Poor Ovarian ResponsePhase 3NCT05703308
Menstrual Blood Stem Cells in Poor Ovarian Responders
A Phase 3 study testing Autologous Menstrual Blood Stem Cells in people with Poor Ovarian Response and Infertility, Female, run by Avicenna Research Institute at 1 site in Iran.
Trial summary
In this controlled trial, poor ovarian responder women will be treated with transplantation of autologous menstrual blood stem cells. The investigators will attempt to assess the safety and efficacy of this procedure for the treatment of infertility in POR patients compared to control group. Read more about this study
- Who is it for?
- Ages 25 to 45 years, women only
- Conditions the study is for
- Poor Ovarian Response, Infertility, Female
- What is being tested?
- Autologous Menstrual Blood Stem Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- 1 siteIran
- Study dates
- 21 Jun 2020to 22 Oct 2022
- Phase
- Phase 3
- 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 25 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Serum AMH < 0.1 ng/ml (at the screening visit and in the absence of OC or sex-steroid intake)
- Antral follicular count (AFC) in both ovaries < 4 (at screening visit and in the absence of OC or sex-steroid intake)
- Positive history of at least1 standard previous IVF-ET or ICSI-ET
- Normal thyroid hormones (TSH and FT4)
- Normal level of prolactin,
- Normal level of fasting blood sugar
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- Normal Liver tests (SGOT, SGPT)
- Normal level of BUN, creatinine
- Negative Infectious tests (HIV, HCV, HBS Ag, VDRL)
- Normal coagulation factors (PT, PTT, BT, CT)
- Normal serum levels of sodium, potassium, calcium, phosphorus
- Negative history of endometrioma or other ovarian cysts
- Negative history of previous ovarian surgery
- Negative history of cancer
- Negative history of a known autoimmune disorder.
Who cannot join
- Positive history of hydrosalpinx or anatomical uterine disorders (In vaginal sonography or HSG)
- Severe male factors of their husbands (count <15 million/ml)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Outcome of Pregnancy in Poor Ovarian Responders by Intraovarian Administration of Autologous Menstrual Blood Derived-Mesenchymal Stromal Cells
In this controlled trial, poor ovarian responder women will be treated with transplantation of autologous menstrual blood stem cells. The investigators will attempt to assess the safety and efficacy of this procedure for the treatment of infertility in POR patients compared to control group.
Read the detailed description
With economic development, procreation delays have resulted in more women seeking medical help for infertility treatment. Because the quality and quantity of oocytes are affected by physiological age, despite advances in assisted reproductive technology (ART), managing infertility in women with poor ovarian response (POR) remains a daily challenge for physicians.
Adult mesenchymal stromal cell (MSC) therapy has gained particular interest in recent years because it may provide a supportive microenvironment for oocyte development from quiescent primordial follicles. Human MSC transplantation has been shown in preclinical studies to host ovaries and restore their function and structure premature ovarian failure (POF) animal models.
Because of their encouraging characteristics such as ease of access, high availability, monthly repeatability of sampling, less ethical considerations, lack of tumor-causing potential, protected property, and significant trans-differentiation capacity, endometrial-derived stromal cells have been considered in a wide range of studies since 2007. Menstrual blood-derived stromal cells (MenSCs), on the other hand, are derived from endometrial tissue and can be collected in a non-invasive manner, making them especially useful in the treatment of reproductive disorders. The investigators attempted to assess the safety and efficacy of intraovarian injection of MenSCs for the treatment of infertility in POR patients based on this evidence.
The results of this clinical trial's phases I and II indicated that Men-MSCs could be considered as a potential treatment to restore the fertility capability of POR women. Based on these findings, the investigators have designed a Phase III controlled trial of autologous MenSC therapy for patients with POR.
- Conditions
- Poor Ovarian Response, Infertility, Female
- Being tested
- Autologous Menstrual Blood Stem Cells
- Keywords
- Poor Ovarian Responders, Menstrual Blood Stem cells, Infertility, Cell therapy, ICSI
- Medical subject headings
- Infertility, Female, Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous Menstrual Blood Stem CellsBiological
The menstrual blood of patients in the MenSCs treatment group was collected in sterile menstrual cups on the second day of menstruation, and directly transferred to a class B clean room for MSC isolation and culture. All cell quality control studies were performed prior to the International Conference of Harmonization Q2 (ICH Q2) guidelines. The density of the final product was 20×106 cells/ml. 150 μl of the prepared suspension was injected intravaginally into each ovary of the patient under general anaesthesia
| Study group | Role | What they receive |
|---|---|---|
| MenSCs group | Experimental | Study group, treated with autologous intra-ovarian MenSCs injection and monitored for spontaneous pregnancy for 3 months after intervention. ICSI was used in cases where the pregnancy did not occur naturally. Receives: Biological: Autologous Menstrual Blood Stem Cells |
| ICSI group | No intervention | Control group, monitored for spontaneous pregnancy for 3 months after their last ovarian stimulation for ICSI or IVF. ICSI was used in cases where the pregnancy did not occur naturally. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Spontaneous pregnancy rate
Number of participants that establish a spontaneous clinical pregnancy after stem cell injection
Measured: 3 months after stem cell injection
Pregnancy rate after ICSI
Number of participants that establish a clinical pregnancy after embryo transfer
Measured: 4 weeks after embryo transfer
Secondary outcomes (9)
Hormone levels
Change from baseline in Anti-Müllerian hormone (AMH), serum follicle stimulating hormone (FSH), and antral follicle count (AFC)
Measured: 2 and 4 months after stem cell injection
Number of oocytes
Mean number of retrieved COCs per protocol
Measured: Day 0 after follicle puncture
Number of MII oocytes
Mean number of metaphase II (MII) oocytes per protocol
Measured: Day 0 after follicle puncture
Number of embryos
Mean number of embryos
Measured: Day 3-5 after follicle puncture
Number of high quality embryos number
Grade A for cleavage stage embryo, >=3BB for blastocyst
Measured: Day 3-5 after follicle puncture
Clinical pregnancy rate
The incidence of gestational sac with heartbeat assessed by TVS
Measured: 4 weeks after embryo transfer
Biochemical pregnancy rate
Incidence of serum beta-hCG test > 25 mIU/ml
Measured: 12-16 days after oocyte pick-up
Live birth rate
Incidence of the birth of at least one live newborn after 22 weeks of gestation
Measured: at a follow-up time of 30 days after delivery
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Incidence of adverse and serious adverse events with potential relationship to treatment
Measured: at a follow-up time after 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2023
- Study start21 Jun 2020
- Primary completion22 Sep 2021
- Study completion22 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Poor Ovarian ResponseStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Lead sponsor
- Avicenna Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Simin Zafardoust, MD, Study director, Nanbiotechnology Research Center Avicenna Research Institute, ACECR, Tehran, Iran.Somaieh Kazemnejad, Study chair, Nanbiotechnology Research Center Avicenna Research Institute, ACECR, Tehran, Iran.Mina Fathi Kazerooni, MD, PhD, Principal investigator, Nanbiotechnology Research Center Avicenna Research Institute, ACECR, Tehran, Iran.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05703308
- Sponsor's protocol ID
- 99008-1023
- Status last verified
- Jan 2023
- First submitted
- 15 Jan 2023
- Last updated
- 30 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Zafardoust S, Kazemnejad S, Fathi-Kazerooni M, Darzi M, Sadeghi MR, Sadeghi Tabar A, Sehat Z. The effects of intraovarian injection of autologous menstrual blood-derived mesenchymal stromal cells on pregnancy outcomes in women with poor ovarian response. Stem Cell Res Ther. 2023 Nov 15;14(1):332. doi: 10.1186/s13287-023-03568-1.
PubMed 37968668
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Outcome of Pregnancy in Poor Ovarian Responders by Intraovarian Administration of Autologous Menstrual Blood Derived-Mesenchymal Stromal Cells
- ClinicalTrials.gov ID
- NCT05703308
- Acronym / sponsor ID
- 99008-1023
- Conditions
- Poor Ovarian Response, Infertility, Female
- Keywords
- Poor Ovarian Responders, Menstrual Blood Stem cells, Infertility, Cell therapy, ICSI
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 180 participants (actual)
- Lead sponsor
- Avicenna Research InstituteUniversity, hospital or other
- Study start
- 21 Jun 2020 (actual)
- Primary completion
- 22 Sep 2021 (actual)
- Study completion
- 22 Oct 2022 (actual)
- First posted
- 30 Jan 2023 (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.
In this controlled trial, poor ovarian responder women will be treated with transplantation of autologous menstrual blood stem cells. The investigators will attempt to assess the safety and efficacy of this procedure for the treatment of infertility in POR patients compared to control group.
Detailed description
With economic development, procreation delays have resulted in more women seeking medical help for infertility treatment. Because the quality and quantity of oocytes are affected by physiological age, despite advances in assisted reproductive technology (ART), managing infertility in women with poor ovarian response (POR) remains a daily challenge for physicians.
Adult mesenchymal stromal cell (MSC) therapy has gained particular interest in recent years because it may provide a supportive microenvironment for oocyte development from quiescent primordial follicles. Human MSC transplantation has been shown in preclinical studies to host ovaries and restore their function and structure premature ovarian failure (POF) animal models.
Because of their encouraging characteristics such as ease of access, high availability, monthly repeatability of sampling, less ethical considerations, lack of tumor-causing potential, protected property, and significant trans-differentiation capacity, endometrial-derived stromal cells have been considered in a wide range of studies since 2007. Menstrual blood-derived stromal cells (MenSCs), on the other hand, are derived from endometrial tissue and can be collected in a non-invasive manner, making them especially useful in the treatment of reproductive disorders. The investigators attempted to assess the safety and efficacy of intraovarian injection of MenSCs for the treatment of infertility in POR patients based on this evidence.
The results of this clinical trial's phases I and II indicated that Men-MSCs could be considered as a potential treatment to restore the fertility capability of POR women. Based on these findings, the investigators have designed a Phase III controlled trial of autologous MenSC therapy for patients with POR.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MenSCs group | Experimental | Biological: Autologous Menstrual Blood Stem CellsStudy group, treated with autologous intra-ovarian MenSCs injection and monitored for spontaneous pregnancy for 3 months after intervention. ICSI was used in cases where the pregnancy did not occur naturally. |
| ICSI group | No intervention | –Control group, monitored for spontaneous pregnancy for 3 months after their last ovarian stimulation for ICSI or IVF. ICSI was used in cases where the pregnancy did not occur naturally. |
Who may qualify
- Ages
- 25 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- Serum AMH < 0.1 ng/ml (at the screening visit and in the absence of OC or sex-steroid intake)
- Antral follicular count (AFC) in both ovaries < 4 (at screening visit and in the absence of OC or sex-steroid intake)
- Positive history of at least1 standard previous IVF-ET or ICSI-ET
- Normal thyroid hormones (TSH and FT4)
- Normal level of prolactin,
Key exclusion criteria (2 listed)
- Positive history of hydrosalpinx or anatomical uterine disorders (In vaginal sonography or HSG)
- Severe male factors of their husbands (count <15 million/ml)
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 |
|---|---|---|
| Autologous Menstrual Blood Stem CellsThe menstrual blood of patients in the MenSCs treatment group was collected in sterile menstrual cups on the second day of menstruation, and directly transferred to a class B clean room for MSC isolation and culture. All cell quality control studies were performed prior to the International Conference of Harmonization Q2 (ICH Q2) guidelines. The density of the final product was 20×106 cells/ml. 150 μl of the prepared suspension was injected intravaginally into each ovary of the patient under general anaesthesia | Biological | MenSCs group |
Primary outcome
Spontaneous pregnancy rate
Time frame: 3 months after stem cell injection
Number of participants that establish a spontaneous clinical pregnancy after stem cell injection
Pregnancy rate after ICSI
Time frame: 4 weeks after embryo transfer
Number of participants that establish a clinical pregnancy after embryo transfer
9 secondary outcomes
Hormone levels
Time frame: 2 and 4 months after stem cell injection
Number of oocytes
Time frame: Day 0 after follicle puncture
Number of MII oocytes
Time frame: Day 0 after follicle puncture
Number of embryos
Time frame: Day 3-5 after follicle puncture
Number of high quality embryos number
Time frame: Day 3-5 after follicle puncture
Clinical pregnancy rate
Time frame: 4 weeks after embryo transfer
Biochemical pregnancy rate
Time frame: 12-16 days after oocyte pick-up
Live birth rate
Time frame: at a follow-up time of 30 days after delivery
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: at a follow-up time after 1 year
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 30 Jan 2023.
- Derived from this study: PubMed 37968668Zafardoust S, Kazemnejad S, Fathi-Kazerooni M, Darzi M, Sadeghi MR, Sadeghi Tabar A, Sehat Z. The effects of intraovarian injection of autologous menstrual blood-derived mesenchymal stromal cells on pregnancy outcomes in women with poor ovarian response. Stem Cell Res Ther. 2023 Nov 15;14(1):332. doi: 10.1186/s13287-023-03568-1.
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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.
Simin Zafardoust, MD study director
Nanbiotechnology Research Center Avicenna Research Institute, ACECR, Tehran, Iran.
Somaieh Kazemnejad study chair
Nanbiotechnology Research Center Avicenna Research Institute, ACECR, Tehran, Iran.
Mina Fathi Kazerooni, MD, PhD principal investigator
Nanbiotechnology Research Center Avicenna Research Institute, ACECR, Tehran, Iran.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Autologous Menstrual Blood Stem Cells in people with Poor Ovarian Response and Infertility, Female, run by Avicenna Research 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 15 inclusion and 2 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 30 Jan 2023. 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 phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Spontaneous pregnancy rate (time frame: 3 months after stem cell injection). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05703308, which also lists 1 linked publication.
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 Jan 2023.