The Effect of Astaxanthin Administration on Oxidative Stress Markers and Inflammatory Cytokines in the Follicular Fluid of Patients with Poor Ovarian Response: A Triple-Blind, Randomized control trial
Therefore, the aim of this study is to investigate the effect of astaxanthin on the oxidative stress and inflammatory cytokines markers in follicular fluid and assisted reproductive technology results in patients with poor ovarian response.
Design
Two arm parallel group, Triple-Blind, Randomized control trial and outcome assessment
Randomization will be in the form of blocking.
40 patients with poor ovarian response will enter the project. Patients will be randomly divided into two groups: group one will receive 12 mg of astaxanthin (2 capsules) per day and group two will receive placebo capsules for 8 weeks.
Settings and conduct
The location of the experiment: Tehran University of Medical Sciences. Sampling location: Omid fertility center.
This clinical trial is a randomized, triple-blind placebo-controlled trial. In any clinical trial, three groups can influence the results of the study, these three groups are 1- the participants in the research, 2- the implementers of the plan, 3- the evaluators or others who analyze the obtained data. If blinding is done for all three groups involved, it is called a triple-blind study.
Participants/Inclusion and exclusion criteria
Inclusion criteria: (i) advanced maternal age (>40 years), (ii) a previous poor response, defined as ≤3 oocytes retrieved after a standard ovarian stimulation, (iii) or an abnormal ovarian reserve test (AFC < 5–7 follicles and/or AMH < 1.1 ng/mL).
Exclusion criteria: including history of ovarian surgery, autoimmune or endocrine disease, severe male factor infertility
Intervention groups
Astaxanthin consumer. Placebo consumer.
Main outcome variables
1- The following markers will be checked in follicular fluid:
MDA, SOD, TAC, IL-6, IL-8, VEGF, Cell free DNA
2- Consequences of ART:
Evaluation of the number of antral follicles, number of retrieved oocytes, oocyte and embryo quality, fertilization rate, chemical pregnancy rate
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20230223057510N1
Registration date:2023-03-16, 1401/12/25
Registration timing:prospective
Last update:2023-03-16, 1401/12/25
Update count:1
Registration date
2023-03-16, 1401/12/25
Registrant information
Name
Anahid Shafie
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 8826 0049
Email address
shafie-a@alumnus.tums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2023-04-04, 1402/01/15
Expected recruitment end date
2024-01-05, 1402/10/15
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
The Effect of Astaxanthin Administration on Oxidative Stress Markers and Inflammatory Cytokines in the Follicular Fluid of Patients with Poor Ovarian Response: A Triple-Blind, Randomized control trial
Public title
The Effect of Astaxanthin Administration on poor Ovarian Response
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
POR will be diagnosed based on Blogna criteria and having at least two of the following three criteria: (i) advanced maternal age (>40 years),
(ii) a previous poor response, defined as ≤3 oocytes retrieved after a standard ovarian stimulation,
(iii) or an abnormal ovarian reserve test (antral follicle count (AFC) < 5–7 follicles and/or anti-Mullerian hormone (AMH) < 1.1 ng/mL).
The couple should be a candidate for ICSI
and do not have any history of male factor infertility.
Exclusion criteria:
including pregnancy,
history of ovarian surgery,
autoimmune or endocrine disease (diabetes, thyroid dysfunction, presence of anti-thyroid antibody or polycystic ovary),
hyperprolactinemia,
severe endometriosis (stages III and IV based on AFS-rAFS classification of endometriosis),
recurrent Spontaneous miscarriage,
ovarian tumor,
chromosomal defect,
uterine disorder,
more than 3 previous IVF cycles,
severe male factor infertility (especially non-obstructive azoospermia),
history of taking drugs that affect ovarian function such as steroids and OCP.
Also, people who have used antioxidant supplements or drugs affecting the hormonal profile 6 months before the start of the plan will not be included in the plan.
Age
From 25 years old to 42 years old
Gender
Female
Phase
3
Groups that have been masked
Participant
Care provider
Investigator
Outcome assessor
Data analyser
Sample size
Target sample size:
40
Randomization (investigator's opinion)
Randomized
Randomization description
Eligible patients will be randomly assigned to the study after visiting the gynecology clinic. Randomization will be in the form of blocking in such a way that the method of replacement blocks is used within each floor. The blocks will be binary, consisting of AB and BA. The randomization tool will be a table of random numbers, that using the sequence AB for numbers zero through 4 in the random number table and the sequence BA for 5 to 9.It should be noted that the letter A means the intervention group and the letter B means the control group For hiding we use concealment allocation in a way that before the individual is assigned, the assigned group is not specified. In this method, each of the random sequences created on a cards are placed in the closed envelopes. In order to maintain a random sequence, the envelopes are numbered in the same way on the outer surface. Finally, the lids of the envelopes are glued and placed inside a box, respectively. At the time of registration of participants, based on the order of entry of the eligible participants in the study, one of the closed envelopes will be opened and the assigned group of the participant will be revealed.
Blinding (investigator's opinion)
Triple blinded
Blinding description
This study will be a three-way blind and the patient, researcher and statistical analyst of the patients' group therapy have no information and the decoder is outside the research team. The drug under study (Astaxanthin) and placebo in a completely similar shape and appearance, each of which is in the same bottle instead of the drug will be provided to the subjects based on random allocation. It should be noted that the drug content of each The bottles are code-tagged on the bottles by the by someone outside the research team consultant and the research team is not aware of their interpretation.
Placebo
Used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
research ethics committees of scholl of medicine- Tehran university of medical sciences
Street address
Building no.1, Northern gate of the university, Poursina St. Qods St. Enqelab St
City
Tehran
Province
Tehran
Postal code
1417653761
Approval date
2023-01-01, 1401/10/11
Ethics committee reference number
IR.TUMS.MEDICINE.REC.1401.636
Health conditions studied
1
Description of health condition studied
Poor ovarian response
ICD-10 code
E28.8
ICD-10 code description
Other ovarian dysfunction: Poor ovarian response
Primary outcomes
1
Description
Malondialdehyde (MDA)
Timepoint
8 weeks after the intervention
Method of measurement
Spectrophotometry
2
Description
Superoxide dismutase (SOD)
Timepoint
8 weeks after the intervention
Method of measurement
Spectrophotometry
3
Description
Total antioxidant capacity (TAC)
Timepoint
8 weeks after the intervention
Method of measurement
Spectrophotometry
4
Description
IL-6
Timepoint
8 weeks after the intervention
Method of measurement
ELISA kit
5
Description
IL-8
Timepoint
8 weeks after the intervention
Method of measurement
ELISA kit
6
Description
VEGF
Timepoint
8 weeks after the intervention
Method of measurement
ELISA kit
7
Description
Cell free DNA
Timepoint
8 weeks after the intervention
Method of measurement
Real time pcr
8
Description
basal FSH
Timepoint
before the beginning of the intervention
Method of measurement
ELISA kit
9
Description
basal LH
Timepoint
before the beginning of the intervention
Method of measurement
ELISA kit
10
Description
Estradiol
Timepoint
before the beginning of the intervention
Method of measurement
ELISA kit
11
Description
Progestrone
Timepoint
before the beginning of the intervention
Method of measurement
ELISA kit
12
Description
AMH
Timepoint
before the beginning of the intervention
Method of measurement
ELISA kit
13
Description
Antral Follicle Count
Timepoint
before the beginning of the intervention
Method of measurement
vaginal sonography
Secondary outcomes
1
Description
Number and quality of oocytes
Timepoint
8 weeks after the intervention
Method of measurement
Counting, light microscope
2
Description
Number and quality of embryos
Timepoint
8 weeks and 3 days after the intervention
Method of measurement
Counting, light microscope
3
Description
Antral Follicle Count
Timepoint
8 weeks after the intervention
Method of measurement
Vaginal sonography
4
Description
fertility rate
Timepoint
8 weeks and 1 day after the intervention (1 day after oocyte pick up)
Method of measurement
light microscope
5
Description
Chemical pregnancy
Timepoint
14 days after embryo transfer
Method of measurement
beta-hCG blood test
Intervention groups
1
Description
Intervention group: in this group patients, will receive 12 mg of astaxanthin capsules per day (in 3 capsules of 4mg a day) for 8 weeks. The appearance of placebo and astaxanthin capsules are completely similar in terms of color, shape, size and packaging, and patients will not know the contents of the package until the end of the project.
Category
Treatment - Drugs
2
Description
Control group: in this group, patients will receive placebo capsules (3 capsules per day) for 8 weeks. The appearance of placebo and astaxanthin capsules are completely similar in terms of color, shape, size and packaging, and patients will not know the contents of the package until the end of the project.
Category
Placebo
Recruitment centers
1
Recruitment center
Name of recruitment center
Omid fertility clinic
Full name of responsible person
Dr. Ashraf Alyasin
Street address
Baharestan street
City
Tehran
Province
Tehran
Postal code
1417653761
Phone
+98 21 7767 0696
Fax
Email
omidivf@yahoo.com
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Dr Akbar Fotoohi
Street address
6th floor of Research and Technology Vice-Chancellor, Central Organization of the University, corner of Qods St, Keshavarz Blvd, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1417653761
Phone
+98 21 8163 3619
Email
tums_edu@tums.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Tehran University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic
Person responsible for general inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Fardin Amidi
Position
professor
Latest degree
Ph.D.
Other areas of specialty/work
Anatomy
Street address
Poursina St. School of Medicine, Tehran University of Medical Sciences
City
Tehran
Province
Tehran
Postal code
1417653761
Phone
+98 21 6405 3411
Email
amidifardin@yahoo.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Fardin Amidi
Position
professor
Latest degree
Ph.D.
Other areas of specialty/work
Anatomy
Street address
Poursina St. School of Medicine, Tehran University of Medical Sciences
City
Tehran
Province
Tehran
Postal code
1417653761
Phone
+98 21 6405 3411
Email
amidifardin@yahoo.com
Person responsible for updating data
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Anahid Shafie
Position
PhD candidate of reproductive biology
Latest degree
Master
Other areas of specialty/work
Reproductive Biology
Street address
Poursina St. School of Medicine, Tehran University of Medical Sciences, Anatomy department
City
Tehran
Province
Tehran
Postal code
1417653761
Phone
+98 21 6405 3404
Fax
Email
shafie.a1996@gmail.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to make this available
Study Protocol
Yes - There is a plan to make this available
Statistical Analysis Plan
Undecided - It is not yet known if there will be a plan to make this available
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Yes - There is a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Undecided - It is not yet known if there will be a plan to make this available
Title and more details about the data/document
All data obtained in the research will be published in one of the valid and related scientific journals.
When the data will become available and for how long
2025
To whom data/document is available
Researchers working in academic institutions
Under which criteria data/document could be used
The data of this study can be used as an adjuvant therapy in patients with poor ovarian response underwent IVF/ICSI.
From where data/document is obtainable
Anahid Shafie
What processes are involved for a request to access data/document