Assess the Efficacy of Differentiated and Undifferentiated Stem Cell Therapy in Improving Endometrial Receptivity.Phase 1NCT01649752
Role of Stem Cells in Improving Implantation Rates in ICSI Patients
A Phase 1 study testing Differentiated stem cells to endometrium is deposited in the uterine cavity through an IUI catheter and Undifferentiated MSC is deposited in the uterine cavity through an IUI catheter. in people with Assess the Efficacy of Differentiated and Undifferentiated Stem Cell Therapy in Improving Endometrial Receptivity., run by Kasr El Aini Hospital at 1 site in Egypt.
Trial summary
Background: Improving implantation rates in ICSI cycles has been the focus of research in recent decades. Because success rates is not satisfactory enough especially when transferring good embryos to the uterine cavity and pregnancy does not occur. Read more about this study
- Who is it for?
- Ages 20 to 40 years, women only
- Conditions the study is for
- Assess the Efficacy of Differentiated and Undifferentiated Stem Cell Therapy in Improving Endometrial Receptivity.
- What is being tested?
- Differentiated stem cells to endometrium is deposited in the uterine cavity through an IUI catheter and Undifferentiated MSC is deposited in the uterine cavity through an IUI catheter.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteEgypt
- Study dates
- Apr 2015to Oct 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- ICSI candidates with repeated implantation failure and history of development of good embryos in previous ICSI cycles.
- Advanced maternal age above 38 years.
- Poor endometrial response to ovulation induction drugs.
- Endometrial atrophy.
Who cannot join
- Presence of infection in the form of vaginitis, cervicitis or hydrosalpinx.
- Presence of uterine abnormality as uterine septum.
- Presence of any pathology distorting the uterine cavity as:
- submucus polyp or submucus myoma.
- Marked sperm morphology abnormality.
- High FSH > 12 IU.
Trial locations and contacts
1 site in 1 country.
Egypt1 site, 1 recruiting
- Recruiting
Kasr El-Aini hospital and private IVF center
Cairo
Nawara M Hashish, MD, 01223372047 ext. 202, nawaram@yahoo.com
About this study
Official title: Phase I Study of Role of Stem Cells in Improving Implantation Rates in ICSI Patients
Background:
Improving implantation rates in ICSI cycles has been the focus of research in recent decades. Because success rates is not satisfactory enough especially when transferring good embryos to the uterine cavity and pregnancy does not occur. Trying to improve endometrial receptivity, the investigators have thought about stem cell therapy as stem cells have played a pivotal role in regenerative medicine in many pathologies as myocardial infarction, Diabetes Mellitus and spinal cord injuries.
Read more
Garget and Healy reported in 2011 treatment of a case with Asherman's syndrome by administration of bone marrow stem cells in the uterine cavity. Endometrial growth and improved vascularity has been observed by ultrasound follow-up and Doppler study of endometrial blood flow. Endometrial regeneration has been enough to support pregnancy through successful IVF trial.
The investigators have succeeded in previous work to isolate MSC from placental tissue and differentiate it to endometrium-like cells. The investigators compared the differentiation ability of placental derived mesenchymal stem cells (MSC) and Wharton Jelly derived MSC to differentiate to endometrium under 3 different culture conditions: endometrium conditioned medium (ECM), follicular fluid (FF) conditioned medium and medium containing both. The investigators found that placental MSC has better differentiating ability to endometrium especially under culture conditions containing both ECM and FF as evidenced by prominent appearance of glandular pattern and expression of progesterone receptors in differentiated cells.
Therefore the investigators need to direct this study and test the effect of placental derived MSC in improving implantation rates in patients with recurrent implantation failure, unresponsive endometrium to ovulation induction drugs or with endometrial atrophy or advanced maternal age planning for ICSI trial.
Patients and Methods:
60 patients attending Kasr El-Aini assisted reproduction unit and private IVF center will be randomized to three groups by computer generated programs:
The first group, patients randomized to receive differentiated stem cell therapy:
After ovum pick-up, MSC differentiated to endometrium is deposited in the uterine cavity through an IUI catheter. Embryo transfer will be done at day 5 at the blastocyst stage to allow enough time for endometrial regeneration and increased endometrial receptivity.
The second group, patients randomized to receive undifferentiated stem cell therapy:
Immediately postmenstrual undifferentiated MSC is deposited in the uterine cavity through an IUI catheter to allow enough time for the MSC to differentiate as it needs 7-10 days for differentiation. Ovum pick-up will be done as usual while all other steps will be the same including embryo transfer which will be done at day 5.
The third group, control group:
Patients are randomized to receive no stem cell therapy; All ICSI steps from ovulation induction protocol to embryo transfer conditions will be the same for all groups.
Informed consent will be taken from the patients after detailed explanation of all steps of the procedure.
- Being tested
- Differentiated stem cells to endometrium is deposited in the uterine cavity through an IUI catheter, Undifferentiated MSC is deposited in the uterine cavity through an IUI catheter.
- Keywords
- Stem cells, Uterine cavity, Implantation, ICSI
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Differentiated stem cells to endometrium is deposited in the uterine cavity through an IUI catheterBiological
Undifferentiated MSC is deposited in the uterine cavity through an IUI catheter.Biological
| Study group | Role | What they receive |
|---|---|---|
| Differentiated stem cell therapy group | Experimental | After ovum pick-up, MSC differentiated to endometrium is deposited in the uterine cavity.Embryo transfer will be done at day 5 at the blastocyst stage. Receives: Biological: Differentiated stem cells to endometrium is deposited in the uterine cavity through an IUI catheter |
| undifferentiated stem cell therapy group | Experimental | Immediately postmenstrual undifferentiated MSC is deposited in the uterine cavity. Ovum pick-up will be done as usual.Embryo transfer will be done at day 5 at the blastocyst stage. Receives: Biological: Undifferentiated MSC is deposited in the uterine cavity through an IUI catheter. |
| Control group | No intervention | ovum pick-up as usual and embryo transfer at day 5 at the blastocyst stage. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Implantation rate
Comparison of the implantation rates of all groups; the differentiated stem cell group, the undifferentiated stem cell group and the control group to assess the efficacy of differentiated and undifferentiated stem cell therapy in improving endometrial receptivity.
Measured: 6 months
Secondary outcomes (1)
Endometrial volume and vascularity
Doppler study of the endometrial blood flow; the VI, FI and VFI and 3D-US assessment of endometrial volume in all groups at the day of embryo transfer to obtain objective assessment of the effect of differentiated and undifferentiated stem cell therapy on endometrial volume and vascularity in ICSI patients with advanced maternal age or history of repeated implantation failure.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2012 (estimated)
- Study startApr 2015
- Primary completionOct 2015 (estimated)
- Study completionOct 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Assess the Efficacy of Differentiated and Undifferentiated Stem Cell Therapy in Improving Endometrial Receptivity.Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kasr El Aini Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nawara Mohamed Hashish, Kasr El Aini Hospital
- Investigators
- Nawara Mohamed Hashish, MD, Principal investigator, Assistant Professor of Gynecology and Obstetrics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01649752
- Sponsor's protocol ID
- Stem cells and implantation
- Status last verified
- Jul 2012
- First submitted
- 23 Jul 2012
- Last updated
- 30 Jun 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Role of Stem Cells in Improving Implantation Rates in ICSI Patients
- ClinicalTrials.gov ID
- NCT01649752
- Acronym / sponsor ID
- Stem cells and implantation
- Keywords
- Stem cells, Uterine cavity, Implantation, ICSI
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Kasr El Aini HospitalUniversity, hospital or other
- Study start
- Apr 2015
- Primary completion
- Oct 2015 (estimated)
- Study completion
- Oct 2015 (estimated)
- First posted
- 25 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Improving implantation rates in ICSI cycles has been the focus of research in recent decades. Because success rates is not satisfactory enough especially when transferring good embryos to the uterine cavity and pregnancy does not occur. Trying to improve endometrial receptivity, the investigators have thought about stem cell therapy as stem cells have played a pivotal role in regenerative medicine in many pathologies as myocardial infarction, Diabetes Mellitus and spinal cord injuries.
Garget and Healy reported in 2011 treatment of a case with Asherman's syndrome by administration of bone marrow stem cells in the uterine cavity. Endometrial growth and improved vascularity has been observed by ultrasound follow-up and Doppler study of endometrial blood flow. Endometrial regeneration has been enough to support pregnancy through successful IVF trial.
The investigators have succeeded in previous work to isolate MSC from placental tissue and differentiate it to endometrium-like cells. The investigators compared the differentiation ability of placental derived mesenchymal stem cells (MSC) and Wharton Jelly derived MSC to differentiate to endometrium under 3 different culture conditions: endometrium conditioned medium (ECM), follicular fluid (FF) conditioned medium and medium containing both. The investigators found that placental MSC has better differentiating ability to endometrium especially under culture conditions containing both ECM and FF as evidenced by prominent appearance of glandular pattern and expression of progesterone receptors in differentiated cells.
Therefore the investigators need to direct this study and test the effect of placental derived MSC in improving implantation rates in patients with recurrent implantation failure, unresponsive endometrium to ovulation induction drugs or with endometrial atrophy or advanced maternal age planning for ICSI trial.
Patients and Methods:
60 patients attending Kasr El-Aini assisted reproduction unit and private IVF center will be randomized to three groups by computer generated programs:
The first group, patients randomized to receive differentiated stem cell therapy:
After ovum pick-up, MSC differentiated to endometrium is deposited in the uterine cavity through an IUI catheter. Embryo transfer will be done at day 5 at the blastocyst stage to allow enough time for endometrial regeneration and increased endometrial receptivity.
The second group, patients randomized to receive undifferentiated stem cell therapy:
Immediately postmenstrual undifferentiated MSC is deposited in the uterine cavity through an IUI catheter to allow enough time for the MSC to differentiate as it needs 7-10 days for differentiation. Ovum pick-up will be done as usual while all other steps will be the same including embryo transfer which will be done at day 5.
The third group, control group:
Patients are randomized to receive no stem cell therapy; All ICSI steps from ovulation induction protocol to embryo transfer conditions will be the same for all groups.
Informed consent will be taken from the patients after detailed explanation of all steps of the procedure.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Differentiated stem cell therapy group | Experimental | Biological: Differentiated stem cells to endometrium is deposited in the uterine cavity through an IUI catheterAfter ovum pick-up, MSC differentiated to endometrium is deposited in the uterine cavity.Embryo transfer will be done at day 5 at the blastocyst stage. |
| undifferentiated stem cell therapy group | Experimental | Biological: Undifferentiated MSC is deposited in the uterine cavity through an IUI catheter.Immediately postmenstrual undifferentiated MSC is deposited in the uterine cavity. Ovum pick-up will be done as usual.Embryo transfer will be done at day 5 at the blastocyst stage. |
| Control group | No intervention | –ovum pick-up as usual and embryo transfer at day 5 at the blastocyst stage. |
Who may qualify
- Ages
- 20 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- ICSI candidates with repeated implantation failure and history of development of good embryos in previous ICSI cycles.
- Advanced maternal age above 38 years.
- Poor endometrial response to ovulation induction drugs.
- Endometrial atrophy.
Key exclusion criteria (6 listed)
- Presence of infection in the form of vaginitis, cervicitis or hydrosalpinx.
- Presence of uterine abnormality as uterine septum.
- Presence of any pathology distorting the uterine cavity as:
- submucus polyp or submucus myoma.
- Marked sperm morphology abnormality.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Differentiated stem cells to endometrium is deposited in the uterine cavity through an IUI catheter | Biological | Differentiated stem cell therapy group |
| Undifferentiated MSC is deposited in the uterine cavity through an IUI catheter. | Biological | undifferentiated stem cell therapy group |
Primary outcome
Implantation rate
Time frame: 6 months
Comparison of the implantation rates of all groups; the differentiated stem cell group, the undifferentiated stem cell group and the control group to assess the efficacy of differentiated and undifferentiated stem cell therapy in improving endometrial receptivity.
1 secondary outcome
Endometrial volume and vascularity
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2015.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nawara Mohamed Hashish, MD principal investigator
Assistant Professor of Gynecology and Obstetrics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Differentiated stem cells to endometrium is deposited in the uterine cavity through an IUI catheter and Undifferentiated MSC is deposited in the uterine cavity through an IUI catheter. in people with Assess the Efficacy of Differentiated and Undifferentiated Stem Cell Therapy in Improving Endometrial Receptivity., run by Kasr El Aini Hospital at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nawara Mohamed Hashish, MD (01223372047 ext. 202, nawaram@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Implantation rate (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2015.