Premature Ovarian FailurePhase 1/2NCT06202547
Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
A Phase 1/2 study testing Intra-ovarian injection of bone marrow mesenchymal stromal cells-derived extracellular vesicles in people with Premature Ovarian Failure, run by Royan Institute at 1 site in Iran.
Trial summary
Premature ovarian failure (POF) is a clinical syndrome defined by loss of ovarian activity before the age of 40 years. POF is characterized by menstrual disturbance (amenorrhea or oligomenorrhea) with raised gonadotrophins and low estradiol. The prevalence of POF is 1-2%. Read more about this study
- Who is it for?
- Ages 20 to 38 years, women only
- Conditions the study is for
- Premature Ovarian Failure
- What is being tested?
- Intra-ovarian injection of bone marrow mesenchymal stromal cells-derived extracellular vesicles
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteIran
- Study dates
- 20 Feb 2023to 8 Jul 2025
- Phase
- Phase 1/2
- 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 20 to 38 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Women between 20-38 years old
- Baseline serum level of follicle stimulating hormone (FSH) higher or equal to 25 IU/l at least twice with an interval of 4 months
- At least one year has passed since secondary amenorrhea and premature ovarian failure (POF) diagnosis
- Normal karyotype and fragile X messenger ribonucleoprotein 1 (FMR1) gene
Who cannot join
- Primary amenorrhea
- Congenital anomaly of the ovary
- Thyroid disease Immune system diseases such as lupus, etc.
- Previous and/or family history of ovarian tumor
- Previous and/or family history of suffering from major diseases in the past and present such as cancer
- Positive serological evidence regarding previous or current hepatitis B and C, Human T-lymphotropic virus 1, Human immunodeficiency virus (HIV), Syphilis Disturbance in the normal range of laboratory tests as levels of Hemoglobin Subunit Alpha 1 (HbA1), Alanine transaminase (ALT), The aspartate aminotransferase (AST), the number of white blood cells (WBCs), The creatinine (Cr), International normalised ratio (INR) , Platelets (Plt), Hematocrit (Hct) tests.
Show all 10Show fewer
- History of specific systemic disease (rheumatology, endocrine, cardiovascular, etc.)
- Severe endometriosis (stage III and IV)
- Small and non-injectable ovaries Lack of patient satisfaction
- The patient's unwillingness to continue participating in the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Safety and Feasibility Study of Intra-ovarian Injection of Bone Marrow Mesenchymal Stromal Cells-derived Extracellular Vesicles in Idiopathic Premature Ovarian Failure Patients: Clinical Trial Phase I
Premature ovarian failure (POF) is a clinical syndrome defined by loss of ovarian activity before the age of 40 years. POF is characterized by menstrual disturbance (amenorrhea or oligomenorrhea) with raised gonadotrophins and low estradiol. The prevalence of POF is 1-2%. Extracellular vesicles (EVs) are membrane-packed vesicles that are secreted by a variety of cell types, including T cells, B cells, dendritic cells, platelets, mast cells, epithelial cells, endothelial cells, neuronal cells, cancerous cells, oligodendrocytes, Schwann cells, embryonic cells, and mesenchymal stromal cells-derived (MSCs). MSCs-EV more stable and induce stronger signaling and are produced in higher concentrations than stem cells. They demonstrate no inherent toxicity, are not associated with any long-term maldifferentiation of engrafted cells or tumor generation, and carry no apparent risk of aneuploidy or immune rejection following in vivo allogenic administration.Several studies have evaluated the safety and possible efficacy of injection MSCs-EV for the treatment of premature ovarian failure in animal models. Based on the available evidence, the study was designed with the aim of investigating the safety and effectiveness of intraovarian injection of MSCs-EV in patients with POF diagnosis.
Read the detailed description
Investigating the effect of intraovarian injection of bone marrow-derived extracellular vesicles (MSC-EV) on serum levels of Follicle-Stimulating Hormone (FSH),Anti-Mullerian Hormone (AMH) levels, as well as the return of the menstrual cycle in infertile patients with premature ovarian failure, as well as the evaluation of its possible side effects. A before/after clinical trial (phase I) on 10 patients is designed. Eligible patients will be included in the study if they have written consent. Infertile women who have been diagnosed with premature ovarian failure and have normal body mass index and normal genetic tests are invited to participate in this project. Patients with early amenorrhea and certain immunological and cardiovascular diseases, as well as a history of ovarian masses or abnormal serological tests will not be included in the study. If the patient has undergone hormone replacement therapy (HRT), the HRT will be stopped for at least two months and then the injection cycle will be started.Injection of bone marrow-derived extracellular vesicles with a dose equivalent to 5 times 10 million clonal mesenchymal stem cells in 2 ml will be performed for all patients. Follow-up of patients in order to respond to treatment for 8 months based on evaluation of Follicle-Stimulating Hormone (FSH),Anti-Mullerian Hormone (AMH) levels, return of menstrual cycle, ovarian ultrasound and also check possible complications due to injection (fever, bacteremia, sepsis, Pelvic inflammatory disease, anaphylactic shock and hematoma from the first 24 hours and in the first week) will be done.
Primary Outcome Measures, Safety evaluation, [Time Frame: 8 months]:Early-onset possible side effects (fever, bacteremia, sepsis, PID, anaphylactic shock, and hematoma will be evaluated at the first 24 h and during the first week. Possible second side effects such as ovarian abscesses and benign or malignant neoplasms will be assessed until 8 months after intra-ovarian EV injection.
Secondary Outcome Measures, Feasibility evaluation, [Time Frame: 8 months]: The Serum FSH, Estradiol and AMH levels measurements and Return of menstrual cycle will be evaluated until months after intra-ovarian EV injection. Ultrasonography evaluation will be performed monthly to evaluate the ovarian volume (cc), the antral follicle count, Endometrium thickness, the number and size of the follicles.
- Conditions
- Premature Ovarian Failure
- Being tested
- Intra-ovarian injection of bone marrow mesenchymal stromal cells-derived extracellular vesicles
- Keywords
- Intra-ovarian injection, Mesenchymal stromal cells-derived extracellular vesicles
- Medical subject headings
- Primary Ovarian Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intra-ovarian injection of bone marrow mesenchymal stromal cells-derived extracellular vesiclesBiological
he patient is anesthetized and placed in a lithotomy position, after preparing and washing the vagina with normal saline, under transvaginal ultrasound guidance (Aloka-40000 vaginal probe, Japan) using needle puncture (Reproline medical Gmbh, Rheinbach/Germany). The injection of 2 ml of extracellular vesicles derived from MSCs (equivalent to 50 million cells) will be performed into one ovary of the patient (the accessible ovary).
| Study group | Role | What they receive |
|---|---|---|
| intraovarian injection of MSC-EVs | Experimental | The patient is anesthetized and placed in a lithotomy position, after preparing and washing the vagina with normal saline, under transvaginal ultrasound guidance (Aloka-40000 vaginal probe, Japan) using needle puncture (Reproline medical Gmbh, Rheinbach/Germany). The injection of 2 ml of extracellular vesicles derived from MSCs (equivalent to 50 million cells) will be performed into one ovary of the patient (the accessible ovary). Receives: Biological: Intra-ovarian injection of bone marrow mesenchymal stromal cells-derived extracellular vesicles |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of ovary abscess
Sonographic evaluation of ovaries will be done for detection of ovarian abscess or any other ovarian lesion formation up to 8 months after intraovarian injection of extracellular vesicles derived from bone marrow mesenchymal stromal cells (any adverse events through follow-up visits (first 24 hours and first week after transplantation, 1, 2, 3, 4, 5, 6, 7 and 8 months after injection) will be checked and recorded.
Measured: First 24 hours, first week and monthly up to 8 months after injection
Secondary outcomes (5)
Basal follicle-stimulating hormone (FSH) serum level
Hormonal examination will be done with standard methods in the specialized laboratory of Royan Institute. A venous blood sample will be collected from all participants. The basal serum levels of FSH will be measured by Electrochemiluminescence immunoassay (ECLIA) using fully automated COBAS E-601 analyzer and a commercial kit (Roche Diagnostics GmbH, Mannheim, Germany). The Units of Measure will be presented as IU/l.
Measured: Baseline,1 week as well as one, two, three, four , five, six, seven and eight months after transplantation
Serum anti-mullerian hormone (AMH) levels
Hormonal examination will be done with standard methods in the specialized laboratory of Royan Institute. A venous blood sample will be collected from all participants. The basal serum levels of AMH will be measured by Electrochemiluminescence immunoassay (ECLIA) using fully automated COBAS E-601 analyzer and a commercial kit (Roche Diagnostics GmbH, Mannheim, Germany). The Units of Measure will be presented as ng/ml.
Measured: Before the intervention (baseline) and also three, six and eight months after transplantation
Menstruation recurrence rate
Through monthly follow-up and asking the questions.The number of patients whose menstrual cycle has returned will be reported.
Measured: one, two, three, four , five, six, seven and eight months after transplantation
Antral follicle count
Through monthly examination of specialized ultrasonography.The number of follicles measuring 2-10 mm in diameter observed in each ovary will be counted and recorded in the ultrasound examination.
Measured: Before the intervention (baseline) as well as one, two, three, four , five, six, seven and eight months after transplantation
The ovaries size and volume
The Ovary size and volume will be determined through monthly examination of specialized ultrasonography. The volume estimate is calculated by the formula for an ellipsoid, where D1, D2, and D3 are the three axial measurements:
D1 x D2 x D3 x 0.52
Measured: One, two, three, four , five, six, seven and eight months after transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2024
- Study start20 Feb 2023
- Primary completion8 Oct 2024
- Study completion8 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Premature Ovarian FailureStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royan Institute
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Faezeh Shekari, Ph.D, Principal investigator, Department of Development of Stem Cell Sciences of Royan Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06202547
- Sponsor's protocol ID
- 400000134
- Other IDs
- IRCT20080831001141N43
- Status last verified
- Jul 2026
- First submitted
- 5 Dec 2023
- Last updated
- 15 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Feasibility Study of Intra-ovarian Injection of Bone Marrow Mesenchymal Stromal Cells-derived Extracellular Vesicles in Idiopathic Premature Ovarian Failure Patients: Clinical Trial Phase I
- ClinicalTrials.gov ID
- NCT06202547
- Acronym / sponsor ID
- 400000134
- Conditions
- Premature Ovarian Failure
- Keywords
- Intra-ovarian injection, Mesenchymal stromal cells-derived extracellular vesicles
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Royan InstituteOther government
- Study start
- 20 Feb 2023 (actual)
- Primary completion
- 8 Oct 2024 (actual)
- Study completion
- 8 Jul 2025 (actual)
- First posted
- 11 Jan 2024 (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.
Premature ovarian failure (POF) is a clinical syndrome defined by loss of ovarian activity before the age of 40 years. POF is characterized by menstrual disturbance (amenorrhea or oligomenorrhea) with raised gonadotrophins and low estradiol. The prevalence of POF is 1-2%. Extracellular vesicles (EVs) are membrane-packed vesicles that are secreted by a variety of cell types, including T cells, B cells, dendritic cells, platelets, mast cells, epithelial cells, endothelial cells, neuronal cells, cancerous cells, oligodendrocytes, Schwann cells, embryonic cells, and mesenchymal stromal cells-derived (MSCs). MSCs-EV more stable and induce stronger signaling and are produced in higher concentrations than stem cells. They demonstrate no inherent toxicity, are not associated with any long-term maldifferentiation of engrafted cells or tumor generation, and carry no apparent risk of aneuploidy or immune rejection following in vivo allogenic administration.Several studies have evaluated the safety and possible efficacy of injection MSCs-EV for the treatment of premature ovarian failure in animal models. Based on the available evidence, the study was designed with the aim of investigating the safety and effectiveness of intraovarian injection of MSCs-EV in patients with POF diagnosis.
Detailed description
Investigating the effect of intraovarian injection of bone marrow-derived extracellular vesicles (MSC-EV) on serum levels of Follicle-Stimulating Hormone (FSH),Anti-Mullerian Hormone (AMH) levels, as well as the return of the menstrual cycle in infertile patients with premature ovarian failure, as well as the evaluation of its possible side effects. A before/after clinical trial (phase I) on 10 patients is designed. Eligible patients will be included in the study if they have written consent. Infertile women who have been diagnosed with premature ovarian failure and have normal body mass index and normal genetic tests are invited to participate in this project. Patients with early amenorrhea and certain immunological and cardiovascular diseases, as well as a history of ovarian masses or abnormal serological tests will not be included in the study. If the patient has undergone hormone replacement therapy (HRT), the HRT will be stopped for at least two months and then the injection cycle will be started.Injection of bone marrow-derived extracellular vesicles with a dose equivalent to 5 times 10 million clonal mesenchymal stem cells in 2 ml will be performed for all patients. Follow-up of patients in order to respond to treatment for 8 months based on evaluation of Follicle-Stimulating Hormone (FSH),Anti-Mullerian Hormone (AMH) levels, return of menstrual cycle, ovarian ultrasound and also check possible complications due to injection (fever, bacteremia, sepsis, Pelvic inflammatory disease, anaphylactic shock and hematoma from the first 24 hours and in the first week) will be done.
Primary Outcome Measures, Safety evaluation, [Time Frame: 8 months]:Early-onset possible side effects (fever, bacteremia, sepsis, PID, anaphylactic shock, and hematoma will be evaluated at the first 24 h and during the first week. Possible second side effects such as ovarian abscesses and benign or malignant neoplasms will be assessed until 8 months after intra-ovarian EV injection.
Secondary Outcome Measures, Feasibility evaluation, [Time Frame: 8 months]: The Serum FSH, Estradiol and AMH levels measurements and Return of menstrual cycle will be evaluated until months after intra-ovarian EV injection. Ultrasonography evaluation will be performed monthly to evaluate the ovarian volume (cc), the antral follicle count, Endometrium thickness, the number and size of the follicles.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| intraovarian injection of MSC-EVs | Experimental | Biological: Intra-ovarian injection of bone marrow mesenchymal stromal cells-derived extracellular vesiclesThe patient is anesthetized and placed in a lithotomy position, after preparing and washing the vagina with normal saline, under transvaginal ultrasound guidance (Aloka-40000 vaginal probe, Japan) using needle puncture (Reproline medical Gmbh, Rheinbach/Germany). The injection of 2 ml of extracellular vesicles derived from MSCs (equivalent to 50 million cells) will be performed into one ovary of the patient (the accessible ovary). |
Who may qualify
- Ages
- 20 to 38 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Women between 20-38 years old
- Baseline serum level of follicle stimulating hormone (FSH) higher or equal to 25 IU/l at least twice with an interval of 4 months
- At least one year has passed since secondary amenorrhea and premature ovarian failure (POF) diagnosis
- Normal karyotype and fragile X messenger ribonucleoprotein 1 (FMR1) gene
Key exclusion criteria (10 listed)
- Primary amenorrhea
- Congenital anomaly of the ovary
- Thyroid disease Immune system diseases such as lupus, etc.
- Previous and/or family history of ovarian tumor
- Previous and/or family history of suffering from major diseases in the past and present such as cancer
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 |
|---|---|---|
| Intra-ovarian injection of bone marrow mesenchymal stromal cells-derived extracellular vesicleshe patient is anesthetized and placed in a lithotomy position, after preparing and washing the vagina with normal saline, under transvaginal ultrasound guidance (Aloka-40000 vaginal probe, Japan) using needle puncture (Reproline medical Gmbh, Rheinbach/Germany). The injection of 2 ml of extracellular vesicles derived from MSCs (equivalent to 50 million cells) will be performed into one ovary of the patient (the accessible ovary). | Biological | intraovarian injection of MSC-EVs |
Primary outcome
Rate of ovary abscess
Time frame: First 24 hours, first week and monthly up to 8 months after injection
Sonographic evaluation of ovaries will be done for detection of ovarian abscess or any other ovarian lesion formation up to 8 months after intraovarian injection of extracellular vesicles derived from bone marrow mesenchymal stromal cells (any adverse events through follow-up visits (first 24 hours and first week after transplantation, 1, 2, 3, 4, 5, 6, 7 and 8 months after injection) will be checked and recorded.
5 secondary outcomes
Basal follicle-stimulating hormone (FSH) serum level
Time frame: Baseline,1 week as well as one, two, three, four , five, six, seven and eight months after transplantation
Serum anti-mullerian hormone (AMH) levels
Time frame: Before the intervention (baseline) and also three, six and eight months after transplantation
Menstruation recurrence rate
Time frame: one, two, three, four , five, six, seven and eight months after transplantation
Antral follicle count
Time frame: Before the intervention (baseline) as well as one, two, three, four , five, six, seven and eight months after transplantation
The ovaries size and volume
Time frame: One, two, three, four , five, six, seven and eight months after transplantation
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 15 Jul 2026.
Related trials for Premature Ovarian Failure
RecruitingPhase 2
Autologous Hair Follicle-Derived Secretome and Platelet-Rich Plasma for Premature Ovarian Insufficiency
Premature Ovarian Insufficiency, POI
RecruitingObservational study
Gonadal Tissue Freezing for Fertility Preservation in Individuals at Risk for Ovarian Dysfunction, Premature Ovarian Insufficiency and Clinically Indicated Gonadectomy
Turner Syndrome, Post-menarcheal Adolescents
Not yet recruitingPhase 1
Oral GDC-0077 in Premature Ovarian Insufficiency
Primary Ovarian Insufficiency
RecruitingPhase 3
Hormone Replacement Therapy in Adolescents With Premature Ovarian Insufficiency
Premature Ovarian Insufficiency
RecruitingObservational study
Gonadotropin-releasing Hormone Agonist (GnRHa) in Ovarian Preservation in SLE Subjects Receiving Cyclophosphamide as Determined by Questionnaires
Systemic Lupus Erythematosus (Sle), Primary Ovarian Insufficiency (Poi)
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.
Faezeh Shekari, Ph.D principal investigator
Department of Development of Stem Cell Sciences of Royan Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Intra-ovarian injection of bone marrow mesenchymal stromal cells-derived extracellular vesicles in people with Premature Ovarian Failure, run by Royan Institute at 1 site in Iran.
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 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 15 Jul 2026. 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 Iran. 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 combined 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.
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?
Rate of ovary abscess (time frame: First 24 hours, first week and monthly up to 8 months after injection). 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 15 Jul 2026.