Asherman’s Syndrome is characterized by intrauterine adhesions or scarring, which cause infertility, menstrual abnormalities, and recurrent pregnancy loss. The pathophysiology of this syndrome remains unknown, with treatment restricted to recurrent surgical removal of intrauterine scarring, which has limited success. Here, we decode the Asherman’s Syndrome endometrial cell niche by analyzing data from over 200,000 cells with single-cell RNA-sequencing in patients with this condition and through in vitro analyses of Asherman’s Syndrome patient-derived endometrial organoids. Our endometrial atlas highlights the loss of the endometrial epithelium, alterations to epithelial differentiation signaling pathways such as Wnt and Notch, and the appearance of characteristic epithelium expressing secretory leukocyte protease inhibitor during the window of implantation. We describe syndrome-associated alterations in cell-to-cell communication and gene expression profiles that support a dysfunctional pro-fibrotic, pro-inflammatory, and anti-angiogenic environment.

A low-cost custom-made pseudo-anthropomorphic lung phantom, offering a model for ultrasound-guided interventions, is presented. The phantom is a rectangular solidstructure fabricated with polyvinyl alcohol cryogel (PVA-C) and cellulose to mimic the healthy parenchyma. The pathologies of interest were embedded as inclusions containing gaseous, liquid, or solid materials. The ribs were 3D-printed using polyethylene terephthalate, and the pleura was made of a bidimensional reticle based on PVA-C. The healthy and pathological tissues were mimicked to display acoustic and echoic properties similar to that of soft tissues. Theflexible fabrication process facilitated the modification of the physical and acoustic properties of the phantom. The phantom’s manufacture offers flexibility regarding the number, shape, location, and composition of the inclusions and the insertion of ribs and pleura. In-plane and out-of-plane needle insertions, fine needle aspiration, and core needle biopsy were performed under ultrasound image guidance. The mimicked tissues displayed a resistance and recoil effect typically encountered in a real scenario for a pneumothorax, abscesses, and neoplasms. The presented phantom accurately replicated thoracic tissues (lung, ribs, and pleura) and associated pathologies providing a useful tool for training ultrasound-guided procedures.

Autologous CD133+ bone marrow-derived stem cell (BMDSC) therapy has been designated as an Orphan Drug by the EMA and FDA for the treatment of Asherman Syndrome (AS). This phase 1/2, non-randomized, open-label, single-arm trial assessed the safety and efficacy of this novel therapy in 20 infertile women with moderate to severe AS, unresponsive to prior hysteroscopic treatments. Primary endpoints were safety and tolerability over 15 months follow-up, including during pregnancy and after live birth. The therapy was well tolerated with a mean dosage of 125.41 × 10⁶ cells, with no treatment-related serious adverse events and only reversible events such as arm pain, headache, and nausea. In pregnant patients, minor obstetric complications were reflux-related cough (n = 1), gestational diabetes (n = 2), cervical shortening requiring pessary placement (n = 2), and postpartum placenta accreta (n = 1). No preterm labor occurred, and all six newborns remained free of significant adverse events. Our findings suggest that autologous CD133 + BMDSC therapy is a safe and effective treatment for AS. Clinical trial registration (Eudra CT): 2016-003975-23

Embryo adhesion represents a critical step of implantation, yet understanding this process has been hindered by the lack of human in vitro platforms that replicate endometrial physiology. Here, we present a dual-channel microfluidic platform containing organoid-derived endometrial epithelium and primary stromal cells. Our model recapitulates important endometrial hallmarks including epithelial polarization, stromal decidualization, extracellular vesicle release, and hormone-induced receptivity. We validated the model using mouse embryos and human blastocysts, where we showed that embryos displayed features of initial adhesion. These included establishment of embryo-epithelial contacts initiated via the polar trophectoderm, inner cell mass repositioning, and lineage reorganization. Moreover, human embryos secreted βhCG indicating a functional trophoblast. Thus, this work provides a platform to study key features of embryo adhesion and endometrial receptivity and disorders affecting embryo-endometrium interactions.

Autologous CD133 + bone marrow-derived stem cell (BMDSC) therapy has been designated an Orphan Drug by the EMA and FDA for the treatment of Asherman Syndrome (AS). This phase 1/2, non-randomized, open-label, single-arm trial assessed the safety, efficacy and biological plausibility of this novel therapy in 20 infertile women with moderate to severe AS unresponsive to prior hysteroscopic treatments. The primary endpoint was safety, with doses ranging from 31 to 212 × 10⁶ cells being well tolerated; reversible limb paresthesia was the most common adverse event. Secondary endpoints demonstrated significant improvements in endometrial morphometry, thickness (3.80 ± 0.95 mm to 5.29 ± 0.77 mm, p < 0.05), endometrial volume (1.26 cm³ to 2.78 cm³, p < 0.05), and hysteroscopic scores (8.0 ± 3.17 to 4.42 ± 2.09, p < 0.05). Clinically, menstruation and reproductive function were restored, culminating in six live births following embryo transfer. Single-cell RNA sequencing of endometrium and organoids pre- and post-treatment revealed partial reversion of AS-related changes. Additionally, mitochondrial variant tracking offered insights into the engraftment of transplanted CD133 + BMDSCs. These findings suggest that autologous CD133 + BMDSC therapy is a safe and effective treatment for moderate to severe AS, warranting further investigation in larger trials.