Thin Endometrial LiningPhase 1/2NCT06896747
Evaluating Mechanically Engineered Stem Cell Exosomes for Treating Endometrial Injury: A Clinical Study
A Phase 1/2 study testing Mechanically Engineered Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes, Umbilical cord mesenchymal stem cell-derived exosomes and platelet-rich plasma in people with Thin Endometrial Lining and Female Infertility, run by Tang-Du Hospital at 2 sites in China.
Trial summary
The goal of this clinical trial is to evaluate if engineered mechanically umbilical cord-derived stem cell exosomes, or conventional umbilical cord -derived stem cell exosomes, can improve endometrial thickness in women with thin endometrium. Read more about this study
- Who is it for?
- Ages 20 to 40 years, women only
- Conditions the study is for
- Thin Endometrial Lining, Female Infertility, Intrauterine Adhesions
- What is being tested?
- Mechanically Engineered Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes, Umbilical cord mesenchymal stem cell-derived exosomes and platelet-rich plasma
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 2 sitesChina
- Study dates
- 21 Feb 2025to 31 Mar 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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
- Females aged 20-40 years (inclusive of boundary values);
- Normal ovarian reserve function (criteria: AFC ≥ 7, AMH > 1.1 ng/mL);
- History of transcervical resection of adhesions (TCRA);
- Received PRP treatment after TCRA;
- At least one embryo transfer (ET) cycle in which they underwent standard ovarian stimulation (fresh cycle) or standard hormone replacement therapy (FET cycle), with an endometrial thickness of <7 mm;
- Planned to continue IVF/ICSI/FET-assisted conception;
- Able to accept and adhere to treatment and follow-up and willing to sign an informed consent form.
Who cannot join
- Patients with severe systemic diseases, surgical contraindications, or cycle contraindications;
- Patients with reproductive tract infections, genital tuberculosis, pelvic inflammatory disease, or malignant tumors of reproductive organs;
- Patients with systemic diseases that cause uterine bleeding;
- Patients allergic to any drugs, materials, or components used in this study;
- Patients at high risk for hormone-dependent tumors such as breast cancer or ovarian tumors;
- Patients with untreated submucosal fibroids of any size (FIGO 0/I/II), uterine fibroids ≥5 cm (FIGO III, IV, V, VI, VII), adenomyosis, unicornuate uterus, bicornuate uterus, or endometrial polyps;
Show all 12Show fewer
- Patients with hydrosalpinx ≥3 cm or hydrosalpinx of any size with significant vaginal discharge;
- Patients with ovarian endometriotic cysts (chocolate cysts) ≥4 cm;
- Patients who participated in other clinical trials within 3 months before surgery or during the study period;
- Patients unable to tolerate anesthesia;
- Patients with genetic abnormalities;
- Other patients deemed unsuitable for participation in this study by the investigator.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Recruiting
Tang-Du Hospital
Xi'an, Shaanxi, 710038
Wanlin Zhang, PhD, +86 18149363396, 1843678023@qq.com
- Recruiting
Tang-Du Hospital
Xi'an, Shaanxi, 710038
Wanlin Zhang, PhD, +86 029-84717216, 1843678023@qq.com
Yafei Tong, MD, +86 13720750251, fequeo1820@126.com
About this study
Official title: Evaluation of the Therapeutic Effects of Mechanically Engineered Umbilical Cord-Derived Stem Cell Exosomes on Endometrial Injury: A Prospective, Non-Randomized, Parallel-Controlled Clinical Study
The goal of this clinical trial is to evaluate if engineered mechanically umbilical cord-derived stem cell exosomes, or conventional umbilical cord -derived stem cell exosomes, can improve endometrial thickness in women with thin endometrium.
The main questions it aims to answer are:
Read more
Can exosomes delivered via subendometrial injection improve endometrial thickness or clinical pregnancy rates compared to PRP (platelet-rich plasma)? Are there significant differences in endometrial thickness between the two treatment groups? Researchers will compare the intervention groups, which one group receives mechanical exosomes and the other receives conventional esosomes via subendometrial injection, to the control group, which receives PRP via the same methods, to see if exosomes provide superior therapeutic effects.
Participants will:
Receive either mechanical exosomesor or conventional esosomes or PRP through subendometrial injection.
Be monitored for changes in endometrial parameters.
Read the detailed description
This study is a prospective, non-randomized controlled clinical trial designed to evaluate the efficacy and safety of mechanically engineered umbilical cord mesenchymal stem cell-derived exosomes (ME-UCMSC-Exo) and conventional umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-Exo) in the treatment of thin endometrium secondary to severe intrauterine adhesions (IUA) following hysteroscopic adhesiolysis. Thin endometrium is a significant challenge in reproductive medicine, associated with poor embryo implantation rates, recurrent implantation failure (RIF), and increased risk of pregnancy complications. Despite conventional hormonal therapies, effective endometrial regeneration remains a clinical challenge.
Emerging regenerative therapies, including exosome-based interventions, offer promising avenues for enhancing endometrial repair and pregnancy outcomes. Exosomes, extracellular vesicles secreted by stem cells, play a crucial role in tissue regeneration by delivering bioactive molecules such as proteins, microRNAs (miRNAs), and growth factors to target cells. The study aims to determine whether mechanically engineered exosomes, which leverage biophysical modulation during the culture process, demonstrate superior efficacy compared to conventional exosomes and platelet-rich plasma (PRP), a widely used biological intervention for thin endometrium.
Study Design This is a prospective, non-randomized, parallel-controlled study.
Patients will be divided into three groups:
Control Group (PRP Group): Endometrial injection of autologous platelet-rich plasma (PRP).
Conventional Exosome Group: Endometrial injection of UCMSC-derived exosomes. Mechanically Engineered Exosome Group: Endometrial injection of ME-UCMSC-derived exosomes.
Primary endpoint: Change in endometrial thickness. Secondary endpoints: Clinical pregnancy rate, implantation rate, live birth rate, miscarriage rate, and safety assessments (including hypersensitivity reactions, infection, and long-term complications).
Intervention Details Each participant will receive a single intra-endometrial injection using a hysteroscopic-guided 17G needle during the proliferative phase (D3-D7 of the menstrual cycle).
PRP Group: 1-1.5mL PRP per injection site (autologous). UCMSC-Exo Group: 1-1.5mL conventional exosome solution per site. ME-UCMSC-Exo Group: 1-1.5mL mechanically engineered exosome solution per site. Rationale for PRP as a Positive Control PRP is used as a positive control due to its established efficacy in improving endometrial thickness and pregnancy outcomes. Meta-analyses of RCTs have demonstrated that PRP significantly enhances endometrial thickness (MD: 1.23mm, 95% CI: 0.87-1.59, p=0.000) and improves clinical pregnancy rates (RR: 2.04, 95% CI: 1.52-2.76, p=0.000). Additionally, PRP is autologous, safe, and widely used in reproductive medicine, making it a suitable comparative intervention for evaluating the therapeutic efficacy of exosomes.
Eligibility Criteria
Inclusion Criteria:
- Females aged 20-40 years (inclusive of boundary values);
- Normal ovarian reserve function (criteria: AFC ≥ 7, AMH > 1.1 ng/mL);
- History of transcervical resection of adhesions (TCRA);
- Received PRP treatment after TCRA;
- At least one embryo transfer (ET) cycle in which they underwent standard ovarian stimulation (fresh cycle) or standard hormone replacement therapy (FET cycle), with an endometrial thickness of <7 mm;
- Planned to continue IVF/ICSI/FET-assisted conception;
- Able to accept and adhere to treatment and follow-up and willing to sign an informed consent form.
Exclusion Criteria:
- Patients with severe systemic diseases, surgical contraindications, or cycle contraindications;
- Patients with reproductive tract infections, genital tuberculosis, pelvic inflammatory disease, or malignant tumors of reproductive organs;
- Patients with systemic diseases that cause uterine bleeding;
- Patients allergic to any drugs, materials, or components used in this study;
- Patients at high risk for hormone-dependent tumors such as breast cancer or ovarian tumors;
- Patients with untreated submucosal fibroids of any size (FIGO 0/I/II), uterine fibroids ≥5 cm (FIGO III, IV, V, VI, VII), adenomyosis, unicornuate uterus, bicornuate uterus, or endometrial polyps;
- Patients with hydrosalpinx ≥3 cm or hydrosalpinx of any size with significant vaginal discharge;
- Patients with ovarian endometriotic cysts (chocolate cysts) ≥4 cm;
- Patients who participated in other clinical trials within 3 months before surgery or during the study period;
- Patients unable to tolerate anesthesia;
- Patients with genetic abnormalities;
- Other patients deemed unsuitable for participation in this study by the investigator.
Statistical Considerations \& Sample Size Estimated sample size: 90 patients (30 per group). Primary outcome variable: Endometrial thickness increase post-treatment. Sample size calculation based on ANOVA analysis and post-hoc Tukey HSD test to compare all intergroup differences while controlling the familywise error rate at α=0.05.
Considering a 10% dropout rate, a total of 90 patients will be recruited.
Follow-up and Outcome Assessment
Patients will be monitored at multiple time points:
- Baseline (Pre-intervention assessment).
- Short-term efficacy evaluations: Day of progesterone (P) transformation P+7 days Next embryo transfer cycle (HCG trigger day / FET cycle day of progesterone start).
- Pregnancy outcomes: Biochemical pregnancy (Day 15 post-ET). Clinical pregnancy confirmation (Week 5-6). Live birth rate and perinatal complications (up to 1 year post-intervention). Safety evaluations:
- Immediate adverse reactions (allergic responses, infections).
- Long-term safety (90-day, 1-year follow-up including tumor markers, liver/kidney function tests, and ultrasound assessments).
Scientific \& Clinical Significance This is the first clinical study evaluating mechanically engineered and conventional umbilical cord-derived stem cell exosome therapy for thin endometrium.
If successful, the study will establish a novel, cell-free regenerative therapy for patients with refractory thin endometrium.
Findings could pave the way for future exosome-based treatments in reproductive medicine, expanding therapeutic options for women with uterine factor infertility.
- Being tested
- Mechanically Engineered Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes, Umbilical cord mesenchymal stem cell-derived exosomes, platelet-rich plasma
- 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.
Mechanically Engineered Umbilical Cord Mesenchymal Stem Cell-Derived ExosomesBiological
Also called ME-UCMSC-Exo, RH-Exo
Mechanically engineered umbilical cord mesenchymal stem cell-derived exosomes (ME-UCMSC-Exo) are isolated from umbilical cord-derived mesenchymal stem cells (UCMSCs) subjected to mechanical stress conditioning during in vitro expansion. This process enhances exosome yield, bioactivity, and regenerative capacity. The exosomes are purified via ultracentrifugation and characterized for size, protein markers, and RNA content.
In this study, ME-UCMSC-Exo is administered via intra-endometrial injection under hysteroscopic guidance. Each participant in this intervention group will receive 1-1.5 mL of exosome solution (containing approximately5*10^10 particles/mL) per injection site during the proliferative phase (Day 3-7 of the menstrual cycle). The aim is to enhance endometrial thickness, receptivity, and pregnancy outcomes in patients with thin endometrium secondary to intrauterine adhesions.
Umbilical cord mesenchymal stem cell-derived exosomesBiological
Also called UCMSC-Exo, TCP-Exo
Umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-Exo) are obtained from standard cultured UCMSCs without mechanical stress preconditioning. These exosomes undergo identical purification and characterization procedures as ME-UCMSC-Exo but lack biomechanical priming. UCMSC-Exo is also administered intra-endometrially via hysteroscopic injection at a dose of 1-1.5 mL (5*10^10 particles/mL) per site.
platelet-rich plasmaBiological
Also called PRP
Platelet-rich plasma (PRP) is an autologous biological preparation obtained from centrifuged whole blood. It contains a high concentration of growth factors, including platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), and vascular endothelial growth factor (VEGF), which promote endometrial regeneration.
In this study, PRP will be administered via hysteroscopically guided intra-endometrial injection at a dose of 1-1.5 mL per injection site, following standard PRP preparation protocols. This group serves as a positive control for evaluating the efficacy of exosome-based therapies.
| Study group | Role | What they receive |
|---|---|---|
| Mechanically Engineered Umbilical Cord Mesenchymal Stem Cell-Derived Exosome Group (ME-UCMSC-Exo) | Experimental | Participants in this arm will receive hysteroscopically guided intra-endometrial injection of 1-1.5 mL mechanically engineered umbilical cord mesenchymal stem cell-derived exosomes (ME-UCMSC-Exo) containing approximately 5×10¹⁰ particles/mL during the proliferative phase (Day 3-7 of the menstrual cycle).
The exosomes are obtained from mechanically preconditioned UC-MSC cultures, which are subjected to biomechanical stress during expansion to enhance regenerative properties.
The study aims to evaluate the efficacy of ME-UCMSC-Exo in improving endometrial thickness and pregnancy outcomes in patients with thin endometrium secondary to intrauterine adhesions. Receives: Biological: Mechanically Engineered Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes |
| Conventional Umbilical Cord Mesenchymal Stem Cell-Derived Exosome Group (UCMSC-Exo) | Experimental | Participants in this arm will receive hysteroscopically guided intra-endometrial injection of 1-1.5 mL conventional umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-Exo) containing approximately 5×10¹⁰ particles/mL during the proliferative phase (Day 3-7 of the menstrual cycle).
Unlike the ME-UCMSC-Exo group, these exosomes are obtained from standard UC-MSC cultures without mechanical stress preconditioning.
This group serves as a comparator to determine whether mechanical preconditioning enhances exosome efficacy in endometrial regeneration and pregnancy outcomes. Receives: Biological: Umbilical cord mesenchymal stem cell-derived exosomes |
| Platelet-Rich Plasma (PRP) Control Group | Active comparator | Participants in this arm will receive hysteroscopically guided intra-endometrial injection of 1-1.5 mL autologous PRP following standard PRP preparation protocols during the proliferative phase (Day 3-7 of the menstrual cycle).
PRP contains growth factors such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-β), which have been shown to improve endometrial receptivity and pregnancy outcomes.
This group serves as a positive control for assessing the efficacy of exosome-based therapies. Receives: Biological: platelet-rich plasma |
What is being measured
The primary outcome is the main question the study is designed to answer.
Endometrial thickness
The endometrial thickness under ultrasound is measured on the HCG trigger day, oocyte retrieval day, day of progesterone Initiationor or embryo transfer day using transvaginal ultrasound in the sagittal/long-axis plane of the uterus. The measurement is taken at the thickest point within a 1 cm range from the uterine fundus, from the basal membrane on one side, perpendicular across the endometrial cavity line to the basal membrane on the opposite side.
Measured: 30-90days
Secondary outcomes (1)
clinical pregnancy
A clinical pregnancy is diagnosed based on the presence of ultrasound confirmation of a gestational sac in the uterus.
Measured: 1-6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2025
- Study start21 Feb 2025
- Primary completion12 Jun 2025 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Thin Endometrial LiningStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tang-Du Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Xi'an Jiaotong University
- Responsible party
- Principal investigator, zhangwanlin, Tang-Du Hospital
- Investigators
- The Fourth Military Medical University, Principal investigator, Air Force Military Medical University, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06896747
- Sponsor's protocol ID
- 2024LC2421
- Status last verified
- Mar 2025
- First submitted
- 18 Mar 2025
- Last updated
- 26 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data on primary outcome measures, including endometrial thickness and pregnancy rates, will be shared after study completion. Requests for data access can be made through the corresponding author or institutional repository.
Publications
Zhang H, Zhu H, Feng J, Zhang Z, Zhang S, Wang Z, Sun L, Zhang W, Gao B, Zhang Y, Lin M. Reprogramming of Activated Pancreatic Stellate Cells via Mechanical Modulation of Transmembrane Force-sensitive N-cadherin Receptor. J Mol Biol. 2023 Jan 15;435(1):167819. doi: 10.1016/j.jmb.2022.167819. Epub 2022 Sep 8.
PubMed 36089055Cheng B, Wan W, Huang G, Li Y, Genin GM, Mofrad MRK, Lu TJ, Xu F, Lin M. Nanoscale integrin cluster dynamics controls cellular mechanosensing via FAKY397 phosphorylation. Sci Adv. 2020 Mar 4;6(10):eaax1909. doi: 10.1126/sciadv.aax1909. eCollection 2020 Mar.
PubMed 32181337Zhang Z, Sha B, Zhao L, Zhang H, Feng J, Zhang C, Sun L, Luo M, Gao B, Guo H, Wang Z, Xu F, Lu TJ, Genin GM, Lin M. Programmable integrin and N-cadherin adhesive interactions modulate mechanosensing of mesenchymal stem cells by cofilin phosphorylation. Nat Commun. 2022 Nov 11;13(1):6854. doi: 10.1038/s41467-022-34424-0.
PubMed 36369425Zhang C, Zhu H, Ren X, Gao B, Cheng B, Liu S, Sha B, Li Z, Zhang Z, Lv Y, Wang H, Guo H, Lu TJ, Xu F, Genin GM, Lin M. Mechanics-driven nuclear localization of YAP can be reversed by N-cadherin ligation in mesenchymal stem cells. Nat Commun. 2021 Oct 28;12(1):6229. doi: 10.1038/s41467-021-26454-x.
PubMed 34711824Sun H, Dong J, Fu Z, Lu X, Chen X, Lei H, Xiao X, Chen S, Lu J, Su D, Xiong Y, Fang Z, Mao J, Chen L, Wang X. TSG6-Exo@CS/GP Attenuates Endometrium Fibrosis by Inhibiting Macrophage Activation in a Murine IUA Model. Adv Mater. 2024 May;36(21):e2308921. doi: 10.1002/adma.202308921. Epub 2024 Apr 15.
PubMed 38588501Zhang W, Tang R, Xiao X, Liu J, Li M, Wang X. A Comparative Study on the Efficacy of Subendometrial Versus Intrauterine Platelet-Rich Plasma Injections for Treating Intrauterine Adhesions: A Retrospective Cohort Study. J Minim Invasive Gynecol. 2025 Apr;32(4):378-385.e1. doi: 10.1016/j.jmig.2024.11.007. Epub 2024 Dec 4.
PubMed 39643206
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Therapeutic Effects of Mechanically Engineered Umbilical Cord-Derived Stem Cell Exosomes on Endometrial Injury: A Prospective, Non-Randomized, Parallel-Controlled Clinical Study
- ClinicalTrials.gov ID
- NCT06896747
- Acronym / sponsor ID
- 2024LC2421
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Tang-Du HospitalUniversity, hospital or other
- Collaborators
- Xi'an Jiaotong University
- Study start
- 21 Feb 2025 (actual)
- Primary completion
- 12 Jun 2025 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 26 Mar 2025 (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.
The goal of this clinical trial is to evaluate if engineered mechanically umbilical cord-derived stem cell exosomes, or conventional umbilical cord -derived stem cell exosomes, can improve endometrial thickness in women with thin endometrium.
The main questions it aims to answer are:
Can exosomes delivered via subendometrial injection improve endometrial thickness or clinical pregnancy rates compared to PRP (platelet-rich plasma)? Are there significant differences in endometrial thickness between the two treatment groups? Researchers will compare the intervention groups, which one group receives mechanical exosomes and the other receives conventional esosomes via subendometrial injection, to the control group, which receives PRP via the same methods, to see if exosomes provide superior therapeutic effects.
Participants will:
Receive either mechanical exosomesor or conventional esosomes or PRP through subendometrial injection.
Be monitored for changes in endometrial parameters.
Detailed description
This study is a prospective, non-randomized controlled clinical trial designed to evaluate the efficacy and safety of mechanically engineered umbilical cord mesenchymal stem cell-derived exosomes (ME-UCMSC-Exo) and conventional umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-Exo) in the treatment of thin endometrium secondary to severe intrauterine adhesions (IUA) following hysteroscopic adhesiolysis. Thin endometrium is a significant challenge in reproductive medicine, associated with poor embryo implantation rates, recurrent implantation failure (RIF), and increased risk of pregnancy complications. Despite conventional hormonal therapies, effective endometrial regeneration remains a clinical challenge.
Emerging regenerative therapies, including exosome-based interventions, offer promising avenues for enhancing endometrial repair and pregnancy outcomes. Exosomes, extracellular vesicles secreted by stem cells, play a crucial role in tissue regeneration by delivering bioactive molecules such as proteins, microRNAs (miRNAs), and growth factors to target cells. The study aims to determine whether mechanically engineered exosomes, which leverage biophysical modulation during the culture process, demonstrate superior efficacy compared to conventional exosomes and platelet-rich plasma (PRP), a widely used biological intervention for thin endometrium.
Study Design This is a prospective, non-randomized, parallel-controlled study.
Patients will be divided into three groups:
Control Group (PRP Group): Endometrial injection of autologous platelet-rich plasma (PRP).
Conventional Exosome Group: Endometrial injection of UCMSC-derived exosomes. Mechanically Engineered Exosome Group: Endometrial injection of ME-UCMSC-derived exosomes.
Primary endpoint: Change in endometrial thickness. Secondary endpoints: Clinical pregnancy rate, implantation rate, live birth rate, miscarriage rate, and safety assessments (including hypersensitivity reactions, infection, and long-term complications).
Intervention Details Each participant will receive a single intra-endometrial injection using a hysteroscopic-guided 17G needle during the proliferative phase (D3-D7 of the menstrual cycle).
PRP Group: 1-1.5mL PRP per injection site (autologous). UCMSC-Exo Group: 1-1.5mL conventional exosome solution per site. ME-UCMSC-Exo Group: 1-1.5mL mechanically engineered exosome solution per site. Rationale for PRP as a Positive Control PRP is used as a positive control due to its established efficacy in improving endometrial thickness and pregnancy outcomes. Meta-analyses of RCTs have demonstrated that PRP significantly enhances endometrial thickness (MD: 1.23mm, 95% CI: 0.87-1.59, p=0.000) and improves clinical pregnancy rates (RR: 2.04, 95% CI: 1.52-2.76, p=0.000). Additionally, PRP is autologous, safe, and widely used in reproductive medicine, making it a suitable comparative intervention for evaluating the therapeutic efficacy of exosomes.
Eligibility Criteria
Inclusion Criteria:
- Females aged 20-40 years (inclusive of boundary values);
- Normal ovarian reserve function (criteria: AFC ≥ 7, AMH > 1.1 ng/mL);
- History of transcervical resection of adhesions (TCRA);
- Received PRP treatment after TCRA;
- At least one embryo transfer (ET) cycle in which they underwent standard ovarian stimulation (fresh cycle) or standard hormone replacement therapy (FET cycle), with an endometrial thickness of <7 mm;
- Planned to continue IVF/ICSI/FET-assisted conception;
- Able to accept and adhere to treatment and follow-up and willing to sign an informed consent form.
Exclusion Criteria:
- Patients with severe systemic diseases, surgical contraindications, or cycle contraindications;
- Patients with reproductive tract infections, genital tuberculosis, pelvic inflammatory disease, or malignant tumors of reproductive organs;
- Patients with systemic diseases that cause uterine bleeding;
- Patients allergic to any drugs, materials, or components used in this study;
- Patients at high risk for hormone-dependent tumors such as breast cancer or ovarian tumors;
- Patients with untreated submucosal fibroids of any size (FIGO 0/I/II), uterine fibroids ≥5 cm (FIGO III, IV, V, VI, VII), adenomyosis, unicornuate uterus, bicornuate uterus, or endometrial polyps;
- Patients with hydrosalpinx ≥3 cm or hydrosalpinx of any size with significant vaginal discharge;
- Patients with ovarian endometriotic cysts (chocolate cysts) ≥4 cm;
- Patients who participated in other clinical trials within 3 months before surgery or during the study period;
- Patients unable to tolerate anesthesia;
- Patients with genetic abnormalities;
- Other patients deemed unsuitable for participation in this study by the investigator.
Statistical Considerations \& Sample Size Estimated sample size: 90 patients (30 per group). Primary outcome variable: Endometrial thickness increase post-treatment. Sample size calculation based on ANOVA analysis and post-hoc Tukey HSD test to compare all intergroup differences while controlling the familywise error rate at α=0.05.
Considering a 10% dropout rate, a total of 90 patients will be recruited.
Follow-up and Outcome Assessment
Patients will be monitored at multiple time points:
- Baseline (Pre-intervention assessment).
- Short-term efficacy evaluations: Day of progesterone (P) transformation P+7 days Next embryo transfer cycle (HCG trigger day / FET cycle day of progesterone start).
- Pregnancy outcomes: Biochemical pregnancy (Day 15 post-ET). Clinical pregnancy confirmation (Week 5-6). Live birth rate and perinatal complications (up to 1 year post-intervention). Safety evaluations:
- Immediate adverse reactions (allergic responses, infections).
- Long-term safety (90-day, 1-year follow-up including tumor markers, liver/kidney function tests, and ultrasound assessments).
Scientific \& Clinical Significance This is the first clinical study evaluating mechanically engineered and conventional umbilical cord-derived stem cell exosome therapy for thin endometrium.
If successful, the study will establish a novel, cell-free regenerative therapy for patients with refractory thin endometrium.
Findings could pave the way for future exosome-based treatments in reproductive medicine, expanding therapeutic options for women with uterine factor infertility.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Mechanically Engineered Umbilical Cord Mesenchymal Stem Cell-Derived Exosome Group (ME-UCMSC-Exo) | Experimental | Biological: Mechanically Engineered Umbilical Cord Mesenchymal Stem Cell-Derived ExosomesParticipants in this arm will receive hysteroscopically guided intra-endometrial injection of 1-1.5 mL mechanically engineered umbilical cord mesenchymal stem cell-derived exosomes (ME-UCMSC-Exo) containing approximately 5×10¹⁰ particles/mL during the proliferative phase (Day 3-7 of the menstrual cycle). The exosomes are obtained from mechanically preconditioned UC-MSC cultures, which are subjected to biomechanical stress during expansion to enhance regenerative properties. The study aims to evaluate the efficacy of ME-UCMSC-Exo in improving endometrial thickness and pregnancy outcomes in patients with thin endometrium secondary to intrauterine adhesions. |
| Conventional Umbilical Cord Mesenchymal Stem Cell-Derived Exosome Group (UCMSC-Exo) | Experimental | Biological: Umbilical cord mesenchymal stem cell-derived exosomesParticipants in this arm will receive hysteroscopically guided intra-endometrial injection of 1-1.5 mL conventional umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-Exo) containing approximately 5×10¹⁰ particles/mL during the proliferative phase (Day 3-7 of the menstrual cycle). Unlike the ME-UCMSC-Exo group, these exosomes are obtained from standard UC-MSC cultures without mechanical stress preconditioning. This group serves as a comparator to determine whether mechanical preconditioning enhances exosome efficacy in endometrial regeneration and pregnancy outcomes. |
| Platelet-Rich Plasma (PRP) Control Group | Active comparator | Biological: platelet-rich plasmaParticipants in this arm will receive hysteroscopically guided intra-endometrial injection of 1-1.5 mL autologous PRP following standard PRP preparation protocols during the proliferative phase (Day 3-7 of the menstrual cycle). PRP contains growth factors such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-β), which have been shown to improve endometrial receptivity and pregnancy outcomes. This group serves as a positive control for assessing the efficacy of exosome-based therapies. |
Who may qualify
- Ages
- 20 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Females aged 20-40 years (inclusive of boundary values);
- Normal ovarian reserve function (criteria: AFC ≥ 7, AMH > 1.1 ng/mL);
- History of transcervical resection of adhesions (TCRA);
- Received PRP treatment after TCRA;
- At least one embryo transfer (ET) cycle in which they underwent standard ovarian stimulation (fresh cycle) or standard hormone replacement therapy (FET cycle), with an endometrial thickness of <7 mm;
Key exclusion criteria (12 listed)
- Patients with severe systemic diseases, surgical contraindications, or cycle contraindications;
- Patients with reproductive tract infections, genital tuberculosis, pelvic inflammatory disease, or malignant tumors of reproductive organs;
- Patients with systemic diseases that cause uterine bleeding;
- Patients allergic to any drugs, materials, or components used in this study;
- Patients at high risk for hormone-dependent tumors such as breast cancer or ovarian tumors;
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 |
|---|---|---|
| Mechanically Engineered Umbilical Cord Mesenchymal Stem Cell-Derived ExosomesAlso: ME-UCMSC-Exo, RH-ExoMechanically engineered umbilical cord mesenchymal stem cell-derived exosomes (ME-UCMSC-Exo) are isolated from umbilical cord-derived mesenchymal stem cells (UCMSCs) subjected to mechanical stress conditioning during in vitro expansion. This process enhances exosome yield, bioactivity, and regenerative capacity. The exosomes are purified via ultracentrifugation and characterized for size, protein markers, and RNA content. In this study, ME-UCMSC-Exo is administered via intra-endometrial injection under hysteroscopic guidance. Each participant in this intervention group will receive 1-1.5 mL of exosome solution (containing approximately5*10^10 particles/mL) per injection site during the proliferative phase (Day 3-7 of the menstrual cycle). The aim is to enhance endometrial thickness, receptivity, and pregnancy outcomes in patients with thin endometrium secondary to intrauterine adhesions. | Biological | Mechanically Engineered Umbilical Cord Mesenchymal Stem Cell-Derived Exosome Group (ME-UCMSC-Exo) |
| Umbilical cord mesenchymal stem cell-derived exosomesAlso: UCMSC-Exo, TCP-ExoUmbilical cord mesenchymal stem cell-derived exosomes (UCMSC-Exo) are obtained from standard cultured UCMSCs without mechanical stress preconditioning. These exosomes undergo identical purification and characterization procedures as ME-UCMSC-Exo but lack biomechanical priming. UCMSC-Exo is also administered intra-endometrially via hysteroscopic injection at a dose of 1-1.5 mL (5*10^10 particles/mL) per site. | Biological | Conventional Umbilical Cord Mesenchymal Stem Cell-Derived Exosome Group (UCMSC-Exo) |
| platelet-rich plasmaAlso: PRPPlatelet-rich plasma (PRP) is an autologous biological preparation obtained from centrifuged whole blood. It contains a high concentration of growth factors, including platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), and vascular endothelial growth factor (VEGF), which promote endometrial regeneration. In this study, PRP will be administered via hysteroscopically guided intra-endometrial injection at a dose of 1-1.5 mL per injection site, following standard PRP preparation protocols. This group serves as a positive control for evaluating the efficacy of exosome-based therapies. | Biological | Platelet-Rich Plasma (PRP) Control Group |
Primary outcome
Endometrial thickness
Time frame: 30-90days
The endometrial thickness under ultrasound is measured on the HCG trigger day, oocyte retrieval day, day of progesterone Initiationor or embryo transfer day using transvaginal ultrasound in the sagittal/long-axis plane of the uterus. The measurement is taken at the thickest point within a 1 cm range from the uterine fundus, from the basal membrane on one side, perpendicular across the endometrial cavity line to the basal membrane on the opposite side.
1 secondary outcome
clinical pregnancy
Time frame: 1-6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2025.
- Results publication: PubMed 36089055Zhang H, Zhu H, Feng J, Zhang Z, Zhang S, Wang Z, Sun L, Zhang W, Gao B, Zhang Y, Lin M. Reprogramming of Activated Pancreatic Stellate Cells via Mechanical Modulation of Transmembrane Force-sensitive N-cadherin Receptor. J Mol Biol. 2023 Jan 15;435(1):167819. doi: 10.1016/j.jmb.2022.167819. Epub 2022 Sep 8.
- Results publication: PubMed 32181337Cheng B, Wan W, Huang G, Li Y, Genin GM, Mofrad MRK, Lu TJ, Xu F, Lin M. Nanoscale integrin cluster dynamics controls cellular mechanosensing via FAKY397 phosphorylation. Sci Adv. 2020 Mar 4;6(10):eaax1909. doi: 10.1126/sciadv.aax1909. eCollection 2020 Mar.
- Results publication: PubMed 36369425Zhang Z, Sha B, Zhao L, Zhang H, Feng J, Zhang C, Sun L, Luo M, Gao B, Guo H, Wang Z, Xu F, Lu TJ, Genin GM, Lin M. Programmable integrin and N-cadherin adhesive interactions modulate mechanosensing of mesenchymal stem cells by cofilin phosphorylation. Nat Commun. 2022 Nov 11;13(1):6854. doi: 10.1038/s41467-022-34424-0.
- Results publication: PubMed 34711824Zhang C, Zhu H, Ren X, Gao B, Cheng B, Liu S, Sha B, Li Z, Zhang Z, Lv Y, Wang H, Guo H, Lu TJ, Xu F, Genin GM, Lin M. Mechanics-driven nuclear localization of YAP can be reversed by N-cadherin ligation in mesenchymal stem cells. Nat Commun. 2021 Oct 28;12(1):6229. doi: 10.1038/s41467-021-26454-x.
- Results publication: PubMed 38588501Sun H, Dong J, Fu Z, Lu X, Chen X, Lei H, Xiao X, Chen S, Lu J, Su D, Xiong Y, Fang Z, Mao J, Chen L, Wang X. TSG6-Exo@CS/GP Attenuates Endometrium Fibrosis by Inhibiting Macrophage Activation in a Murine IUA Model. Adv Mater. 2024 May;36(21):e2308921. doi: 10.1002/adma.202308921. Epub 2024 Apr 15.
- Results publication: PubMed 39643206Zhang W, Tang R, Xiao X, Liu J, Li M, Wang X. A Comparative Study on the Efficacy of Subendometrial Versus Intrauterine Platelet-Rich Plasma Injections for Treating Intrauterine Adhesions: A Retrospective Cohort Study. J Minim Invasive Gynecol. 2025 Apr;32(4):378-385.e1. doi: 10.1016/j.jmig.2024.11.007. Epub 2024 Dec 4.
- Individual participant dataSharing planned: Yes. Data on primary outcome measures, including endometrial thickness and pregnancy rates, will be shared after study completion. Requests for data access can be made through the corresponding author or institutional repository.
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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.
The Fourth Military Medical University principal investigator
Air Force Military Medical University, China
2 sites 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 Mechanically Engineered Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes, Umbilical cord mesenchymal stem cell-derived exosomes and platelet-rich plasma in people with Thin Endometrial Lining and Female Infertility, run by Tang-Du Hospital at 2 sites in China.
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 7 inclusion and 12 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: looking for participants now, as of the sponsor's last update on 26 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wanlin Zhang, PhD (+86 18149363396, 1843678023@qq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Endometrial thickness (time frame: 30-90days). 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 NCT06896747, which also lists 6 linked publications.
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 26 Mar 2025.