Vaginal Approach to Cesarean Section Scar Pregnancies: A Standardized Ten-step Surgical Procedure.

OBJECTIVE: To show a 10-step standardized vaginal surgical technique to treat first-trimester cesarean section scar pregnancies. DESIGN: A video article with a stepwise demonstration captured in an operation room of a tertiary medical center of a low-income country (Bolivia). SETTING: Cesarean section scar pregnancies have a wide variety of management options. We present a vaginal surgical approach that has been developed by our group with no observed complications in 6 consecutive cases at the time of this publication. INTERVENTIONS: A 10-step technique: (1) patient positioning, (2) cervical exposure and traction, (3) cervical infiltration with vasoconstrictor solution, (4) anterior mucosal incision and dissection of vesicovaginal space, (5) identification of vascular pedicle and ligation, (6) cold-knife isthmocele incision and ectopic pregnancy evacuation, (7) uterine cavity curettage, (8) hysterorrhaphy with interrupted suture, (9) cystoscopy, and (10) vaginal mucosa closure with running suture. We have used this technique in 6 consecutive patients. Operating time ranged between 20 and 25 minutes. All patients were discharged in postoperative day 1. CONCLUSION: We prefer surgical options for these patients because it provides both a complete removal of the ectopic pregnancy and repair of the isthmocele. A vaginal approach to such cases has proven to be a safe, simple, and fully reproductible technique. We find it applicable for any patient with this pathology but especially suitable for low-resource or somehow financially challenged hospitals.

Chlamydia trachomatis infection regulates the expression of tetraspanins, activin-A, and inhibin-A in tubal ectopic pregnancy.

Mechanism of Chlamydia trachomatis causing tubal ectopic pregnancy (EP) is not well understood. Tetraspanins (tspans), activin-A, and inhibin-A might play a role in the development of pathological conditions leading to EP. The study aimed to elucidate the expression of tspans, activin-A, and inhibin-A with a role of associated cytokines in C. trachomatis-associated EP and analyze interacting partners of DEGs, with an expression of a few important interacting genes. Fallopian tissue and serum were collected from 100 EP (Group I) and 100 controls (Group II) from SJH, New Delhi, India. Detection of C. trachomatis was done by polymerase chain reaction (PCR) and IgG antibodies were detected by enzyme-linked immunosorbent assay. Expression of tspans, activin-A, inhibin-A, and cytokines was analyzed by real time (RT)-PCR and their interacting genes were assessed by STRING. Expression of few disease-associated interacting genes was studied by RT-PCR. A total of 29% (Group I) were C. trachomatis positive. Tspans and activin-A were significantly upregulated, while inhibin-A was significantly downregulated in Group Ia. ITGA1, TLR-2, ITGB2, and Smad-3 were a few interacting genes. Expression of ITGA1, TLR-2, and Smad-3 was significantly upregulated in C. trachomatis-positive EP. Results suggested dysregulated tspans, activin-A, and inhibin-A might play a role in C. trachomatis-infected tubal EP.

Establishment and verification of hysteroscopic scoring system for chronic endometritis in infertile patients. / ä¸å­•æ‚£è€ æ ¢æ€§å­å®«å† è†œç‚Žå®«è ”é•œè¯„åˆ†ç³»ç»Ÿçš„æž„å»ºåŠéªŒè¯.

OBJECTIVES: To establish and verify a hysteroscopic scoring system for the diagnosis of chronic endometritis (CE) in infertile patients. METHODS: A total of 238 infertile patients who underwent hysteroscopy and endometrial biopsy in the Reproductive Medicine Center, Shijiazhuang Obstetrics and Gynecology Hospital Affiliated to Hebei Medical University from October 1 to December 31, 2019 were enrolled in the study. According to the results of CD138 immunohistochemistry, the patients were divided into CE group (n=73) and non-CE group (n=165). Univariate and binary logistic regression analyses were used to screen the risk factors of CE and a nomogram was establish for hysteroscopic scoring. Receiver operating characteristic (ROC) curve, calibration curve and Bootstrap resampling method were used to evaluate and verify the system. RESULTS: Univariate and binary logistic regression analyses showed that hyperemia area (HA) degree ≥2, micropolyps, polypoid hyperplasia of endometrium and history of ectopic pregnancy were independent risk factors for CE (all P<0.05). A nomogram was generated to establish a hysteroscopy scoring system based on the above four factors. The area under ROC curve of the hysteroscopy scoring system for predicting CE was 0.801 (95%CI:0.742-0.861), the sensitivity was 74.0% and the specificity was 73.9%. The calibration curve showed that the predicting value of the scoring system was highly consistent with the actual value. In the internal verification, the C-index was 0.7811. The predicting value of the verification group in the calibration curve was basically consistent with the actual value, indicating that the scoring system had good stability. CONCLUSIONS: The hysteroscopic scoring system composed of HA, micropolyp, polypoid hyperplasia of endometrium and history of ectopic pregnancy can effectively and intuitively predict CE, which is conducive to improving the diagnosis of CE.

Modeling human ectopic pregnancies with trophoblast and vascular organoids.

Ruptured ectopic pregnancy (REP), a pregnancy complication caused by aberrant implantation, deep invasion, and overgrowth of embryos in fallopian tubes, could lead to rupture of fallopian tubes and accounts for 4%-10% of pregnancy-related deaths. The lack of ectopic pregnancy phenotypes in rodents hampers our understanding of its pathological mechanisms. Here, we employed cell culture and organoid models to investigate the crosstalk between human trophoblast development and intravillous vascularization in the REP condition. Compared with abortive ectopic pregnancy (AEP), the size of REP placental villi and the depth of trophoblast invasion are correlated with the extent of intravillous vascularization. We identified a key pro-angiogenic factor secreted by trophoblasts, WNT2B, that promotes villous vasculogenesis, angiogenesis, and vascular network expansion in the REP condition. Our results reveal the important role of WNT-mediated angiogenesis and an organoid co-culture model for investigating intricate communications between trophoblasts and endothelial/endothelial progenitor cells.

Placenta accreta spectrum disorders in the first trimester: a systematic review.

Placenta accreta spectrum (PAS) disorders involve an abnormality in the implantation of the placenta, being rarely diagnosed in the first trimester. To conduct a systematic review of the risk factors, clinical and imaging features, and outcomes of histopathologically confirmed cases of PAS disorders in the first trimester of pregnancy. Different databases including PubMed, MEDLINE Complete, Scopus, Web of Science, EMBASE, SciELO, LILACS, and Ovid were reviewed up to November 2018. 55 patients with a definitive histopathological diagnosis were reported. About 18 had a history of prior curettage and 47 of previous caesarean deliveries (CD). About 74.54% presented with miscarriage and ultrasound signs of caesarean scar pregnancy (CSP) were reported in 22.49%. Temporal sequence of diagnostic studies could be determined in 52 women, and, among these, PAS disorders were defined through imaging techniques in 11 (21.15%) while surgical findings unveiled them in 15 (28.84%). Nonetheless, in half of the cases, the diagnosis was concluded only on histopathological samples. PAS disorders in the first trimester of pregnancy are rarely diagnosed through imaging techniques and lead to hysterectomy in most cases. Ultrasound training to detect PAS disorders in women with risk factors is crucial for early diagnosis and prevention of adverse outcomes.

Differential expression of matrix metalloproteinases in the fallopian tube of women with Chlamydia trachomatis-associated tubal ectopic pregnancy.

Chlamydia trachomatis is an established risk factor for ectopic pregnancy (EP) in fallopian tube (FT). Matrix metalloproteinases (MMPs) have potential role in disease pathogenesis, however, dysregulation of extracellular matrix by MMPs/TIMPs (tissue inhibitors of MMPs) in infection-associated EP remains unknown. The aim was to study the expression of MMP-2, -9, -14/TIMP-1, -2, -3 in C. trachomatis-positive tubal EP patients. The study comprised of 100 tubal EP (Group I) and 100 tubal ligation patients (Group II; controls) enrolled from Department of Obstetrics and Gynaecology, VMMC and Safdarjung hospital, New Delhi (India) for collection of FT. Detection of C. trachomatis MOMP was done by PCR while quantitative expression of MMPs/TIMPs was studied by real-time PCR. Data was statistically evaluated by Graphpad prism. Overall, C. trachomatis was found in 18/100 tubal EP patients. After ruling out Neisseria gonnorhoeae and Mycoplasma genitalium, Group I was divided into Group Ia (C. trachomatis DNA-positive) and Group Ib (C. trachomatis DNA-negative; internal controls). Significant upregulation of MMP-2, -9, -14 and downregulated TIMP-1, -2, -3 were found in Group Ia versus controls (Groups Ib/II) (p < 0.05). Fold-change in MMP was significantly higher in Group Ia versus controls ('p' < 0.05). Maximum 5.5-fold upregulation was found in MMP-2. It is apparent by molecular analysis that differential expression of MMPs/TIMPs, particularly enhanced MMP-2 leads to tubal EP in C. trachomatis DNA-positive women.

Proteome-defined changes in cellular pathways for decidua and trophoblast tissues associated with location and viability of early-stage pregnancy.

BACKGROUND: In early pregnancy, differentiating between a normal intrauterine pregnancy (IUP) and abnormal gestations including early pregnancy loss (EPL) or ectopic pregnancy (EP) is a major clinical challenge when ultrasound is not yet diagnostic. Clinical treatments for these outcomes are drastically different making early, accurate diagnosis imperative. Hence, a greater understanding of the biological mechanisms involved in these early pregnancy complications could lead to new molecular diagnostics. METHODS: Trophoblast and endometrial tissue was collected from consenting women having an IUP (n = 4), EPL (n = 4), or EP (n = 2). Samples were analyzed by LC-MS/MS followed by a label-free proteomics analysis in an exploratory study. For each tissue type, pairwise comparisons of different pregnancy outcomes (EPL vs. IUP and EP vs. IUP) were performed, and protein changes having a fold change ≥ 3 and a Student's t-test p-value ≤ 0.05 were defined as significant. Pathway and network classification tools were used to group significantly changing proteins based on their functional similarities. RESULTS: A total of 4792 and 4757 proteins were identified in decidua and trophoblast proteomes. For decidua, 125 protein levels (2.6% of the proteome) were significantly different between EP and IUP, whereas EPL and IUP decidua were more similar with only 68 (1.4%) differences. For trophoblasts, there were 66 (1.4%) differences between EPL and IUP. However, the largest group of 344 differences (7.2%) was observed between EP and IUP trophoblasts. In both tissues, proteins associated with ECM remodeling, cell adhesion and metabolic pathways showed decreases in EP specimens compared with IUP and EPL. In trophoblasts, EP showed elevation of inflammatory and immune response pathways. CONCLUSIONS: Overall, differences between an EP and IUP are greater than the changes observed when comparing ongoing IUP and nonviable intrauterine pregnancies (EPL) in both decidua and trophoblast proteomes. Furthermore, differences between EP and IUP were much higher in the trophoblast than in the decidua. This observation is true for the total number of protein changes as well as the extent of changes in upstream regulators and related pathways. This suggests that biomarkers and mechanisms of trophoblast function may be the best predictors of early pregnancy location and viability.

Embarazo molar cervical: diagnóstico y tratamiento quirúrgico con legrado uterino y ligadura de arterias cervicales / Cervical molar pregnancy: diagnosis and surgical treatment with uterine curettage and cervical arteries ligation

Resumen Reportamos el caso de una mujer de 28 años con atraso menstrual de 14 días, diagnosticada en el servicio de urgencia obstétrica del Hospital Félix Bulnes con un embarazo ectópico cervical mediante ultrasonido, en contexto de metrorragia grave. El tratamiento consistió en legrado uterino segmentario más ligadura de arterias cervicales. El estudio histopatológico reveló una mola hidatiforme parcial en el producto del curetaje. La paciente evolucionó favorablemente sin requerir más intervenciones. Este caso da cuenta del exitoso manejo de un embarazo cervical con tratamiento quirúrgico, dando una oportunidad de preservar la fertilidad de la paciente.

Abstract We are reporting the case of a 28-year-old woman with 14-day menstrual delay diagnosed, in the obstetric emergency department of Félix Bulnes Hospital, with a cervical pregnancy through ultrasound, in the context of severe metrorrhagia. The treatment consisted in uterine curettage and ligation of cervical arteries. A histopathological study revealed a partial hydatidiform mole in the curettage product. The patient evolved favorably without other interventions. This case its an example of the successful management of a cervical pregnancy with surgical treatment, giving a chance of preserving the fertility of the patient.

Caesarean scar ectopic pregnancy: a case series and case report to highlight the experience in regional New Zealand.

AIMS: To evaluate the approach to diagnosis and management of caesarean scar pregnancy (CSP) at a regional New Zealand hospital. METHODS: A retrospective case series of ten patients between June 2015 and May 2020. The data review included demographic information, ultrasound findings, human chorionic gonadotropin (HCG) levels, primary and subsequent treatment, outcomes and complications. RESULTS: Nine women were diagnosed with CSP at a gestational age between four and ten weeks. One of these women was treated twice for two separate CSP within the study period. Treatment varied according to clinical presentation, HCG levels, gestational age, ultrasound findings and patient preference. Two thirds of women were successfully treated with primary management, with one third requiring multiple treatment modalities. We report one severe life-threatening haemorrhage and three cases resulting in hysterectomy. We also show a disproportionate number of Maori women presenting with CSP. CONCLUSION: We present a series of ten cases of CSP and demonstrate similar challenges in regional New Zealand to those reported elsewhere. Management is heterogeneous with little guidance from the literature, and primary management was successful in seven out of ten cases. We report a disproportionately high number of cases in Maori women. Our results would support the development of a national register for caesarean scar pregnancy to improve diagnosis and management across New Zealand.

The correlation between endometrial thickness and the criteria for MTX treatment for ectopic pregnancy.

Ectopic pregnancy (EP) occurs in approximately 2% of all pregnancies. A common method of treatment is methotrexate therapy, considered in haemodynamically stable patients. Endometrial thickness has been investigated as a tool for diagnosing EP. The objective of this study was to evaluate the association between endometrial thickness and the criteria for MTX treatment, in an attempt to facilitate outcome prediction. We retrospectively collected data from records of patients diagnosed with EP between 2012 and 2014 including information regarding the mode of treatment and outcome. The endometrial thickness was compared between cases that met the criteria for MTX treatment and those who did not. Of 267 cases of EP that were reviewed, 108 patients were treated with MTX. The MTX treatment success rate was 88%. Endometrial thickness was found to be significantly and inversely associated with criteria for MTX treatment. In conclusion, an association was found between the endometrial thickness and the criteria for selection of MTX treatment for EP. This may be a useful tool in treatment selection for EP.Impact StatementWhat is already known on this subject? Transvaginal sonography along with ß-human chorionic gonadotrophin (ß-hCG) monitoring is the standard for evaluation of suspected ectopic pregnancy (EP). The most specific sonographic finding for EP is the presence of a live extra uterine pregnancy. In research conducted with the purpose of finding intrauterine sonographic findings associated with EP, this condition has been shown to be correlated with a thinner endometrial lining, compared with that of an intrauterine pregnancy.What the results of this study add? The results of this study add information on the subject of methotrexate treatment success rates in correlation with the endometrial thickness.What the implications are of these findings for clinical practice and/or further research? The findings of this study contribute to the process of treatment selection for ectopic pregnancy by emphasising the association between a thick endometrium and the lower success rates of MTX treatment.

Targeting colony stimulating factor-1 receptor signalling to treat ectopic pregnancy.

1-2% of pregnancies are ectopic, the majority implanting in the Fallopian tube. A single, systemic dose of methotrexate, a DNA-synthesis (S phase) inhibitor, has been used since 1991 for outpatient treatment of women with stable EP. However, methotrexate has limited clinical and cost effectiveness, restricting its use to 25-30% of these women. There is an unmet need for better medical treatment for EP. Colony stimulating factor-1 (CSF-1) promotes placentation and creates a pro-inflammatory environment that is fundamental for the maintenance of a normal pregnancy. We hypothesised that CSF-1 is also involved in the placentation and maintenance of an EP. Herein, we demonstrate the immunolocalisation of the CSF-1 receptor (CSF-1R) as well as its ligand (CSF-1) in immortalised first trimester trophoblast cells. We show that a specific CSF-1R kinase inhibitor, GW2580, abolishes CSF-1 induced trophoblast cell proliferation and migration and can be cytotoxic. We then demonstrate the expression of CSF-1R and CSF-1 in the cytotrophoblast and syncytiotrophoblast within ectopic implantation sites from women with EP. Our data suggests that CSF-1 is involved in the survival and proliferation of trophoblast cells in EP. This suggests that pharmacological disruption of CSF-1/CSF-1R signaling axis could be the basis of a new therapeutic for EP.

Uterine Scarring Leads to Adverse Pregnant Consequences by Impairing the Endometrium Response to Steroids.

Uterine surgical scarring is an increasing risk factor for adverse pregnant consequences that threaten fetal-maternal health. The detailed molecular features of scar implantation remain largely unknown. We aim to study the pathologic features of uterine surgical scarring and the mechanisms of compromised pregnancy outcomes of scar implantation. We generated a mouse model of uterine surgical scarring with a uterine incision penetrating the myometrium to endometrium to examine the pathologic changes and transcriptome profiles of uterine scarring at various postsurgery (PS) time points, as well as features of the feto-maternal interface during scar implantation. We found that uterine surgical scar recovery was consistently poor at PS3 until PS90, as shown by a reduced number of endometrial glands, inhibition of myometrial smooth muscle cell growth but excessive collagen fiber deposition, and massive leukocyte infiltration. Transcriptome annotation indicated significant chronic inflammation at the scarring site. At the peri-implantation and postimplantation stages, abnormal expression of various steroid-responsive genes at the scarring site was in parallel with lumen epithelial cell hyperplasia, inappropriate luminal closure, and disorientation of the implanted embryo, restricted stromal cell proliferation, and defective decidualization. High embryonic lethality (around 70%) before E10.5 was observed, and the small amount of survival embryos at E10.5 exhibited restricted growth and aberrant placenta defects including overinvasion of trophoblast cells into the decidua and insufficient fetal blood vessel branching in the labyrinth. The findings indicate that chronic inflammation and compromised responses to steroids in uterine scar tissues are the pivotal molecular basis for adverse pregnancy consequences of scar implantation.

Clinical characteristics and treatment of different types of cesarean scar pregnancy.

OBJECTIVES: The purpose of this study was to evaluate the clinical characteristics and compare the treatment efficacy of different types of cesarean scar pregnancy (CSP). MATERIAL AND METHODS: We performed a retrospective chart review of 66 women (69 cases) with CSP who received treatment with mifepristone/methotrexate (MTX) plus curettage, uterine artery embolization (UAE) plus curettage, additional MTX, or laparotomy, and compared the clinical characteristics, treatment efficacy, and occurrence of complications among 3 types of CSP (partial, complete, and mass type). RESULTS: Review of the 69 cases revealed a considerable increase of gestational duration(p < 0.001), sac/lesion size(p < 0.001) and vaginal bleeding (p < 0.05) in patients with mass-type CSP compared to that of other types. All CSP cases were successfully treated, 4 cases of mass-type received laparotomy and none of the cases required a hysterectomy. Severe bleeding was observed in 2 cases of partial-type and complete-type, respectively, and 3 cases for mass-type. Moreover, bleeding occurred during initial treatment with mifepristone plus curettage in partial-type cases, but not with UAE plus curettage. CONCLUSIONS: UAE plus curettage is a more effective treatment option for partial- and complete-type of CSP than mifepristone plus curettage. The cases of mass-type often need surgery and are prone to have longer gestational duration, larger lesions, and more vaginal bleeding.

Upregulation of elafin expression in the fallopian tube of ectopic tubal pregnancies compared to the normal tubes.

BACKGROUND: Ectopic pregnancy is one of the most important causes of maternal deaths and fallopian tubes are the location of 95% of ectopic pregnancies. Elafin is a natural antimicrobial molecule that plays an important role as an anti-inflammatory agent in mucosal surfaces and has been found in the female reproductive tract. OBJECTIVES: The aim of this study was to investigate elafin expression, in the fallopian tube mucosa of ectopic pregnancies compared to the normal tubes using immunohistochemistry (IHC) techniques and quantitative reverse transcription (qRT)-PCR. METHODS: In this case-control study, uterine tube samples were obtained from patients with an indication for surgical removal of the tubes. The case group (n = 20) consisted of patients who were undergoing salpingectomy due to an ectopic pregnancy, the control group (n = 20) included patients who had a salpingectomy and hysterectomy. Using qRT-PCR and IHC, the expression of elafin was investigated in both study groups. RESULTS: Immunohistochemical expression of elafin in the epithelium and connective tissue was significantly increased in the implantation site of the patients in comparison with the control group (P < 0.001). The level of elafin mRNA increased in the mucous membrane of the fallopian tube from patients with the ectopic pregnancy compared to the normal mucosa (P < 0.001). CONCLUSION: Increasing expression of elafin during an ectopic pregnancy may be a mechanism for enhancing innate immune response and be involved in related pathological conditions such as infection and ectopic implantation.

Rudimentary horn pregnancy - ten years of experience.

OBJECTIVES: This study aimed to evaluate data on early diagnosis and therapeutic management of rudimentary horn pregnancy (RHP). MATERIAL AND METHODS: Patients diagnosed with RHP at a tertiary center between for two periods of 2008-2012 and 2013-2018 were analysed retrospectively. We obtained information of patients from hospital electronic archive registration system. Data on demographic characteristics, clinical presentation, gestational age at presentation, presenting symptoms, diagnostic methods, and therapeutic management were noted and analysed by descriptive statistical method. Demographic datas, the complaint of patient's admission to hospital, history of cesarean section, preliminary diagnosis and intraoperative diagnosis were compared between periods of 2008-2012 and 2013-2018. RESULTS: A total of 14 RHP patients were included. Eight (57.1%) of these patients were diagnosed between 2008-2012 (Group 1), whereas six patients (42.9%) were diagnosed between 2013-2018 (Group 2). Rudimentary horn was non-communicating in 13 patients (92.8%). Communicated form was observed in 1 patient in group 1. RHP was diagnosed on the left side in nine patients (64.2%). Six of these patients were observed in group 1 and 3 were in group 2. The pre-rupture diagnosis was made in 10 (71.4%) patients. Six (100%) of 10 patients were in group 2. In addition, in group 1, four patients (50%) experienced intraoperative RHP rupture. RHP was diagnosed before rupture in 2 (33.3%) patients in group 2. CONCLUSIONS: It is an indication of advanced ultrasonographic technology as well as increased carefulness on the physician side and raised alertness on the patient side that today both RHP and preoperative rupture of RHP are less frequent. Still, further awareness is required among physicians of the necessity of excision of a rudimentary horn that is detected at the time of C-section.

Serum ß-human chorionic gonadotropin profile and its correlations with ultrasound parameters in low-lying-implantation ectopic pregnancy in the first trimester.

AIM: Cervical pregnancy (CP) and cesarean scar pregnancy (CSP), defined as low-lying-implantation ectopic pregnancy (LLIEP), are rare conditions of aberrant implantation around the lowest portion of the uterus. This study aimed to illustrate the serum ß-human chorionic gonadotropin (ß-hCG) profile of LLIEP and to explore its implications with the clinical characteristics. METHODS: Women with LLIEP during the first trimester were retrospectively evaluated at a tertiary referral center from August 1999 to July 2016. Demographic and clinical data were recorded, including maternal age, gestational age (GA), serum ß-hCG level, maximal diameter of the gestational mass/sac (MDM/MDS) by ultrasonography and CSP implantation types. The serum ß-hCG level was measured on the day of ultrasound imaging. The significance of pretreatment the serum ß-hCG level and its correlations with the clinical characteristics were analyzed. RESULTS: A total of 88 LLIEP with 64 CSP and 24 CP was included. The mean GA at the time of diagnosis was 7 weeks (range, 5-12 weeks). The ß-hCG concentrations rapidly increased from GA 5 to 9 weeks and fluctuated thereafter. The ß-hCG levels correlated positively with GA and ultrasound MDM/MDS. In the CSP group, there was no difference in the ß-hCG level between superficial and deep implantation types. ß-hCG levels demonstrated no significant differences among simple and complicated LLIEP. CONCLUSION: This study established the serum ß-hCG profile in LLIEP in the first trimester. The exponential increase of ß-hCG levels was similar to that of normal intrauterine pregnancies. The ß-hCG levels were not associated with placentation complexity of CSP. Higher ß-hCG levels did not implicate less success in conservative surgical management.

Adrenomedullin insufficiency alters macrophage activities in fallopian tube: a pathophysiologic explanation of tubal ectopic pregnancy.

Ectopic pregnancy is the major cause of maternal morbidity and mortality in the first trimester of pregnancy. Tubal ectopic pregnancy (TEP) accounts for nearly 98% of all ectopic pregnancies. TEP is usually associated with salpingitis but the underlying mechanism in salpingitis leading to TEP remains unclear. Adrenomedullin (ADM) is a peptide hormone abundantly expressed in the fallopian tube with potent anti-inflammatory activities. Its expression peaks at the early luteal phase when the developing embryo is being transported through the fallopian tube. In the present study, we demonstrated reduced expression of ADM in fallopian tubes of patients with salpingitis and TEP. Using macrophages isolated from the fallopian tubes of these women, our data revealed that the salpingistis-associated ADM reduction contributed to aggravated pro-inflammatory responses of the tubal macrophages resulting in production of pro-inflammatory and pro-implantation cytokines IL-6 and IL-8. These cytokines activated the expression of implantation-associated molecules and Wnt signaling pathway predisposing the tubal epithelium to an adhesive and receptive state for embryo implantation. In conclusion, this study provided evidence for the role of ADM in the pathogenesis of TEP through regulating the functions of tubal macrophages.

Diagnostic accuracy and cut-off of contrast-enhanced ultrasound in caesarean scar pregnancy.

OBJECTIVES: To investigate the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) and to search for cut-offs in caesarean scar pregnancy (CSP) patients for making quantitative diagnoses. STUDY DESIGN: Thirty patients in the first trimester of pregnancy were enrolled in our study. They were suspected as being at risk of caesarean scar pregnancy by conventional ultrasound and insisted on abortions. Transvaginal ultrasonography (TVU) and CEUS were performed, and parameters were analysed on the time-intensity curve (TIC). Laparotomy, laparoscopy, hysteroscopy or curettage under the guidance of ultrasound were performed, and pathological finding of villi in the uterine scar is the gold standard for a diagnosis of CSP. The area under the receiver operating characteristic (ROC) curve (AUC) was used to estimate the probability of the correct prediction of CSP. RESULTS: CSP was diagnosed in 27 patients: pathological diagnosis revealed villus tissue in the scar. The peak intensity ratios of caesarean scar to myometrium have the overall best diagnostic performances (AUC: 0.877, 95 % CI: 0.74-1.00). Using a cut-off value of 1.08 for the peak intensity ratio of caesarean scar to myometrium, the diagnosis sensitivity, specificity, PPV and NPV for CSP were 77.8, 100, 100, and 81.8 %, respectively. CONCLUSIONS: CEUS offers good diagnostic performance, and the peak intensity ratio of caesarean scar to myometrium can be used as a quantitative index to diagnose CSP accurately.