Adding Antioxidants Into Human Sequential Culture Media System (Antioxidants)

November 30, 2018 updated by: Vitrolife

Comparison of G-Series Media System With Antioxidants Versus Standard G-Series Media System

Upon collection, human oocytes are fertilized and culture up to the blastocyst stage, followed by transfer and / or cryopreservation. Culture media systems have been developed that support each step of this process. Although these culture media systems try to mimic the natural environment, several components of the in-vivo situation are not present in today´s media. One such component is anti-oxidants that may protect embryos against damage by reactive oxygen species.

This investigation aims to compare blastocyst development using 2 different types of culture media systems, one of which contains antioxidants. Patients having at least eight oocytes and meeting other inclusion criteria can be included in this investigation.

It is a prospective randomized multicenter study randomly dividing oocytes into two groups and assessing parameters of embryo development from fertilization up to blastocyst formation until day six. Embryos with acceptable developmental characteristics can be transferred into the uterus or cryopreserved for later use.

The investigation is designed as a superiority study comparing utilization rate of blastocysts per normally fertilized oocyte using both media systems. In patients receiving embryo transfer in the fresh treatment cycle, detection of clinical pregnancy by ultrasound after 12 weeks gestation is the final endpoint of the investigation.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Study objective:

Study comparing blastocyst development on the same cohort of oocytes using two different media systems, sequential G-Series media versus sequential G-Series media supplemented with antioxidants.

Primary endpoint:

Percentage of good quality blastocysts (GQB) per fertilized oocyte on day 5.

Secondary endpoints:

Embryo development day 3, 5 and 6 Embryo quality day 3, 5 and 6 Total blastocyst formation (day 5 and day 6) Utilization rate (embryos available for transfer and cryopreservation) Biochemical pregnancy rate Implantation rate Clinical pregnancy rate

Setup:

Prospective oocyte sibling, superiority study

MATERIALS AND METHODS

Intervention:

New type of embryo culture media used for in vitro culture of human IVF embryos.

Power analysis:

The planning and the power analysis was made together with a statistician, Nils-Gunnar Pehrsson.

From retrospective data using simulation, the intra individual SD for the difference in % GQB between the two media strategies was estimated to 32%. In order to find a difference in 8% in GQB between the two media with power 80% with paired T-test 128 couples will be needed.

Randomization:

Couples will be enrolled in the study at oocyte pick up (day 0). A minimum of 8 cumulus-oocyte-complexes is required for participation.

Stratified randomization of the oocytes by couple will be performed. For each couple the oocytes will be numbered.

These oocytes for each couple will then be block (by two) randomized to the two media types; A (Traditional G-Series media system = Control) and B (G-Series media system with antioxidant = intervention). In both groups traditional culture will be performed. Allocation will be performed in a 1:1 ratio according to a unique randomization list for each couple.

Blinding:

To minimize possible bias for the primary outcome (GQB D5) the embryologist performing the morphological evaluation on day 5/6 will not know which group the embryos belong to.

Both the physician and the couple will be blinded in respect to from which group an embryo was selected for transfer.

IVF treatment procedure:

A traditional IVF treatment will be performed including ovarian stimulation and oocyte pick-up using the standard methods at the clinics.

Embryo assessment on day 3 according to Alpha/ESHRE consensus criteria and on day 5 according to Gardner score.

Morphological scoring Embryo development and morphology on day 3 will be scored based on the Alpha/ESHRE Consensus criteria. Blastocyst development and morphology will be scored according to a published scoring system for blastocysts and will be documented with individual photos of each blastocyst. Embryo & Blastocyst scoring will be performed under an inverted microscope on day 3 and days 5 & 6, respectively. Blastocysts that have a score equal or higher than 3BB are considered as GQB.

DOCUMENTATION All patients participating in the study will be documented on a computerized CRF. This document will contain study-specific relevant clinical and laboratory data from the specific IVF cycle.

STATISTICAL ANALYSIS Both an Intention-to-Treat (ITT) population and a Per Protocol (PP) population will be defined. Primary efficacy variable in this superiority study will be difference in % GQB between the two media types for each couple. Primary statistical analysis will be two-sided paired T-test regarding the mean of difference in % GQB between Standard sequential culture media and Antioxidant media on the ITT population. A two sided 95% confidence interval for the mean difference in % GOB between the two media will be calculated. All significance tests will be two-sided and conducted at the 5% significance level.

Study Type

Interventional

Enrollment (Actual)

128

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
      • Fukuoka, Japan, 8120013
        • Kuramoto Women´s Clinic
      • Tokyo, Japan, 135-0042
        • Kiba Park Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Minimum eight cumulus-oocyte-complexes.
  • Couples with female, male or unexplained infertility intending to undergo IVF
  • The couple should have received verbal and written information/consent about the study.
  • Blastocyst culture and embryo transfer is decided.
  • If the couple fulfills the criteria above their consent to participate must be given and documented in the couple's medical journal.

Exclusion Criteria:

  • Previous participation in the study
  • PGD/PGS
  • Surgically retrieved sperm cells (TESA / TESE)
  • If split IVF is needed
  • Less than eight cumulus-oocyte-complexes
  • More than thirty cumulus-oocyte-complexes

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control
Sequential culture media without addition of antioxidants
Active Comparator: Treatment
Sequential culture media with the addition of antioxidants
Biological: Antioxidants
In the Treatment Arm, the G-Series culture media system will be used with antioxidants
Other Names:
  • Acetyl-L-carnitine (ALC)
  • N-acetyl-L-cysteine (NAC)
  • alpha-Lipoic acid (ALA)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Percentage of good quality blastocyst (GQB) per fertilized oocyte on day 5
Time Frame: 7 months
7 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Embryo development on day 3, 5 & 6
Time Frame: 7 months
7 months
Embryo quality on day 3, 5 & 6
Time Frame: 7 months
7 months
Total blastocyst rate
Time Frame: 7 months
7 months
Blastocyst utilization rate per fertilized oocyte
Time Frame: 7 months
7 months
Biochemical pregnancy rate
Time Frame: 8 months
8 months
Clinical pregnancy rate
Time Frame: 9 months
9 months
Implantation rate
Time Frame: 8 months
8 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vitrolife

Investigators

  • Principal Investigator: A Yoshida, MD, PhD, Kiba Park Clinic, Tokyo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2016

Primary Completion (Actual)

May 1, 2018

Study Completion (Actual)

May 1, 2018

Study Registration Dates

First Submitted

December 16, 2016

First Submitted That Met QC Criteria

December 16, 2016

First Posted (Estimate)

December 21, 2016

Study Record Updates

Last Update Posted (Actual)

December 3, 2018

Last Update Submitted That Met QC Criteria

November 30, 2018

Last Verified

November 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AOX-G_Series-2016

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Blastocyst

Clinical Trials on Antioxidants

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Pakistan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe