Oxidative Stress-related Gene Expression in Cumulus Cells Among Low Responders

May 15, 2017 updated by: Porntip Sirayapiwat, Chulalongkorn University

Oxidative Stress-related Gene Expression in Cumulus Cells Among Low Responders to Controlled Ovarian Hyperstimulation During in Vitro Fertilization

In Vitro Fertilization is considered one of effective treatment for infertile couple. However, some women do not have adequate response to controlled ovarian hyperstimulation, resulting in low response which defined as less than 5 retrieved oocytes. There are studies claiming that live birth rates in these patient lower than normal responder (10-15 retrieved oocytes). Among factors contributing low response, oxidative stress, resulting from increased pro-oxidant and/or reduced antioxidant, is considered to effect the functions of follicles and quality of oocytes. However, there are few studies demonstrating this relation. Objective of our study is to find the difference of oxidative stress-related gene expression in cumulus cell and oocyte competence biomarkers from follicular fluid between low responders and normal responder to controlled ovarian hyperstimulation.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Low response to controlled ovarian hyperstimulation (less than 5 retrieved oocytes) is a problem in some of couple receiving treatment for infertility. Studies showed that success rate in treatment for these patients is lower than normal response group. Among many factors contributing low response, oxidative stress is suspected to be involved in malfunction of follicular environment and oocyte maturation. However, direct relationship between oxidative and oocyte function cannot be studied due to ethical concern, so many studies had studied oocyte's surrounding environment such as cumulus cell and follicular fluid instead.

In our study , we aim to study the difference in level of oxidative stress-related gene expression and oocyte competence biomarkers among low responders and normal responders. For oxidative stress-related gene expression of cumulus cell , we will measure mRNA expression by quantitative PCR for Superoxide dismutase 1 (SOD1) , SOD2 , Glutathione peroxidase (GPX) and Inducible nitric oxide synthase (iNOS) . For oocyte competent biomarkers, we will use ELISA technique to measure the level of GDF(, BMP15, Amphiregulin and CoQ10 in follicular fluid.

Sample size calculation was done with data from study performed by Donnabela et al , which found that Mean SOD gene expression in control group was 2.06 2-Δ ΔCT (SD = 0.53) . The formula for comparing two different mean was used with expectation that low responders group would have lower SOD gene expression by 20%.:

n/group = 2(Z α/2 + Z β)2 σ2 / (X̅ 1- X̅ 2)2

α = 0.05 , β = 0.2 Z α/2 = Z0.05/2 = 1.96 (two tail) Z β = Z0.8 = 0.84

Mean in group1 (X̅ 1) = 2.06, SD. in group1 (σ₁) = 0.53 Mean in group2 (X̅ 2) = 1.64, SD. in group2 (σ₂)= 0.53 Sample size: Group1 (n₁) = 25, Group2 (n₂) = 25 Total number is 56 patients (added 10% for possible data loss)

Statistical analysis

  1. Mean and Standard deviation will be used for descriptive data.
  2. Mann-Whitney U test , unpaired t-test and chi square will be used as appropriate
  3. p value less than 0.05 is considered statistical significant.

Study Type

Observational

Enrollment (Anticipated)

56

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

  • Thailand
      • Bangkok, Thailand, 10330
        • Faculty of Medicine ,Chulalongkorn University
        • Contact:
        • Contact:
        • Principal Investigator:
          • Porntip Sirayapiwat, MD,MSc
        • Principal Investigator:
          • Nalina Bhupornvivat, MD
        • Sub-Investigator:
          • Wisan Sereepapong, MD
        • Sub-Investigator:
          • Ruttachuk Rungsiwiwut, DVM,PhD

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

25 years to 49 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

Women aged 25-49 years old , who receiving care at infertile clinic ,King Chulalongkorn Memorial hospital

Description

Inclusion Criteria:

  • Low responder : women aged 25-49 years old with less than 5 oocytes (1-4 oocytes) retrieved during controlled ovarian hyperstimulation
  • Normal responder women aged 25-49 years old with 5-15 oocytes retrieved during controlled ovarian hyperstimulation

Exclusion Criteria:

  • Active ovarian pathology ( ovarian cyst or tumor)
  • Basal FSH more than 20 IU/L or Antimullerian hormone less than 0.5 ng/ml
  • Ovarian hyperstimulation syndrome

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

  • Observational Models: Case-Control
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Low responder

Low responder : women aged 25-49 years old with less than 5 oocytes (1-4 oocytes) retrieved during controlled ovarian hyperstimulation

Oxidative stress-related gene expression and oocyte competence biomarkers will be performed to access the difference between low and normal responders.
Diagnostic test: Oxidative stress-related gene expression (RNA expression)
Oxidative stress-related gene expression (RNA expression),Superoxide dismutase 1 (SOD1) , SOD2 , Glutathione peroxidase (GPX) and Inducible nitric oxide synthase (iNOS) , measured by Real time PCR technique.
Diagnostic test: oocyte competence biomarkers
Oocyte competence biomarkers ,GDF9, BMP15, Amphiregulin and CoQ10 measured by ELISA
Normal responder

Normal responder women aged 25-49 years old with 5-15 oocytes retrieved during controlled ovarian hyperstimulation

Oxidative stress-related gene expression and oocyte competence biomarkers will be performed to access the difference between low and normal responders.
Diagnostic test: Oxidative stress-related gene expression (RNA expression)
Oxidative stress-related gene expression (RNA expression),Superoxide dismutase 1 (SOD1) , SOD2 , Glutathione peroxidase (GPX) and Inducible nitric oxide synthase (iNOS) , measured by Real time PCR technique.
Diagnostic test: oocyte competence biomarkers
Oocyte competence biomarkers ,GDF9, BMP15, Amphiregulin and CoQ10 measured by ELISA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Oxidative stress-related gene expression
Time Frame: June 2017-May 2018
mRNA expression by quantitative PCR for Superoxide dismutase 1 (SOD1) SOD2 , Glutathione peroxidase (GPX) and Inducible nitric oxide synthase (iNOS).
June 2017-May 2018

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
oocyte competent biomarkers
Time Frame: June 2017-May 2018
ELISA technique to measure the level of GDF9, BMP15, Amphiregulin and CoQ10 in follicular fluid.
June 2017-May 2018

Collaborators and Investigators

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

Sponsor

Chulalongkorn University

Investigators

  • Principal Investigator: Porntip Sirayapiwat, MD, Chulalongkorn University

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 (Anticipated)

June 1, 2017

Primary Completion (Anticipated)

March 30, 2018

Study Completion (Anticipated)

May 31, 2018

Study Registration Dates

First Submitted

May 15, 2017

First Submitted That Met QC Criteria

May 15, 2017

First Posted (Actual)

May 16, 2017

Study Record Updates

Last Update Posted (Actual)

May 16, 2017

Last Update Submitted That Met QC Criteria

May 15, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • RA60/041
  • Med Chula IRB No.688/59 (Other Identifier: Faculty of Medicine,Chulalongkorn university)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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.

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