A Phase 1/2 interventional study of Mechanically Engineered Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes and Umbilical cord mesenchymal stem cell-derived exosomes in Thin Endometrial Lining, Female Infertility and Intrauterine Adhesions, sponsored by Tang-Du Hospital. Recruiting at 2 sites in China. Open to female participants aged 20 Years to 40 Years. Per ClinicalTrials.gov, last updated 2025-03-26.
Sponsored by Tang-Du Hospital · Phase 1/2, Interventional, and Treatment
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.
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:
Exclusion Criteria:
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:
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:
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.
2,506 studies on the registry are indexed under Infertility; 407 are open to participants now.
This study's planned enrollment of 90 is below the median of 120 across 1,698 interventional studies indexed under Infertility.
Browse Infertility studies →Tang-Du Hospital is the lead sponsor of 164 studies on the registry; 77 are open to participants now.
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Exclusion Criteria:
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.
Biological: Mechanically Engineered Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes
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.
Biological: Umbilical cord mesenchymal stem cell-derived exosomes
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.
Biological: platelet-rich plasma
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.
Also known as: ME-UCMSC-Exo, RH-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.
Also known as: UCMSC-Exo, TCP-Exo
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.
Also known as: PRP
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.
Time frame: 30-90days
clinical pregnancy
A clinical pregnancy is diagnosed based on the presence of ultrasound confirmation of a gestational sac in the uterus.
Time frame: 1-6 months
Plan to share: 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.
Supporting information: Csr
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