mtDNA and Embryo Metabolism

Definition: Evaluation of Mitichondrial Values and it Relationship With Embryo Metabolism and Mitochondrial Homeostasis.

The present study has the objective to study whether the mitochondrial DNA copy number values that can be generated when human embryos are analyzed for chromosomal content before embryo transfer correlates with the actual number of mitochondria as well as their energy requirements of the human embryo.

Study Overview

• Status: Unknown
• Conditions: Embryo Metabolic Activity
• Intervention / Treatment: Other: Mitochondrial DNA content and metabolic parameters

Detailed Description

The possibility of analyzing trophectoderm cells from human blastocyst during preimplantational genetic testing offers the opportunity of analyzing not only the chromosomal constitution of the trophoblastic cells, and by extension, to infer not with certain degree of uncertainty, the chromosomal content in the inner cell cells mass and the entire embryo; but analyzing other interesting aspects related to cellular physiology such us the mtDNA content.

The number of mitochondrial copy number has a huge variation among oocytes from the same cohort and also from oocytes from different patients. It is believed that this initial number of mtDNA content is correlated with the ability of oocytes to fertilized and to achieve blastocyst stage. Whatever the initial concentration of mtDNA a given oocyte will have, it expected to equally segregate into the number of blastomeres along embryo development, so the mtDNA copy number of per daughter cell will transiently decrease, being the smallest at the blastocyst stage. Studies in different mammalian species including humans have shown that mtDNA replication does not occur before morula stage so the mitochondrial content of the oocytes should be enough to sustain embryo development before implantation occurs.

The net amount of mitochondrial DNA will exponentially increase at blastocyst stage coinciding with an increases in oxygen consumption. Despite the mtDNA copy number is higher in ICM compared to TE cells the proportion of moderate and high activity mitochondria is higher in the TE cells. This also agrees with mitochondrial morphological changes in the trophectoderm cells where mitochondria are much more elongated, less matrix electrodense and have more cristae, in ICM the will be rounded and more electrodense.

The objective of the present work is to analyze whether a correlation exist between the mitochondrial DNA copy number and both the actual number of mitochondria in the blastocyst and the metabolic needs of the human blastocysts and the ATP production.

• Study Type: Observational
• Enrollment (Anticipated): 171

Contacts and Locations

Study Locations

• Spain
  • Valencia, Spain, 46015
    • Recruiting
    • Maria Jose DeLosSantos
    • Contact: Maria Jose DeLosSantos, PhD; Phone Number: +34963050900; Email: mjdelossantos@ivi.es
    • Contact: Leslie Atkinson; Phone Number: +34963050925; Email: leslie.atkinson@ivi.es
    • Principal Investigator: Maria Jose Delossantos, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 days to 5 days (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Blastocysts from women undergoing PGT-A and available for analysis )

Description

Inclusion Criteria of women whose blastocysts will undergo PGT-A and be eligible for study:

• > 38 years old
• Sperm count: > 2 million spermatozoids/ml
• Oocytes retrieved > 4 oocytes MII
• Antral Follicles (AFC: ≥4)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Aneuploid mitochondria; Mitochondrial DNA content and metabolic parameters	Other: Mitochondrial DNA content and metabolic parameters; Analyze the correlation between the mitochondrial DNA content and metabolic parameters.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between mitochondrial DNA content and number of mitochondria and Correlation between mitochondrial DNA content and metabolic turnover	Correlation index between each variable	Each embryo will need an average of one week for assessment

Collaborators and Investigators

• Sponsor: Instituto Valenciano de Infertilidad, IVI VALENCIA
• Collaborators: Igenomix

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 30, 2017
• Primary Completion (ANTICIPATED): December 1, 2018
• Study Completion (ANTICIPATED): February 1, 2019

Study Registration Dates

• First Submitted: June 29, 2017
• First Submitted That Met QC Criteria: June 29, 2017
• First Posted (ACTUAL): July 2, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 11, 2017
• Last Update Submitted That Met QC Criteria: July 7, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: mitochondrial copy, number and energy
• Other Study ID Numbers: 1606-VLC-047-MD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No