The main objective of this study is evaluation of implantation rate and clinical pregnancy after flushing of uterine in infertile patients with follicular fluid plus granulosa cells in IVF/ ICSI cycles.
Design
A randomized clinical trial with control group, double blind, two arm parallel group design of 140 patients. Randomization is performed using a computer-generated random assignment schedule for each patient. Sealed and numbered envelopes are used to conceal the treatment allocation until randomization.
Settings and conduct
Female infertility Clinic of ROYAN institute.
Participants/Inclusion and exclusion criteria
- Age 20-38 years
- Normal ovarian reserve
- Normal Hormonal profile (FSH, LH, AMH) and normal AFC
- Regular menstrual cycle
- IVF / ICSI or IVF or ICSI cycles with Agonist Protocol
- Existence of at least 2 oocytes in dominant follicular fluids
Intervention groups
Intervention group: Flushing of follicular fluid with granulosa cells is performed 36-34 hours after hCG injection. Non-intervention group: control
Follicular fluid flushing with granulosa cells is not performed on the day of hCG injection.
Main outcome variables
Determination of implantation and clinical pregnancy rates after flushing of uterine cavity in the intervention group (with follicular fluid flushing with granulosa cells) in comparison with the control group (without follicular fluid flushing with granulosa cells)
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20080831001141N29
Registration date:2020-12-19, 1399/09/29
Registration timing:registered_while_recruiting
Last update:2020-12-19, 1399/09/29
Update count:0
Registration date
2020-12-19, 1399/09/29
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
2018-11-01, 1397/08/10
Expected recruitment end date
2022-03-21, 1401/01/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Evaluation of implantation rate and clinical pregnancy after intrauterine flushing of infertile patients with follicular fluid plus granulosa cells
Public title
Intrauterine Flushing With Follicular Fluid Plus Granulosa Cells
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Normal Hormonal profile (FSH, LH, AMH) and normal AFC
Normal ovarian reserve
Age 20-38 years
Regular menstrual cycle
IVF / ICSI or IVF or ICSI cycles with Agonist Protocol
Existence of at least 2 oocytes in dominant follicular fluids
Exclusion criteria:
Presence of Endometriosis and Endometrioma
Hydrosalpinx
OHSS (Ovarian Hyper Stimulating Syndrome)
Tubal factor infertility
Age <38 years old
Male factor infertility with azoospermia
Low/Poor Response
Myoma with a compression effect or submocusa myometrium
Intra mural or subserouse Myoma > 5cm
Presence of untreated Thyroid, Diabetic and Hepatitis diseases, vaginal infection
Endometrial tuberculosis
Patients with any special drug intake
The follicular fluid which contains any oocyte or contaminated with blood will be discarded
Age
From 20 years old to 38 years old
Gender
Female
Phase
3
Groups that have been masked
Participant
Investigator
Sample size
Target sample size:
140
Randomization (investigator's opinion)
Randomized
Randomization description
Consecutive sampling until the required sample size is reached. Women by Balanced Block Randomization method are randomly divided into 2 equal groups of 70 people (intervention group and control group). Block randomization method is designed by epidemiologist using STATA software version 13 and the number of blocks considered is 4. Envelopes are prepared for 140 people and inside each envelope is written the group in which the patient should be placed. The envelopes are prepared in a way that the writing inside is not clear. A nurse before the patient enters the operating room, removes the envelope and sends the patients in one of the two groups.
Blinding (investigator's opinion)
Double blinded
Blinding description
In this study, a doctor performs intrauterine flushing of follicular fluid with granulosa cells in the intervention group. COCs aspiration will be performed 34-36h after hCG injection. Clear Follicular Fluids (without blood cells) which contain COCs will be used. Therefore, in this study, it is not possible to blind the doctor. In order to blind the patients participating in this study, all conditions will be the same between the two groups (participating patients blindness). All patients in case and control groups will receive GnRH agonist protocol. Ovarian stimulation will be carried out when pituitary desensitization is achieved and is continued until the day of hCG administration. The control group would not have FF endometrial flushing. In both groups, embryo transfer will be carried out 2-3 days later. Luteal phase support will be started the day after ovum pick up by the vaginal administration of progesterone daily for 16 days and will continued for up to12 weeks if pregnancy occurred. Pregnancy was diagnosed by measurement of β-hCG level and later was confirmed by Transvaginal sonography. The researcher also reviews the results based on the received code (researcher blindness).
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
1
Registry name
مرکز ثبت کارآزمائي هاي باليني ايالات متحده آمريکا (www.clinicaltrial.gov)
Secondary trial Id
NCT04077970
Registration date
2018-11-01, 1397/08/10
Ethics committees
1
Ethics committee
Name of ethics committee
Ethics Committee of Royan Institute
Street address
Royan Institute, Number 12, East Hafez Avenue, Banihashem Street, Resalat Highway
City
Tehran
Province
Tehran
Postal code
148- 16635
Approval date
2017-08-15, 1396/05/24
Ethics committee reference number
IR.ACECR.ROYAN.REC.1396.135
Health conditions studied
1
Description of health condition studied
Infertile women with male factor
ICD-10 code
N97.9
ICD-10 code description
Female infertility, unspecified
Primary outcomes
1
Description
Evaluation of implantation rate
Timepoint
Only once, day 35-42 post ovum pick-up
Method of measurement
Based on the number of gestational sacs observed, divided by the number of embryos transferred
Secondary outcomes
1
Description
clinical pregnancy rate
Timepoint
Only once; 6 weeks after embryo transfer
Method of measurement
Vaginal ultrasound
Intervention groups
1
Description
Intervention group: Women will undergo intrauterine flushing with follicular fluid plus granulosa cells. COCs aspiration will be performed 34-36h after hCG injection. Clear Follicular Fluids (without blood cells) which contain COCs will be used. Follicular fluid flushing after oocyte retrieval with 2 ml of clear FF plus granulose cells will be performed by an IUI catheter.
Category
Treatment - Other
2
Description
Control group: Women will not undergo intrauterine flushing with follicular fluid plus granulosa cells.
Category
Treatment - Other
Recruitment centers
1
Recruitment center
Name of recruitment center
ROYAN Institute
Full name of responsible person
Maryam Hafezi
Street address
Royan Institute, Number 12, East Hafez Avenue, Banihashem Street, Resalat Highway
City
Iran
Province
Tehran
Postal code
148- 16635
Phone
+98 21 2356 2727
Fax
+98 21 2230 6481
Email
maryamhafezi90@yahoo.com
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
ROYAN Institute
Full name of responsible person
Parvaneh Afsharian
Street address
Royan Institute, Number 12, East Hafez Avenue, Banihashem Street, Resalat Highway.
City
Tehran
Province
Tehran
Postal code
148- 16635
Phone
+98 21 2356 2727
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
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Other
Person responsible for general inquiries
Contact
Name of organization / entity
ROYAN Institute
Full name of responsible person
Maryam Hafezi
Position
Associate professor
Latest degree
Specialist
Other areas of specialty/work
Gynecology and Obstetrics
Street address
Royan Institute, Number 12, East Hafez Avenue, Banihashem Street, Resalat Highway
City
Tehran
Province
Tehran
Postal code
148- 16635
Phone
+98 21 2356 2727
Email
maryamhafezi90@yahoo.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
ROYAN Institute
Full name of responsible person
Maryam Hafezi
Position
Associate professor
Latest degree
Specialist
Other areas of specialty/work
Gynecology and Obstetrics
Street address
Royan Institute, Number 12, East Hafez Avenue, Banihashem Street, Resalat Highway
City
Tehran
Province
Tehran
Postal code
148- 16635
Phone
+98 21 2356 2727
Email
maryamhafezi90@yahoo.com
Person responsible for updating data
Contact
Name of organization / entity
ROYAN Institute
Full name of responsible person
Maryam Hafezi
Position
Associate professor
Latest degree
Specialist
Other areas of specialty/work
Gynecology and Obstetrics
Street address
Royan Institute, Number 12, East Hafez Avenue, Banihashem Street, Resalat Highway.
City
Tehran
Province
Tehran
Postal code
148- 16635
Phone
+98 21 2356 2727
Email
maryamhafezi90@yahoo.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Yes - There is a plan to make this available
Study Protocol
Undecided - It is not yet known if there will be 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
Clinical study report (published article)
When the data will become available and for how long
After the publication of the article
To whom data/document is available
Available to the public
Under which criteria data/document could be used
Scientific use by citing the source
From where data/document is obtainable
Dr. Maryam Hafezi
What processes are involved for a request to access data/document