Clinical trial NCT05737381: Quality of Human Embryos in IVF, Culturing in Differentiated Oxygen
Official title: Can a Differentiated Oxygen Setup Improve Embryo Quality and Increase the Number of Usable Embryos After in Vitro Fertilization (IVF)?
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Infertility
IVF
Embryo
Keywords: Oxygen
Blastocyst
Time lapse
ROS
Embryology
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
Collaborators: name: Odense Patient Data Explorative Network
name: University of Southern Denmark
First posted: 2023-02-21
Enrollment: 350
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 41
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Sibling study
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Improved morphokinetics parameters
timeFrame: Analysis of morphokinetic, will be finalised approximately 12 months after last intervention.
Secondary outcomes:
measure: Decreased ROS-activity
timeFrame: Analysis of ROS will be finalised approximately 12 months after interventions have been completed.
measure: Number of transferable/frozen blastocyst
timeFrame: Number count of transferable/vitrified blastocysts will be finalised approximately 6 months after interventions have been complete
measure: Clinical pregnancy (CP)
timeFrame: Data of CP from fresh transfers can be finalised 12 months after last intervention. Data of CP from frozen blastocyst can be finalized either within the project or if not used within the following year, in a followup project.
Other outcomes:
Locations:
city: Odense
country: Denmark
facility: Odense University Hospital
Study officials:
affiliation: Odense University Hospital
name: Tilde Eskildsen
role: PRINCIPAL_INVESTIGATOR
References: