Infertility, FemalePhase 2NCT03166189
Autologous Bone Marrow-derived Mesenchymal Stem Cells for Atrophic Endometrium in Patients With Repeated IVF Failures
A Phase 2 study testing bone marrow-derived MSC and HRT and hormonal replacement therapy in people with Infertility, Female and Infertility of Uterine Origin, run by D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology at 1 site in Russia.
Trial summary
Investigators will examine safety and efficiency of the cell product of autologous bone marrow-derived mesenchymal stem cells (MSC) for patients with repeated IVF failures and hypoplastic or/and fibrosis process of endometrium Read more about this study
- Who is it for?
- Ages 21 to 44 years, women only
- Conditions the study is for
- Infertility, Female, Infertility of Uterine Origin, Asherman Syndrome
- What is being tested?
- bone marrow-derived MSC and HRT and hormonal replacement therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteRussia
- Study dates
- 20 Dec 2017to 28 Dec 2019
- Phase
- Phase 2
- 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 21 to 44 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Repeated IVF attempts with high and good quality embryo transfer in fresh and frozen IVF cycles;
- Age 20-44 years;
- Endometrial thickness less than 6 mm in 2 or more of HRT cycles for endometrial preparation for embryo transfer
- Hysteroscopic evidence of fibrosis processes of uterine cavity with the absence of positive dynamics of HRT in 3 months following operation;
- Signed informed consent.
Who cannot join
- Contraindication for pregnancy;
- Absence of cryopreserved embryos, stored at clinic's cryobank;
- BMI > 30 kg/m2;
- Impaired carbohydrate metabolism according to glucose tolerance test;
- Thrombosis in anamnesis;
- Oncological diseases in anamnesis;
Show all 10Show fewer
- Diagnosed inherited thrombophilia;
- Uterine fibroids of more than 4 cm or more than 2 fibroids of 2.5 cm diameter;
- Nodal form of adenomiosis;
- Ovarian cysts more than 4 cm in diameter.
Trial locations and contacts
1 site in 1 country.
Russia1 site
D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology
Saint Petersburg, 199034
About this study
Official title: Open Randomized Trial of Clinical Efficiency and Safety of Cell Product of Autologous Bone Marrow-derived Mesenchymal Stem Cells for Reparative Treatment of Destructively Changed Endometrium in Patients With Repeated IVF Failures
Investigators will examine safety and efficiency of the cell product of autologous bone marrow-derived mesenchymal stem cells (MSC) for patients with repeated IVF failures and hypoplastic or/and fibrosis process of endometrium
Read the detailed description
Sixty patients eligible for the study will be divided to two groups (experimental and control) according to randomization (envelope) procedure in 1:1 ratio.
For patients of the main group bone marrow stem cells will be extracted from the crest of the ilium using standard methodology. After extraction and cultivation final product of autologous bone marrow-derived mesenchymal stem cells will be transplanted to endometrial cavity on menstrual cycle day 5-6. Meanwhile patients will receive three cycles of hormonal replacement therapy (4 mg Progynova (Bayer Pharma, Germany) daily on menstrual cycle day 5-25 in combination with 20 mg Duphaston (Abbott Healthcare Products, B.V., Netherlands) daily from day 15 to day 25. On day 20 of hormonal replacement therapy (HRT) of the last (third) cycle Pipelle-biopsy of endometrium will be performed. Obtained material will be analyzed by immunohistochemistry with the assessment of estrogen and progesterone receptors, VEGFa, GM-CSF, CD133+, CD34 and CD56. Ultrasound characteristics of endometrial quality will be registered on day 9-10 and day 19-21 of every cycle. When morphological and echographic parameters of endometrium are found satisfactory for embryo transfer, the HRT for endometrial preparation for frozen/thawed embryo transfer cycle will be initiated. If acceptable endometrial characteristics are not achieved, patients could be offered to undergo repeated (not more than 3) transplantation of MSC procedures.
Control group will receive three standard cycles of HRT following hysteroscopy before frozen/thawed embryo transfer. If endometrial characteristics are found unsatisfactory, gestational surrogacy might be offered.
- Being tested
- bone marrow-derived MSC and HRT, hormonal replacement therapy
- Keywords
- Repeated IVF failure, Stem cell
- Medical subject headings
- Infertility, Female, Gynatresia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bone marrow-derived MSC and HRTBiological
- Transplantation procedure to endometrial cavity is performed with ultrasound guidance on menstrual cycle day 5-6 through uterine cervix using cater for embryo transfer with 1 ml of suspension containing 5 millions of autologous bone marrow-derived mesenchymal stem cells
- Three cycles of HRT following MSC transplantation;
- Pipelle-biopsy of endometrium on day 20 of hormonal replacement therapy of the last (third) cycle;
- Frozen/thawed embryo transfer 3-6 months after transplantation.
hormonal replacement therapyOther
standard treatment of hypoplastic endometrium or Asherman's syndrome:
- Three cycles of HRT preceding frozen/thawed embryo transfer;
- Frozen/thawed embryo transfer.
| Study group | Role | What they receive |
|---|---|---|
| bone marrow-derived MSC and HRT | Experimental | endometrial injection of autologous cell product of MSC with hormonal replacement therapy before frozen/thawed ET Receives: Biological: bone marrow-derived MSC and HRT |
| hormonal replacement therapy | Active comparator | standard endometrial preparation for frozen/thawed ET Receives: Other: hormonal replacement therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of endometrial receptivity
combination of endometrial thickness on ultrasound and immunohistochemistry of endometrium assessed at the biopsy day of the third cycle of HRT
Measured: 3-6 month after randomization
Secondary outcomes (2)
Clinical pregnancy rate
presence of intrauterine gestational sac at transvaginal ultrasound at 5-6 weeks of gestation or 5-6 weeks after starting the intervention; measured per frozen/thawed embryo transfer
Measured: 3-4 weeks after embryo transfer
Treatment-Emergent Adverse Events
Incidence of adverse events: side reactions, abdominal discomfort and patient's tolerance (Safety and Tolerability)
Measured: 3-6 month after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2017
- Study start20 Dec 2017
- Primary completion16 Mar 2019
- Study completion28 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infertility, FemaleStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Valeria Muller, D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology
- Investigators
- Alexandr Gzgzyan, Prof, PhD, Principal investigator, D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03166189
- Sponsor's protocol ID
- MSC-001
- Status last verified
- Dec 2019
- First submitted
- 23 May 2017
- Last updated
- 2 Jan 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Randomized Trial of Clinical Efficiency and Safety of Cell Product of Autologous Bone Marrow-derived Mesenchymal Stem Cells for Reparative Treatment of Destructively Changed Endometrium in Patients With Repeated IVF Failures
- ClinicalTrials.gov ID
- NCT03166189
- Acronym / sponsor ID
- MSC-001
- Keywords
- Repeated IVF failure, Stem cell
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- D.O. Ott Research Institute of Obstetrics, Gynecology, and ReproductologyUniversity, hospital or other
- Study start
- 20 Dec 2017 (actual)
- Primary completion
- 16 Mar 2019 (actual)
- Study completion
- 28 Dec 2019 (actual)
- First posted
- 25 May 2017 (actual)
- 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.
Investigators will examine safety and efficiency of the cell product of autologous bone marrow-derived mesenchymal stem cells (MSC) for patients with repeated IVF failures and hypoplastic or/and fibrosis process of endometrium
Detailed description
Sixty patients eligible for the study will be divided to two groups (experimental and control) according to randomization (envelope) procedure in 1:1 ratio.
For patients of the main group bone marrow stem cells will be extracted from the crest of the ilium using standard methodology. After extraction and cultivation final product of autologous bone marrow-derived mesenchymal stem cells will be transplanted to endometrial cavity on menstrual cycle day 5-6. Meanwhile patients will receive three cycles of hormonal replacement therapy (4 mg Progynova (Bayer Pharma, Germany) daily on menstrual cycle day 5-25 in combination with 20 mg Duphaston (Abbott Healthcare Products, B.V., Netherlands) daily from day 15 to day 25. On day 20 of hormonal replacement therapy (HRT) of the last (third) cycle Pipelle-biopsy of endometrium will be performed. Obtained material will be analyzed by immunohistochemistry with the assessment of estrogen and progesterone receptors, VEGFa, GM-CSF, CD133+, CD34 and CD56. Ultrasound characteristics of endometrial quality will be registered on day 9-10 and day 19-21 of every cycle. When morphological and echographic parameters of endometrium are found satisfactory for embryo transfer, the HRT for endometrial preparation for frozen/thawed embryo transfer cycle will be initiated. If acceptable endometrial characteristics are not achieved, patients could be offered to undergo repeated (not more than 3) transplantation of MSC procedures.
Control group will receive three standard cycles of HRT following hysteroscopy before frozen/thawed embryo transfer. If endometrial characteristics are found unsatisfactory, gestational surrogacy might be offered.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| bone marrow-derived MSC and HRT | Experimental | Biological: bone marrow-derived MSC and HRTendometrial injection of autologous cell product of MSC with hormonal replacement therapy before frozen/thawed ET |
| hormonal replacement therapy | Active comparator | Other: hormonal replacement therapystandard endometrial preparation for frozen/thawed ET |
Who may qualify
- Ages
- 21 to 44 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Repeated IVF attempts with high and good quality embryo transfer in fresh and frozen IVF cycles;
- Age 20-44 years;
- Endometrial thickness less than 6 mm in 2 or more of HRT cycles for endometrial preparation for embryo transfer
- Hysteroscopic evidence of fibrosis processes of uterine cavity with the absence of positive dynamics of HRT in 3 months following operation;
- Signed informed consent.
Key exclusion criteria (10 listed)
- Contraindication for pregnancy;
- Absence of cryopreserved embryos, stored at clinic's cryobank;
- BMI > 30 kg/m2;
- Impaired carbohydrate metabolism according to glucose tolerance test;
- Thrombosis in anamnesis;
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 |
|---|---|---|
| bone marrow-derived MSC and HRT* Transplantation procedure to endometrial cavity is performed with ultrasound guidance on menstrual cycle day 5-6 through uterine cervix using cater for embryo transfer with 1 ml of suspension containing 5 millions of autologous bone marrow-derived mesenchymal stem cells * Three cycles of HRT following MSC transplantation; * Pipelle-biopsy of endometrium on day 20 of hormonal replacement therapy of the last (third) cycle; * Frozen/thawed embryo transfer 3-6 months after transplantation. | Biological | bone marrow-derived MSC and HRT |
| hormonal replacement therapystandard treatment of hypoplastic endometrium or Asherman's syndrome: * Three cycles of HRT preceding frozen/thawed embryo transfer; * Frozen/thawed embryo transfer. | Other | hormonal replacement therapy |
Primary outcome
Assessment of endometrial receptivity
Time frame: 3-6 month after randomization
combination of endometrial thickness on ultrasound and immunohistochemistry of endometrium assessed at the biopsy day of the third cycle of HRT
2 secondary outcomes
Clinical pregnancy rate
Time frame: 3-4 weeks after embryo transfer
Treatment-Emergent Adverse Events
Time frame: 3-6 month after randomization
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2020.
- Individual participant dataSharing planned: No
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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.
Alexandr Gzgzyan, Prof, PhD principal investigator
D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing bone marrow-derived MSC and HRT and hormonal replacement therapy in people with Infertility, Female and Infertility of Uterine Origin, run by D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology at 1 site in Russia.
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 5 inclusion and 10 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: finished, as of the sponsor's last update on 2 Jan 2020. 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 Russia. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of endometrial receptivity (time frame: 3-6 month after randomization). 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 2 Jan 2020.