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Comparison of the effect of letrozole with N-acetylcysteine on the expression levels of genes involved in glucose metabolism and the proliferation of cumulus cells in patients with polycystic ovarian syndrome.

Protocol summary

Study aim
The aim of this study is to help treat infertility in patients with polycystic ovary syndrome who are candidates for assisted reproductive techniques.
Design
A clinical trial with control and intervention groups, with parallel groups, without blinding, randomized, phase 2 will be conducted on 20 patients with polycystic ovary syndrome. The rand function of Excel software will be used for randomization.
Settings and conduct
In this clinical trial, 20 patients with polycystic ovary syndrome referred to the infertility clinic of Al-Zahra Hospital, are evaluated in terms of the effect of letrozole and N-acetylcysteine on the expression levels of genes involved in glucose metabolism and expansion in the cumulus cells of these patients.
Participants/Inclusion and exclusion criteria
Inclusion criteria: patients are based on two of the three main criteria of lack of proper ovulation (oligo/anovulation), clinical or laboratory evidence of hyperandrogenism, polycystic ovary morphology on ultrasound (Rotterdam criteria), normal thyroid function and prolactin, and the patient's infertility for at least one year. Exclusion criteria: thyroid and prolactin dysfunction, uterine disorders leading to infertility.
Intervention groups
Intervention group1: patients with polycystic ovary syndrome(PCOS ) treated with gonadotropin, metformin and letrozole. Intervention group 2: patients with PCOS treated with gonadotropin, metformin and N-acetylcysteine(NAC) Intervention group 3:patients with PCOS treated with gonadotropin, metformin and letrozole plus NAC Control group: patients with PCOS treated with gonadotropin and metformin
Main outcome variables
Expression level of genes involved in glucose metabolism in cumulus cells of patients with polycystic ovary syndrome (PCOS) Expression level of genes involved in the expansion of cumulus cells in patients with PCOS.

General information

Reason for update
Acronym
IRCT registration information
IRCT registration number: IRCT20221019056244N1
Registration date: 2023-03-30, 1402/01/10
Registration timing: registered_while_recruiting

Last update: 2023-03-30, 1402/01/10
Update count: 0
Registration date
2023-03-30, 1402/01/10
Registrant information
Name
Ebrahim Jaefarzadeh arabshah
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 41 3328 5258
Email address
jaefarzadeharabshah@tbzmed.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2023-03-21, 1402/01/01
Expected recruitment end date
2023-05-22, 1402/03/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Comparison of the effect of letrozole with N-acetylcysteine on the expression levels of genes involved in glucose metabolism and the proliferation of cumulus cells in patients with polycystic ovarian syndrome.
Public title
The effect of letrozole and N-acetylcysteine in the treatment of infertility in patients with polycystic ovary syndrome
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Ovulation disorder (oligo ovulation or anovulation). Clinical or laboratory evidence of high testosterone levels Morphology of polycystic ovary in ultrasound Normal thyroid function Normal prolactin test At least one year has passed since the patient's infertility. Normal analysis of the patient’s husband’s semen
Exclusion criteria:
Thyroid dysfunction. Uterine abnormalities leading to infertility Ovarian cysts larger than 6 centimeters. History of asthma. Taking any drug effective in glucose metabolism Abnormality of prolactin tests
Age
No age limit
Gender
Female
Phase
2
Groups that have been masked
No information
Sample size
Target sample size: 20
Randomization (investigator's opinion)
Randomized
Randomization description
A simple randomization method will be used to grouping the participants. In this method, the list of all participants names obtained firstly, then a score or number is assigned to each of them, and finally the Excel software function RAND will be used for randomization. In order to conceal the random allocation, sealed opaque envelopes with the random sequence will be used. In this method, a random sequence is created by the RAND function of Excel software firstly, then 20 envelopes, based on the sample size of the research, with aluminum wrapper (in order to make the contents of the envelopes unclear) are prepared and each of the random sequences is registered on the card. Then the cards are placed in the envelopes in order. In order to maintain a random sequence, the outer surface of the envelopes is numbered in the same order. Finally the envelopes is glued and placed in a box. At the time of registration, based on the order of eligible participants entered the study, one of the envelopes will be opened and the assigned group of that participant will be revealed
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Parallel
Other design features

Secondary Ids

empty

Ethics committees

1

Ethics committee
Name of ethics committee
Ethics committee of Tabriz University of Medical Sciences
Street address
Al-Zahra educational and treatment center, Baghshamal intersection, South Army street, Tabriz, East Azerbaijan,
City
Tabriz
Province
East Azarbaijan
Postal code
۵۱۳۸۶۶۵۷۹۳
Approval date
2022-08-29, 1401/06/07
Ethics committee reference number
IR.TBZMED.1401.511

Health conditions studied

1

Description of health condition studied
Polycystic ovary syndrome
ICD-10 code
E28.2
ICD-10 code description
Polycystic ovarian syndrome

Primary outcomes

1

Description
Hyaluronan synthase 2 gene expression level
Timepoint
About 14 days after the start of the treatment, we will not measure at the beginning of the study.
Method of measurement
Polymerase chain reaction device

2

Description
Versican gene expression level
Timepoint
About 14 days after the start of the treatment, we will not measure at the beginning of the study.
Method of measurement
Polymerase chain reaction device

Secondary outcomes

1

Description
Phosphofructokinase, Platelet gene expression level
Timepoint
About 14 days after the start of the treatment, we will not measure at the beginning of the study.
Method of measurement
Polymerase chain reaction device

2

Description
Pyruvate kinase M2 gene expression level
Timepoint
About 14 days after the start of the treatment, we will not measure at the beginning of the study.
Method of measurement
Polymerase chain reaction device

Intervention groups

1

Description
"Intervention group1:" This group receive a daily dose of 1500 mg of Metformin (Tehran Chemie Pharmaceutical Company) along with 5 mg of letrozole (Iran Hormon Pharmaceutical Company) from the second or third day of the menstrual cycle until one day before human chorionic gonadotropin injection. On the third day of stimulation with letrozole, a hormonal combination similar to the follicle stimulating hormone, which is SinalF here (containing follitropin alpha and manufactured by Synagen Pharmaceutical Company) with a daily dose of 150 to 225 units and in if necessary (according to the patient's age and ultrasound condition and predicting the response to the treatment), he will receive up to 75 international units. Three days after the prescription of Sinal F, the patients will undergo transvaginal ultrasound to measure the thickness of the endometrium, as well as the number and diameter of mature follicles and when the size of the follicles reaches 13-14 mm, the gonadotropin-stimulating hormone agonist which is an injectable powder of 250 micrograms of Sterotide with a dose of 25 hundred micrograms is prescribed daily for the patient until the day of human chorionic gonadotropin injection. After identifying at least three follicles with a size above 17 to 18 mm by ultrasound (especially on one of the eighth to tenth days of injection), 5000 to 10000 units of human chorionic gonadotropin are injected to the patient intramuscularly. Next, 34-36 hours after the prescription of human chorionic gonadotropin, oocytes are aspirated from the ovaries under ultrasound guidance using the transvaginal method. And then the cumulus-oocyte complex is separated from the aspirated sample. At this stage, the oocytes are examined from the point of view of development by a stereomicroscope, and the oocytes of the metaphase stage 2 are collected with a frequency of more than 80 percent. Then, in order to remove cellular pollutants and reduce the possibility of contamination of granulosa cells, the cumulus-oocyte complex was serially washed three times by an experienced embryologist in an enzyme-free culture medium, and then the cumulus cells were separated from the cumulus-oocyte complex through mechanical and enzymatic methods within an hour of egg retrieval. After that, the mass of cumulus cells taken from cumulus-oocytes collection is kept in separate tubes containing 5 times the sample volume of one liter of RNA solution for one day and night at 4 degrees Celsius. And then it will be kept at minus 80 degrees Celsius until the stage of ribonucleic acid extraction and evaluation of the expression of the studied genes with a thermocycler device.
Category
Treatment - Drugs

2

Description
"Intervention group2:" This group receive a daily dose of 1500 mg of Metformin (Tehran Chemie Pharmaceutical Company) along with 1200 mg of N-acetylcysteine (Osveh Pharmaceutical Company) from the second or third day of the menstrual cycle until one day before human chorionic gonadotropin injection and on the third day of stimulation with N-acetylcysteine, a hormonal combination similar to the follicle stimulating hormone, which is SinalF here (containing follitropin alpha and manufactured by Synagen Pharmaceutical Company) with a daily dose of 150 to 225 units and in if necessary (according to the patient's age and ultrasound condition and predicting the response to the treatment), he will receive up to 75 international units. Three days after the prescription of Sinal F, the patients will undergo transvaginal ultrasound to measure the thickness of the endometrium, as well as the number and diameter of mature follicles and when the size of the follicles reaches 13-14 mm, the gonadotropin-stimulating hormone agonist which is an injectable powder of 250 micrograms of Sterotide with a dose of 25 hundred micrograms is prescribed daily for the patient until the day of human chorionic gonadotropin injection. After identifying at least three follicles with a size above 17 to 18 mm by ultrasound (especially on one of the eighth to tenth days of injection), 5000 to 10000 units of human chorionic gonadotropin are injected to the patient intramuscularly. Next, 34-36 hours after the prescription of human chorionic gonadotropin, oocytes are aspirated from the ovaries under ultrasound guidance using the transvaginal method. And then the cumulus-oocyte complex is separated from the aspirated sample. At this stage, the oocytes are examined from the point of view of development by a stereomicroscope, and the oocytes of the metaphase stage 2 are collected with a frequency of more than 80 percent. Then, in order to remove cellular pollutants and reduce the possibility of contamination of granulosa cells, the cumulus-oocyte complex was serially washed three times by an experienced embryologist in an enzyme-free culture medium, and then the cumulus cells were separated from the cumulus-oocyte complex through mechanical and enzymatic methods within an hour of egg retrieval. After that, the mass of cumulus cells taken from cumulus-oocytes collection is kept in separate tubes containing 5 times the sample volume of one liter of RNA solution for one day and night at 4 degrees Celsius. And then it will be kept at minus 80 degrees Celsius until the stage of ribonucleic acid extraction and evaluation of the expression of the studied genes with a thermocycler device.
Category
Treatment - Drugs

3

Description
"Intervention group 3:" This group receive a daily dose of 1500 mg of Metformin (Tehran Chemie Pharmaceutical Company) along with 5 mg of Letrozole (Iran Horton Pharmaceutical Company) and 1200 mg of N-acetylcysteine (Osveh Pharmaceutical Company) from the second or third day of the menstrual cycle until one day before human chorionic gonadotropin injection. On the third day of stimulation with letrozole plus N-acetylcysteine, a hormonal combination similar to the follicle stimulating hormone, which is SinalF here (containing follitropin alpha and manufactured by Synagen Pharmaceutical Company) with a daily dose of 150 to 225 units and in if necessary (according to the patient's age and ultrasound condition and predicting the response to the treatment), he will receive up to 75 international units. Three days after the prescription of Sinal F, the patients will undergo transvaginal ultrasound to measure the thickness of the endometrium, as well as the number and diameter of mature follicles and when the size of the follicles reaches 13-14 mm, the gonadotropin-stimulating hormone agonist which is an injectable powder of 250 micrograms of Sterotide with a dose of 25 hundred micrograms is prescribed daily for the patient until the day of human chorionic gonadotropin injection. After identifying at least three follicles with a size above 17 to 18 mm by ultrasound (especially on one of the eighth to tenth days of injection), 5000 to 10000 units of human chorionic gonadotropin are injected to the patient intramuscularly. Next, 34-36 hours after the prescription of human chorionic gonadotropin, oocytes are aspirated from the ovaries under ultrasound guidance using the transvaginal method. And then the cumulus-oocyte complex is separated from the aspirated sample. At this stage, the oocytes are examined from the point of view of development by a stereomicroscope, and the oocytes of the metaphase stage 2 are collected with a frequency of more than 80 percent. Then, in order to remove cellular pollutants and reduce the possibility of contamination of granulosa cells, the cumulus-oocyte complex was serially washed three times by an experienced embryologist in an enzyme-free culture medium, and then the cumulus cells were separated from the cumulus-oocyte complex through mechanical and enzymatic methods within an hour of egg retrieval. After that, the mass of cumulus cells taken from cumulus-oocytes collection is kept in separate tubes containing 5 times the sample volume of one liter of RNA solution for one day and night at 4 degrees Celsius. And then it will be kept at minus 80 degrees Celsius until the stage of ribonucleic acid extraction and evaluation of the expression of the studied genes with a thermocycler device.
Category
Treatment - Drugs

4

Description
"Control group:" This group receive a daily dose of 1500 mg of Metformin (Tehran Chemie Pharmaceutical Company) from the second or third day of the menstrual cycle until one day before human chorionic gonadotropin injection. From the fifth day of the menstrual cycle, they receive a hormonal combination similar to the follicle stimulating hormone, which is SinalF here (containing follitropin alpha and manufactured by Synagen Pharmaceutical Company) with a daily dose of 150 to 225 units and in if necessary (according to the patient's age and ultrasound condition and predicting the response to the treatment), he will receive up to 75 international units. Three days after the prescription of Sinal F, the patients will undergo transvaginal ultrasound to measure the thickness of the endometrium, as well as the number and diameter of mature follicles and when the size of the follicles reaches 13-14 mm, the gonadotropin-stimulating hormone agonist which is an injectable powder of 250 micrograms of Sterotide with a dose of 25 hundred micrograms is prescribed daily for the patient until the day of human chorionic gonadotropin injection. After identifying at least three follicles with a size above 17 to 18 mm by ultrasound (especially on one of the eighth to tenth days of injection), 5000 to 10000 units of human chorionic gonadotropin are injected to the patient intramuscularly. Next, 34-36 hours after the prescription of human chorionic gonadotropin, oocytes are aspirated from the ovaries under ultrasound guidance using the transvaginal method. And then the cumulus-oocyte complex is separated from the aspirated sample. At this stage, the oocytes are examined from the point of view of development by a stereomicroscope, and the oocytes of the metaphase stage 2 are collected with a frequency of more than 80 percent. Then, in order to remove cellular pollutants and reduce the possibility of contamination of granulosa cells, the cumulus-oocyte complex was serially washed three times by an experienced embryologist in an enzyme-free culture medium, and then the cumulus cells were separated from the cumulus-oocyte complex through mechanical and enzymatic methods within an hour of egg retrieval. After that, the mass of cumulus cells taken from cumulus-oocytes collection is kept in separate tubes containing 5 times the sample volume of one liter of RNA solution for one day and night at 4 degrees Celsius. And then it will be kept at minus 80 degrees Celsius until the stage of ribonucleic acid extraction and evaluation of the expression of the studied genes with a thermocycler device.
Category
Treatment - Drugs

Recruitment centers

1

Recruitment center
Name of recruitment center
Al-Zahra Hospital
Full name of responsible person
Maryam Pashaei Asl
Street address
Al-Zahra educational and treatment center, Baghshamal intersection, South Army street, Tabriz, East Azerbaijan,
City
Tabriz
Province
East Azarbaijan
Postal code
۵۱۳۸۶۶۵۷۹۳
Phone
+98 41 3553 9161
Fax
+98 41 3556 6449
Email
pashaim@tabzmed.ac.ir
Web page address

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
Tabriz University of Medical Sciences
Full name of responsible person
Dr. Maryam Pashaei Asl
Street address
Al-Zahra educational and treatment center, Baghshamal intersection, South Army street, Tabriz, East Azerbaijan
City
Tabriz
Province
East Azarbaijan
Postal code
۵۱۳۸۶۶۵۷۹۳
Phone
+98 41 3553 9161
Fax
+98 41 3556 6449
Email
pashaim@tabzmed.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Tabriz 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
Tabriz University of Medical Sciences
Full name of responsible person
Maryam Pashaei Asl
Position
Associate Professor
Latest degree
Medical doctor
Other areas of specialty/work
Reproductive Biology
Street address
Al-Zahra medical training center, Baghshamal intersection, South Army street, Tabriz , Eastern Azerbaijan
City
Tabriz
Province
East Azarbaijan
Postal code
5138663134
Phone
+98 41 3553 9161
Email
pashaim@tbzmed.ac.ir

Person responsible for scientific inquiries

Contact
Name of organization / entity
Tabriz University of Medical Sciences
Full name of responsible person
Maryam Pashaei Asl
Position
Associate Professor
Latest degree
Medical doctor
Other areas of specialty/work
Reproductive Biology
Street address
Al-Zahra medical training center, Baghshamal intersection, South Army street, Tabriz , Eastern Azerbaijan
City
Tabriz
Province
East Azarbaijan
Postal code
5138663134
Phone
+98 41 3553 9161
Email
pashaim@tbzmed.ac.ir

Person responsible for updating data

Contact
Name of organization / entity
Tabriz University of Medical Sciences
Full name of responsible person
Maryam Pashaei Asl
Position
Associate Professor
Latest degree
Medical doctor
Other areas of specialty/work
Reproductive Biology
Street address
Al-Zahra medical training center, Baghshamal intersection, South Army street, Tabriz , Eastern Azerbaijan
City
Tabriz
Province
East Azarbaijan
Postal code
5138663134
Phone
+98 41 3553 9161
Email
pashaim@tbzmed.ac.ir

Sharing plan

Deidentified Individual Participant Data Set (IPD)
No - There is not a plan to make this available
Justification/reason for indecision/not sharing IPD
No more information
Study Protocol
No - There is not a plan to make this available
Statistical Analysis Plan
No - There is not a plan to make this available
Informed Consent Form
No - There is not a plan to make this available
Clinical Study Report
No - There is not a plan to make this available
Analytic Code
No - There is not a plan to make this available
Data Dictionary
No - There is not a plan to make this available
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