Unraveling the significance of AGPAT4 for the pathogenesis of endometriosis via a multi-omics approach.

Endometriosis is characterized by the ectopic proliferation of endometrial cells, posing considerable diagnostic and therapeutic challenges. Our study investigates AGPAT4's involvement in endometriosis pathogenesis, aiming to unveil new therapeutic targets. Our investigation by analyzing eQTL data from GWAS for preliminary screening. Subsequently, within the GEO dataset, we utilized four machine learning algorithms to precisely identify risk-associated genes. Gene validity was confirmed through five Mendelian Randomization methods. AGPAT4 expression was measured by Single-Cell Analysis, ELISA and immunohistochemistry. We investigated AGPAT4's effect on endometrial stromal cells using RNA interference, assessing cell proliferation, invasion, and migration with CCK8, wound-healing, and transwell assays. Protein expression was analyzed by western blot, and AGPAT4 interactions were explored using AutoDock. Our investigation identified 11 genes associated with endometriosis risk, with AGPAT4 and COMT emerging as pivotal biomarkers through machine learning analysis. AGPAT4 exhibited significant upregulation in both ectopic tissues and serum samples from patients with endometriosis. Reduced expression of AGPAT4 was observed to detrimentally impact the proliferation, invasion, and migration capabilities of endometrial stromal cells, concomitant with diminished expression of key signaling molecules such as Wnt3a, ß-Catenin, MMP-9, and SNAI2. Molecular docking analyses further underscored a substantive interaction between AGPAT4 and Wnt3a.Our study highlights AGPAT4's key role in endometriosis, influencing endometrial stromal cell behavior, and identifies AGPAT4 pathways as promising therapeutic targets for this condition.

METTL3 and METTL14-mediated N6-methyladenosine modification promotes cell proliferation and invasion in a model of endometriosis.

RESEARCH QUESTION: Could METTL3 and METTL14-mediated N6-methyladenosine (m6A) modification play possible cooperative roles in pathogenesis and progression of endometriosis? DESIGN: An investigation into m6A methylation profiles and the roles of METTL3 and METTL14 in the m6A regulation and pathogenesis of endometriosis. The m6A methylation and mRNA levels in paired ectopic endometrium and eutopic endometrium were measured using m6A-mRNA epitranscriptomic microarrays. The functions of m6A methylation in mRNAs were predicted using bioinformatics analysis. The levels of m6A methyltransferases were detected using quantitative polymerase chain reaction. The role of METTL3 and METTL14 in endometriosis was explored using eutopic endometrium stromal cells. RESULTS: The m6A methylation levels were decreased in 1312 mRNAs and increased in 518 mRNAs; 1797 mRNAs were increased and 2580 mRNAs were reduced in the ectopic endometrium compared with the eutopic endometrium. Pathway analysis found that the genes with hypo-methylated m6A were significantly associated with important pathways in endometriosis, including oestrogen, Hippo, and PI3K-Akt signalling and cell-cell adhesion. Furthermore, METTL3 and METTL14 were downregulated in the ectopic endometrium compared with the eutopic endometrium (P < 0.001). Simultaneous METTL3 and METTL14 knockdown increased cell proliferation and invasion. CONCLUSION: Taken together, these data reveal a differential m6A epitranscriptomic pattern in endometriosis. The N6-methyladenosine modification mediated by METTL3 and METTL14 play a cooperative role in promoting cell proliferation and invasion in a model of endometriosis. Therefore, METTL3 and METTL14 may be a novel treatment target of the disease.

ARID1A loss derepresses a group of human endogenous retrovirus-H loci to modulate BRD4-dependent transcription.

Transposable elements (TEs) through evolutionary exaptation have become an integral part of the human genome, offering ample regulatory sequences and shaping chromatin 3D architecture. While the functional impacts of TE-derived sequences on early embryogenesis have been recognized, their roles in malignancy are only starting to emerge. Here we show that many TEs, especially the pluripotency-related human endogenous retrovirus H (HERVH), are abnormally activated in colorectal cancer (CRC) samples. Transcriptional upregulation of HERVH is associated with mutations of several tumor suppressors, particularly ARID1A. Knockout of ARID1A in CRC cells leads to increased transcription at several HERVH loci, which involves compensatory contribution by ARID1B. Suppression of HERVH in CRC cells and patient-derived organoids impairs tumor growth. Mechanistically, HERVH transcripts colocalize with nuclear BRD4 foci, modulating their dynamics and co-regulating many target genes. Altogether, we uncover a critical role for ARID1A in restraining HERVH, whose abnormal activation can promote tumorigenesis by stimulating BRD4-dependent transcription.

Endoplasmic reticulum stress related IncRNA signature predicts the prognosis and immune response evaluation of uterine corpus endometrial carcinoma.

Background: Endoplasmic reticulum (ER) stress is closely related to the occurrence, development and treatment of tumors. Recent studies suggest ER stress as a therapeutic strategy of choice for cancer. However, ER stress-related long non-coding RNA (lncRNA) predictive value in endometrial carcinoma (UCEC) remains to be further evaluated. The purpose of this study was to establish relies on the signature of ER stress-related lncRNA forecast to predict the prognosis of patients with UCEC. Methods: We downloaded the RNA expression profile dataset and matched clinical data from the Cancer Genome Atlas (TCGA) database, and applied univariate and multivariate Cox regression analysis to build predictive signature. Kaplan-meier method was used to evaluate overall survival (OS) and disease-free survival (DFS). Gene set enrichment analysis (GSEA) was used to study the functional characteristics. Single sample Gene set enrichment analysis (ssGSEA) was used to analyze the relationship between immune status and predicted signature. Correlations between the potential usefulness of treatment for UCEC patients and predictive signature were also analyzed. Results: We established a signature composed of eight ER stress-related lncRNAs (MIR34AHG, AC073842.2, PINK1AS, AC024909.2, MIR31HG, AC007422.2, AC061992.1, AC003102.1). The signature of ER stress-related lncRNA provided better diagnostic value compared with age and tumor grade, and the area under the receiver operating curve was 0.788. The overall and disease-free survival probability of patients in the high-risk group is lower than that in the low-risk group. GSEA indicated that the pathways were mainly enriched for cancer, immunity and reproduction related pathways. ss-GSEA shows that prediction signature and activation of dendritic cells, immature dendritic cells, T helper cells and immune status of the Treg are significantly related. High-risk groups may against PD - 1/L1 immunotherapy and JNK inhibitors VIII, Z.LLNle.CHO, DMOG and JNK. 9 l more sensitive. Conclusion: The ER stress signature can independently predict the prognosis of UCEC patients, and provide guidance for conventional chemotherapy and immunotherapy of UCEC patients.

Downregulation of circ_0000673 Promotes Cell Proliferation and Migration in Endometriosis via the Mir-616-3p/PTEN Axis.

Endometriosis is a common gynecological disease, affecting up to 10% of women of reproductive age and approximately 50% of women with infertility. Circular RNAs (circRNAs) have been shown to be involved in a number of diseases. Dysregulated expression of circRNAs in endometriosis has been reported, and circ_0000673 was significantly downregulated. However, the details of its role in the pathogenesis of endometriosis are still poorly understood. We investigated the location and effects of the downregulation of circ_0000673 in endometriosis. We demonstrated that knockdown of circ_0000673 significantly increased the proliferation and migration of eutopic and normal endometrial cells. Bioinformatics analysis predicted that circ_0000673 might act as a sponge for miR-616-3p. We found that the effect of circ_0000673 knockdown could be recovered by miR-616-3p inhibitor and enhanced by miR-616-3p mimics. qPCR and western blot assays showed that circ_0000673 knockdown could decrease the expression of PTEN and increase the expression of PI3K and p-AKT. PTEN was confirmed to be a target of miR-616-3p. These results demonstrated that the downregulation of circ_0000673 could promote the progression of endometriosis by inactivating PTEN via the deregulation of miR-616-3p.

Interventions for non-tubal ectopic pregnancy.

BACKGROUND: Non-tubal ectopic pregnancy is the implantation of an embryo at a site lying outside the uterine cavity or fallopian tubes. Sites include a caesarean scar, the cornua uteri, the ovary, the cervix, and the abdomen. There has been an increasing trend in the occurrence of these rare conditions, especially caesarean scar pregnancy (CSP). OBJECTIVES: To evaluate the clinical effectiveness and safety of surgery, medical treatment, and expectant management of non-tubal ectopic pregnancy in terms of fertility outcomes and complications. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility (CGF) Group Specialised Register of Controlled Trials, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, the World Health Organization (WHO) search portal and nine other databases to 12 December 2019. We handsearched reference lists of articles retrieved and contacted experts in the field to obtain additional data. SELECTION CRITERIA: We included randomized controlled trials (RCTs) published in all languages that examined the effects and safety of surgery, medical treatment, and expectant management of non-tubal ectopic pregnancy. DATA COLLECTION AND ANALYSIS: We used Cochrane standard methodological procedures. Primary outcomes were treatment success and complications. MAIN RESULTS: We included five RCTs with 303 women, all reporting Caesarean scar pregnancy. Two compared uterine arterial embolization (UAE) or uterine arterial chemoembolization (UACE) plus methotrexate (MTX) versus systemic MTX and subsequent dilation and suction curettage; one compared UACE plus MTX versus ultrasonography-guided local MTX injection; and two compared suction curettage under hysteroscopy versus suction curettage under ultrasonography after UAE/UACE. The quality of evidence ranged from moderate to very low. The main limitations were imprecision (small sample sizes and very wide confidence intervals (CI) for most analyses), multiple comparisons with a small number of trials, and insufficient data available to assess heterogeneity. UAE/UACE versus systemic MTX prior to suction curettage Two studies reported this comparison. One compared UAE with systemic MTX and one compared UACE plus MTX versus systemic MTX, in both cases followed by a suction curettage. We are uncertain whether UAE/UACE improved success rates after initial treatment (UAE: risk ratio (RR) 1.00, 95% CI 0.90 to 1.12; 1 RCT, 72 women; low-quality evidence; UACE: RR 0.87, 95% CI 0.54 to 1.38; 1 RCT, 28 women; low-quality evidence). We are uncertain whether UAE/UACE reduced rates of complications (UAE: RR 0.47, 95% CI 0.13 to 1.75; 1 RCT, 72 women; low-quality evidence; UACE: RR 0.62, 95% CI 0.26 to 1.48; 1 RCT, 28 women; low-quality evidence). We are uncertain whether UAE/UACE reduced adverse effects (UAE: RR 1.58, 95% CI 0.41 to 6.11; 1 RCT, 72 women; low-quality evidence; UACE: RR 1.16, 95% CI 0.32 to 4.24; 1 RCT, 28 women; low-quality evidence), and it was not obvious that the types of events had similar values to participants (e.g. fever versus vomiting). Blood loss was lower in UAE/UACE groups than systemic MTX groups (UAE: mean difference (MD) -378.70 mL, 95% CI -401.43 to -355.97; 1 RCT, 72 women; moderate-quality evidence; UACE: MD -879.00 mL, 95% CI -1135.23 to -622.77; 1 RCT, 28 women; moderate-quality evidence). Data were not available on time to normalize ß-human chorionic gonadotropin (ß-hCG). UACE plus MTX versus ultrasonography-guided local MTX injection We are uncertain whether UACE improved success rates after initial treatment (RR 0.95, 95% CI 0.56 to 1.60; 1 RCT, 45 women; very low-quality evidence). Adverse effects: the study reported the same number of failed treatments in each arm (RR 0.88, 95% CI 0.40 to 1.92; 1 RCT, 45 women). We are uncertain whether UACE shortened the time to normalize ß-hCG (MD 1.50 days, 95% CI -3.16 to 6.16; 1 RCT, 45 women; very low-quality evidence). Data were not available for complications. Suction curettage under hysteroscopy versus under ultrasonography after UAE/UACE. Two studies reported this comparison. One compared suction curettage under hysteroscopy versus under ultrasonography after UAE, and one compared these interventions after UACE. We are uncertain whether suction curettage under hysteroscopy improved success rates after initial treatment (UAE: RR 0.91, 95% CI 0.81 to 1.03; 1 RCT, 66 women; very low-quality evidence; UACE: RR 1.02, 95% CI 0.96 to 1.09; 1 RCT, 92 women; low-quality evidence). We are uncertain whether suction curettage under hysteroscopy reduced rates of complications (UAE: RR 4.00, 95% CI 0.47 to 33.91; 1 RCT, 66 women; very low-quality evidence; UACE: RR 0.18, 95% CI 0.01 to 3.72; 1 RCT, 92 women; low-quality evidence). We are uncertain whether suction curettage under hysteroscopy reduced adverse effects (UAE: RR 3.09, 95% CI 0.12 to 78.70; 1 RCT, 66 women; very low-quality evidence; UACE: not estimable; 1 RCT, 92 women; very low-quality evidence). We are uncertain whether suction curettage under hysteroscopy shortened the time to normalize ß-hCG (UAE: MD 4.03 days, 95% CI -1.79 to 9.85; 1 RCT, 66 women; very low-quality evidence; UACE: MD 0.84 days, 95% CI -1.90 to 3.58; 1 RCT, 92 women; low-quality evidence). Non-tubal ectopic pregnancy other than CSP No studies reported on non-tubal ectopic pregnancies in locations other than on a caesarean scar. AUTHORS' CONCLUSIONS: For Caesarean scar pregnancies (CSP) it is uncertain whether there is a difference in success rates, complications, or adverse events between UAE/UACE and administration of systemic MTX before suction curettage (low-quality evidence). Blood loss was lower if suction curettage is conducted after UAE/UACE than after administration of systemic MTX (moderate-quality evidence). It is uncertain whether there is a difference in treatment success rates, complications, adverse effects or time to normalize ß-hCG between suction curettage under hysteroscopy and under ultrasonography (very low-quality evidence). There are no studies of non-tubal ectopic pregnancy other than CSP and RCTs for these types of pregnancy are unlikely.

Expression profiles of tRNA-derived fragments and their potential roles in ovarian endometriosis.

Aim: Transfer RNA-derived fragments have been reported to play a vital role in disease progression, but their role in the pathogenesis of endometriosis remains unknown. Materials & methods: Small RNA sequencing was conducted in three paired ovarian endometriomas and eutopic endometria. The data from 22 paired samples were validated by quantitative real-time polymerase chain reaction (qPCR) and bioinformatic analysis was performed to establish the roles of these fragments in endometriosis pathogenesis. Results: We identified 19 upregulated and five downregulated tRNA-derived fragments, of which tiRNA-5 was the most common. Gene Ontology and pathway analyses revealed that these molecules could have roles in the pathogenesis of endometriosis. Conclusion: tRNA-derived fragments are dysregulated and could be involved in the pathogenesis and progression of ovarian endometriosis.

Circular RNA expression in ovarian endometriosis.

AIM: Circular RNAs (circRNAs) with miRNA response elements (MREs) could function as competing endogenous RNA (ceRNA) in regulating gene expression. This study was carried out to identify the expression profile and role of circRNAs in endometriosis. MATERIALS & METHODS: Microarray assay was performed in four paired ovarian endometriomas and eutopic endometrium, followed by quantitative real-time RT-PCR in 24 paired samples. Bioinformatical algorithms were used to predict MREs, as well as ceRNA and KEGG pathway analysis. RESULTS: We identified 262 upregulated and 291 downregulated circRNAs, binding with 1225 MREs. The ceRNA network included 122 miRNAs and 137 mRNAs, which are involed in nine pathways. CONCLUSION: CircRNAs are differentially expressed in endometriosis, which might be related with pathogenesis of endometriosis.

[Expression of miR23b and Sp1 in ovarian endometriosisand their clinic significance].

OBJECTIVE: To investigate the expressions of miR23b and Sp1 in ovarian endometriosis and their clinic significance.
 Methods: qPCR was used to detect the expression of miR23b and Sp1 mRNA in paired ectopic/eutopic and normal endometrium. Immunohistochemistry and Western bolt were used to determine the expression and distribution of Sp1 in paired ectopic/eutopic and normal endometrium. The association of miR23b and Sp1 with the endometriosis was analyzed.
 Results: MiR23b mRNA expression in paired ectopic/eutopic and normal endometrium was gradually increased (P<0.05). Sp1 protein mainly distributed in the nucleus of endometrial glandular epithelial and stromal cells, with a little or without expression in cytoplasm. Sp1 mRNA and protein expression in paired ectopic/eutopic and normal endometrium was gradually reduced (P<0.05). Pearson correlation analysis showed that miR23b was negatively correlated with Sp1 (r=-0.526, P<0.05).
 Conclusion: MiR23b and Sp1 are involved in the pathogenesis of ovarian endometriosis, which may facilitate the formation of ectopic lesions.

Evaluation of transvaginal sonography in detecting endometrial polyps and the pregnancy outcome following hysteroscopic polypectomy in infertile women.

The aims of the present study were to evaluate the effectiveness of transvaginal sonography (TVS) in the detection of endometrial polyps (EPs), and to assess the pregnancy outcome in infertile women following hysteroscopic polypectomy. A total of 145 women diagnosed with primary or secondary infertility and intrauterine disorders by TVS and hysterosalpingography (HSG) were included in the current study. All subjects were divided into three groups based on hysteroscopic findings, including the EP, intrauterine adhesion and normal groups. EPs were removed for biopsy and intrauterine adhesions were treated. Pregnancy rates between groups were compared. In total, 34 EPs were detected by TVS, while 45 subjects were later confirmed with EP by hysteroscopy. The sensitivity, specificity, positive predictive value and negative predictive value of TVS in the detection of EPs were 67, 96, 88.23 and 86.49%, respectively. Of the included patients, 120 subjects were followed up, including 40 patients diagnosed with EPs, 42 with intrauterine adhesions and 38 with normal cavities. The results indicated no statistically significant differences in the age, type and duration of infertility, least function (LF) score and classification of the extent of tubal disease with the distal fimbrial obstruction between the three groups. In addition, pregnancy rate and spontaneous abortion rate in the EP group following hysteroscopic polypectomy were 45 and 5.6%, respectively. No significant difference was observed in the fertility rate following surgery. In conclusion, TVS features high sensitivity, specificity and certain unique sonographic characteristics in diagnosing EPs, and may be used as a preliminary diagnostic procedure to select patients for hysteroscopy. Furthermore, hysteroscopic polypectomy is an important approach for the treatment of infertile patients with EPs and appears to help increase the pregnancy rate of previously infertile women.

Increased cystic fibrosis transmembrane conductance regulators expression and decreased epithelial sodium channel alpha subunits expression in early abortion: findings from a mouse model and clinical cases of abortion.

The status of the maternal endometrium is vital in regulating humoral homeostasis and for ensuring embryo implantation. Cystic fibrosis transmembrane conductance regulators (CFTR) and epithelial sodium channel alpha subunits (ENaC-α) play an important role in female reproduction by maintaining humoral and cell homeostasis. However, it is not clear whether the expression levels of CFTR and ENaC-α in the decidual component during early pregnancy are related with early miscarriage. CBA×DBA/2 mouse mating has been widely accepted as a classical model of early miscarriage. The abortion rate associated with this mating was 33.33% in our study. The decidua of abortion-prone CBA female mice (DBA/2 mated) had higher CFTR mRNA and protein expression and lower ENaC-α mRNA and protein expression, compared to normal pregnant CBA mice (BLAB/C mated). Furthermore, increased CFTR expression and decreased ENaC-α expression were observed in the uterine tissue from women with early miscarriage, as compared to those with successful pregnancy. In conclusion, increased CFTR expression and decreased ENaC-α expression in the decidua of early abortion may relate with failure of early pregnancy.

Vasculogenesis of decidua side population cells of first-trimester pregnancy.

INTRODUCTION: Sufficient uterine blood supply is essential for the fetus to develop normally in the uterus. Several mechanisms are involved in the process of vessel development in deciduas and villus. We focus on whether first-trimester decidua side population (SP) cells contain cells capable of differentiating into endothelial cells. METHODS: Eight decidua samples were collected from healthy women, 22- to 30-years old, undergoing elective terminations of early pregnancy (six to eight gestational weeks). The cell suspensions from human deciduas were stained by Hoechst 33342 and sorted by flow cytometry, further cultured under differentiation conditions and analyzed for specific markers. These cells were implanted into ischemic limbs of nude mice to test the capacity of angiogenesis in vivo by DiI tracers and immunohistochemistry. RESULTS: Decidua CD31(-)CD146(-) SP cells of first-trimester human pregnancy can differentiate into endothelial cells, express the corresponding specific markers of endothelial cells, such as CD31 and CD146, and form tube-like structures on Matrigel and part of newly formed vessels in the ischemic limbs of nude mice. Vascular endothelial growth factor was more effective in promoting proliferation of CD31(-)CD146(-)SP cells compared with other growth factors, and estrogen and progesterone at a final concentration of 10 µmol/L and 30 µmol/L, respectively, promoted the migration of CD31()-CD146(-)SP cells in a dose-dependent manner. CONCLUSIONS: CD31(-)CD146(-) SP cells may be involved in the formation of new vessels in the maternal aspect of the placenta in the first trimester.

MicroRNA23a and microRNA23b deregulation derepresses SF-1 and upregulates estrogen signaling in ovarian endometriosis.

CONTEXT: Steroidogenic factor (SF)-1 and its downstream target genes involved in estrogen signaling are aberrantly expressed in ovarian endometriosis. OBJECTIVE: Our objective was to explore the microRNA-mediated mechanism controlling aberrant SF-1 expression in ovarian endometriosis. DESIGN: Bioinformatics analysis predicted that microRNA23a and microRNA23b (miR23a/b) target the NR5A1 3'-untranslated region. We investigated the relative expression and spatial distribution of miR23a/b and analyzed the relationship between miR23a/b and SF-1 expression in endometriotic tissues. SETTING: The study was conducted at the Department of Gynecology and Obstetrics, West China Second University Hospital of Sichuan University. PATIENTS OR OTHER PARTICIPANTS: We enrolled 23 women with American Fertility Society stage III-IV ovarian endometriosis and 15 disease-free control subjects. INTERVENTIONS: Quantitative real-time RT-PCR, in situ hybridization, cell culture, transfections, and luciferase reporter assays were used in this study. MAIN OUTCOME MEASURES: The expression of miR23a/b and SF-1, CYP19A1, and StAR mRNAs; the relationships between miRNAs and SF-1 mRNA levels; and the effect of miR23a/b on SF-1 expression were measured in normal and eutopic endometrial stromal cells (ESCs) and 293T cells. RESULTS: Both miR23a and miR23b were downregulated in ectopic and eutopic endometrium, compared with normal endometrium, and their expression was inversely correlated with NR5A1 mRNA levels. SF-1 expression was inhibited by miR23a/b overexpression in eutopic ESCs and upregulated by miR23a/b inhibition in normal ESCs. CONCLUSIONS: MiR23a and miR23b are potential biomarkers of ovarian endometriosis. This study provides a novel approach for targeting the mechanisms controlling aberrant local estrogen biosynthesis in endometriosis.

Fertility in older women following removal of long-term intrauterine devices in the wake of a natural disaster.

BACKGROUND: In order to evaluate the effect of long-term intrauterine device (IUD) use on female fertility, we interviewed 2301 women who lost children in the 2008 Wenchuan earthquake in China, which prompted IUD removal. STUDY DESIGN: A clinical retrospective survey. RESULT: Five hundred and twenty-four women were lost to follow-up, and data from the remaining 1770 women were analyzed. The completed questionnaires revealed that 80.11% (1418/1770) became pregnant following IUD removal and about 88% (1256) of whom conceived within 1 year. Among women with different durations of IUD use, pregnancy rates and miscarriage rates were as follows: <5 years, 89.77% and 4.27%; 6-10 years, 81.10% and 10.19%; and >10 years, 75.20% and 12.98%, respectively. Age, duration of IUD use, a history of a previous miscarriage and abnormal menstruation before the earthquake were independently associated with reduced fertility, but a higher gravidity pre-earthquake was associated with a higher conception rate. CONCLUSION: Long-term IUD use in older women had a high rate of pregnancy after removal of IUD, but with an increased risk of fertility problems.

Bilateral uterine artery chemoembolization with methotrexate for cesarean scar pregnancy.

OBJECTIVE: The objective of the study was to assess the efficacy of uterine arteries embolization (UAE) for the treatment of cesarean scar pregnancies (CSP). STUDY DESIGN: Forty-six women with CSP were identified between March 2008 and March 2010. All of the patients underwent UAE combined with local methotrexate. RESULTS: Forty-five patients were successfully treated. One patient had an emergency hysterectomy after 20 days because of massive vaginal hemorrhage. The mean time until normalization of serum ß-human chorionic gonadotrophin was 37.7 days, and the mean time until CSP mass disappearance was 33.3 days. The mean hospitalization time was 10.5 days. The complications were mainly fever and pain, which were alleviated with symptomatic treatment. All 45 patients had recovered their normal menstruation at follow-up. CONCLUSION: Bilateral uterine artery chemoembolization with methotrexate appears to be a safe and effective treatment for CSP and causes less morbidity than current approaches.

NF κB expression increases and CFTR and MUC1 expression decreases in the endometrium of infertile patients with hydrosalpinx: a comparative study.

BACKGROUND: Hydrosalpinx are associated with infertility, due to reduced rates of implantation and increased abortion rates. The aims of this study were to investigate the expression of cystic fibrosis transmembrane conductance regulator (CFTR), nuclear factor kappa B (NF KappaB) and mucin-1 (MUC-1), and analyze the correlation between the expression of CFTR and NF KappaB or MUC1, in the endometrium of infertile women with and without hydrosalpinx. METHODS: Thirty-one infertile women with laparoscopy-confirmed unilateral or bilateral hydrosalpinx and 20 infertile women without hydrosalpinx or pelvic inflammatory disease (control group) were recruited. Endometrial biopsy samples were collected and the expression of CFTR, NF KappaB and MUC1 were analyzed using immunohistochemistry and quantitative real-time PCR. RESULTS: CFTR, NF KappaB and MUC1 mRNA and protein expression tended to increase in the secretory phase compared to the proliferative phase in both groups; however, these differences were not significantly different. The endometrium of infertile patients with hydrosalpinx had significantly higher NF KappaB mRNA and protein expression, and significantly lower CFTR and MUC1 mRNA and protein expression, compared to control infertile patients. A positive correlation was observed between CFTR and MUC1 mRNA expression (r = 0.65, P < 0.05); a negative correlation was observed between CFTR mRNA and NF KappaB mRNA expression (r = -0.59, P < 0.05). CONCLUSIONS: Increased NF KappaB expression and decreased CFTR and MUC1 expression in the endometrium of infertile patients with hydrosalpinx reinforce the involvement of a molecular mechanism in the regulation of endometrial receptivity.

Diagnostic value of endometrial thickness determined by transvaginal sonography in infertile women with endometrial polyps.

BACKGROUND: Endometrial polyps (EPs) occur in approximately 34.9% of infertile women. Transvaginal sonography (TVS) is a routine, non-invasive component of fertility evaluation. Most ultrasonographic studies of EPs have focused on abnormal uterine bleeding; few have assessed EPs in infertile women. Furthermore, no studies have explored endometrial thickness and its correlation with EPs in infertile women. This study aimed to assess transvaginal sonographic assessment of endometrial thickness and its value in diagnosis and prediction of EPs in infertile women. METHODS: A retrospective study on 314 infertile women was conducted from June to December 2010. After TVS, endometrial biopsies were obtained by hysteroscopy. Pathologically confirmed EPs were taken as the gold standard. RESULTS: Based on recognized criteria, TVS had a sensitivity of 37.04%, specificity of 98.71%, positive predictive value of 90.91%, negative predictive value of 81.85%, and accuracy of 82.80% for diagnosing EPs. Mean endometrial thickness was significantly different in patients with and without EPs (P = 0.0001). In women in the mid and late-proliferative phase, the endometrial thickness was significantly greater in those with EPs than in those without them (P = 0.0001 and 0.024). Receiver operating characteristic analysis showed that endometrial thickness had a sensitivity of 85.2% and specificity of 38% in the diagnosis of EPs, the area under the curve being 0.64. In the mid-proliferative phase, sensitivity was up to 90.9%, the area under the curve being 0.70. CONCLUSIONS: TVS is poor at detecting EPs in infertile women; however, transvaginal sonographic measurement of endometrial thickness is helpful. It is suggested that the diagnostic value of TVS for EPs in infertile women could be improved by adding the measurement of endometrial thickness to the variables that are routinely assessed.

High prevalence of endometrial polyps in endometriosis-associated infertility.

In a retrospective study, examination of 431 infertile women (158 cases with endometriosis and 273 without endometriosis) showed a significantly increased frequency of endometrial polyps in patients with endometriotic infertility and no significant differences among different stages and locations of endometriosis. Hysteroscopic polypectomy and removal of endometriotic foci significantly increased the chances of achieving a pregnancy compared with those without polyps.