The effect of adding L-carnitine during ovarian stimulation with antagonistic protocol in patients with polycystic ovarian syndrome (PCOS) on the outcome of in-vitro fertilization/intracytoplasmic sperm injection (IVF / ICSI) cycle: A double-blind randomized clinical trial
To evaluate the effect of oral L-carnitine supplementation during controlled ovarian stimulation (COS) in patients with polycystic ovary syndrome (PCOS) in a double-blind randomized clinical trial
Design
A controlled randomized double-blind clinical trial with parallel groups, phase III
Settings and conduct
The study at Royan Research Institute was designed as a clinical trial and both patients and researchers will not be aware of the type of grouping and only the main researcher who is not involved in the sampling process will know the coding of the main drugs and placebo.
Participants/Inclusion and exclusion criteria
All patients with a diagnosis of polycystic ovary syndrome will be evaluated according to Rotterdam criteria who were eligible and had written consent to participate in the study.
Intervention groups
The controlled ovarian stimulation procedure in all the study participants will be the same by using a flexible regimen of GnRH-antagonist with E2 priming. In the experimental group, the women received 3 tablets of L-carnitine daily (L-carnitine® tablet 1000 mg, Karen Pharmaceutical Company, Iran) from day 2 of the previous menstrual cycle until pregnancy test day. The method of ovarian stimulation in the control group is completely similar to the intervention group and they take placebo tablets instead of L-carnitine supplements.
Main outcome variables
Total number of retrieved oocytes; Total number of MII oocytes;
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20080831001141N42
Registration date:2023-07-19, 1402/04/28
Registration timing:retrospective
Last update:2023-07-19, 1402/04/28
Update count:0
Registration date
2023-07-19, 1402/04/28
Registrant information
Name
Kiandokht Kiani
Name of organization / entity
Royan Institute
Country
Iran (Islamic Republic of)
Phone
+98 21 2230 7960
Email address
kiandokht.kiani@royaninstitute.org
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2020-03-01, 1398/12/11
Expected recruitment end date
2022-12-29, 1401/10/08
Actual recruitment start date
2023-02-28, 1401/12/09
Actual recruitment end date
2023-02-28, 1401/12/09
Trial completion date
2023-02-28, 1401/12/09
Scientific title
The effect of adding L-carnitine during ovarian stimulation with antagonistic protocol in patients with polycystic ovarian syndrome (PCOS) on the outcome of in-vitro fertilization/intracytoplasmic sperm injection (IVF / ICSI) cycle: A double-blind randomized clinical trial
Public title
The effect of L-carnitine supplementation on the results of infertility treatment cycle in women with polycystic ovary syndrome
Purpose
Supportive
Inclusion/Exclusion criteria
Inclusion criteria:
Patients between 20 to 37 years old, presenting with primary or secondary infertility following regular intercourse for at least 1 year and diagnosed with PCO according to Rotterdam's criteria who had received two to three failures of intrauterine insemination (IUI) cycle therapy were included. The diagnosis was based on a complete history taking, physical examination, and a complete file documented infertility work-up within the previous 6 months, either conducted within the setting of the hospital or at a licensed infertility management clinic.
Exclusion criteria:
Patients diagnosed with hyperprolactinemia, diabetes mellitus, epilepsy, and/or any chronic endocrine and cardiovascular diseases
Patients are treated with a special diet, medication supplement (ovaboost), and metformin before or during ovarian stimulation
History of pelvic surgery on ovaries and uterus
Presence of submucosal and intramural fibroids larger than 5 cm or the presence of uterine polyps and congenital uterine malformations
The cause of severe male infertility (sperm extraction through surgery)
Age
To 37 years old
Gender
Female
Phase
3
Groups that have been masked
Participant
Care provider
Investigator
Outcome assessor
Data analyser
Sample size
Target sample size:
110
Actual sample size reached:
97
Randomization (investigator's opinion)
Randomized
Randomization description
The medicine packages, as well as the appearance and smell of L-carnitine and placebo tablets, are completely similar to each other. The methodologist prepared the drugs based on the block randomization method and prepared the coded list and put an English three-letter code label on the medicine cans. When an eligible patient is referred to a clinical physician, the principal investigator provides him with an envelope containing a drug code based on a randomized list, and the drug package with the same code is delivered to the patient. In this way, the patient and the clinical doctor following the patient will not know the type of drug (L-carnitine or placebo).
Blinding (investigator's opinion)
Double blinded
Blinding description
The patients in the control group will receive 3 placebo tablets for 8 weeks. All the placebo tablets were produced by Karen company (Tehran, Iran), which is approved by the Food and Drug Administration of Iran. The appearance of the placebo was indistinguishable in color, shape, size, and smell from L-carnitine tablets.
Day of oocyte pick-up, 32-34 hours after hCG administration (approximately Stimulation Day 10)
Method of measurement
At the point of ovum pick-up, we can count the total number of retrieved oocytes. Therefore, in one hour after ovum pick-up, outcome measurement will be possible.
2
Description
Total number of mature (MII) oocytes
Timepoint
Day of oocyte pick-up, 32-34 hours after hCG administration (approximately Stimulation Day 10)
Method of measurement
At the point of ovum pick-up, we can count the total number of mature (MII) oocytes. Therefore, in one hour after ovum pick-up, outcome measurement will be possible.
Secondary outcomes
1
Description
Fertilization rate
Timepoint
17-18 h after intracytoplasmic sperm injection and/or in-vitro insemination by checking the number of polar bodies and pronuclei
Method of measurement
The fertilization rate was defined as the ratio between the number of diploid zygotes and the number of mature oocytes
2
Description
Quality of obtained embryos
Timepoint
3 days after IVF/ICSI procedure
Method of measurement
Embryo grade was assessed under an inverted microscope 3 days after the intracytoplasmic sperm injection procedure. The quality of embryos was graded from 1 to 3 under inverted microscope 3 days after the intracytoplasmic sperm injection procedure. Embryos with even-sized blastomeres and/or ≤10% fragments were classified as Grade 1 (Excellent or good quality). Grade 2 embryos (moderate or fair quality) had blastomeres with slightly-moderate size differences and/or 10- 20% fragments. Grade 3 embryos (poor quality) had markedly different-sized blastomeres and/or >20% fragments.
3
Description
Clinical pregnancy rate
Timepoint
7 weeks after embryo transfer
Method of measurement
It was defined as the presence of a gestational sac with a heartbeat under vaginal ultrasonography
Intervention groups
1
Description
In the experimental group: patients receive 3 grams daily (3 tablets of L-carnitine 1000 mg, Karen Pharmaceutical Company, Iran) from the second day of menstruation of the previous cycle until the day of the pregnancy test (for 8 weeks).
Category
Treatment - Drugs
2
Description
In the control group: patients receive 3 placebo tablets daily (containing cellulose similar to L-carnitine tablets in terms of size, shape, color, and smell, Karen Pharmaceutical Company, Iran) from the second day of menstruation of the previous cycle until the day of the pregnancy test (for 8 weeks).
Category
Placebo
Recruitment centers
1
Recruitment center
Name of recruitment center
Royan Institute
Full name of responsible person
Maryam Hafezi
Street address
No. 12, Shahid Soleimani Highway, Bani Hashem St., East Hafez St., Royan Institute
City
Tehran
Province
Tehran
Postal code
1165659711
Phone
+98 21 2356 2000
Email
maryamhafezi90@yahoo.com
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Royan Institute
Full name of responsible person
Dr. Parvaneh Afsharian
Street address
No. 12, Shahid Soleimani Highway, Bani Hashem St., East Hafez St., Royan Institute
City
Tehran
Province
Tehran
Postal code
1165659711
Phone
+98 21 2356 2674
Email
pafshar@royaninstitute.org
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Royan Institute
Proportion provided by this source
100
Public or private sector
Private
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
Royan Institute
Full name of responsible person
Arezoo Arabipoor
Position
Researcher
Latest degree
Master
Other areas of specialty/work
Midwifery
Street address
No. 12, Shahid Soleimani Highway, Bani Hashem St., East Hafez St., Royan Institute
City
Tehran
Province
Tehran
Postal code
1165659711
Phone
+98 21 2356 2640
Email
arezoo.arabipoor@gmail.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Royan Institute
Full name of responsible person
Maryam Hafezi
Position
Assistance Professor
Latest degree
Specialist
Other areas of specialty/work
Gynecology and Obstetrics
Street address
No. 12, Shahid Soleimani Highway, Bani Hashem St., East Hafez St., Royan Institute
City
Tehran
Province
Tehran
Postal code
1165659711
Phone
+98 21 2356 2642
Email
maryamhafezi90@yahoo.com
Person responsible for updating data
Contact
Name of organization / entity
Royan Institute
Full name of responsible person
Arezoo Arabipoor
Position
Reseacher
Latest degree
Master
Other areas of specialty/work
Midwifery
Street address
No. 12, Shahid Soleimani Highway, Bani Hashem St., East Hafez St., Royan Institute
City
Tehran
Province
Tehran
Postal code
1165659711
Phone
+98 21 2356 2640
Email
arezoo.arabipoor@gmail.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Yes - There is a plan to make this available
Study Protocol
Yes - There is a plan to make this available
Statistical Analysis Plan
Not applicable
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
Not applicable
Data Dictionary
Not applicable
Title and more details about the data/document
The personal data of the participants in the study as well as the data related to the main outcome will be reported between the two groups without mentioning their names.
When the data will become available and for how long
The access period starts 6 months after the results are published
To whom data/document is available
The study data will be available only to researchers working in academic and scientific institutions
Under which criteria data/document could be used
Researchers who intend to write a review and meta-analysis study can access the project data and documentation through correspondence with the project facilitator, whose details are provided on the site.
From where data/document is obtainable
To access the documents and raw data, it is necessary to study the administrative correspondence with the research deputy of Royan Institute and correspondence with the respondent whose details have been announced on the site.
What processes are involved for a request to access data/document
6 months after the publication of the article in scientific journals, they can send their request through official correspondence or email with the research deputy of the Royan Institute. Access to the data may take up to one month after the application is submitted.