Role of Stem Cells in Improving Implantation Rates in ICSI Patients

June 27, 2015 updated by: Nawara Mohamed Hashish, Kasr El Aini Hospital

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.

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 Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Nawara Mohamed Hashish, MD
  • Phone Number: 202 01223372047
  • Email: nawaram@yahoo.com

Study Locations

  • Egypt
      • Cairo, Egypt
        • Recruiting
        • Kasr El-Aini hospital and private IVF center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Differentiated stem cell therapy group
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.
Biological: Differentiated stem cells to endometrium is deposited in the uterine cavity through an IUI catheter
Experimental: undifferentiated stem cell therapy group
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.
Biological: Undifferentiated MSC is deposited in the uterine cavity through an IUI catheter.
No Intervention: Control group
ovum pick-up as usual and embryo transfer at day 5 at the blastocyst stage.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Endometrial volume and vascularity
Time Frame: 6 months
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.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kasr El Aini Hospital

Investigators

  • Principal Investigator: Nawara Mohamed Hashish, MD, Assistant Professor of Gynecology and Obstetrics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2015

Primary Completion (Anticipated)

October 1, 2015

Study Completion (Anticipated)

October 1, 2015

Study Registration Dates

First Submitted

July 23, 2012

First Submitted That Met QC Criteria

July 24, 2012

First Posted (Estimate)

July 25, 2012

Study Record Updates

Last Update Posted (Estimate)

June 30, 2015

Last Update Submitted That Met QC Criteria

June 27, 2015

Last Verified

July 1, 2012

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • Stem cells and implantation

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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