whereas the second part of the collected oocytes will be included as study group.

According to standard treatment, both groups of oocytes will be placed in an incubator with 5% O2. From time-lapse videos, observations of fertilization and cleavage after 20 hours ± 1h and 44 hours ± 1h, respectively will be annotated. After 3 days of cultivation (68h± 1h), the dishes with the study-embryos will be transferred to a time-lapse incubator with ultralow O2 tension (2%). The control embryos will remain in the conventional 5% O2 time-lapse incubator.

On the fifth day, the embryos will be evaluated by a trained embryologist, and the blastocyst with expected greatest implantation potential will be transferred to the patients uterus. Surplus embryos with expected implantation potential will be cryopreserved. After transfer or cryopreservation, the media from the wells with used blastocysts will be collected and stored for ROS analysis.

Primary outcome:

a) Improved morphokinetics parameters; decreased time difference from 5-cell (t5) to blastocyst stage (tB) in the embryos cultured in differential O2 tensions.

As secondary outcomes:

1. Decreased ROS-activity in spent media from the developing blastocysts cultivated in differential O2 tensions.
2. Number of transferable/vitrified blastocyst in both study and test groups
3. Verification of clinical pregnancy, using ultrasound scanning around week 7. All pregnancies or miscarriage will be registered for all patients if possible.

Value for public Health:

If our hypothesis is confirmed as expected, we will be able to optimize the developmental conditions i.e. faster developmental rate from t5 to tB and decreased ROS levels for the embryo in vitro. From a clinical perspective, this could affect the implantation rate of the blastocyst and thus the success of pregnancies for infertile couples while reducing the number of treatments to obtain a viable pregnancy.

Conditions

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Infertility IVF Embryo

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Sibling study
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

SINGLE

Participants
Intervention for embryos will be masked when performing the morphokinetic and ROS analysis

Study Groups

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Control group

The oocytes from a patient, retrieving more than 8 oocytes will be divided into 2 sibling groups. The control group and the study group.

The first part of the collected oocytes, will be included as controls. If an unequal numbers of oocytes are collected, the extra oocyte will be included into the control group.

Control oocytes are, after fertilization, placed in conventional 5% O2 incubators and cultured herein for 5 days.

Group Type NO_INTERVENTION

No interventions assigned to this group

Study group

The second part of the collected oocytes, from a patient retrieving more than 8 oocytes, will be included as study group.

Study oocytes, are after fertilization, placed and cultured in conventional 5% O2 incubators for the first 3 days. At day 3, the embryos are moved to an incubator with 2% O2 tension and cultured until day 5.

Group Type EXPERIMENTAL

Differential oxygen tension

Intervention Type OTHER

By culturing the embryos in a differential O2 set-up, changing the O2 tension from reduced (5% O2) to ultralow (2% O2) from day 3 to day 5 of embryo development in vitro, we mimic the physiological differential changes in O2 as the embryo migrate from the oviduct to the uterus and develops in vivo.

Interventions

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Differential oxygen tension

By culturing the embryos in a differential O2 set-up, changing the O2 tension from reduced (5% O2) to ultralow (2% O2) from day 3 to day 5 of embryo development in vitro, we mimic the physiological differential changes in O2 as the embryo migrate from the oviduct to the uterus and develops in vivo.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

Patients undergoing assisted reproductive technology (ART), with planned IVF or intracytoplasmic sperm injection (ICSI) cycles.

Women age 18 - 41 years and BMI 18 - 35 kg/m2 (both inclusive) with ≥ 8 oocytes.

Patients will be included no later than at oocyte pick-up.

Exclusion Criteria

Patients with sperm from testes biopsy, congenital uterine abnormalities, presence of fibromas or polyps, or suspected hydro salpinges. Oocytes from donors.
Minimum Eligible Age

18 Years

Maximum Eligible Age

41 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Odense Patient Data Explorative Network

OTHER

Sponsor Role collaborator

University of Southern Denmark

OTHER

Sponsor Role collaborator

Odense University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tilde Eskildsen

Role: PRINCIPAL_INVESTIGATOR

Odense University Hospital

Locations

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Odense University Hospital

Odense, , Denmark

Site Status RECRUITING

Countries

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Denmark

Central Contacts

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Tilde Eskildsen

Role: CONTACT

+4565412324

Kirsten Simonsen

Role: CONTACT

+4586101388

Facility Contacts

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Tilde Eskildsen

Role: primary

+4565412324

Kirsten Simonsen

Role: backup

+4586101388

Other Identifiers

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S-20210143

Identifier Type: -

Identifier Source: org_study_id

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