RARE DISEASE
Asherman syndrome
Asherman syndrome
Asherman syndrome
Drug discovery
1
drug
With orphan designation
Overview
Asherman Syndrome Overview
Asherman syndrome is an acquired uterine condition characterized by intrauterine adhesions, typically resulting from endometrial trauma (e.g., post-pregnancy curettage, cesarean section, or infection) [1][3][12]. Symptoms include amenorrhea, hypomenorrhea, infertility, recurrent miscarriage, and cyclic pelvic pain [1][2][7]. Diagnosis relies on hysteroscopy, the gold standard [3][11]. Treatment involves hysteroscopic adhesiolysis, often supplemented with estrogen therapy and intrauterine barriers (e.g., balloon stents) to prevent recurrence [5][10][13]. Prognosis varies with adhesion severity, with successful pregnancy rates up to ~64% post-treatment [9].
Burden
Associated with infertility (up to 45% prevalence in affected populations), recurrent pregnancy loss, and obstetric complications (e.g., placenta accreta, preterm birth) [9][12][17].
Psychosocial impact includes distress from infertility and prolonged treatment; recurrence rates reach 30% despite therapy [6][13][16].
Economic burden stems from repeated surgeries and specialized care needs, particularly in severe cases [6][12].
Therapies
Hysteroscopic adhesiolysis using cold scissors to minimize endometrial damage [5][13][16].
Postoperative estrogen therapy to stimulate endometrial regeneration and intrauterine devices (e.g., balloon stents) to prevent re-adhesion [3][10][19].
Severe cases may require multiple surgeries and adjuvant therapies (e.g., hyaluronic acid gel) [13][19].
Categories: rare gynecological and obstetric diseases
Research Papers
519 drug discovery papers about Asherman syndrome, with 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
519 drug discovery papers about Asherman syndrome, with 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-06-26 | Cornual type 3 retained products of conception – a fertility-sparing win with methotrexate
Retained products of conception (RPOC) with marked vascularity represent a diagnostic and therapeutic challenge due to the high risk of hemorrhage associated with surgical evacuation. Cornual localization further complicates management because of minimal myometrial thickness and proximity to major vascular structures. Cornual ectopic pregnancies are broadly classified into interstitial, angular, and true cornual types, each differing in anatomical location and clinical implications. Advanced imaging and individualized management are crucial, particularly in women desiring future fertility. We report a case of a 34-year-old multiparous woman with prior cesarean section who presented with amenorrhea of 2 months following dilatation and curettage for a blighted ovum. The patient was examined and was vitally stable. Further investigations were done. Her ultrasound with color Doppler demonstrated a highly vascular lesion with high peak systolic velocity in uterine cornua, with thin myometrium and findings to be correlated with beta human chorionic gonadotropin (β-hCG) and magnetic resonance imaging (MRI) SOS. Her β-hCG was negligible. Magnetic resonance imaging revealed a well-defined hyperintense lesion in the right uterine cornua with beak-like communication with the endometrial cavity, consistent with hyper vascular cornual RPOC. The patient was hemodynamically stable and desirous of future fertility and was managed conservatively with multidose methotrexate therapy. Serial Doppler follow-up demonstrated progressive reduction in vascularity and lesion size, followed by spontaneous expulsion. This case represents a diagnostic conundrum, as the patient presented with persistent amenorrhea following curettage rather than the typical bleeding seen with retained products of conception. The key differential diagnoses include Asherman syndrome, retained products of conception, chronic endometritis, and persistent trophoblastic activity. This case also highlights the need for a high index of clinical suspicion in atypical presentations, with supportive investigations aiding in differentiating hypervascular RPOC from cornual ectopic pregnancy and uterine arteriovenous malformation. Conservative medical management with methotrexate can be a safe and fertility-preserving option in carefully selected patients.
2026-05-08 | Mitochondria-targeted antioxidant mitoquinone attenuates TGF-β-induced fibrosis and restores impaired decidualization in mouse endometrial stromal cells.
This study aimed to investigate the therapeutic effects of mitoquinone (MitoQ) in endometrial fibrosis and to examine its role in restoring impaired decidualization associated with intrauterine adhesion. We further sought to delineate the underlying mechanisms through which MitoQ exerts its protective effects. Finally, we propose mitochondrial-targeted antioxidant therapy as a potential strategy for the treatment of gynecological diseases. An in vitro mouse endometrial fibrosis model was established by treating mouse endometrial stromal cells with transforming growth factor-β (TGF-β). MitoQ was subsequently administered to fibrotic cells to evaluate its therapeutic effects on fibrosis and defective decidualization. These effects were analyzed using quantitative real-time polymerase chain reaction, immunoblotting, immunofluorescence staining, and additional molecular and cellular assays. The underlying mechanisms were further investigated. TGF-β treatment (5 ng/mL for 48 hours) effectively induced a markedly fibrotic phenotype in mouse endometrial stromal cells. These cells were subsequently treated with 1 μM MitoQ for 24 hours. MitoQ treatment significantly reduced collagen type I alpha 1 chain (COL1A1) expression at both the mRNA and protein levels and downregulated inflammation-related markers. These effects were accompanied by reduced mitochondrial stress and suppression of suppressor of mothers against decapentaplegic (SMAD) signaling. Furthermore, MitoQ treatment restored impaired decidualization in fibrotic cells, as supported by increased expression of prolactin and insulin-like growth factor binding protein 1 (IGFBP1). MitoQ treatment effectively attenuates TGF-β-induced endometrial fibrosis by reducing collagen deposition and inflammatory marker expression, while restoring impaired decidualization. These findings suggest that MitoQ may serve as a promising therapeutic candidate for fibrosis-associated uterine dysfunction.
2026-04-30 | EXPLORING THE CORRELATION BETWEEN MALATU PUZHU AND SCHISTOSOMIASIS: SIDDHA APPROACHES TO TREAT INFERTILITY CAUSED BY PARASITIC INFECTIONS
Infertility affects 60–80 million couples globally, with 15–20 million in India each year. While multiple factors contribute to infertility, parasitic infections like Schistosomiasis, a neglected tropical disease, are often overlooked. Schistosomiasis may lead to azoospermia in males and Asherman syndrome in females; early diagnosis and treatment are crucial to prevent complications. In Siddha texts, infertility caused by pathogens was addressed as Malatu Puzhu, Suronitha Kirumi, and Karba Poochi, with a detailed description of symptoms, progression, and treatments. This study explores the correlation between Malatu Puzhu and Schistosomiasis, as well as Siddha treatments for the condition. This review examines the conceptual correlation between Malatu Puzhu in Siddha texts and schistosomiasis in modern medicine. Classical Siddha textbooks were analyzed using relevant keywords to identify disease descriptions and formulations. Contemporary biomedical literature indexed in PubMed, Web of Science, and Medline was also reviewed to understand the pathophysiology and reproductive consequences of schistosomiasis. The findings reveal a correlation between the manifestations of schistosomal infection and the Siddha concept of pathogen-induced infertility. Several Siddha formulations indicated for Malatu Puzhu and commonly used herbs, which were reported to have antiparasitic, anti-inflammatory, and fertility-supportive properties, were documented. Overall, this review emphasizes the underrecognized role of parasitic infections in infertility and the importance of early intervention. It also highlights the potential of Siddha therapeutic approaches as complementary strategies in managing infertility associated with parasitic infections, warranting further pharmacological and clinical research.
2025-11-21 | Fertility and Obstetric Outcomes in Asherman Syndrome: Assessing the Impact of Hyaluronic Acid Post-Hysteroscopic Adhesiolysis.
Installation of hyaluronic acid following hysteroscopic adhesiolysis is suggested to reduce intrauterine adhesion (IUA) reformation in women with Asherman's Syndrome (AS). We aimed to assess the impact of hyaluronic acid following hysteroscopic adhesiolysis on menstrual, surgical, fertility, obstetric and neonatal outcomes. We identified 128 women treated hysteroscopically for AS over an 11-year period and invited them to participate in a questionnaire-based study. A total of 43 women were included; 21 treated surgically with hyaluronic acid administered immediately following adhesiolysis and 22 having surgery alone. Outcomes were assessed by reviewing medical records retrospectively and using a structured questionnaire at 3 months and 4 years post procedure. There were no differences in the rates of repeat adhesiolysis procedures to treat recurrent IUAs between the treatment and control groups (19% vs. 18%, p = 0.94). All women in the treatment group reported resumption of menses 6 months following the procedure, with 9% in the control group reported ongoing amenorrhoea. There was no difference in the overall pregnancy rate (77% vs. 81%, p = 0.76), maternal and neonatal outcomes between the groups. Intrauterine application of hyaluronic acid at the time of hysteroscopic adhesiolysis for women with AS was not associated with the number of repeat surgical interventions, menstrual patterns, fertility, obstetric, or neonatal outcomes.
2025-11-10 | The Challenges of Asherman’s Syndrome: a clinical view
This thesis focused on enhancing the care for women with Ashermans Syndrome (AS) from various perspectives. For a long time, AS was considered a relatively simple disease with a simple cure, namely adhesions which were resolved by adhesiolysis. We show, however, that despite a high rate of successful (chapter 2) and safe (chapter 3) adhesiolyses in our center, rates to get pregnant are not as high as in the normal population (chapter 5) and that the use of adjuvant estrogen is to be debated (chapter 4). Even after achieving a successful pregnancy, the risk of adverse events was not over, as many women suffer from pregnancy and post-partum complications (chapters 6 & 7). We also showed that we were not able to distinguish those with a high risk of adverse events from those with a low risk (chapter 8). This results in a very high rate of women suffering from depression and anxiety disorders (chapter 9).
proteins
2026-08-13 | First-in-human pilot trial of G-CSF–mobilised platelet–leukocyte concentrate for severe refractory Asherman syndrome
Introduction Severe refractory Asherman syndrome (SRAS) remains difficult to treat, and the benefit of regenerative blood-derived therapies remains uncertain. This study evaluated whether systemic granulocyte colony-stimulating factor (G-CSF) mobilisation combined with targeted intrauterine delivery of autologous peripheral blood platelet–leukocyte concentrate (PBPLC) could improve endometrial thickness in women with SRAS. Methods This prospective, single-centre, single-arm pilot study enrolled 10 women with infertility for at least 3 years, severe intrauterine adhesions, poor endometrial development, and failure of previous adhesiolysis, hormonal therapy, and platelet-rich plasma treatment. After G-CSF mobilisation, autologous PBPLC was injected into the endometrial–myometrial junction under hysteroscopic guidance without concurrent formal adhesiolysis. The primary outcome was the change in late pre-ovulatory endometrial thickness (LPO-EMT), analysed using the exact Wilcoxon signed-rank test and Hodges–Lehmann estimates. Results LPO-EMT increased from 4.6 mm (SD 0.7) to 5.8 mm (SD 1.3), with a Hodges–Lehmann paired difference of 1.08 mm (95% CI 0.45–2.50; p = 0.0039). Hysteroscopic cavity restoration, reduced adhesion severity, and subjective menstrual improvement were observed in all participants, and the AFS score decreased from 10.8 to 4.5. No grade 3 or higher treatment-related adverse events occurred. Among nine women who attempted conception, pregnancy was detected in six (66.7%; exact 95% CI 29.9–92.5), including four clinical pregnancies (44.4%; exact 95% CI 13.7–78.8). However, all clinical pregnancies ended in first-trimester miscarriage, and no ongoing pregnancies or live births were achieved during follow-up. Discussion These preliminary findings suggest that G-CSF-mobilised autologous PBPLC may be a feasible approach for improving endometrial thickness and uterine cavity restoration in women with SRAS. However, the findings do not establish reproductive efficacy, and larger controlled studies are warranted. Clinical trial registration https://cris.nih.go.kr/ , identifier KCT0004208.
2026-07-25 | SUBENDOMETRIAL PLATELET-RICH PLASMA IMPROVES EMBRYO TRANSFER FEASIBILITY AND PREGNANCY OUTCOMES IN PATIENTS WITH POOR ENDOMETRIAL DEVELOPMENT
Objective: To assess whether subendometrial PRP administered at hysteroscopy improves embryo transfer rates and clinical outcomes. Design: Retrospective cohort study. Materials and Methods: Nine patients undergoing hysteroscopy with PRP were evaluated. Outcomes included ability to proceed with embryo transfer, biochemical pregnancy, and miscarriage rates before and after intervention. Results: Prior to PRP, 2 of 9 patients (22%) proceeded to embryo transfer. Following PRP, 7 of 9 patients (78%) underwent embryo transfer. Among patients undergoing transfer post-PRP (n = 7), 3 (43%) achieved a positive pregnancy test. Of these, 2 resulted in ongoing pregnancies and 1 resulted in miscarriage. Importantly, patients previously unable to proceed to transfer due to inadequate endometrial development or cavity abnormalities were able to undergo transfer following PRP, including those with Asherman syndrome and intrauterine fluid. Conclusions: Subendometrial PRP may improve the likelihood of proceeding to embryo transfer and may be associated with favorable pregnancy outcomes in patients with poor endometrial receptivity. These findings support further investigation in larger, prospective studies.
2026-07-01 | L26/P-486 Characteristics associated with ongoing pregnancy after single euploid frozen embryo transfer in a true natural cycle
Abstract Study question What factors are associated with ongoing pregnancy (OP) in a true natural cycle (tNC) following a single euploid frozen embryo transfer (FET)? Summary answer Ongoing pregnancy in a tNC was significantly associated with age, Body Mass index (BMI) and embryo quality before FET. What is known already Recent evidence suggests a higher live birth rate in a tNC FET compared to an artificial FET. The presence of a corpus luteum in a tNC may contribute to an increased uterine receptivity, as the corpus luteum produces natural progesterone and additional luteal factors that are absent in artificial cycles. Most comparative studies have focused on overall cycle outcomes, rather than dissecting patient and cycle characteristics within a tNC. There is limited information about which specific variables most strongly influence success when a tNC FET is performed. Study design, size, duration This retrospective multicenter cohort study analyzed 1,373 single euploid FET cycles from 1,186 patients performed between March 2017 and September 2024. The primary outcome was ongoing pregnancy, defined as fetal cardiac activity. Participants/materials, setting, methods Cycles included women undergoing a single euploid FET prepared in a tNC at three tertiary referral IVF centers. Patients with uterine abnormalities or Asherman syndrome were excluded. Luteal phase support (LPS) was administered at clinician discretion. Mixed-effects logistic regression with a random intercept for patient ID was used to assess factors associated with OP and to account for repeated cycles. Main results and the role of chance Age was similar between groups [Median (Q1–Q3): 35.00 (31.00–38.00) for both groups], whereas BMI was lower among ongoing pregnancies [Median (Q1–Q3): 25.00 (22.00–28.00) vs. Median (Q1–Q3): 26.00 (23.00–29.00); p < 0.001]. A mixed-effects logistic regression model based on 1,351 cycles from 1,171 patients showed that increasing age was independently associated with higher odds of OP (aOR 1.03 per year, 95% CI 1.01–1.06; p = 0.010), while higher BMI was associated with lower odds (aOR 0.95 per kg/m², 95% CI 0.92–0.97; p < 0.001). Endometrial thickness was not associated with outcome (aOR 1.02 per mm, 95% CI 0.97–1.09; p = 0.432). Transfers involving Fair/Poor embryos had lower odds compared with Top/Good embryos (aOR 0.34, 95% CI 0.24–0.49; p < 0.001). LPS regimen and reproductive history variables were not significant. History of Cesarean section (p = 0.067) and D&C (p = 0.078) showed borderline associations. Limitations, reasons for caution Limitations include the retrospective design and heterogeneity in luteal phase support. Findings are restricted to embryos undergoing preimplantation genetic testing for aneuploidy (PGT-A) and may not be generalizable to untested populations. The impact of the number of prior Cesarean sections could not be specifically evaluated. Wider implications of the findings In tNC single euploid FET, BMI and embryo quality are associated with OP, whereas endometrial thickness is not. Prior Cesarean section or D&C may negatively influence outcomes, warranting further investigation. Trial registration number No
2026-04-28 | The value of platelet rich plasma in women with intrauterine adhesions. A systematic review and meta-analysis.
To evaluate the benefits of platelet-rich plasma administration after adhesiolysis in women with intrauterine adhesions. A database search using the keywords (autologous platelet-rich plasma) AND (intrauterine adhesions) and their Medical Subject Headings terms revealed 11 studies with 1,130 participants. Endometrial thickness was reported in four studies with 274 participants. The mean difference effect estimate was 0.53 with a 95% confidence interval (CI) of 0.23, 0.82; P<0.001, and I²=0%. The menstrual pattern after the procedure showed that the odds ratio (OR) effect estimates for amenorrhea, hypomenorrhea, and normal menstruation were 6.47 (0.24, 174.08), 0.84 (0.41, 1.73), and 1.21 (0.51, 2.84), respectively, and the P-values were 0.27, 0.63, and 0.66, respectively. The number of women with adhesions after the procedure showed that the OR effect estimates for grade I, II, and III adhesions were 1.74 (0.41, 7.45), 0.76 (0.21, 2.70), and 0.31 (0.11, 0.88), respectively, and the P-values were 0.46, 0.67, and 0.03, respectively. Changes in the American Fertility Society (AFS) score after the operation were reported in three studies with 276 participants. The mean difference effect estimate was 0.87, with a 95% CI of 0.17, 1.56; P=0.01; I²=0%. The clinical pregnancy rate was reported in five studies involving 506 participants. The OR effect estimate was 1.80 with a 95% CI of 1.18, 2.75; a P-value of 0.006, and I² of 0%. Platelet-rich plasma administration after hysteroscopic adhesiolysis improved endometrial thickness (low evidence), recurrence of grade III adhesions (low evidence), AFS score of adhesions (low evidence), and clinical pregnancy rates (moderate evidence).
2026-02-19 | Endometrial Autologous Intrauterine Platelet-Rich Plasma (PRP) Instillation Treatment and Its Potential on In Vitro Fertilization (IVF): Narrative Review.
Implantation failure remains a major challenge in assisted reproductive technology, particularly in women with thin endometrium, repeated implantation failure (RIF), Asherman's syndrome (AS), or chronic endometritis (CE). In recent years, autologous intrauterine platelet-rich plasma (PRP) has been proposed as a regenerative approach aimed at improving endometrial receptivity through the local release of growth factors, cytokines, and angiogenic mediators. A narrative review of the literature published between 2015 and 2021 was performed using PubMed, Google Scholar, and Web of Science. Studies assessing intrauterine PRP administration in women undergoing assisted reproduction were included. Due to the limited availability of high-quality randomized evidence, data from a wide range of study designs-including randomized controlled trials, observational studies, pilot studies, and case reports-were reviewed in order to reflect current clinical experience. Reported outcomes included endometrial thickness, implantation rate, clinical pregnancy rate, and live birth rate in patients with thin endometrium, RIF, AS, and CE. Most studies described an association between PRP administration and improvements in endometrial thickness, vascularity, implantation, and clinical pregnancy rates. In women with thin endometrium, PRP was frequently associated with an increase in endometrial thickness to at least 7 mm and improved reproductive outcomes. In cases of repeated implantation failure, some randomized controlled trials suggested higher pregnancy and implantation rates in PRP-treated patients compared with controls. Evidence regarding AS and CE was largely derived from case reports and small case series, reporting enhanced endometrial regeneration and occasional successful pregnancies. Overall, intrauterine PRP appears to be a promising and well-tolerated autologous intervention for women with poor prognostic factors. Nevertheless, the available evidence remains preliminary, and further large-scale randomized controlled trials using standardized PRP preparation and administration protocols are required to clarify its effectiveness and define its role in evidence-based assisted reproduction.
oligonucleotides
2025-03-26 | Quantum dots as biocompatible small RNA nanocarriers modulating macrophage polarization to treat Asherman's syndrome.
Macrophages play a key role in host defense and inflammation, with polarization ranging from pro-inflammatory M1 to anti-inflammatory M2 states. However, effective modulation of macrophage polarity via nucleotide delivery is challenging. This study developed polyethyleneimine-modified carboxyl quantum dots (QDP) as a biocompatible carrier for small RNA delivery to modulate macrophage polarization. QDP-mediated delivery of miR-10a (QDP/miR-10a) rebalanced macrophage polarity and alleviated uterine inflammation and fibrosis in a mouse model of Asherman's syndrome (AS). In vitro, QDP effectively delivered small RNA into RAW 264.7 cells without cytotoxicity, converting LPS-induced M1 to M2 macrophages by inhibiting NF-κB, MAPK, and AKT signaling. In vivo, QDP/miR-10a reduced M1 macrophages, restored polarization, and enhanced uterine restoration in AS mice without affecting systemic immunity. Thus, QDP represents a safe and effective nanocarrier for small RNA delivery to modulate macrophage polarization for inflammatory disease treatment, including AS.
2023-11-13 | MicroRNA-122-5p alleviates endometrial fibrosis via inhibiting the TGF-β/SMAD pathway in Asherman's syndrome.
What is the effect of miR-122 on the progression and recovery of fibrosis in Asherman's syndrome? Endometrial tissue was collected from 21 patients, 11 with intrauterine adhesion (IUA) and 10 without IUA. Quantitative real-time polymerase chain reaction, immunofluorescence and Western blot were applied to observe the expression of mRNAs/miRNAs and protein, respectively. The endometrial physical injury was carried out in C57BL/6 mice to create an endometrial fibrosis model, with intrauterine injection of adenovirus to compare the antifibrosis and repair function of miR-122 on endometrium. The morphology of the uterus was observed using haematoxylin and eosin staining, and fibrosis markers were detected by immunohistochemistry. miR-122 expression was reduced in patients with IUAs, accompanied by fibrosis. MiR-122 overexpression reduced the degree of fibrosis in endometrial stromal cells. Further molecular analyses demonstrated that miR-122 inhibited fibrosis through the TGF-β/SMAD pathway by directly targeting the 3' untranslated region of SMAD family member 3, suppressing its expression. Notably, miR-122 promoted endometrial regeneration and recovery of pregnancy capacity in a mouse endometrial injury model. miR-122 is a critical regulator for repair of endometrial fibrosis and provided new insight for the clinical treatment of intrauterine adhesions.
2022-10-28 | Role of noncoding RNA in the pathophysiology and treatment of intrauterine adhesion
Intrauterine adhesion (IUA) is one of the most common diseases of the reproductive system in women. It is often accompanied by serious clinical problems that damage reproductive function, such as menstrual disorder, infertility, or recurrent abortion. The clinical effect of routine treatment is not ideal, and the postoperative recurrence rate is still very high. Therefore, exploring the pathological mechanism of IUA and finding new strategies for the effective prevention and treatment of IUA are needed. The main pathological mechanism of IUA is endometrial fibrosis and scar formation. Noncoding RNA (ncRNA) plays an important role in the fibrosis process, which is one of the latest research advances in the pathophysiology of IUA. Moreover, the exosomal miRNAs derived from mesenchymal stem cells can be used to improve IUA. This paper reviewed the role of ncRNAs in IUA pathogenesis, summarized the core pathways of endometrial fibrosis regulated by ncRNAs, and finally introduced the potential of ncRNAs as a therapeutic target.
2021-04-29 | MiR-543 Inhibits the Migration and Epithelial-To-Mesenchymal Transition of TGF-β-Treated Endometrial Stromal Cells via the MAPK and Wnt/β-Catenin Signaling Pathways
Intrauterine adhesion (IUA) is one of the most prevalent reproductive system diseases in females. MicroRNAs (miRNAs) are reported to be master regulators in a variety of diseases, including IUA, but the role of microRNA-543 (miR-543) in IUA remains to be elucidated. In this study, we observed that miR-543 was downregulated in transforming growth factor-beta (TGF-β)-treated endometrial stromal cells (ESCs). Functionally, we observed that miR-543 suppressed the migration, epithelial-to-mesenchymal transition (EMT), and inhibited expression of extracellular matrix (ECM) proteins in TGF-β-treated ESCs. Mechanistically, MAPK1 is targeted by miR-543 after prediction and screening. A luciferase reporter assay demonstrated that miR-543 complementarily binds with the 3' untranslated region of mitogen-activated protein kinase 1 (MAPK1), and western blot analysis indicated that miR-543 negatively regulates MAPK1 protein levels. In addition, results from rescue assays showed that miR-543 inhibits the migration and EMT of TGF-β-treated ESCs by targeting MAPK1. In addition, we observed that miR-543 inactivates the Wnt/β-catenin signaling pathway through inhibiting the phosphorylation of MAPK1 and β-catenin. Finally, we confirmed that miR-543 represses migration, EMT and inhibits levels of ECM proteins in TGF-β-treated ESCs by targeting the Wnt/β-catenin signaling pathway. Our results demonstrated that miR-543 suppresses migration and EMT of TGF-β-treated ESCs by targeting the MAPK and Wnt/β-catenin pathways.
2016-03-30 | MicroRNA-29b inhibits TGF-β1-induced fibrosis via regulation of the TGF-β1/Smad pathway in primary human endometrial stromal cells
Transforming growth factor (TGF)‑β1 has a key role in the regulation of fibrosis and organ dysfunction. During the pathogenesis and progression of vital organ fibrosis, the microRNA (miR)‑29 family is irregularly downregulated and exogenous supplementation of miR‑29b has a strong anti‑fibrotic capacity. However, whether TGF‑β1 is able to provoke endometrial fibrosis, and the role of miR‑29 in endometrial fibrosis remain unclear. In the present study, RT‑qPCR, immunocytochemistry, western blot analysis, scanning electron microscopy, immunofluorescence staining, cell proliferation assay and flow cytometric analysis were employed. The results demonstrated that the expression levels of collagen, type 1, alpha 1 (COL1A1), α‑smooth muscle actin (α‑SMA) and phosphorylated (p)‑Smad2/3 were increased, whereas miR‑29b and maternally expressed gene 3 (MEG3) were decreased in primary endometrial stromal cells (ESCs) in response to TGF‑β1 stimulation, in a time and dose‑dependent manner. Furthermore, overexpression of miR‑29b markedly reduced the expression levels of COL1A1 and α‑SMA, and decreased the expression and nuclear accumulation of p‑Smad2/3. In addition, ectopic overexpression of miR‑29b increased the expression levels of MEG3, inhibited myofibroblast‑like cell proliferation and induced apoptosis. These findings indicated that miR‑29b may have a significant anti‑fibrotic role, and may attenuate TGF‑β1‑induced fibrosis in ESCs. Therefore, exogenous miR‑29b may serve as a potential therapeutic agent for the treatment of endometrial fibrosis.
cell therapies
2026-08-08 | INTRAUTERINE ADHESIONS (ASHERMAN SYNDROME): CURRENT PERSPECTIVES ON ETIOLOGY, DIAGNOSIS, PREVENTION, AND TREATMENT (LITERATURE REVIEW)
<p>Intrauterine adhesions (Asherman syndrome) are recognized as one of the major causes of secondary infertility, menstrual disorders, and recurrent pregnancy loss. Despite more than seventy years of research into this condition, a unified standardized approach to its diagnosis, prevention, and treatment has not yet been established. This literature review summarizes current evidence on the etiology and pathogenesis of intrauterine adhesions, methods of diagnosis, and classification systems. It also analyzes existing strategies for the primary and secondary prevention of adhesion recurrence, including barrier agents, intrauterine devices, and hormonal therapy. Particular attention is given to a promising therapeutic approach involving cell-based technologies using autologous bone marrow-derived and menstrual-derived stem cells. The review was prepared based on an analysis of the clinical guidelines of the Society of Obstetricians and Gynaecologists of Canada (SOGC, 2010), the joint practice guidelines of the American Association of Gynecologic Laparoscopists (AAGL) and the European Society for Gynaecological Endoscopy (ESGE, 2017), as well as the original clinical study on menstrual stromal cell transplantation conducted by Tan et al. (2016).</p>
2026-07-25 | Subendometrial Platelet-Rich Plasma at Time of Hysteroscopy Improves Endometrial Thickness and Cavity Characteristics in Patients with Thin Endometrium
Objective: To evaluate the effect of subendometrial platelet-rich plasma (PRP) administered at the time of hysteroscopy on endometrial thickness and uterine cavity characteristics. Design: Retrospective cohort study. Materials and Methods: Nine patients who underwent hysteroscopy with subendometrial PRP were included. Indications for treatment included thin endometrium and Asherman syndrome. Endometrial thickness (ES), trilaminar pattern, and intrauterine fluid were compared before and after PRP prior to embryo transfer attempts. Results: Endometrial thickness improved in 8 of 9 patients (89%), with mean thickness increasing from 6.1 mm pre-PRP to 8.1 mm post-PRP. Several patients demonstrated clinically meaningful, including increases from 7.03 mm to 12.78 mm and from 5.10 mm to 8.96 mm. Endometrial pattern also improved following treatment. 5 of 9 patients lacked a trilaminar pattern prior to PRP, compared to 0 of 9 after PRP, with all patients demonstrating a trilaminar pattern post-treatment. Intrauterine fluid was present in 2 patients before PRP and resolved in both cases following treatment. These improvements occurred despite similar or fewer days of estrogen exposure in multiple patients. Conclusions: Subendometrial PRP administered at the time of hysteroscopy was associated with improved endometrial thickness, restoration of trilaminar pattern, and resolution of intrauterine fluid in patients with thin endometrium or intrauterine pathology. This approach may represent a useful adjunct for optimizing the endometrium prior to embryo transfer.
2026-02-28 | Mesenchymal Stem Cell Therapy for Thin Endometrium: Mechanisms, Delivery Strategies, and Clinical Outcomes: A Systematic Review
Thin endometrium constitutes a significant cause of infertility that demonstrates an inadequate response to conventional treatments, prompting the investigation of mesenchymal stem cell (MSC)-based regenerative therapies as alternative interventions. This systematic review, conducted in accordance with PRISMA guidelines, evaluated primary research from January 2020 to January 2026, analyzing fourteen studies that investigated MSC therapies across six cell sources and four delivery platforms for the treatment of thin endometrium. The findings demonstrate that umbilical cord-derived MSCs (UC-MSCs) exhibited superior therapeutic efficacy compared to other MSC sources, achieving restoration of endometrial thickness to 80–95% of control values with mean improvements of 2.4 mm, glandular regeneration yielding 20.9–24.8 glands per high-power field, pregnancy rates ranging from 60 to 80%, and substantial fibrosis reduction of 60–79%. Advanced delivery strategies significantly enhanced treatment outcomes; specifically, hydrogel encapsulation using Pluronic F-127 or hyaluronic acid extended MSC retention 4.7-fold—from 3 to 14 days—compared to direct injection, which correlated with a 23% greater improvement in endometrial thickness. Concurrently, scaffold-based delivery provided comparable efficacy while offering additional three-dimensional structural support. Mechanistic investigations revealed that MSC therapies activate five coordinated regenerative pathways: VEGF-mediated angiogenesis with 2.5–3.8 fold upregulation, TGF-β/Smad anti-fibrotic signaling that decreases TGF-β1 by 2.9–3.2 fold, the STAT3 proliferation pathway with a 3.8-fold increase, SDF-1/CXCR4 chemotactic signaling enhanced by 1.8-fold, and immunomodulation promoting M2 macrophage polarization with a 62% reduction in pro-inflammatory cytokines. Notably, MSC-derived exosomes demonstrated therapeutic potential equal to or exceeding that of cellular preparations; UC-MSC exosomes achieved a 23% greater increase in thickness and 80% pregnancy rates versus 60% for cellular formulations. A single clinical pilot study involving five patients with refractory Asherman syndrome utilizing collagen scaffold-delivered UC-MSCs reported encouraging outcomes, including an 81% improvement in endometrial thickness (from 4.2 ± 0.8 mm to 7.6 ± 1.2 mm), a 60% pregnancy rate, and a 40% live birth rate. Despite robust preclinical evidence supporting UC-MSC therapies delivered via biodegradable platforms for endometrial regeneration through multi-mechanistic pathways, clinical translation requires well-designed randomized controlled trials incorporating standardized manufacturing protocols, adequate statistical power, mechanistic biomarker validation, and comprehensive long-term safety monitoring before widespread implementation for treating thin endometrium-related infertility.
2026-01-31 | Stem cell therapy in thin endometrium and Asherman's syndrome: a systematic review and meta-analysis.
To evaluate the efficacy and safety of mesenchymal stem cell (MSC)-based therapies in improving endometrial thickness and reproductive outcomes in women with refractory thin endometrium or Asherman's syndrome. Following PRISMA 2020 guidelines, a systematic search of PubMed, Cochrane Library, Embase, Scopus, ClinicalTrials.gov, and Google Scholar through June 2025 was performed. Eighteen clinical studies involving 323 patients were included. MSCs derived from umbilical cord, bone marrow, adipose tissue, endometrium, or menstrual blood were administered via intrauterine infusion, transmyometrial injection, or scaffold-assisted delivery. The primary outcome was change in endometrial thickness; secondary outcomes included clinical pregnancy rate, live birth rate, and miscarriage rate. Meta-analysis demonstrated a significant increase in endometrial thickness following MSC therapy compared to baseline or control (mean difference = 2.35 mm; 95 % CI, 1.97-2.74; p < 0.00001). Subgroup analysis showed the largest gains in endometrial- and adipose-derived MSC groups. Randomized controlled trials confirmed higher clinical pregnancy (OR = 2.72; p = 0.002) and live birth rates (OR = 2.27; p = 0.01), with a reduced miscarriage rate (OR = 0.24; p = 0.004). No serious adverse events were reported. While MSC therapy appears to be safe, its efficacy must be confirmed by large-scale randomized trials before it can be presented to the public or recommended as an effective approach for endometrial regeneration.
2025-12-18 | Mesenchymal stem cell therapy for endometrial injury: a meta-analysis of preclinical studies.
BACKGROUND: Endometrial injury is a common cause of menstrual changes, abortion, and even infertility in women, including intrauterine adhesions (Asherman’s syndrome) and a thin endometrium. Hysteroscopic surgery and drug treatment are currently the main treatment methods; however, their effect is not satisfactory. Increasingly, studies have demonstrated that mesenchymal stem cells (MSCs) may be a safe and promising option for treating endometrial injury. This study aimed to evaluate the efficacy of MSCs in an endometrial injury model. METHODS: We searched PubMed, Cochrane Library, Web of Science, and EMBASE from the establishment of the databases to December 2023. Preclinical studies examining the role of MSCs in treating endometrial injury were included. The main outcome measures were the endometrial thickness, fibrosis area ratio, and recovery of reproductive function. Risk of bias assessment was performed using the SYRCLE tool. RevMan 5.3 was used for the meta-analysis and testing heterogeneity. RESULTS: A total of 10 Randomized Controlled Trials (RCTs) involving 230 animals were included. The analysis showed that after treatment with MSCs, the endometrium was significantly thickened (WMD 115.01 μm, 95% CI (94.07–135.95 μm)), the area ratio of endometrial fibrosis reduced (WMD − 29.88, 95% CI (− 36.61–−23.15)), and the pregnancy rate increased (RR 4.60, 95% CI (2.09–10.13)). Subgroup analyses indicated that Human amniotic mesenchymal stem cells (HA-MSCs) seemed to be more effective than other types. In addition, we found that the treatment’s efficacy is also affected by the route of administration, the type of transplantation, and other factors. CONCLUSIONS: The results of this study indicate that treatment with MSCs (HA-MSCs delivered via intrauterine injection) exerts beneficial effects on endometrial injury in rats.Xenogeneic MSCs showed enhanced therapeutic potential relative to allogeneic MSCs in our experimental models.Taken together, these data highlight MSCs as a potentially valuable approach warranting additional research for the treatment of endometrial injury.
other
2025-05-14 | Endometrial Stromal Senescence Mediates the Progression of Intrauterine Adhesions.
Cellular senescence has emerged as a key mediator in organ-specific fibrosis. Here, we have established the role of endometrial stromal senescence in the progression of endometrial fibrosis, termed intrauterine adhesions (IUA). IUA have significant negative effects on women's reproductive health and are associated with infertility. We have generated original gene signatures to identify endometrial stromal senescence in single-cell and bulk RNA-sequencing data. By applying generated gene signatures, we revealed an increased level of stromal senescence during the proliferative phase in the endometrium of patients with IUA. Further comparative analysis of cell-cell communications demonstrated that senescent stromal cells in the IUA endometrium create an immunosuppressive and profibrotic microenvironment through an elevated expression of LGALS9. Endometrial stromal senescence persists during the window of implantation and correlates with impaired embryo receptivity of the IUA endometrium. Therefore, stromal senescence can be regarded as a primary cause of an unresponsive endometrium with decreased receptivity and thickness in IUA patients. A LGALS9 immunotherapy protocol, specifically designed to neutralize LGALS9 immunosuppressive activity of senescent cells, may offer a promising opportunity to restore effective immune clearance of these cells within the IUA stroma. Consequently, an LGALS9-based strategy could emerge as a novel therapeutic avenue in the treatment of IUA.
2024-02-16 | LAMB3 Promotes Myofibrogenesis and Cytoskeletal Reorganization in Endometrial Stromal Cells via the RhoA/ROCK1/MYL9 Pathway.
LAMB3, a major extracellular matrix and basal membrane component, is involved in wound healing. We aimed to understand its role in Asherman's syndrome (AS), which is associated with infertility, by using bioinformatics analysis and cultured endometrial stromal cells (ESCs). MRNAs extracted from tissues obtained from control subjects and patients with severe intrauterine adhesion were sequenced and subjected to bioinformatics analysis and the RhoA/ROCK1/MYL9 pathway was implicated and this subsequently studied using cultured primary ESCs. The effects of overexpression and knockdown and activation and inhibition of LAMB3 on the mesenchymal to myofibroblastic phenotypic transformation of ECCs were assessed using PCR and western blot analysis. Phalloidin was used to localize the actin cytoskeletal proteins. Silencing of LAMB3 reversed the TGF-β-induced ESC myofibroblast phenotype conversion, whereas overexpression of LAMB3 promoted this process. Activation and silencing of LAMB3 led to remodeling of the ESC cytoskeleton. Overexpression and silencing of LAMB3 caused activation and inhibition of ESCs, respectively. Y-27632 and LPA reversed the activation and inhibition of the RhoA/ROCK1/MYL9 pathway after overexpression and silencing, respectively. These results suggest that LAMB3 can regulate ESC fibrosis transformation and cytoskeleton remodeling via the RhoA/ROCK1/MYL9 pathway. This study provides a potential new target for gene therapy and drug intervention of AS.
small molecules
2026-06-26 | Cornual type 3 retained products of conception – a fertility-sparing win with methotrexate
Retained products of conception (RPOC) with marked vascularity represent a diagnostic and therapeutic challenge due to the high risk of hemorrhage associated with surgical evacuation. Cornual localization further complicates management because of minimal myometrial thickness and proximity to major vascular structures. Cornual ectopic pregnancies are broadly classified into interstitial, angular, and true cornual types, each differing in anatomical location and clinical implications. Advanced imaging and individualized management are crucial, particularly in women desiring future fertility. We report a case of a 34-year-old multiparous woman with prior cesarean section who presented with amenorrhea of 2 months following dilatation and curettage for a blighted ovum. The patient was examined and was vitally stable. Further investigations were done. Her ultrasound with color Doppler demonstrated a highly vascular lesion with high peak systolic velocity in uterine cornua, with thin myometrium and findings to be correlated with beta human chorionic gonadotropin (β-hCG) and magnetic resonance imaging (MRI) SOS. Her β-hCG was negligible. Magnetic resonance imaging revealed a well-defined hyperintense lesion in the right uterine cornua with beak-like communication with the endometrial cavity, consistent with hyper vascular cornual RPOC. The patient was hemodynamically stable and desirous of future fertility and was managed conservatively with multidose methotrexate therapy. Serial Doppler follow-up demonstrated progressive reduction in vascularity and lesion size, followed by spontaneous expulsion. This case represents a diagnostic conundrum, as the patient presented with persistent amenorrhea following curettage rather than the typical bleeding seen with retained products of conception. The key differential diagnoses include Asherman syndrome, retained products of conception, chronic endometritis, and persistent trophoblastic activity. This case also highlights the need for a high index of clinical suspicion in atypical presentations, with supportive investigations aiding in differentiating hypervascular RPOC from cornual ectopic pregnancy and uterine arteriovenous malformation. Conservative medical management with methotrexate can be a safe and fertility-preserving option in carefully selected patients.
2026-05-08 | Mitochondria-targeted antioxidant mitoquinone attenuates TGF-β-induced fibrosis and restores impaired decidualization in mouse endometrial stromal cells.
This study aimed to investigate the therapeutic effects of mitoquinone (MitoQ) in endometrial fibrosis and to examine its role in restoring impaired decidualization associated with intrauterine adhesion. We further sought to delineate the underlying mechanisms through which MitoQ exerts its protective effects. Finally, we propose mitochondrial-targeted antioxidant therapy as a potential strategy for the treatment of gynecological diseases. An in vitro mouse endometrial fibrosis model was established by treating mouse endometrial stromal cells with transforming growth factor-β (TGF-β). MitoQ was subsequently administered to fibrotic cells to evaluate its therapeutic effects on fibrosis and defective decidualization. These effects were analyzed using quantitative real-time polymerase chain reaction, immunoblotting, immunofluorescence staining, and additional molecular and cellular assays. The underlying mechanisms were further investigated. TGF-β treatment (5 ng/mL for 48 hours) effectively induced a markedly fibrotic phenotype in mouse endometrial stromal cells. These cells were subsequently treated with 1 μM MitoQ for 24 hours. MitoQ treatment significantly reduced collagen type I alpha 1 chain (COL1A1) expression at both the mRNA and protein levels and downregulated inflammation-related markers. These effects were accompanied by reduced mitochondrial stress and suppression of suppressor of mothers against decapentaplegic (SMAD) signaling. Furthermore, MitoQ treatment restored impaired decidualization in fibrotic cells, as supported by increased expression of prolactin and insulin-like growth factor binding protein 1 (IGFBP1). MitoQ treatment effectively attenuates TGF-β-induced endometrial fibrosis by reducing collagen deposition and inflammatory marker expression, while restoring impaired decidualization. These findings suggest that MitoQ may serve as a promising therapeutic candidate for fibrosis-associated uterine dysfunction.
2026-04-30 | EXPLORING THE CORRELATION BETWEEN MALATU PUZHU AND SCHISTOSOMIASIS: SIDDHA APPROACHES TO TREAT INFERTILITY CAUSED BY PARASITIC INFECTIONS
Infertility affects 60–80 million couples globally, with 15–20 million in India each year. While multiple factors contribute to infertility, parasitic infections like Schistosomiasis, a neglected tropical disease, are often overlooked. Schistosomiasis may lead to azoospermia in males and Asherman syndrome in females; early diagnosis and treatment are crucial to prevent complications. In Siddha texts, infertility caused by pathogens was addressed as Malatu Puzhu, Suronitha Kirumi, and Karba Poochi, with a detailed description of symptoms, progression, and treatments. This study explores the correlation between Malatu Puzhu and Schistosomiasis, as well as Siddha treatments for the condition. This review examines the conceptual correlation between Malatu Puzhu in Siddha texts and schistosomiasis in modern medicine. Classical Siddha textbooks were analyzed using relevant keywords to identify disease descriptions and formulations. Contemporary biomedical literature indexed in PubMed, Web of Science, and Medline was also reviewed to understand the pathophysiology and reproductive consequences of schistosomiasis. The findings reveal a correlation between the manifestations of schistosomal infection and the Siddha concept of pathogen-induced infertility. Several Siddha formulations indicated for Malatu Puzhu and commonly used herbs, which were reported to have antiparasitic, anti-inflammatory, and fertility-supportive properties, were documented. Overall, this review emphasizes the underrecognized role of parasitic infections in infertility and the importance of early intervention. It also highlights the potential of Siddha therapeutic approaches as complementary strategies in managing infertility associated with parasitic infections, warranting further pharmacological and clinical research.
2025-11-21 | Fertility and Obstetric Outcomes in Asherman Syndrome: Assessing the Impact of Hyaluronic Acid Post-Hysteroscopic Adhesiolysis.
Installation of hyaluronic acid following hysteroscopic adhesiolysis is suggested to reduce intrauterine adhesion (IUA) reformation in women with Asherman's Syndrome (AS). We aimed to assess the impact of hyaluronic acid following hysteroscopic adhesiolysis on menstrual, surgical, fertility, obstetric and neonatal outcomes. We identified 128 women treated hysteroscopically for AS over an 11-year period and invited them to participate in a questionnaire-based study. A total of 43 women were included; 21 treated surgically with hyaluronic acid administered immediately following adhesiolysis and 22 having surgery alone. Outcomes were assessed by reviewing medical records retrospectively and using a structured questionnaire at 3 months and 4 years post procedure. There were no differences in the rates of repeat adhesiolysis procedures to treat recurrent IUAs between the treatment and control groups (19% vs. 18%, p = 0.94). All women in the treatment group reported resumption of menses 6 months following the procedure, with 9% in the control group reported ongoing amenorrhoea. There was no difference in the overall pregnancy rate (77% vs. 81%, p = 0.76), maternal and neonatal outcomes between the groups. Intrauterine application of hyaluronic acid at the time of hysteroscopic adhesiolysis for women with AS was not associated with the number of repeat surgical interventions, menstrual patterns, fertility, obstetric, or neonatal outcomes.
2025-11-10 | The Challenges of Asherman’s Syndrome: a clinical view
This thesis focused on enhancing the care for women with Ashermans Syndrome (AS) from various perspectives. For a long time, AS was considered a relatively simple disease with a simple cure, namely adhesions which were resolved by adhesiolysis. We show, however, that despite a high rate of successful (chapter 2) and safe (chapter 3) adhesiolyses in our center, rates to get pregnant are not as high as in the normal population (chapter 5) and that the use of adjuvant estrogen is to be debated (chapter 4). Even after achieving a successful pregnancy, the risk of adverse events was not over, as many women suffer from pregnancy and post-partum complications (chapters 6 & 7). We also showed that we were not able to distinguish those with a high risk of adverse events from those with a low risk (chapter 8). This results in a very high rate of women suffering from depression and anxiety disorders (chapter 9).
proteins
2026-08-13 | First-in-human pilot trial of G-CSF–mobilised platelet–leukocyte concentrate for severe refractory Asherman syndrome
Introduction Severe refractory Asherman syndrome (SRAS) remains difficult to treat, and the benefit of regenerative blood-derived therapies remains uncertain. This study evaluated whether systemic granulocyte colony-stimulating factor (G-CSF) mobilisation combined with targeted intrauterine delivery of autologous peripheral blood platelet–leukocyte concentrate (PBPLC) could improve endometrial thickness in women with SRAS. Methods This prospective, single-centre, single-arm pilot study enrolled 10 women with infertility for at least 3 years, severe intrauterine adhesions, poor endometrial development, and failure of previous adhesiolysis, hormonal therapy, and platelet-rich plasma treatment. After G-CSF mobilisation, autologous PBPLC was injected into the endometrial–myometrial junction under hysteroscopic guidance without concurrent formal adhesiolysis. The primary outcome was the change in late pre-ovulatory endometrial thickness (LPO-EMT), analysed using the exact Wilcoxon signed-rank test and Hodges–Lehmann estimates. Results LPO-EMT increased from 4.6 mm (SD 0.7) to 5.8 mm (SD 1.3), with a Hodges–Lehmann paired difference of 1.08 mm (95% CI 0.45–2.50; p = 0.0039). Hysteroscopic cavity restoration, reduced adhesion severity, and subjective menstrual improvement were observed in all participants, and the AFS score decreased from 10.8 to 4.5. No grade 3 or higher treatment-related adverse events occurred. Among nine women who attempted conception, pregnancy was detected in six (66.7%; exact 95% CI 29.9–92.5), including four clinical pregnancies (44.4%; exact 95% CI 13.7–78.8). However, all clinical pregnancies ended in first-trimester miscarriage, and no ongoing pregnancies or live births were achieved during follow-up. Discussion These preliminary findings suggest that G-CSF-mobilised autologous PBPLC may be a feasible approach for improving endometrial thickness and uterine cavity restoration in women with SRAS. However, the findings do not establish reproductive efficacy, and larger controlled studies are warranted. Clinical trial registration https://cris.nih.go.kr/ , identifier KCT0004208.
2026-07-25 | SUBENDOMETRIAL PLATELET-RICH PLASMA IMPROVES EMBRYO TRANSFER FEASIBILITY AND PREGNANCY OUTCOMES IN PATIENTS WITH POOR ENDOMETRIAL DEVELOPMENT
Objective: To assess whether subendometrial PRP administered at hysteroscopy improves embryo transfer rates and clinical outcomes. Design: Retrospective cohort study. Materials and Methods: Nine patients undergoing hysteroscopy with PRP were evaluated. Outcomes included ability to proceed with embryo transfer, biochemical pregnancy, and miscarriage rates before and after intervention. Results: Prior to PRP, 2 of 9 patients (22%) proceeded to embryo transfer. Following PRP, 7 of 9 patients (78%) underwent embryo transfer. Among patients undergoing transfer post-PRP (n = 7), 3 (43%) achieved a positive pregnancy test. Of these, 2 resulted in ongoing pregnancies and 1 resulted in miscarriage. Importantly, patients previously unable to proceed to transfer due to inadequate endometrial development or cavity abnormalities were able to undergo transfer following PRP, including those with Asherman syndrome and intrauterine fluid. Conclusions: Subendometrial PRP may improve the likelihood of proceeding to embryo transfer and may be associated with favorable pregnancy outcomes in patients with poor endometrial receptivity. These findings support further investigation in larger, prospective studies.
2026-07-01 | L26/P-486 Characteristics associated with ongoing pregnancy after single euploid frozen embryo transfer in a true natural cycle
Abstract Study question What factors are associated with ongoing pregnancy (OP) in a true natural cycle (tNC) following a single euploid frozen embryo transfer (FET)? Summary answer Ongoing pregnancy in a tNC was significantly associated with age, Body Mass index (BMI) and embryo quality before FET. What is known already Recent evidence suggests a higher live birth rate in a tNC FET compared to an artificial FET. The presence of a corpus luteum in a tNC may contribute to an increased uterine receptivity, as the corpus luteum produces natural progesterone and additional luteal factors that are absent in artificial cycles. Most comparative studies have focused on overall cycle outcomes, rather than dissecting patient and cycle characteristics within a tNC. There is limited information about which specific variables most strongly influence success when a tNC FET is performed. Study design, size, duration This retrospective multicenter cohort study analyzed 1,373 single euploid FET cycles from 1,186 patients performed between March 2017 and September 2024. The primary outcome was ongoing pregnancy, defined as fetal cardiac activity. Participants/materials, setting, methods Cycles included women undergoing a single euploid FET prepared in a tNC at three tertiary referral IVF centers. Patients with uterine abnormalities or Asherman syndrome were excluded. Luteal phase support (LPS) was administered at clinician discretion. Mixed-effects logistic regression with a random intercept for patient ID was used to assess factors associated with OP and to account for repeated cycles. Main results and the role of chance Age was similar between groups [Median (Q1–Q3): 35.00 (31.00–38.00) for both groups], whereas BMI was lower among ongoing pregnancies [Median (Q1–Q3): 25.00 (22.00–28.00) vs. Median (Q1–Q3): 26.00 (23.00–29.00); p < 0.001]. A mixed-effects logistic regression model based on 1,351 cycles from 1,171 patients showed that increasing age was independently associated with higher odds of OP (aOR 1.03 per year, 95% CI 1.01–1.06; p = 0.010), while higher BMI was associated with lower odds (aOR 0.95 per kg/m², 95% CI 0.92–0.97; p < 0.001). Endometrial thickness was not associated with outcome (aOR 1.02 per mm, 95% CI 0.97–1.09; p = 0.432). Transfers involving Fair/Poor embryos had lower odds compared with Top/Good embryos (aOR 0.34, 95% CI 0.24–0.49; p < 0.001). LPS regimen and reproductive history variables were not significant. History of Cesarean section (p = 0.067) and D&C (p = 0.078) showed borderline associations. Limitations, reasons for caution Limitations include the retrospective design and heterogeneity in luteal phase support. Findings are restricted to embryos undergoing preimplantation genetic testing for aneuploidy (PGT-A) and may not be generalizable to untested populations. The impact of the number of prior Cesarean sections could not be specifically evaluated. Wider implications of the findings In tNC single euploid FET, BMI and embryo quality are associated with OP, whereas endometrial thickness is not. Prior Cesarean section or D&C may negatively influence outcomes, warranting further investigation. Trial registration number No
2026-04-28 | The value of platelet rich plasma in women with intrauterine adhesions. A systematic review and meta-analysis.
To evaluate the benefits of platelet-rich plasma administration after adhesiolysis in women with intrauterine adhesions. A database search using the keywords (autologous platelet-rich plasma) AND (intrauterine adhesions) and their Medical Subject Headings terms revealed 11 studies with 1,130 participants. Endometrial thickness was reported in four studies with 274 participants. The mean difference effect estimate was 0.53 with a 95% confidence interval (CI) of 0.23, 0.82; P<0.001, and I²=0%. The menstrual pattern after the procedure showed that the odds ratio (OR) effect estimates for amenorrhea, hypomenorrhea, and normal menstruation were 6.47 (0.24, 174.08), 0.84 (0.41, 1.73), and 1.21 (0.51, 2.84), respectively, and the P-values were 0.27, 0.63, and 0.66, respectively. The number of women with adhesions after the procedure showed that the OR effect estimates for grade I, II, and III adhesions were 1.74 (0.41, 7.45), 0.76 (0.21, 2.70), and 0.31 (0.11, 0.88), respectively, and the P-values were 0.46, 0.67, and 0.03, respectively. Changes in the American Fertility Society (AFS) score after the operation were reported in three studies with 276 participants. The mean difference effect estimate was 0.87, with a 95% CI of 0.17, 1.56; P=0.01; I²=0%. The clinical pregnancy rate was reported in five studies involving 506 participants. The OR effect estimate was 1.80 with a 95% CI of 1.18, 2.75; a P-value of 0.006, and I² of 0%. Platelet-rich plasma administration after hysteroscopic adhesiolysis improved endometrial thickness (low evidence), recurrence of grade III adhesions (low evidence), AFS score of adhesions (low evidence), and clinical pregnancy rates (moderate evidence).
2026-02-19 | Endometrial Autologous Intrauterine Platelet-Rich Plasma (PRP) Instillation Treatment and Its Potential on In Vitro Fertilization (IVF): Narrative Review.
Implantation failure remains a major challenge in assisted reproductive technology, particularly in women with thin endometrium, repeated implantation failure (RIF), Asherman's syndrome (AS), or chronic endometritis (CE). In recent years, autologous intrauterine platelet-rich plasma (PRP) has been proposed as a regenerative approach aimed at improving endometrial receptivity through the local release of growth factors, cytokines, and angiogenic mediators. A narrative review of the literature published between 2015 and 2021 was performed using PubMed, Google Scholar, and Web of Science. Studies assessing intrauterine PRP administration in women undergoing assisted reproduction were included. Due to the limited availability of high-quality randomized evidence, data from a wide range of study designs-including randomized controlled trials, observational studies, pilot studies, and case reports-were reviewed in order to reflect current clinical experience. Reported outcomes included endometrial thickness, implantation rate, clinical pregnancy rate, and live birth rate in patients with thin endometrium, RIF, AS, and CE. Most studies described an association between PRP administration and improvements in endometrial thickness, vascularity, implantation, and clinical pregnancy rates. In women with thin endometrium, PRP was frequently associated with an increase in endometrial thickness to at least 7 mm and improved reproductive outcomes. In cases of repeated implantation failure, some randomized controlled trials suggested higher pregnancy and implantation rates in PRP-treated patients compared with controls. Evidence regarding AS and CE was largely derived from case reports and small case series, reporting enhanced endometrial regeneration and occasional successful pregnancies. Overall, intrauterine PRP appears to be a promising and well-tolerated autologous intervention for women with poor prognostic factors. Nevertheless, the available evidence remains preliminary, and further large-scale randomized controlled trials using standardized PRP preparation and administration protocols are required to clarify its effectiveness and define its role in evidence-based assisted reproduction.
oligonucleotides
2025-03-26 | Quantum dots as biocompatible small RNA nanocarriers modulating macrophage polarization to treat Asherman's syndrome.
Macrophages play a key role in host defense and inflammation, with polarization ranging from pro-inflammatory M1 to anti-inflammatory M2 states. However, effective modulation of macrophage polarity via nucleotide delivery is challenging. This study developed polyethyleneimine-modified carboxyl quantum dots (QDP) as a biocompatible carrier for small RNA delivery to modulate macrophage polarization. QDP-mediated delivery of miR-10a (QDP/miR-10a) rebalanced macrophage polarity and alleviated uterine inflammation and fibrosis in a mouse model of Asherman's syndrome (AS). In vitro, QDP effectively delivered small RNA into RAW 264.7 cells without cytotoxicity, converting LPS-induced M1 to M2 macrophages by inhibiting NF-κB, MAPK, and AKT signaling. In vivo, QDP/miR-10a reduced M1 macrophages, restored polarization, and enhanced uterine restoration in AS mice without affecting systemic immunity. Thus, QDP represents a safe and effective nanocarrier for small RNA delivery to modulate macrophage polarization for inflammatory disease treatment, including AS.
2023-11-13 | MicroRNA-122-5p alleviates endometrial fibrosis via inhibiting the TGF-β/SMAD pathway in Asherman's syndrome.
What is the effect of miR-122 on the progression and recovery of fibrosis in Asherman's syndrome? Endometrial tissue was collected from 21 patients, 11 with intrauterine adhesion (IUA) and 10 without IUA. Quantitative real-time polymerase chain reaction, immunofluorescence and Western blot were applied to observe the expression of mRNAs/miRNAs and protein, respectively. The endometrial physical injury was carried out in C57BL/6 mice to create an endometrial fibrosis model, with intrauterine injection of adenovirus to compare the antifibrosis and repair function of miR-122 on endometrium. The morphology of the uterus was observed using haematoxylin and eosin staining, and fibrosis markers were detected by immunohistochemistry. miR-122 expression was reduced in patients with IUAs, accompanied by fibrosis. MiR-122 overexpression reduced the degree of fibrosis in endometrial stromal cells. Further molecular analyses demonstrated that miR-122 inhibited fibrosis through the TGF-β/SMAD pathway by directly targeting the 3' untranslated region of SMAD family member 3, suppressing its expression. Notably, miR-122 promoted endometrial regeneration and recovery of pregnancy capacity in a mouse endometrial injury model. miR-122 is a critical regulator for repair of endometrial fibrosis and provided new insight for the clinical treatment of intrauterine adhesions.
2022-10-28 | Role of noncoding RNA in the pathophysiology and treatment of intrauterine adhesion
Intrauterine adhesion (IUA) is one of the most common diseases of the reproductive system in women. It is often accompanied by serious clinical problems that damage reproductive function, such as menstrual disorder, infertility, or recurrent abortion. The clinical effect of routine treatment is not ideal, and the postoperative recurrence rate is still very high. Therefore, exploring the pathological mechanism of IUA and finding new strategies for the effective prevention and treatment of IUA are needed. The main pathological mechanism of IUA is endometrial fibrosis and scar formation. Noncoding RNA (ncRNA) plays an important role in the fibrosis process, which is one of the latest research advances in the pathophysiology of IUA. Moreover, the exosomal miRNAs derived from mesenchymal stem cells can be used to improve IUA. This paper reviewed the role of ncRNAs in IUA pathogenesis, summarized the core pathways of endometrial fibrosis regulated by ncRNAs, and finally introduced the potential of ncRNAs as a therapeutic target.
2021-04-29 | MiR-543 Inhibits the Migration and Epithelial-To-Mesenchymal Transition of TGF-β-Treated Endometrial Stromal Cells via the MAPK and Wnt/β-Catenin Signaling Pathways
Intrauterine adhesion (IUA) is one of the most prevalent reproductive system diseases in females. MicroRNAs (miRNAs) are reported to be master regulators in a variety of diseases, including IUA, but the role of microRNA-543 (miR-543) in IUA remains to be elucidated. In this study, we observed that miR-543 was downregulated in transforming growth factor-beta (TGF-β)-treated endometrial stromal cells (ESCs). Functionally, we observed that miR-543 suppressed the migration, epithelial-to-mesenchymal transition (EMT), and inhibited expression of extracellular matrix (ECM) proteins in TGF-β-treated ESCs. Mechanistically, MAPK1 is targeted by miR-543 after prediction and screening. A luciferase reporter assay demonstrated that miR-543 complementarily binds with the 3' untranslated region of mitogen-activated protein kinase 1 (MAPK1), and western blot analysis indicated that miR-543 negatively regulates MAPK1 protein levels. In addition, results from rescue assays showed that miR-543 inhibits the migration and EMT of TGF-β-treated ESCs by targeting MAPK1. In addition, we observed that miR-543 inactivates the Wnt/β-catenin signaling pathway through inhibiting the phosphorylation of MAPK1 and β-catenin. Finally, we confirmed that miR-543 represses migration, EMT and inhibits levels of ECM proteins in TGF-β-treated ESCs by targeting the Wnt/β-catenin signaling pathway. Our results demonstrated that miR-543 suppresses migration and EMT of TGF-β-treated ESCs by targeting the MAPK and Wnt/β-catenin pathways.
2016-03-30 | MicroRNA-29b inhibits TGF-β1-induced fibrosis via regulation of the TGF-β1/Smad pathway in primary human endometrial stromal cells
Transforming growth factor (TGF)‑β1 has a key role in the regulation of fibrosis and organ dysfunction. During the pathogenesis and progression of vital organ fibrosis, the microRNA (miR)‑29 family is irregularly downregulated and exogenous supplementation of miR‑29b has a strong anti‑fibrotic capacity. However, whether TGF‑β1 is able to provoke endometrial fibrosis, and the role of miR‑29 in endometrial fibrosis remain unclear. In the present study, RT‑qPCR, immunocytochemistry, western blot analysis, scanning electron microscopy, immunofluorescence staining, cell proliferation assay and flow cytometric analysis were employed. The results demonstrated that the expression levels of collagen, type 1, alpha 1 (COL1A1), α‑smooth muscle actin (α‑SMA) and phosphorylated (p)‑Smad2/3 were increased, whereas miR‑29b and maternally expressed gene 3 (MEG3) were decreased in primary endometrial stromal cells (ESCs) in response to TGF‑β1 stimulation, in a time and dose‑dependent manner. Furthermore, overexpression of miR‑29b markedly reduced the expression levels of COL1A1 and α‑SMA, and decreased the expression and nuclear accumulation of p‑Smad2/3. In addition, ectopic overexpression of miR‑29b increased the expression levels of MEG3, inhibited myofibroblast‑like cell proliferation and induced apoptosis. These findings indicated that miR‑29b may have a significant anti‑fibrotic role, and may attenuate TGF‑β1‑induced fibrosis in ESCs. Therefore, exogenous miR‑29b may serve as a potential therapeutic agent for the treatment of endometrial fibrosis.
cell therapies
2026-08-08 | INTRAUTERINE ADHESIONS (ASHERMAN SYNDROME): CURRENT PERSPECTIVES ON ETIOLOGY, DIAGNOSIS, PREVENTION, AND TREATMENT (LITERATURE REVIEW)
<p>Intrauterine adhesions (Asherman syndrome) are recognized as one of the major causes of secondary infertility, menstrual disorders, and recurrent pregnancy loss. Despite more than seventy years of research into this condition, a unified standardized approach to its diagnosis, prevention, and treatment has not yet been established. This literature review summarizes current evidence on the etiology and pathogenesis of intrauterine adhesions, methods of diagnosis, and classification systems. It also analyzes existing strategies for the primary and secondary prevention of adhesion recurrence, including barrier agents, intrauterine devices, and hormonal therapy. Particular attention is given to a promising therapeutic approach involving cell-based technologies using autologous bone marrow-derived and menstrual-derived stem cells. The review was prepared based on an analysis of the clinical guidelines of the Society of Obstetricians and Gynaecologists of Canada (SOGC, 2010), the joint practice guidelines of the American Association of Gynecologic Laparoscopists (AAGL) and the European Society for Gynaecological Endoscopy (ESGE, 2017), as well as the original clinical study on menstrual stromal cell transplantation conducted by Tan et al. (2016).</p>
2026-07-25 | Subendometrial Platelet-Rich Plasma at Time of Hysteroscopy Improves Endometrial Thickness and Cavity Characteristics in Patients with Thin Endometrium
Objective: To evaluate the effect of subendometrial platelet-rich plasma (PRP) administered at the time of hysteroscopy on endometrial thickness and uterine cavity characteristics. Design: Retrospective cohort study. Materials and Methods: Nine patients who underwent hysteroscopy with subendometrial PRP were included. Indications for treatment included thin endometrium and Asherman syndrome. Endometrial thickness (ES), trilaminar pattern, and intrauterine fluid were compared before and after PRP prior to embryo transfer attempts. Results: Endometrial thickness improved in 8 of 9 patients (89%), with mean thickness increasing from 6.1 mm pre-PRP to 8.1 mm post-PRP. Several patients demonstrated clinically meaningful, including increases from 7.03 mm to 12.78 mm and from 5.10 mm to 8.96 mm. Endometrial pattern also improved following treatment. 5 of 9 patients lacked a trilaminar pattern prior to PRP, compared to 0 of 9 after PRP, with all patients demonstrating a trilaminar pattern post-treatment. Intrauterine fluid was present in 2 patients before PRP and resolved in both cases following treatment. These improvements occurred despite similar or fewer days of estrogen exposure in multiple patients. Conclusions: Subendometrial PRP administered at the time of hysteroscopy was associated with improved endometrial thickness, restoration of trilaminar pattern, and resolution of intrauterine fluid in patients with thin endometrium or intrauterine pathology. This approach may represent a useful adjunct for optimizing the endometrium prior to embryo transfer.
2026-02-28 | Mesenchymal Stem Cell Therapy for Thin Endometrium: Mechanisms, Delivery Strategies, and Clinical Outcomes: A Systematic Review
Thin endometrium constitutes a significant cause of infertility that demonstrates an inadequate response to conventional treatments, prompting the investigation of mesenchymal stem cell (MSC)-based regenerative therapies as alternative interventions. This systematic review, conducted in accordance with PRISMA guidelines, evaluated primary research from January 2020 to January 2026, analyzing fourteen studies that investigated MSC therapies across six cell sources and four delivery platforms for the treatment of thin endometrium. The findings demonstrate that umbilical cord-derived MSCs (UC-MSCs) exhibited superior therapeutic efficacy compared to other MSC sources, achieving restoration of endometrial thickness to 80–95% of control values with mean improvements of 2.4 mm, glandular regeneration yielding 20.9–24.8 glands per high-power field, pregnancy rates ranging from 60 to 80%, and substantial fibrosis reduction of 60–79%. Advanced delivery strategies significantly enhanced treatment outcomes; specifically, hydrogel encapsulation using Pluronic F-127 or hyaluronic acid extended MSC retention 4.7-fold—from 3 to 14 days—compared to direct injection, which correlated with a 23% greater improvement in endometrial thickness. Concurrently, scaffold-based delivery provided comparable efficacy while offering additional three-dimensional structural support. Mechanistic investigations revealed that MSC therapies activate five coordinated regenerative pathways: VEGF-mediated angiogenesis with 2.5–3.8 fold upregulation, TGF-β/Smad anti-fibrotic signaling that decreases TGF-β1 by 2.9–3.2 fold, the STAT3 proliferation pathway with a 3.8-fold increase, SDF-1/CXCR4 chemotactic signaling enhanced by 1.8-fold, and immunomodulation promoting M2 macrophage polarization with a 62% reduction in pro-inflammatory cytokines. Notably, MSC-derived exosomes demonstrated therapeutic potential equal to or exceeding that of cellular preparations; UC-MSC exosomes achieved a 23% greater increase in thickness and 80% pregnancy rates versus 60% for cellular formulations. A single clinical pilot study involving five patients with refractory Asherman syndrome utilizing collagen scaffold-delivered UC-MSCs reported encouraging outcomes, including an 81% improvement in endometrial thickness (from 4.2 ± 0.8 mm to 7.6 ± 1.2 mm), a 60% pregnancy rate, and a 40% live birth rate. Despite robust preclinical evidence supporting UC-MSC therapies delivered via biodegradable platforms for endometrial regeneration through multi-mechanistic pathways, clinical translation requires well-designed randomized controlled trials incorporating standardized manufacturing protocols, adequate statistical power, mechanistic biomarker validation, and comprehensive long-term safety monitoring before widespread implementation for treating thin endometrium-related infertility.
2026-01-31 | Stem cell therapy in thin endometrium and Asherman's syndrome: a systematic review and meta-analysis.
To evaluate the efficacy and safety of mesenchymal stem cell (MSC)-based therapies in improving endometrial thickness and reproductive outcomes in women with refractory thin endometrium or Asherman's syndrome. Following PRISMA 2020 guidelines, a systematic search of PubMed, Cochrane Library, Embase, Scopus, ClinicalTrials.gov, and Google Scholar through June 2025 was performed. Eighteen clinical studies involving 323 patients were included. MSCs derived from umbilical cord, bone marrow, adipose tissue, endometrium, or menstrual blood were administered via intrauterine infusion, transmyometrial injection, or scaffold-assisted delivery. The primary outcome was change in endometrial thickness; secondary outcomes included clinical pregnancy rate, live birth rate, and miscarriage rate. Meta-analysis demonstrated a significant increase in endometrial thickness following MSC therapy compared to baseline or control (mean difference = 2.35 mm; 95 % CI, 1.97-2.74; p < 0.00001). Subgroup analysis showed the largest gains in endometrial- and adipose-derived MSC groups. Randomized controlled trials confirmed higher clinical pregnancy (OR = 2.72; p = 0.002) and live birth rates (OR = 2.27; p = 0.01), with a reduced miscarriage rate (OR = 0.24; p = 0.004). No serious adverse events were reported. While MSC therapy appears to be safe, its efficacy must be confirmed by large-scale randomized trials before it can be presented to the public or recommended as an effective approach for endometrial regeneration.
2025-12-18 | Mesenchymal stem cell therapy for endometrial injury: a meta-analysis of preclinical studies.
BACKGROUND: Endometrial injury is a common cause of menstrual changes, abortion, and even infertility in women, including intrauterine adhesions (Asherman’s syndrome) and a thin endometrium. Hysteroscopic surgery and drug treatment are currently the main treatment methods; however, their effect is not satisfactory. Increasingly, studies have demonstrated that mesenchymal stem cells (MSCs) may be a safe and promising option for treating endometrial injury. This study aimed to evaluate the efficacy of MSCs in an endometrial injury model. METHODS: We searched PubMed, Cochrane Library, Web of Science, and EMBASE from the establishment of the databases to December 2023. Preclinical studies examining the role of MSCs in treating endometrial injury were included. The main outcome measures were the endometrial thickness, fibrosis area ratio, and recovery of reproductive function. Risk of bias assessment was performed using the SYRCLE tool. RevMan 5.3 was used for the meta-analysis and testing heterogeneity. RESULTS: A total of 10 Randomized Controlled Trials (RCTs) involving 230 animals were included. The analysis showed that after treatment with MSCs, the endometrium was significantly thickened (WMD 115.01 μm, 95% CI (94.07–135.95 μm)), the area ratio of endometrial fibrosis reduced (WMD − 29.88, 95% CI (− 36.61–−23.15)), and the pregnancy rate increased (RR 4.60, 95% CI (2.09–10.13)). Subgroup analyses indicated that Human amniotic mesenchymal stem cells (HA-MSCs) seemed to be more effective than other types. In addition, we found that the treatment’s efficacy is also affected by the route of administration, the type of transplantation, and other factors. CONCLUSIONS: The results of this study indicate that treatment with MSCs (HA-MSCs delivered via intrauterine injection) exerts beneficial effects on endometrial injury in rats.Xenogeneic MSCs showed enhanced therapeutic potential relative to allogeneic MSCs in our experimental models.Taken together, these data highlight MSCs as a potentially valuable approach warranting additional research for the treatment of endometrial injury.
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2025-05-14 | Endometrial Stromal Senescence Mediates the Progression of Intrauterine Adhesions.
Cellular senescence has emerged as a key mediator in organ-specific fibrosis. Here, we have established the role of endometrial stromal senescence in the progression of endometrial fibrosis, termed intrauterine adhesions (IUA). IUA have significant negative effects on women's reproductive health and are associated with infertility. We have generated original gene signatures to identify endometrial stromal senescence in single-cell and bulk RNA-sequencing data. By applying generated gene signatures, we revealed an increased level of stromal senescence during the proliferative phase in the endometrium of patients with IUA. Further comparative analysis of cell-cell communications demonstrated that senescent stromal cells in the IUA endometrium create an immunosuppressive and profibrotic microenvironment through an elevated expression of LGALS9. Endometrial stromal senescence persists during the window of implantation and correlates with impaired embryo receptivity of the IUA endometrium. Therefore, stromal senescence can be regarded as a primary cause of an unresponsive endometrium with decreased receptivity and thickness in IUA patients. A LGALS9 immunotherapy protocol, specifically designed to neutralize LGALS9 immunosuppressive activity of senescent cells, may offer a promising opportunity to restore effective immune clearance of these cells within the IUA stroma. Consequently, an LGALS9-based strategy could emerge as a novel therapeutic avenue in the treatment of IUA.
2024-02-16 | LAMB3 Promotes Myofibrogenesis and Cytoskeletal Reorganization in Endometrial Stromal Cells via the RhoA/ROCK1/MYL9 Pathway.
LAMB3, a major extracellular matrix and basal membrane component, is involved in wound healing. We aimed to understand its role in Asherman's syndrome (AS), which is associated with infertility, by using bioinformatics analysis and cultured endometrial stromal cells (ESCs). MRNAs extracted from tissues obtained from control subjects and patients with severe intrauterine adhesion were sequenced and subjected to bioinformatics analysis and the RhoA/ROCK1/MYL9 pathway was implicated and this subsequently studied using cultured primary ESCs. The effects of overexpression and knockdown and activation and inhibition of LAMB3 on the mesenchymal to myofibroblastic phenotypic transformation of ECCs were assessed using PCR and western blot analysis. Phalloidin was used to localize the actin cytoskeletal proteins. Silencing of LAMB3 reversed the TGF-β-induced ESC myofibroblast phenotype conversion, whereas overexpression of LAMB3 promoted this process. Activation and silencing of LAMB3 led to remodeling of the ESC cytoskeleton. Overexpression and silencing of LAMB3 caused activation and inhibition of ESCs, respectively. Y-27632 and LPA reversed the activation and inhibition of the RhoA/ROCK1/MYL9 pathway after overexpression and silencing, respectively. These results suggest that LAMB3 can regulate ESC fibrosis transformation and cytoskeleton remodeling via the RhoA/ROCK1/MYL9 pathway. This study provides a potential new target for gene therapy and drug intervention of AS.
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Drug Discovery Landscape
1 orphan drug designation for Asherman syndrome.
1 orphan drug designation for Asherman syndrome.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Autologous adult bone marrow-derived non-expanded CD133+ haematopoietic stem cells | cell therapies | EMA | Asherman Therapy S.L. |
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