MRI for Diagnosing Intrauterine Adhesions.

OBJECTIVES: To prospectively assess the diagnostic accuracy of MRI and transvaginal ultrasound (TVS) as well as the prognostic value of MRI for intrauterine adhesions (IUAs), using hysteroscopy as the reference standard. DESIGN: Prospective observational study. SETTING: Tertiary medical centre. PATIENT(S): Ninety-two women with amenorrhea, hypomenorrhea, subfertility, or recurrent pregnancy loss who underwent MRI and in whom Asherman's syndrome was suspected upon TVS. INTERVENTION(S): MRI and TVS were conducted approximately 1 week before hysteroscopy. METHODS: Ninety-two patients suspected of having Asherman's syndrome were examined by MRI and TVS within 7 days of an upcoming hysteroscopy. All hysteroscopy procedures were performed during the early proliferative phase of the menstrual cycle. All hysteroscopic diagnoses were performed by an experienced expert. All MRIs were read by 2 experienced, blinded radiologists. RESULTS: MRI was highly accurate (94.57%), sensitive (98.8%), and specific (42.9%) for diagnosing IUAs with a positive predictive value of 95.5% and a negative predictive value of 75%. The diagnostic values of MRI and TVS were significantly different according to McNemar tests. Junctional zone signal and junctional zone alterations correlated with the stage of IUAs. CONCLUSION: MRI is markedly superior to TVS in terms of diagnostic accuracy for IUAs, with total agreement with hysteroscopic findings. However, the main advantage of MRI is that, unlike TVS and hysterosalpingography, it can be used to assess the risk of hysteroscopy and to predict postoperative recovery and future pregnancy based on the uterine junctional zone.

Autologous platelet-rich plasma treatment for moderate-severe Asherman syndrome: the first experience.

PURPOSE: Treatment of Asherman syndrome (AS) presents a significant clinical challenge. Based on our in vitro data showing that PRP could activate endometrial cell proliferation and migration, we hypothesized that intrauterine infusion of autologous platelet-rich plasma (PRP) may improve endometrial regeneration and fertility outcomes in patients with moderate-severe AS. MATERIALS AND METHODS: Subjects with moderate-severe AS were randomized to PRP or saline control administered following hysteroscopic adhesiolysis. Due to relative inability to randomize patients to the control group, after initial randomization of 10 subjects (6 in PRP and 4 in control groups), the remainder were prospectively enrolled in PRP group (n = 9), with 11 historic controls added to control group, for a total of 30 subjects (PRP n = 15; saline control n = 15). Right after hysteroscopy, 0.5-1 mL of PRP or saline was infused into the uterus via a Wallace catheter, followed by estrogen therapy. The primary outcomes were changes in endometrial thickness (EMT, checked in 3 weeks) and in menstrual flow; secondary outcomes were pregnancy and live birth rates. EMT and menstrual bleeding pattern were assessed before and after the intervention. Pregnancy was assessed over a 6-month period. RESULTS: There were no statistically significant differences in age, gravidity/parity, cause of AS, preoperative menses assessment, AS hysteroscopy score, and intrauterine balloon placement between the groups. There was no statistically significant difference (p = 0.79) in EMT pre-PRP infusion for control (5.7 mm, 4.0-6.0) and study arm (5.3 mm, 4.9-6.0). There was no statistically significant change (p = 0.78) in EMT after PRP infusion (1.4 mm, - 0.5-2.4) vs saline (1.0 mm, 0.0-2.5). Patients tolerated the procedure well, with no adverse effects. There was no difference in the predicted likelihood of pregnancy (p = 0.45) between the control (0.67, 0.41-0.85) and study arm (0.53, 0.29-0.76). CONCLUSIONS: PRP was well accepted and tolerated in AS patients. However, we did not observe any significant EMT increase or improved pregnancy rates after adding PRP infusion, compared to standard treatment only. The use of intrauterine PRP infusion may be a feasible option, and its potential use must be tested on a larger sample size of AS patients.

Prevention of de novo adhesion formation in patients with Asherman's syndrome.

OBJECTIVE: To summarize recent data and knowledge of secondary prevention of the recurrence of intrauterine adhesions in patients with Ashermans syndrome. METHODS: Analysis of literature evidence and clinical experience of the authors. RESULTS: Ashermans syndrome is iatrogenic disease with problematic therapy. One of the basic issues is a need for repeated surgical interventions since the recurrence of adhesions is very frequent. Secondary prevention is a crucial factor for successful therapy in these patients. The methods applied include second--look hysteroscopy, hormonal treatment and different types of barriers. To compare their efficacy is difficult and the results of meta-analysis are contradictory. CONCLUSION: There are many different possibilities of secondary prevention of the recurrence of intrauterine adhesions; unfortunately, none of them is perfect. The usage of solid or semi-solid barriers in combination with the support of endometrium regeneration with hormonal therapy seems most reasonable.

Strategies for managing Asherman's syndrome and endometrial atrophy: Since the classical experimental models to the new bioengineering approach.

Endometrial function is essential for embryo implantation and pregnancy, but managing endometrial thickness that is too thin to support pregnancy or an endometrium of compromised functionality due to intrauterine adhesions is an ongoing challenge in reproductive medicine. Here, we review current and emerging therapeutic and experimental options for endometrial regeneration with a focus on animal models used to study solutions for Asherman's syndrome and endometrial atrophy, which both involve a damaged endometrium. A review of existing literature was performed that confirmed the lack of consensus on endometrial therapeutic options, though promising new alternatives have emerged in recent years (platelet-rich plasma, exosomes derived from stem cells, bioengineering-based techniques, endometrial organoids, among others). In the future, basic research using established experimental models of endometrial pathologies (combined with new high-tech solutions) and human clinical trials with large population sizes are needed to evaluate these emerging and new endometrial therapies.

Classification systems of Asherman's syndrome. An old problem with new directions.

Intrauterine adhesion (IUA) formation and the resulting Asherman's syndrome (AS) is an unfortunate clinical condition that occurs when the endometrium is damaged as a consequence of trauma, such as vigorous curettage, infection, or some Müllerian anomaly. The most frequent symptoms include hypo/amenorrhea, infertility, and adverse reproductive outcomes. Prevention of IUA formation is essential; however, when present, accurate diagnosis and surgical intervention (hysteroscopic adhesiolysis) are required. The outcome of this treatment is based on the technique and the extent of surgery performed which depends on the severity and complexity of the disease. Hence its classification becomes particularly important to determine a standardized therapy for each case and patient counseling regarding the prognosis. In this article, we aim to describe the IUAs classification systems that have been proposed comparing the merits and demerits of each one.

Intrauterine infusion of platelet-rich plasma for severe Asherman syndrome: a cutting-edge approach.

Asherman syndrome (AS) consists of intrauterine adhesions development as a consequence of trauma, radiation, or infection in the endometrium. Clinical symptoms include menstrual alterations, infertility, and pregnancy complications, such as recurrent pregnancy loss or abnormal placentation. In this article, we performed a narrative review of the literature, searching electronic databases (i.e., Medline, Pubmed, and Google Scholar) to summarize the available pieces of evidence about epidemiology, pathophysiology, diagnosis, and treatment of AS. Hysteroscopy is essential for diagnosis and treatment, although adhesions may recur. Different postoperative therapies have been proposed to prevent recurrence and restore impaired endometrial function and promote endometrial regeneration, although these effects are usually temporary. We report a case of AS with adhesion recurrence and endometrial atrophy who was successfully treated with intrauterine autologous platelet-rich plasma (PRP) infusion. This therapy allowed endometrial tissue regeneration, leading to increased vascularity and endometrium thickness, and restoration of endometrial function that led to a successful pregnancy. Though there is limited experience supporting the use of PRP to improve endometrial function, it has been safely used in other fields of medicine; besides, it is easy to obtain, not expensive, and harmless being an autologous source. Future studies are encouraged to further assess this approach to treat AS.

Suppression of the inflammation and fibrosis in Asherman syndrome rat model by mesenchymal stem cells: histological and immunohistochemical studies.

INTRODUCTION: Asherman syndrome (AS) is a symptomatic intrauterine adhesion caused by endometrial basal layer fibrosis as a result of either uterine cavity surgery or infection leading to many complications. There is a concern to repair the injured tissues by using bone marrow mesenchymal stem cells (BM-MSCs). We aimed in this study to develop an animal model of AS and evaluate the anti-inflammatory and anti-fibrotic effects of BM-MSCs in this model through histological, immunohistochemical, and morphometric studies. MATERIAL AND METHODS: Forty-two adult female adult albino rats were divided into (i) donor group composed of 2 rats used for isolation and propagation of BM-MSCs, and (ii) experimental groups: 40 rats equally divided into 4 groups: GpI (control), GpII (AS model), GpIII (BM-MSCs-treated AS rats), GpIV (untreated AS rats). Histological staining and immunohistochemical (IHC) detection of proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), and nuclear factor-kappa beta (NF-kB) were performed. The results were evaluated by morphometric and statistical analysis. RESULTS: Significant endometrial thinning, fibrosis, and degeneration of the endometrial epithelium with a significant decrease in PCNA and VEGF immunoexpression and a significant increase in NF-kB immunoexpression were detected in GpII and GpIV groups. These changes were substantially reversed in BM-MSCs-treated animals. CONCLUSIONS: BM-MSCs treatment resulted in substantial improvement of intrauterine adhesion in the rat model of Asherman syndrome.

Comparison of the regenerative effects of bone marrow/adipose-derived stem cells in the Asherman model following local or systemic administration.

PURPOSE: Cell therapy is a promising strategy for the treatment of Asherman's syndrome (AS), but the origin of these cells and injection route influence the therapeutic effect and complications of cell therapy. Herein, we compared the effects of systemic or local intrauterine injection of bone marrow or adipose-derived mesenchymal stem cells (BMSCs/AMSCs) on the endometrium in a rat model of AS. METHODS: After induction of AS in adult Wistar rats, the CM-Dil-positive BMSCs or AMSCs were injected either locally or intravenously. After 3 weeks, endometrial thickness, collagen deposition, cell migration, and VEGF expression were evaluated using histochemistry/immunofluorescence studies. RESULTS: In all stem cell-treated groups, an ameliorative effect on the damaged endometrium was noted. Collagen deposition diminished in both groups (IV and local injection) compared to the AS model. In rats injected locally with MSC, fibrosis decreased compared to the other groups. Moreover, endometrial thickness increased in the groups that received local injection of BMSCs and AMSCs more than the IV-transplanted AMSCs group. Immunofluorescent staining demonstrated that although the systemic transplantation of BMSCs was more effective than the other groups on VEGF expression, it led to the lowest number of CM-Dil+ stem cells in the damaged endometrium. CONCLUSION: Stem cell transplantation may reconstruct the damaged endometrium, but it is recommended to select the most effective stem cells and injection route. Because the removal of the fibrosis and the replacement of the epithelia cells is an effective therapeutic strategy for AS, in this study, we conclude that the local injection of AMSCs is more appropriate than BMSCs to treat AS.

Perivascular Stem Cell-Derived Cyclophilin A Improves Uterine Environment with Asherman's Syndrome via HIF1α-Dependent Angiogenesis.

Asherman's syndrome (AS) is characterized by intrauterine adhesions or fibrosis resulting from scarring inside the endometrium. AS is associated with infertility, recurrent miscarriage, and placental abnormalities. Although mesenchymal stem cells show therapeutic promise for the treatment of AS, the molecular mechanisms underlying its pathophysiology remain unclear. We ascertained that mice with AS, like human patients with AS, suffer from extensive fibrosis, oligo/amenorrhea, and infertility. Human perivascular stem cells (hPVSCs) from umbilical cords repaired uterine damage in mice with AS, regardless of their delivery routes. In mice with AS, embryo implantation is aberrantly deferred, which leads to intrauterine growth restriction followed by no delivery at term. hPVSC administration significantly improved implantation defects and subsequent poor pregnancy outcomes via hypoxia inducible factor 1α (HIF1α)-dependent angiogenesis in a dose-dependent manner. Pharmacologic inhibition of HIF1α activity hindered hPVSC actions on pregnancy outcomes, whereas stabilization of HIF1α activity facilitated such actions. Furthermore, therapeutic effects of hPVSCs were not observed in uterine-specific HIF1α-knockout mice with AS. Secretome analyses of hPVSCs identified cyclophilin-A as the major paracrine factor for hPVSC therapy via HIF1α-dependent angiogenesis. Collectively, we demonstrate that hPVSCs-derived cyclophilin-A facilitates HIF1α-dependent angiogenesis to ameliorate compromised uterine environments in mice with AS, representing the major pathophysiologic features of humans with AS.

An update on stem cell therapy for Asherman syndrome.

The current treatment for Asherman syndrome is limited and not very effective. The aim of this review is to summarize the most recent evidence for stem cells in the treatment of Asherman syndrome. The advent of stem cell therapy has propagated experimentation on mice and humans as a novel treatment. The consensus is that the regenerative capacity of stem cells has demonstrated improved outcomes in terms of fertility and fibrosis in both mice and humans with Asherman syndrome. Stem cells have effects on tissue repair by homing to the injured site, recruiting other cells by secreting chemokines, modulating the immune system, differentiating into other types of cells, proliferating into daughter cells, and potentially having antimicrobial activity. The studies reviewed examine different origins and administration modalities of stem cells. In preclinical models, therapeutic systemic injection of stem cells is more effective than direct intrauterine injection in regenerating the endometrium. In conjunction, bone marrow-derived stem cells have a stronger effect on uterine regeneration than uterine-derived stem cells, likely due to their broader differentiation potency. Clinical trials have demonstrated the initial safety and effectiveness profiles of menstrual, bone marrow, umbilical cord, and adipose tissue-derived stem cells in resumption of menstruation, fertility outcomes, and endometrial regeneration.

Asherman syndrome and insufficient endometrial thickness: A hypothesis of integrated approach to restore the endometrium.

Asherman syndrome consists in an acquired condition characterized by the development of fibrous intrauterine adhesions involving until two-thirds of the uterine cavity. Common signs of the syndrome are represented by alterations of regular menses, hypomenorrhea and amenorrhea. Moreover, women affected by Asherman syndrome, often struggle with fertility problems such as difficulty in spontaneous conceiving as well as complications including recurrent pregnancy loss and invasive placentation. The abnormality of the endometrial line consisting in insufficient thickness and/or endometrial trauma damaging the decidua basalis, are characteristic elements of the disease. Several studies have been conducted during the last ten years to find a solution restoring the regular endometrial line solving the fertility issue in Asherman women. Hormonal therapy as well as the use of stem cells seem to represent valid options to regenerate the endometrium opening a new scenario in the fertility treatment of these women. In this context, the presented study proposes an integrated approach to reach an adequate endometrial reconstitution and consequentially optimal fertility outcomes.

Effects of uterus derived mesenchymal stem cells and their exosomes on asherman's syndrome.

Asherman's syndrome has become a growing problem with the incidence of cesarean and endometrial surgical procedures. A surgical procedure that can damage to the basal layer of the endometrium is formed as intrauterine adhesion and can cause asherman's syndrome. Mesenchymal stem cells (MSCs) are characterized by some characteristics such as non-immunogenic, angiogenic, antifibrotic, antiapoptotic and antiinflammatory properties, also they support tissue repair by secretion of various factors and chemokines in cellular therapy. Exosomes are active paracrine components with a great potential for repairing damaged tissue. Exosomes include many paracrine factors responsible for regeneration and angiogenesis. In this study, 10 newborn Wistar rats were used to obtain MSCs. A total of 24 adult Wistar rats were also used. The rats were divided into 4 groups: untreated control group; asherman control group; asherman + uterine-derived MSCs group; asherman + uterine-derived MSCs-exosomes group. At the end of the experiment, uterine tissues were evaluated by histochemical and immunohistochemical. As a result of MSCs and exosomes treatments, proliferation and vascularization in uterine tissue was increased. It was also shown to reduce fibrosis with masson's trichrome staining. MMP-2 and MMP-9 expression was enhanced by MSC and exosomal therapy; in addition, TIMP-2 expression was decreased. In our study, it was shown that proliferation and vascularization increased and fibrosis decreased in uterus as a result of MSC and exosome treatments. Our results indicate that the exosomal treatment restored the damage of asherman's syndrome at tissue at a shorter time than the MSCs group.

A cohort study comparing the severity and outcome of intrauterine adhesiolysis for Asherman syndrome after first- or second-trimester termination of pregnancy.

OBJECTIVE: To compare the clinical characteristics of Asherman syndrome and the outcomes of hysteroscopic adhesiolysis in women after first or second-trimester termination of pregnancy (TOP). METHODS: This was a retrospective descriptive analysis of patients with moderate-to-severe intrauterine adhesiolysis (IUAs) after TOP and treated by hysteroscopic adhesiolysis and followed by "second-look" hysteroscopy 3 months later at The Beijing Obstetrics and Gynecology Hospital (China) between January 2013 and March 2016. The American Fertility Society (AFS) scoring system was used to evaluate the intrauterine adhesions. RESULTS: A total of 236 patients with 180 first-trimester TOP and 56 s-trimester TOP patients were included. The severe adhesion and amenorrhea rates during the second-trimester group (69.6% and 39.3%, respectively) were significantly higher than those in the first-trimester group (36.7% and 7.2%, respectively). AFS score reduction in the second-trimester group (6.2 ± 2.8) was significantly lower than in the first-trimester group (6.5 ± 2.5). The pregnancy rates in the second-trimester group (21.4%) were significantly lower than that in the first-trimester group (43.3%). The pregnancy rate of severe intrauterine adhesions in second-trimester TOP (10.3%) was significantly lower than in first-trimester TOP (40.9%). CONCLUSION: These findings suggested that second trimester TOP was associated with more severe intrauterine adhesion and a worse prognosis after hysteroscopic adhesiolysis in women with Asherman syndrome when compared to first-trimester TOP.

Single cell-derived clonally expanded mesenchymal progenitor cells from somatic cell nuclear transfer-derived pluripotent stem cells ameliorate the endometrial function in the uterus of a murine model with Asherman's syndrome.

OBJECTIVES: Because primary mesenchymal progenitor cells (adult-MPCs) have various functions that depend on the tissue origin and donor, de novo MPCs from human pluripotent stem cells (hPSCs) would be required in regenerative medicine. However, the characteristics and function of MPCs derived from reprogrammed hPSCs have not been well studied. Thus, we show that functional MPCs can be successfully established from a single cell-derived clonal expansion following MPC derivation from somatic cell nuclear transfer-derived (SCNT)-hPSCs, and these cells can serve as therapeutic contributors in an animal model of Asherman's syndrome (AS). MATERIALS AND METHODS: We developed single cell-derived clonal expansion following MPC derivation from SCNT-hPSCs to offer a pure population and a higher biological activity. Additionally, we investigated the therapeutic effects of SCNT-hPSC-MPCs in model mice of Asherman's syndrome (AS), which is characterized by synechiae or fibrosis with endometrial injury. RESULTS: Their humoral effects in proliferating host cells encouraged angiogenesis and decreased pro-inflammatory factors via a host-dependent mechanism, resulting in reduction in AS. We also addressed that cellular activities such as the cell proliferation and population doubling of SCNT-hPSC-MPCs resemble those of human embryonic stem cell-derived MPCs (hESC-MPCs) and are much higher than those of adult-MPCs. CONCLUSIONS: Somatic cell nuclear transfer-derived-hPSCs-MPCs could be an advanced therapeutic strategy for specific diseases in the field of regenerative medicine.

Cellular therapies for the endometrium: An update.

An update on the current state of endometrial cell therapies in terms of cell types, mechanisms of action, delivery, safety, regulatory frameworks and future perspectives. This review focuses on clinical trials using angiogenesis-promoting therapies and stromal therapies piloted in the last 10 years for alleviating Asherman's syndrome and long-term infertility. All studies present promising preliminary results, indicating increased endometrial thickness and resumed menstruation. Further characterization of individual cell products, their mode of action and larger clinical trials will be essential to establishing cell therapy as a viable option for the treatment of infertility and fertility preservation.

Bone Marrow Mesenchymal Stem Cells (BMSCs) Restore Functional Endometrium in the Rat Model for Severe Asherman Syndrome.

OBJECTIVE: To investigate the feasibility to restore functional endometrium using bone marrow mesenchymal stem cells (BMSCs) in the Sprague Dawley (SD["SD" has been defined as both "Sprague Dawley" and "standard deviation." Please clarify which one is to be followed.]) rat model for Asherman syndrome (AS). DESIGN: Basic research on treatment of AS utilizing an optimized rat model. SETTING: University research laboratories. ANIMAL(S): Sprague Dawley rat model in which AS was induced in accordance to an optimized protocol. INTERVENTION(S): Bone marrow mesenchymal stem cells were harvested from the rat's bone marrow and labeled with green fluorescent protein (GFP) in the second passage of BMSCs. The fifth passage of GFP-labeled BMSCs was injected systemically through the tail vein in the optimized AS rat model. MAIN OUTCOME MEASURE(S): We examined the reproliferation of the endometrial lining and the expression of markers for endometrium and endometrial receptivity. The localization of engrafted GFP-labeled BMSCs was determined by a laser scanning confocal microscope and a fluorescence microscope. The number of pregnant rats and implanted embryos in each uterus was recorded to evaluate the function of endometrium. RESULT(S): We had demonstrated that in the in vivo experiments on our rat model for AS, the group which received BMSC injection had significantly improved reproductive outcomes-70% of these rats conceived, whereas none of the rats in the control group got pregnant ( P < .01, χ2 test). The mean number of embryos undergoing implantation was 14 ± 1.24 in the sham group and 7 ± 5.70 in the BMSC group (Levene test, P = .001). There was no significant difference between the groups from the time of coitus to conception. To further determine how BMSC injection could have resulted in the improved reproductive outcomes in rats with AS, we employed immunohistochemical techniques to examine the endometrium of these treated rats. On hematoxylin-eosin staining, we noted the reproliferation of all layers of the endometrium and with Masson staining, we noted significant reduction in fibrosis in the damaged endometrium of rats treated with BMSCs. Counterstaining for GFP and cytokeratin-positive cells was noted in the endometrial lining of treated rats, which might suggest the action of BMSCs in regenerating the damaged endometrial lining. The expression of the endometrial receptivity marker, Leukemia inhibitory factor (LIF), in this regenerated endometrial lining could have resulted in the improved reproductive outcomes observed in the AS rat model treated with BMSCs. CONCLUSION: Bone marrow mesenchymal stem cells were likely to play an important role in the reconstruction of the injured endometrium and improvement of reproductive outcomes in the optimized AS rat model.

Antifibrotic Effects of Decellularized and Lyophilized Human Amniotic Membrane Transplant on the Formation of Intrauterine Adhesion.

OBJECTIVES: Intrauterine adhesion is a disease involving endometrial fibrosis that arises from injury to the basal layer of the endometrium. Here, we aimed to explore the preventive effects of decellularized and lyophilized amniotic membrane on endometrial fibrosis in a rat model of intrauterine adhesion. MATERIALS AND METHODS: Twenty-four Sprague-Dawley rats were randomly divided into 2 groups. For the intrauterine adhesion group, endometria of left uteri were scraped without treatment. For the intrauterine adhesion plus decellularized and lyophilized amniotic membrane transplant group, decellularized and lyophilized amniotic membrane was sutured onto the scraped wound of left uteri. Right uteri were kept as the control group. At 3, 7, 14, and 28 days after transplant, uteri were sampled for histologic and immunohistochemical evaluation. RESULTS: Histology examination revealed extensive fibrosis with significantly reduced numbers of endometrial glands in uteri in the intrauterine adhesion group. Immunohistochemical staining showed a remarked increase in expression of transforming growth factor ß1 (P < .01) and decreased expression of matrix metalloproteinase-9 (P < .01) in the intrauterine adhesion group. In rats with transplant of decellularized and lyophilized amniotic membrane, endometrial fibrosis apparently improved (P < .05) with reduced expression of transforming growth factor ß1 and increased matrix metalloproteinase-9 expression (P < .05). However, there were no significant differences in the number of endometrial glands or endometrial thickness between the 2 groups (P > .05). CONCLUSIONS: Development of intrauterine adhesion was prevented with transplant of decellularized and lyophilized amniotic membrane via suppression of transforming growth factor ß1 and increased production of matrix metalloproteinase-9 in a rat model.

Stem Cells and Endometrial Regeneration: From Basic Research to Clinical Trial.

Monthly changes in the endometrial cycle indicate the presence of endometrial stem cells. In recent years, various stem cells that exist in the endometrium have been identified and characterized. Additionally, many studies have shown that Bone Marrow Mesenchymal Stem Cells (BM-MSCs) provide an alternative source for regenerating the endometrium and repairing endometrial injury. This review discusses the origin of endometrial stem cells, the characteristics and main biomarkers among five types of putative endometrial stem cells, applications of endometrium-derived stem cells and menstrual blood-derived stem cells, the association between BM-MSCs and endometrial stem cells, and progress in repairing endometrial injury.

Detection of Asherman's syndrome after conservative management of placenta accreta: a case report.

BACKGROUND: We present a case involving conservative treatment of placenta accreta, with a subsequent diagnosis of Asherman's syndrome. CASE PRESENTATION: A 41-year-old Japanese woman (G2P0A2) delivered a healthy male infant via cesarean section due to preeclampsia. The placenta did not spontaneously separate and was manually removed. Adhesion was tight and placenta accreta was diagnosed. During the procedure, no uterine inversion or perforation, and no uterine cavity adhesion, were observed. Four months postoperatively, hysteroscopy was performed. Adhesion was detected at the fundus of her uterus where the placenta had adhered to the uterus. Asherman's syndrome was diagnosed. CONCLUSIONS: Asherman's syndrome might occur after conservative management of placenta accreta, which may be a direct cause of placenta accreta recurrence. When Asherman's syndrome is diagnosed, the site of the placenta and adhesion should be monitored during subsequent pregnancies.