Ectopic pregnancy: a single-center experience over ten years.

PURPOSE: The aim of this study was to investigate characteristics associated with ectopic pregnancy (EP) that could be utilized for predicting morbidity or mortality. METHODS: This was a retrospective analysis of pregnancy-related records from a tertiary center over a period of ten years. Data on age, gravidity, parity, EP risk, amenorrhea duration, abdominal pain presence and location, ß-human chorionic gonadotropin (ß-HCG) level, ultrasound findings, therapeutic intervention, exact EP implantation site and length of hospital stay (LOS) were obtained from the database. The LOS was used as a proxy for morbidity and was tested for an association with all variables. All statistical analyses were conducted with Stata® (ver. 16.1, Texas, USA). RESULTS: The incidence of EP in a cohort of 30,247 pregnancies over a ten-year period was 1.05%. Patients presented with lower abdominal pain in 87.9% of cases, and the likelihood of experiencing pain was tenfold higher if fluid was detectable in the pouch of Douglas. Only 5.1% of patients had a detectable embryonic heartbeat, and 18.15% had one or more risk factors for EP. While most EPs were tubal, 2% were ovarian. The LOS was 1.9 days, and laparoscopic intervention was the main management procedure. The cohort included one genetically proven dizygotic heterotopic pregnancy (incidence, 3.3 × 10- 5) that was diagnosed in the 7th gestational week. The only association found was between the ß-HCG level and LOS, with a linear regression ß coefficient of 0.01 and a P-value of 0.04. CONCLUSION: EP is a relatively common condition affecting approximately 1% of all pregnancies. ß-HCG correlates with EP-related morbidity, but the overall morbidity rate of EP is low regardless of the implantation site. Laparoscopic surgery is an effective therapeutic procedure that is safe for managing EP, even in cases of heterotopic pregnancy.

Increase rate of ruptured tubal ectopic pregnancy during the COVID-19 pandemic.

OBJECTIVE: During the 2020 COVID-19 pandemic there was a decrease in emergency room arrivals. There is limited evidence about the effect of this change in behavior on women's health. We aimed to evaluate the impact of the COVID-19 pandemic on the diagnosis, treatment and complications of women presenting with a tubal Ectopic Pregnancy (EP). STUDY DESIGN: This is a single centre retrospective cohort study. We compared the clinical presentation, treatment modalities and complications of all women presenting in our institution with a tubal EP during the COVID-19 pandemic between 15 March and 15 June 2020, with women who were treated in our institution with the same diagnosis in the corresponding period for the years 2018-2019. RESULTS: The study group included 19 cases of EP (N = 19) that were treated between the 15 March 2020 and 15 June 2020. The control group included 30 cases of EP (N = 30) that were admitted to in the corresponding period during 2018 and 2019. Maternal age, parity, gravity and mode of conception (natural vs. assisted) were similar between the two groups. There was no difference in the mean gestational age (GA) according to the last menstrual period. In the study group more women presented with sonographic evaluation of high fluid volume in the abdomen than in the control group (53 % vs 17 %, P value 0.01). This finding is correlated with a more advanced disease status. In the study group there was a highly statistically significant 3-fold increase in rupture among cases (P < 0.005) and a 4-fold larger volume of blood in the entrance to the abdomen (P < 0.002). We found that there were no cases of ruptured EP in the group of women who were pregnant after assisted reproduction. CONCLUSION: We found a higher rate of ruptured ectopic pregnancies in our institution during the COVID-19 pandemic. Health care providers should be alerted to this collateral damage in the non-infected population during the COVID-19 pandemic.

Reproductive outcomes following a ruptured ectopic pregnancy.

Purpose: To determine the effect of ruptured ectopic pregnancies on the rate of future intrauterine pregnancies.Materials and Methods: This was a retrospective study of patients at a University-affiliated hospital with a history of an ectopic pregnancy between January 1991 to December 2016. All patients that underwent a salpingectomy for a tubal ectopic pregnancy were considered for this study. Intrauterine pregnancy rates for patients with a history of a ruptured ectopic pregnancy were compared to those with non-ruptured ectopic pregnancies. Fisher's exact test was used for analysis.Results: During the study period, 77 patients met the inclusion criteria. In this cohort, 14 patients with a history of a tubal ruptured ectopic pregnancy had achieved pregnancy within 12 months, compared to 24 patients in the non-ruptured group (52% vs 48%, p = 0.81). The rate of intrauterine pregnancies, compared to repeat ectopic pregnancy, in both the ruptured and non-ruptured group, was 71% (p > 0.99).Conclusion(s): Ruptured ectopic pregnancies did not adversely affect the rate of intrauterine pregnancy within 12 months of rupture when compared to non-ruptured ectopic pregnancies.

Severe morbidity with ectopic pregnancy is associated with late presentation.

This article investigates if severe morbidity associated with ectopic pregnancy (EP) is related to patient characteristics or the quality of patient care after presentation. This is a retrospective study of women who had surgical management of tubal EP between 2008 and 2012. Severe maternal morbidity was defined as a blood loss ≥800 mL. Women of a white ethnicity were statistically more likely to have a blood loss of <800 mL (p = .0228). The patient related risk factors were significantly higher in the women with a blood loss of <800 mL (p = .0139). The incidence of substandard care was low in both groups although a substandard care due to a misdiagnosis of EP was significantly higher in the patients with a blood loss ≥800 mL (p = .0150). We found that a severe morbidity from EP is multifactorial involving patient awareness of risk factors and timely diagnosis by healthcare professionals. IMPACT STATEMENT What is already known on the subject? Ectopic pregnancy (EP) can be associated with severe maternal morbidity with up to a third of women with EP being managed after the pregnancy has ruptured. To try and reduce severe maternal morbidity and improve management for these women it is vital to identify the important risk factors associated with severe maternal morbidity. What do the results of this study add? We found ethnicity to be a predictive factor of severe maternal morbidity, with women of white ethnicity significantly more likely to have reduced severe maternal morbidity compared to other ethnicities. We also found multiple risk factors for an EP were statistically protective of severe maternal morbidity. We found the rate of substandard care to be low in our study but identified that where there was substandard care it was associated with diagnostic and therapeutic delays. Our findings lead us to conclude that a severe maternal morbidity from EP is multifactorial, and an improvement will involve both a patient awareness of risk factors and a timely diagnosis by health care professionals. What are the implications of these findings for clinical practice and/or further research? We believe that this to be an important article as it identifies the importance of the increasing knowledge both of women in the community but also educating health care professionals on the signs and symptoms of EP. These steps are vital to improve severe maternal morbidity associated with EP.

TRPV4 is involved in levonorgestrel-induced reduction in oviduct ciliary beating.

Previous studies revealed the increasing risk of tubal pregnancy following failure of levonorgestrel (LNG)-induced emergency contraception, which was attributed to the reduced ciliary motility in response to LNG. However, understanding of the mechanism of LNG-induced reduction in the ciliary beat frequency (CBF) is limited. The transient receptor potential vanilloid (TRPV) 4 channel is located widely in the female reproductive tract and generates an influx of Ca2+ following its activation under normal physiological conditions, which regulates the CBF. The present study aimed to explore whether LNG reduced the CBF in the Fallopian tubes by modulating TRPV4 channels, leading to embryo retention in the Fallopian tubes and subsequent tubal pregnancy. The study provided evidence that the expression of TRPV4 was downregulated in the Fallopian tubes among patients with tubal pregnancy and negatively correlated with the serum level of progesterone. LNG downregulated the expression of TRPV4, limiting the calcium influx to reduce the CBF in mouse oviducts. Furthermore, the distribution of ciliated cells and the morphology of cilia did not change following the administration of LNG. LNG-induced reduction in the CBF and embryo retention in the Fallopian tubes and in mouse oviducts were partially reversed by the progesterone receptor antagonist RU486 or the TRPV4 agonist 4α-phorbol 12,13-didecanoate (4α-PDD). The results indicated that LNG could downregulate the expression of TRPV4 to reduce the CBF in both humans and mice, suggesting the possible mechanism of tubal pregnancy. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

A multi-centre, double-blind, placebo-controlled, randomised trial of combination methotrexate and gefitinib versus methotrexate alone to treat tubal ectopic pregnancies (GEM3): trial protocol.

BACKGROUND: Tubal ectopic pregnancy (tEP) is the most common life-threatening condition in gynaecology. Treatment options include surgery and medical management. Stable women with tEPs with pre-treatment serum human chorionic gonadotrophin (hCG) levels < 1000 IU/L respond well to outpatient medical treatment with intramuscular methotrexate. However, tEPs with hCG > 1000 IU/L can take significant time to resolve with methotrexate and require multiple outpatient monitoring visits. In pre-clinical studies, we found that tEP implantation sites express high levels of epidermal growth factor receptor. In early-phase trials, we found that combination therapy with gefitinib, an orally active epidermal growth factor receptor antagonist, and methotrexate resolved tEPs without the need for surgery in over 70% of cases, did not cause significant toxicities, and was well tolerated. We describe the protocol of a randomised trial to assess the efficacy of combination gefitinib and methotrexate, versus methotrexate alone, in reducing the need for surgical intervention for tEPs. METHODS AND ANALYSIS: We propose to undertake a multi-centre, double-blind, placebo-controlled, randomised trial (around 70 sites across the UK) and recruit 328 women with tEPs (with pre-treatment serum hCG of 1000-5000 IU/L). Women will be randomised in a 1:1 ratio by a secure online system to receive a single dose of intramuscular methotrexate (50 mg/m2) and either oral gefitinib or matched placebo (250 mg) daily for 7 days. Participants and healthcare providers will remain blinded to treatment allocation throughout the trial. The primary outcome is the need for surgical intervention for tEP. Secondary outcomes are the need for further methotrexate treatment, time to resolution of the tEP (serum hCG ≤ 15 IU/L), number of hospital visits associated with treatment (until resolution or scheduled/emergency surgery), and the return of menses by 3 months after resolution. We will also assess adverse events and reactions until day of resolution or surgery, and participant-reported acceptability at 3 months. DISCUSSION: A medical intervention that reduces the need for surgery and resolves tEP faster would be a favourable treatment alternative. If effective, we believe that gefitinib and methotrexate could become standard care for stable tEPs. TRIAL REGISTRATION: ISRCTN Registry ISRCTN67795930 . Registered 15 September 2016.

Dysregulated erythropoietin-producing hepatocellular receptor A2 (EphA2) is involved in tubal pregnancy via regulating cell adhesion of the Fallopian tube epithelial cells.

BACKGROUND: Tyrosine kinase receptor erythropoietin-producing hepatocellular receptor A2 (EphA2) is abundant in the endometrium and plays a role in the establishment of eutopic implantation. A similar molecular mechanism may exist between uterine implantation and tubal implantation, therefore EphA2 involvement in tubal pregnancy is suspected. Due to the limited availability of human Fallopian tube specimens, EphA2 expression in human Fallopian tube epithelium remains largely unknown. METHODS: A total of 31 women with tubal pregnancy and 41 non-pregnant women with benign uterine diseases were enrolled in this study. Immunohistochemistry was used to investigate the expression pattern of EphA2 in the Fallopian tube epithelium of non-pregnant women (n = 29) and women with tubal pregnancy (n = 17). The changes of EphA2 and its activated form, phosphorylated-EphA2 (Pho-EphA2), in the Fallopian tube epithelium from non-pregnant women (n = 12) and women with tubal pregnancy (n = 14) were compared by quantitative RT-PCR and western blot assay. RESULTS: EphA2 was expressed throughout the Fallopian tube epithelium, including the isthmus, the ampulla and the infundibulum. EphA2 concentration remained unchanged throughout the whole menstrual cycle, irrespective of menstrual phases and tubal regions. EphA2 mRNA in the Fallopian tube epithelium did not differ between normal women and women with tubal pregnancy (P > 0.05). With respect to the protein level, a significantly higher ratio of EphA2 over Pho-EphA2 was shown in women with tubal pregnancy (P < 0.05). CONCLUSIONS: EphA2 is widely expressed in human Fallopian tube epithelium in a temporospatial-independent manner. Dysregulated EphA2 and its phosphorylation-dependent regulatory mechanism may unexpectedly enhance the cell adhesion activity of the Fallopian tube epithelial cells, leading to a mis-contact between the Fallopian tube epithelium and the embryo.

Decreased Toll-like receptor-2 messenger ribonucleic acid and increased Toll-like receptor-4 in the tubal epithelium next to the infiltrated trophoblasts during tubal pregnancy.

OBJECTIVE: To explore the expression patterns of Toll-like receptor (TLR)2 and TLR4 in the tubal epithelial cells next to the infiltrated trophoblasts at the maternal-fetal interface during tubal pregnancy. DESIGN: Prospective, observational study. SETTING: University-based obstetrics and gynecology hospital. PATIENT(S): Thirty-seven women undergoing salpingectomy for tubal ampullary pregnancy and nine nonpregnant patients with benign uterine or appendix disease. INTERVENTION(S): Oviduct tissues with ectopic gestations were separated into implantation site (group 1) and nonimplantation site (group 2). Tissues from ampullary fallopian tubes during mid-secretory phase (group 3) were collected as the control group. Immunohistochemistry and quantitative real-time polymerase chain reaction were performed. MAIN OUTCOME MEASURE(S): Differences of TLR2 and TLR4 expression patterns between group 1 and group 2 and between the pregnant group (combined group 1 and group 2) and the nonpregnant group (group 3). RESULT(S): Comparing the pregnant group with group 3, TLR4 messenger RNA (mRNA) and protein were both significantly up-regulated in the pregnant group. In contrast, TLR2 mRNA was significantly down-regulated, whereas TLR2 protein showed a tendency toward reduction. Detailed analysis between group 1 and group 3 revealed statistically significantly higher TLR2 and TLR4 protein in group 1. In terms of mRNA, TLR4 expression was still shown to be significantly increased in group 1, whereas TLR2 expression was markedly decreased in group 1. CONCLUSION(S): Decreased TLR2 mRNA and increased TLR4 in the tubal epithelial cells next to the infiltrated trophoblasts may be associated with aspects of the pathophysiology of tubal ectopic pregnancy in immune defense.

Diagnostic significance of IL-6 and IL-8 in tubal ectopic pregnancy.

As there are no specific non-invasive markers for the diagnosis of tubal ectopic pregnancy, our objective in the present study was to explore the role of inflammatory cytokines IL-6 and IL-8 in the diagnosis of ruptured tubal ectopic pregnancy. Twenty-eight women with tubal ectopic pregnancy, 31 patients with intrauterine abortion and 29 gestational age matched women having normal intrauterine pregnancy were included in the study. Five millilitre of blood was collected at the time of admission, serum was separated and stored at -70 °C for subsequent analysis of ß hCG, IL-6 and IL-8 levels. The level of IL-6 was a significant increase in the women with tubal ectopic pregnancy compared to intrauterine abortion and normal pregnancy. IL-8 levels decrease significantly in the tubal ectopic pregnancy and in intrauterine abortion patients when compared with the normal pregnancy group. At the cutoff of 26.48 pg/ml IL-6 level predicted the tubal ectopic pregnancy with moderate accuracy. Therefore, it can be concluded that measurement of IL-6 may have relevance in the diagnosis of ectopic pregnancy as a novel inflammatory serum biomarkers.

Bilateral tubal and intrauterine pregnancies diagnosed at laparoscopy.

A 32-year-old woman had bilateral tubal and intrauterine pregnancies after hyperovulation with clomiphene citrate and subsequent artificial insemination with husband's semen. Laparoscopic surgery revealed bilateral tubal pregnancies. Salpingectomy was performed on the left tube and linear salpingotomy was performed on the right tube. The postoperative course was uneventful. The patient delivered a healthy girl vaginally at 39 weeks' gestation. Only eight cases with bilateral and intrauterine pregnancy have been reported. The live birth rate of bilateral tubal pregnancy and intrauterine pregnancy is 60% (6/10), which is similar to that of heterotopic pregnancy. Laparoscopic surgery is effective for confirming the diagnosis and treating heterotopic pregnancy.

Enhanced beta-catenin expression and inflammation are associated with human ectopic tubal pregnancy.

STUDY QUESTION: Is there a molecular link between Wnt signaling in fallopian tube inflammation and ectopic tubal implantation? SUMMARY ANSWER: Enhanced beta-catenin expression, reduced E-cadherin expression and glycogen accumulation in the tubal epithelia and hyperplasia in tubal arteries were found in ectopic tubal pregnancy, consistent with the effects induced by Wnt signaling and inflammation. WHAT IS KNOWN ALREADY: Chronic inflammation caused by infection can alter gene expression in the fallopian tube cells possibly leading to the development of ectopic pregnancy. Knockout mouse models have shown a relationship between Wnt/beta-catenin signaling and predisposition to tubal ectopic pregnancy. STUDY DESIGN, SIZE, DURATION: Women with ectopic tubal pregnancy (n = 18) were included in the case group, while women with chronic salpingitis (n = 13) and non-pregnant women undergoing sterilization procedures or salpingectomy for benign uterine disease (n = 10) were set as the controls. This study was performed between January 2012 and November 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: The ampullary segments of fallopian tubes were collected from patients. Tissues of tubal pregnancy were separated into implantation sites and non-implantation sites. Beta-catenin and E-cadherin expression were determined using immunohistological and immunofluorescence staining. Glycogen production was measured with periodic acid Schiff by staining. The diameter and wall thickness of tubal arteries were evaluated by histological analysis method. MAIN RESULTS AND THE ROLE OF CHANCE: Immunohistological staining revealed that beta-catenin protein expression was 100% positive in the ectopic pregnant and inflamed tubal tissues, and the staining intensity was significantly higher than in non-pregnant tubal tissues. In contrast, E-cadherin expression was reduced in ectopic pregnant fallopian tubes, possibly as a consequence of increased Wnt signaling. Moreover, glycogen accumulated in the tubal cells, and hyperplasia was observed in the tubal arteries with ectopic pregnancy, which is consistent with the effects induced by Wnt signaling and inflammation. All these changes could create the permissive environment that promotes embryos to ectopically implant into the fallopian tube. LIMITATIONS, REASONS FOR CAUTION: This finding requires a further confirmation about what activates Wnt signaling in ectopic tubal pregnancies. Also, it is generally recognized that Chlamydia infection is associated with ectopic pregnancy, and disturbs tubal epithelia via the Wnt signaling. However, the infection type in the samples used was salpingitis. WIDER IMPLICATIONS OF THE FINDINGS: A better understanding of the underlying mechanisms leading to ectopic pregnancies may contribute to our knowledge of the pathogenesis of tubal disorders and infertility and to the prevention of tubal ectopic pregnancy.

Decreases in adrenomedullin expression and ciliary beat frequency in the nasal epithelium in tubal pregnancy.

OBJECTIVE: To study adrenomedullin (ADM) expression and its relation to ciliary beat frequency (CBF) in the nasal mucociliated epithelium in tubal ectopic pregnancy (tEP). DESIGN: Experimental study. SETTING: University teaching hospital. PATIENT(S): Women with tEP and normal intrauterine pregnancy matched for age and gestational age were recruited. Healthy nonpregnant women were also recruited as nonpregnant controls. INTERVENTION(S): Nasal epithelial brushing. MAIN OUTCOME MEASURE(S): Adrenomedullin expression in nasal epithelium (measured by real-time reverse transcription-polymerase chain reaction, plasma ADM concentration (measured by ELISA), and CBF (measured by photometric method). RESULT(S): We have demonstrated a similar decrease in ADM expression and CBF in the nasal mucociliated epithelium, as well as in plasma ADM concentration, in women with tEP compared with normal pregnant women. Adrenomedullin up-regulates nasal CBF via the ADM receptor, as in the oviduct. There is significant correlation between nasal and oviductal CBF. CONCLUSION(S): Nasal epithelium ADM and CBF, as well as plasma ADM, are possible predictors of women at risk of tEP.

Aberrant alteration of vascular endothelial growth factor-family signaling in human tubal ectopic pregnancy: what is known and unknown?

More than 98% of ectopic pregnancies occur in the Fallopian tube. Because many facets of tubal ectopic pregnancy remain unclear, prediction, prevention and treatment of tubal ectopic pregnancy are still a major clinical challenge. Compelling evidence suggests that angiogenic growth factors are involved in normal and abnormal implantation. While acknowledging the importance of an intrauterine pregnancy requires the development of a local blood supply and angiogenesis, we hypothesize that the hypoxic- and estrogen-dependent regulation of vascular endothelial growth factor/placental growth factor expression, secretion, and signaling pathways that are possibly involved in the pathophysiology of tubal ectopic pregnancy. Our hypothesis may also lead to a new therapeutic strategy for women with tubal ectopic pregnancy.

Possible role of adrenomedullin in the pathogenesis of tubal ectopic pregnancy.

CONTEXT: Tubal ectopic pregnancy (tEP) is currently the leading cause of pregnancy-related deaths during the first trimester. Our current knowledge on the molecular pathogenesis is limited. OBJECTIVE: The objective of the study was to find out the possible role of adrenomedullin (ADM) in the pathogenesis of tEP. DESIGN: This was an experimental in vitro study on oviductal tissue. SETTING: The study was conducted at a university teaching hospital. PATIENTS AND INTERVENTIONS: Patients included those having oviducts removed surgically during salpingectomy for tEP or hysterectomy for benign gynecological conditions. Oviductal tissues were incubated in hormonal condition mimicking early pregnancy before used for in vitro experiments. MAIN OUTCOME MEASURES: Plasma ADM concentration, oviductal expression of ADM and its receptors, ciliary beat frequency, smooth muscle contraction were measured. RESULTS: The ciliary beat frequency and frequency of muscle contraction were lower in the oviducts from patients with tEP than those from simulated normal pregnancy. The plasma and oviductal tissue ADM levels were also lower. The decreases in ciliary beat and frequency of contraction were restored to normal after ADM treatment. CONCLUSIONS: The results suggest that the lower ADM level in the oviducts of tEP may lead to the decrease in ciliary beating and muscle contraction, with the result that the embryo is retained and implanted in the oviduct. Our findings explain for the first time the etiology of tubal pregnancy on the basis of an impairment of the transport of the fertilized ovum resulting from an ADM deficiency and raise the possibility of using the plasma ADM level as a predictor for tubal ectopic pregnancy.

Wnt activation downregulates olfactomedin-1 in Fallopian tubal epithelial cells: a microenvironment predisposed to tubal ectopic pregnancy.

Ectopic pregnancy (EP) occurs when the embryo fails to transit to the uterus and attach to the luminal epithelium of the Fallopian tube (FT). Tubal EP is a common gynecological emergency and more than 95% of EP occurs in the ampullary region of the FT. In humans, Wnt activation and downregulation of olfactomedin-1 (Olfm-1) occur in the receptive endometrium and coincided with embryo implantation in vivo. Whether similar molecular changes happen in the FT leading to EP remains unclear. We hypothesized that activation of Wnt signaling downregulates Olfm-1 expression predisposes to EP. We investigated the spatiotemporal expression of Olfm-1 in FT from non-pregnant women and women with EP, and used a novel trophoblastic spheroid (embryo surrogate)-FT epithelial cell co-culture model (JAr and OE-E6/E7 cells) to study the role of Olfm-1 on spheroid attachment. Olfm-1 mRNA expression in the ampullary region of non-pregnant FT was higher (P<0.05) in the follicular phase than in the luteal phase. Ampullary tubal Olfm-1 expression was lower in FT from women with EP compared to normal controls at the luteal phase (histological scoring (H-SCORE)=1.3±0.2 vs 2.4±0.5; P<0.05). Treatment of OE-E6/E7 with recombinant Olfm-1 (0.2-5 µg/ml) suppressed spheroid attachment to OE-E6/E7 cells, while activation of Wnt-signaling pathway by Wnt3a or LiCl reduced endogenous Olfm-1 expression and increased spheroid attachment. Conversely, suppression of Olfm-1 expression by RNAi increased spheroid attachment to OE-E6/E7 cells. Taken together, Wnt activation suppresses Olfm-1 expression, and this may predispose a favorable microenvironment of the retained embryo in the FT, leading to EP in humans.

Laboratory models for studying ectopic pregnancy.

PURPOSE OF REVIEW: Understanding the cause of tubal ectopic pregnancy (tEP) remains incomplete. We aim to summarize the latest advances in laboratory models of tEP that we believe will, ultimately, contribute to improving the diagnosis and management of the condition. RECENT FINDINGS: Progress in proteome prefractionation and multidimensional protein identification technology has proved particularly effective in identifying novel biomarkers of tEP. These, and related global proteomic and genomic approaches, have as yet to be fully exploited in this context but do have substantial potential to inform future hypothesis-driven studies. The majority of data generated since 2009 to explain the cause of tEP continues to derive from descriptive human ex-vivo studies. In-vitro models of fallopian tube ciliary and smooth muscle function have improved to a limited degree, on the back of continuing advances in imaging and data acquisition. We believe that the recent development of a primary human fallopian tube epithelium culture system represents the most significant recent advance in laboratory models for studying ectopic pregnancy. There remain no good animal models of tEP. SUMMARY: The establishment of a viable animal model of tEP remains the key obstacle to a complete understanding of the cause of the condition.

Vascular endothelial growth factor and ß-human chorionic gonadotropin are associated with trophoblastic invasion into the tubal wall in ectopic pregnancy.

OBJECTIVE: To assess the association between the depth of trophoblastic penetration into the tubal wall with serum concentrations of vascular endothelial growth factor (VEGF) and ß-hCG and to assess its predictive value. DESIGN: Prospective study. SETTING: Tertiary care university hospital. PATIENT(S): Thirty patients with ampullary pregnancy undergoing salpingectomy were analyzed. INTERVENTION(S): Trophoblastic invasion was histologically classified as stage I when limited to the tubal mucosa, stage II when extending to the muscle layer, and stage III in the case of complete tubal wall infiltration. MAIN OUTCOME MEASURE(S): The relation between depth of trophoblastic infiltration into the tubal wall with VEGF and ß-hCG serum concentrations on the day of surgery. RESULT(S): An association between the depth of trophoblastic invasion and maternal serum concentrations of VEGF and ß-hCG was observed. VEGF levels of 297.2 pg/mL showed 100.0% sensitivity and 90.0% specificity for stage I, and levels of 440.1 pg/mL showed 81.8% sensitivity and 88.8% specificity for stage III. Beta-hCG levels of 2590.0 mIU/mL showed 88.9% sensitivity and 80.0% specificity for stage I, and levels of 10,827.0 mUI/mL showed 72.7% sensitivity and 88.9% specificity for stage III. CONCLUSION(S): Maternal serum VEGF and ß-hCG concentrations are associated with depth of trophoblastic penetration into the tubal wall.