Promising therapeutic targets of endometriosis obtained from microRNA studies.

Endometriosis is a benign tumor that affect 6-10% women of reproductive age. To date, it is suggested that the aberrant microRNA (miRNA) expressions play important roles in the pathogenesis of endometriosis. Reviewing the literature, we found nine overexpressed miRNAs, which were thoroughly investigated in the context of endometriotic tissues and cells. Most of the overexpressed miRNAs induced endometriosis-specific characteristics including inhibition of apoptosis and decidualization, upregulation of fibrogenesis, invasion, migration, cell proliferation, attachment to extracellular matrix, inflammation, and angiogenesis in the endometriotic cells. Then, we found that the downstream target molecules of these miRNAs, such as early growth response protein-1, extracellular signal-regulated kinase, matrix metallopeptidase 1, signal transducer and activator of transcription 3, cyclooxygenase-2, phosphoinositide 3-kinase, AKT, mammalian target of rapamycin, and vascular endothelial growth factor-A are promising for the therapeutic targets of endometriosis. Recent findings suggest that complex molecular mechanisms leading to development and progression of endometriosis by miRNAs may exist in endometriosis. The meticulous balance between tumorigenic miRNAs and tumoristatic miRNAs may destine the natural course and response to the surgical, medical, and hormonal treatments of this disease. Further investigations into endometriosis-associated miRNAs may elucidate the pathogenesis of endometriosis and help to develop novel therapeutics.

Role of repressed microRNAs in endometriosis.

Endometriosis is a common, estrogen-dependent benign tumor that affect 3-10% women of reproductive age, and is characterized by the ectopic growth of endometrial tissue, which is found primarily in the rectovaginal septum, ovaries, and pelvic peritoneum. To date, accumulating evidence suggests that various epigenetic aberrations, including the expression of aberrant microRNAs (miRNAs), play definite roles in the pathogenesis of endometriosis. This review summarizes the recent findings on the aberrantly repressed miRNAs, as well as their potential roles regarding the pathogenesis of endometriosis.

The inhibitory effect of AMP-activated protein kinase (AMPK) on chemokine and prostaglandin production in human endometrial stromal cells.

BACKGROUND: To investigate the role of adenosine monophosphate (AMP)-activated protein kinase (AMPK) on the production of interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, prostaglandin E2 and F2α induced by IL-1ß in endometrial stromal cells (ESCs) following treatment with 5-aminoimidazole-4- carboxamide ribonucleoside (AICAR). METHODS: Endometrial specimens were obtained and cultured. We examined the effects of IL-1ß, IL-1 ra and AICAR on the production of IL-8, MCP-1, PGE2 and PGF2α in human ESCs. The phosphorylations of AMPK, IκB, 4EBP-1, p70S6K and S6 ribosomal protein were analyzed by Western immunoblotting. RESULTS: Following stimulation by IL-1ß, the production of IL-8, MCP-1, PGE2 and PGF2α showed significant increases, and these increases were suppressed by AICAR. The expression of cyclooxygenase-2 (COX-2) induced by IL-1ß and suppressed by AICAR. The phosphorylation of IκB, 4EBP-1, p70S6K and S6 ribosomal protein were inhibited via an AMPK-dependent signal transduction. CONCLUSIONS: The production of IL-8, MCP-1, PGE2 and PGF2α induced by IL-1ß in ESCs were involved in the negative regulatory mechanisms of AMPK. The substances that activate AMPK may be promising agents for the treatment of pathological problems such as dysmenorrhea.

Expression of angiogenic factors in sclerosing stromal tumours of the ovary.

Sclerosing stromal tumours (SSTs) are rare benign tumours and are generally observed in individuals in their teens to 20 s. Many cases are suspected as malignant tumours pre-operatively, owing to their high vascularity on diagnostic imaging. Herein, we aimed to evaluate the expressions of various angiogenic factors in SSTs. The expressions of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF) were examined by immunohistochemical staining. Upon immunohistochemistry, overexpressions of VEGF, bFGF, and HGF in the ovarian stroma were observed in SSTs. In the normal ovary, the expressions were strong around the vessels and weak in the stroma of the ovary, while a Sertoli-Leydig cell tumour showed weak staining with VEGF, locally strong staining with bFGF and negative staining with HGF. This is the first report about angiogenic factors such as bFGF, and HGF in SST. Impact statement What is already known on this subject? Sclerosing stromal tumour (SST) is a rare benign tumour with high vascularity. The high vascularity of SSTs are reported to be related to the overexpression of vascular endothelial growth factor (VEGF). But there is no study on the expressions of other angiogenic factors in SST. What do the results this study add? In the immunohistochemical analysis, VEGF, bFGF and HGF were found to be widely stained in SSTs. This results suggest the possibility that the high vascularity seen on diagnostic imaging, and the many small vessels observed microscopically may be related to the expressions of VEGF, bFGF and HGF in SSTs. What are the implications of these findings for clinical practice and/or further research? Our results suggest the possibility that the combined expression pattern of VEGF, bFGF, and HGF may be used as marker of SSTs.

A possible role for AMP-activated protein kinase activated by metformin and AICAR in human granulosa cells.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are generally insulin- resistant and are consequently often treated with metformin. We investigated the effect of metformin and AICAR on the AMP-activated protein kinase (AMPK) pathway. METHODS: We evaluated the effects of 5-amino-imidazole-4-carboxyamide-1- beta-D-ribofuranoside (AICAR) and metformin on tumor necrosis factor (TNF)-alpha- stimulated chemokine production in human granulosa cells. The phosphorylations of AMPK, I-kappaB, 4E-BP-1, p70S6K were analyzed by western immunoblotting. RESULTS: AICAR and metformin markedly reduced the IL-8 and GROalpha production induced by TNF-alpha. AICAR and metformin also reduced the TNF-alpha-induced phosphorylation of I-kappaB. The phosphorylations of I-kappaB, 4EBP-1, p70S6K were inhibited via an AMPK-dependent signal transduction. CONCLUSIONS: These results suggest that metformin promotes granulosa cell function by reducing a TNF-alpha- and chemokine-mediated inflammatory reaction through an AMPK-dependent pathway. These finding may have implications for metformin's actions during the treatment of PCOS with metformin.

Retrospective analysis of outcomes of secondary debulking surgery for recurrent epithelial ovarian cancer with favorable prognostic factors.

AIM: Ovarian cancer is the second most common gynecological malignancy, yet it has the highest case-fatality ratio of all gynecologic malignancies. Surgery followed by combination platinum-taxane chemotherapy is the standard approach to the management of primary epithelial ovarian cancer. However, standard treatment of patients with recurrent ovarian cancer remains poorly defined. Secondary cytoreductive surgery (SDS) at the time of relapse has been proposed as a means of improving the prognosis of recurrent ovarian cancer patients with a treatment-free interval of at least 6 months. METHODS: In the present study, we retrospectively collected 16 patients with recurrent epithelial ovarian cancer who might benefit most from SDS and evaluated the impact of SDS on the outcomes for this highly select patient group. RESULTS: We found that SDS led to excellent outcomes, with a 73.1% 8-year overall survival rate after initial treatment, a 67.9% 5-year overall survival rate after prior SDS, and a 31.3% 5-year progression-free survival rate after prior SDS. Although the findings were not significant, these results suggest that repeated SDS might improve outcomes for this patient group. CONCLUSION: The present study may provide a platform for discussion of the impact of aggressive or repeated SDS on the survival of patients with recurrent epithelial ovarian cancer and favorable prognostic factors. Further multi-institutional studies with larger number of patients are mandatory to confirm the present findings.

The Postpartum Period Can Worsen Myelin Oligodendrocyte Glycoprotein Antibody-associated Encephalomyelitis.

Myelin oligodendrocyte glycoprotein (MOG) antibodies are associated with relapsing inflammatory demyelinating disease. Pregnancy complicates the disease course, potentially leading to either symptom improvement or worsening. A 28-year-old woman with MOG antibody-associated encephalomyelitis had 2 pregnancies; her disease worsened during both postpartum periods despite continuing prednisolone and levetiracetam. The umbilical cord blood was positive for MOG antibodies following her second pregnancy, but neither baby had MOG antibody-associated disease. This is the first case report of MOG antibody-associated demyelinating disease that worsened postpartum despite continuous medication. Furthermore, we observed the placental transfer of MOG antibodies for the first time.

Coexistence of Ovarian Endometrioma and Ovarian Pregnancy: A Case Report.

Both ovarian pregnancy and endometrioma can rupture and cause life-threatening hemoperitoneum. However, little is known about their coexistence. We report the case of a 34-year-old Japanese woman with a life-threatening hemoperitoneum in the first trimester coexisting with ovarian endometrioma and ovarian pregnancy. The patient was hospitalized in our department for acute hypogastric pain and massive hemoperitoneum during pregnancy. She had a history of miscarriage at eight weeks of gestation one year prior. Her serum beta-human chorionic gonadotropin (hCG) level was >2,000 mIU/mL. Also, a transvaginal ultrasound showed an empty uterus, an intact right ovary, an inhomogeneous left ovary, and a massive hemoperitoneum. An exploratory laparoscopy revealed a rupture of the left ovarian endometrioma, a left corpus luteal cyst, and intraperitoneal bleeding of approximately 1,200 mL. However, no ectopic lesions were observed. Microscopic examination revealed an endometriotic cyst with decidual changes in the stroma, a corpus luteal cyst, and chorionic villi with hemorrhage. Serum beta-hCG levels became negative on the 27th postoperative day. The postoperative course was uneventful. This case shows that, in addition to the differential diagnosis of ovarian pregnancy from ovarian endometrioma, clinicians should consider the coexistence of both conditions.

Prophylactic oophorectomy and aromatase inhibitors for premenopausal deep angiomyxoma: A case report and literature review.

Deep angiomyxoma is a rare, infiltrative, hormone-dependent, benign-mesenchymal neoplasm that occurs in the deep soft tissues of the perineal regions. In total, 33% females with newly diagnosed deep angiomyxoma will typically relapse within 5 years after the standard treatment of radical resection. Postoperative hormone therapy is frequently administered to prevent recurrence, but the role of prophylactic oophorectomy in premenopausal women remain to be fully elucidated. In the present report, a 42-year-old Japanese woman was referred for a refractory Bartholin's cyst that is 14 cm in diameter. Based on the results of imaging (unenhanced CT and MRI) and histopathology, deep angiomyxoma was suspected, but no definitive diagnosis was possible. Tumor resection and bilateral salpingo-oophorectomy were performed before the postoperative diagnosis was confirmed to be deep angiomyxoma. The patient received an aromatase inhibitor (2.5 mg letrozole daily) as adjuvant hormonal therapy. There was no evidence of recurrence at the 1-year postoperative follow-up. In conclusion, prophylactic oophorectomy and postoperative adjuvant therapy with aromatase inhibitors may be a promising treatment option for deep angiomyxoma to optimize the outcome of surgical treatment. Long-term follow-up is required to monitor for the late and/or local recurrence of deep angiomyxoma and possible adverse effects of adjuvant hormonal therapy.

Lymphocyte-activation gene 3 protein expression in tumor-infiltrating lymphocytes is associated with a poor prognosis of ovarian clear cell carcinoma.

BACKGROUND: Histological analysis has revealed the need for new treatment techniques for epithelial ovarian cancer. Immune checkpoint inhibitors may be a new therapeutic strategy for ovarian clear cell carcinoma (OCCC). Lymphocyte-activation gene 3 (LAG-3), an immune checkpoint, is a poor prognostic factor and a new therapeutic target for several malignancies. In this study, we demonstrated the correlation between LAG-3 expression and the clinicopathological features of OCCC. We evaluated LAG-3 expression in tumor-infiltrating lymphocytes (TILs) via immunohistochemical analysis using tissue microarrays containing surgically resected specimens from 171 patients with OCCC. RESULTS: The number of LAG-3-positive cases was 48 (28.1%), whereas the number of LAG-3-negative cases was 123 (71.9%). LAG-3 expression significantly increased in patients with advanced stages (P = 0.036) and recurrence (P = 0.012); however, its expression did not correlate with age (P = 0.613), residual tumor (P = 0.156), or death (P = 0.086). Using the Kaplan - Meier method, LAG-3 expression was found to be correlated with poor overall survival (P = 0.020) and progression-free survival (P = 0.019). Multivariate analysis revealed LAG-3 expression (hazard ratio [HR] = 1.86; 95% confidence interval [CI], 1.00 - 3.44, P = 0.049) and residual tumor (HR = 9.71; 95% CI, 5.13 - 18.52, P < 0.001) as independent prognostic factors. CONCLUSION: Our study demonstrated that LAG-3 expression in patients with OCCC may be a useful biomarker for the prognosis of OCCC and could serve as a new therapeutic target.

Undiagnosed myotonic dystrophy: A case report and literature review.

Myotonic dystrophy (MD) is an autosomal dominant disorder primarily characterized by myotonia. The present study describes the case of a 42-year-old woman who was transferred to the authors' department with acute abdomen and restrictive respiratory failure. Computed tomography revealed a 15-cm right ovarian tumor and atelectasis. An abdominal right salpingo-oophorectomy was performed under general anesthesia. She was then extubated after surgery; however, shortly thereafter she was re-incubated due to poor oxygenation and was then moved to the intensive care unit (ICU) for a further analysis of weaning failure. During her stay in the ICU, weaning was attempted twice, but failed both times. The patient underwent a tracheotomy 7 days after surgery. Consultation with a neurologist suggested possible MD. Following genetic testing, type I MD with ~700-1,100 cytosine-thymine-guanine repeats in the dystrophia myotonia protein kinase gene was confirmed. The patient was then transferred to a specialty hospital at 2 months after surgery. On the whole, the case described herein suggests that clinicians need to become familiar with this disease as a differential diagnosis for post-operative weaning failure.

The effects of epidermal growth factor and transforming growth factor-α on secretion of interleukin-8 and growth-regulated oncogene-α in human granulosa-lutein cells.

BACKGROUND: In order to investigate the roles of epidermal growth factor (EGF) and transforming growth factor (TGF)-α in ovulation, we studied the production of interleukin (IL)-8 and growth-regulated oncogene (GRO)-α in cultured human granulosa-lutein cells. METHODS: Granulosa-lutein cells obtained from the follicular fluids of in vitro fertilization and embryo transfer patients were cultured and treated with EGF, TGF-α, tumor necrosis factor (TNF)-α or 12-O-tetradecanoylphorbol 13-acetate (TPA). An immortalized granulosa cell line (GC1a) was also cultured and treated with EGF, TGF-α or mitogen-activated protein kinase kinase inhibitor. The supernatants were collected, and IL-8 and GRO-α were measured by ELISA. RESULTS: The levels of IL-8 and GRO-α were significantly increased after treatment with EGF, TGF-α, TNF-α and TPA by primary cultured granulosa-lutein cells. The levels of IL-8 and GRO-α were also significantly increased after treatment with EGF or TGF-α in a dose-dependent manner by GC1a. When GC1a was treated with EGF, TGF-α or U0126, the levels of IL-8 and GRO-α were significantly decreased. CONCLUSION: Our data indicate that the production of IL-8 and GRO-α is upregulated by EGF and TGF-α. It is suggested that EGF and TGF-α may play an important role in luteinization processes involving IL-8 and GRO-α production.

Life-threatening anemia due to uterine fibroids: A case series.

Uterine fibroids are associated with heavy menstrual bleeding, abdominal discomfort, subfertility and a reduced quality of life. The present study reported a case series of life-threatening anemia with hemoglobin levels <2.0 g/dl caused by uterine fibroids and genital bleeding. Case 1 was of a 34-year-old woman who was transported to the emergency department of the Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University because of a decline in consciousness level. She had been experiencing excessive and prolonged menstruation for many years but had not sought medical help. A 5-cm uterine submucosal leiomyoma was detected and the patient underwent hysteroscopic myomectomy. Case 2 was of a 36-year-old woman with a history of blood transfusions owing to severe anemia who was presented with progressive dyspnea. Although it was repeatedly explained her that her condition was life threatening, she refused to be hospitalized. Her hemoglobin level was 1.7 g/dl. Multiple uterine fibroids and adenomyosis were detected and total hysterectomy was performed. Case 3 was of a 49-year-old woman who was transported to the emergency department of the Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University due to abdominal pain and severe anemia. Blood testing revealed a hemoglobin level of 1.9 g/dl. Multiple uterine fibroids with a maximum diameter of 8.5 cm were detected. However, the patient insisted on discharge because of lack of disease awareness. Total hysterectomy was performed. The present study is the largest case series showing a detailed clinical course of patients with life-threatening anemia with hemoglobin levels <2.0 g/dl. Additionally, Case 1 of the present series exhibited the lowest hemoglobin level (1.1 g/dl) reported to date. The present cases and a review of the literature suggested that the most important risk factors of life-threatening anemia are the patient's mental, social and personal factors, rather than the organic and functional abnormalities of the uterus.

Demons syndrome with pericardial effusion followed by intensive care unit-acquired weakness: A case report and literature review.

Demons syndrome is defined by hydrothorax and ascites associated with a benign genital tumor that resolves after resection of the tumor. However, Demons syndrome with pericardial effusion has never been reported. Intensive care unit-acquired weakness is a neurological sequela to sepsis/systemic inflammatory response syndrome, or multi-organ failure. A 47-year-old, nulligravid, Japanese woman, was transferred to our hospital for refractory heart failure and a ruptured ovarian tumor. She had an 11-cm left ovarian tumor with ascites, hydrothorax, and pericardial effusion; she was intubated for pulmonary hypertension and admitted to the intensive care unit for septic shock. Four days later, a left salpingo-oophorectomy was performed for Demons syndrome with pericardial effusion. The histological diagnosis indicated a serous cystadenoma with fibrotic changes. Following surgery, ventilator weaning was delayed due to intensive care unit-acquired weakness. The association between Demons syndrome and pericardial effusion should be recognized to ensure early treatment and for preventing sequalae from the disease.

Effect of heparin-binding EGF-like growth factor and amphiregulin on the MAP kinase-induced production of vascular endothelial growth factor by human granulosa cells.

The function of granulosa cells is regulated by various hormones and growth factors. Our aim is to clarify the regulation of vascular endothelial growth factor (VEGF) production induced by heparin-binding EGF-like growth factor (HB-EGF) and amphiregulin (AR) in a human granulosa cell line, KGN. KGN cells were cultured and incubated for 24 h with HB-EGF and AR. The levels of VEGF in the culture media were measured by an enzyme-linked immunosorbent assay. The activation of MAP kinase in KGN cells was detected by Western blot analysis. VEGF production was significantly increased by HB-EGF or AR alone in a dose-dependent manner, whereas it was decreased by AG1478 or U0126. The MAP kinase activity was increased by treatment with HB-EGF or AR. The results suggested that VEGF is induced by HB-EGF and AR through mechanisms involving MAP kinase. The increase in VEGF may contribute to neovascularization, which in turn would promote various ovulation phenomena as well as follicular growth.

Thrombin-induced chemokine production in endometrial stromal cells.

BACKGROUND: In order to investigate the regulation of chemokines [interleukin-8 (IL-8), growth-regulated oncogene (GRO)α, monocyte chemoattractant protein-1 (MCP-1)) induced by thrombin in endometrial stromal cells (ESCs), the effects of thrombin, a protease activated receptor (PAR)-1 antagonist (PPACK), mitogen-activated protein kinase kinase inhibitor (U0126), phospholipase C inhibitor (U-73122), an antagonist of the intracellular InsP3 receptor (2-aminoethoxy-diphenylborate (2-APB)] and a protein kinase C inhibitor (GF-109203X) on the production of chemokines by ESCs were evaluated. METHODS: ESCs from eight endometrial specimens in the secretory phase were cultured and incubated for 24h with thrombin and PPACK, U0126, U-73122, 2-APB or GF-109203X. The levels of IL-8, GROα and MCP-1 in the culture medium were measured by means of ELISA. The activation of MAP kinase was detected by western blot analysis using anti-phosphorylated MAP kinase (ERK1/2) antibody. RESULTS: Following stimulation by thrombin, the production of IL-8, GROα and MCP-1 increased significantly in a dose-dependent manner. PPACK, U0126, U-73122, 2-APB or GF-109203X suppressed the increases in production of IL-8, GROα and MCP-1 induced by thrombin (P < 0.001, P <0.001 and P <0.001, respectively). MAP kinase activities were induced by treatment with thrombin, and were suppressed by PPACK, U0126, U-73122, 2-APB or GF-109203X. CONCLUSIONS: Our results suggest that thrombin stimulates the production of IL-8, GROα and MCP-1 via PAR-1 by a mechanism involving the MAP kinase system. The increases in IL-8, GROα and MCP-1 may contribute to the maintenance of implantation involving leukocyte chemotaxis.

Cadmium chloride induces the expression of metallothionein mRNA by endometrial stromal cells and amnion-derived (WISH) cells.

BACKGROUND: Metallothionein (MT) is known to bind to metals with high affinity. The potential for MT-1 mRNA expression in endometrial stromal cells (ESC) and amniotic cells in response to cytokines and cadmium chloride (CdCl(2)) was evaluated. METHODS: Human ESC were cultured and treated with interleukin-1α, 12-O-tetradecanoylphobol 13-acetate (TPA), forskolin, transforming growth factor-ß, and CdCl(2). Amnion-derived (WISH) cells were also cultured and treated with the same reagents. The levels of MT mRNA were evaluated by Northern blot analysis in ESC and WISH cells. RESULTS: In response to treatment with CdCl(2) (0.01-10 µM), the expression of MT mRNA markedly increased in ESC and WISH cells in a dose-dependent manner. On the other hand, the expression of MT mRNA did not increase after treatment with interleukin-1α (1 nM), TPA (10 nM), forskolin (1 µM) or transforming growth factor-ß (1 nM) in these cells. CONCLUSION: These findings indicate that MT expression in ESC and WISH cells is sensitive to the CdCl(2) concentration, which is known to be evaluated in cigarette smokers. The present results suggest that increased levels of MT may affect metal metabolism at the feto-maternal interface.

The Possibility of Analyzing Endometrial Receptivity Using Cells from Embryo Transfer Catheters.

It is very important to investigate the expression of endometrial receptive markers in the endometrium during implantation. Therefore, we examined whether it would be possible to analyze endometrial receptivity using cells from embryo transfer catheters. A total of 81 cycles from 81 consenting patients were enrolled in this study. The tip of the embryo transfer (ET) catheter was cut and immersed in a dedicated reagent. Confirmation of cell distribution was carried out using a Papanicolaou stain and immunocytochemistry. Protein expression was carried out by immunocytochemistry. The expressions of estrogen receptor α, progesterone receptor, and homeobox A10 mRNA were analyzed using quantitative reverse transcription-polymerase chain reaction. We analyzed the relationship between the gene expression profiles associated with pregnancy from endometrial cells. Samples collected from the ET catheter showed clear staining for endometrial cells. Most of the cells were endometrial epithelial cells. Cervical cells were not observed. The protein expression was also confirmed. Three genes were analyzed that are associated with endometrial receptivity. Progesterone receptor expression was 1.4-fold (p<0.05) and homeobox A10 was 2.8-fold (p<0.01) higher in patients who became non-pregnant group, compared to the pregnant group. Estrogen receptor α expression tended to be higher in the non-pregnant group (p=0.18). Our results suggest that endometrial receptivity can be evaluated using cells obtained from the ET catheter. This method may be useful for elucidating the cause of implantation failure by comparing a receptive and non-receptive endometrium at the time of ET.

Angiographic features and transarterial embolization of retained placenta with abnormal vaginal bleeding.

OBJECTIVES: To clarify characteristic angiographic features and clinical efficacy of selective transarterial embolization (TAE) of retained placenta with abnormal vaginal bleeding. METHODS: The study cohort comprised 22 patients (mean age, 33.5 years; range, 22-24 years) who underwent selective TAE for retained placenta with abnormal bleeding between January 2018 and December 2020 at our institution. Angiographic images were reviewed by two certified radiologists with consensus. Medical records were reviewed to evaluate the efficacy of TAE. Angiographic features of retained placenta, technical success (disappearance of abnormal findings on angiography), complications, clinical outcomes (hemostatic effects and recurrent bleeding) were evaluated. RESULTS: Pelvic angiography showed a dilated vascular channel mimicking arteriovenous fistulas or an aneurysm contiguous with dilated uterine arteries in the mid-arterial-capillary phase in 20 patients; it showed contrast brush in the remaining two patients. TAE technical success was achieved in all patients. No major complications were observed in any patients. Fifteen patients were followed up with expectant management after TAE; all but one patient showed no re-bleeding during the follow-up period (mean follow-up interval, 3.4 months; range, 1-17 months). One patient showed minor rebleeding, which resolved spontaneously. Seven patients underwent scheduled hysteroscopic resection within 1 week after TAE, and no excessive bleeding was observed during or after the surgical procedure in all seven patients. CONCLUSIONS: The characteristic angiographic feature of retained placenta is "dilated vascular channel that mimic low flow AVM." TAE is a safe and effective treatment to manage retained placenta with abnormal bleeding.