Talk:Abnormal Development - Ectopic Implantation
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Cite this page: Hill, M.A. (2024, April 24) Embryology Abnormal Development - Ectopic Implantation. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Abnormal_Development_-_Ectopic_Implantation |
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Ectopic Implantation
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2012Why does the fallopian tube fail in ectopic pregnancy? The role of activins, inducible nitric oxide synthase, and MUC1 in ectopic implantationFertil Steril. 2012 May;97(5):1115-23. doi: 10.1016/j.fertnstert.2012.02.035. Epub 2012 Mar 15. Refaat B, Simpson H, Britton E, Biswas J, Wells M, Aplin JD, Ledger W. Source Laboratory Medicine Department, College of Applied Medical Sciences, Umm Al-Qura University, Mecca, Saudi Arabia. Abstract OBJECTIVE: To investigate the role of activin-βA subunit, activin type II receptors, inducible nitric oxide synthase (iNOS), and MUC1 in the pathogenesis of ectopic pregnancy (EP) and their involvement in the determination of the implantation site. DESIGN: Observational study. SETTING: Academic unit of reproductive and developmental medicine. PATIENT(S): Four women at the luteal phase, three pseudopregnant women at the time of hysterectomy for benign disease, and 10 archived cases of EP. We collected 14 Fallopian tubes were collected from four women at the luteal phase and three pseudopregnant women at the time of hysterectomy for benign disease; specimens from implantation site, trophoblast and remote sites from the implantation site were collected from 10 archived cases of EP. INTERVENTION(S): Immunohistochemistry and quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). MAIN OUTCOME MEASURE(S): Comparison of the expression of candidate molecules between the different groups. RESULT(S): The expression of activin-βA subunit, activin type II receptors, and iNOS was statistically significantly increased and expression of MUC1 statistically significantly decreased in tubes bearing an EP. There was no statistically significant difference in the expression of the candidate molecules between the implantation and remote sites. Candidate molecules were also expressed in the trophoblast. CONCLUSION(S): The pathological expression of candidate molecules by tubes bearing an EP is not involved in the determination of implantation site. Additionally, candidate molecules may play a role in the regulation of trophoblast cells in vivo during early pregnancy. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved. PMID 22425195 Cholinergic receptors in the murine oviduct: inventory and coupling to intracellular calcium concentrationLife Sci. 2012 Nov 27;91(21-22):1003-8. doi: 10.1016/j.lfs.2012.03.016. Epub 2012 Mar 28. Wolff M, Noreikat K, Ibanez-Tallon I, Lips KS, Kölle S, Kummer W. Source Institute of Anatomy and Cell Biology, Justus-Liebig-University, 35385 Giessen, Germany. miriamwolff@web.de Abstract AIMS: In the oviduct, muscarinic acetylcholine receptors (MR) are linked with motility regulation and nicotinic receptors (nAChR) with ectopic pregnancy. We here aimed to determine the repertoire of cholinergic receptor expression in the murine oviduct and their functional coupling to regulation of intracellular calcium concentration ([Ca(2+)](i)). MAIN METHODS: Cholinergic receptor transcripts were assessed by RT-PCR in oviductal segments (ampulla, isthmus, uterotubar junction) in all cyclic stages and pregnancy, and in laser-microdissected samples of epithelium and smooth muscle, nAChR subunit α3 distribution in tissue sections using an appropriate genetic reporter mouse strain. [Ca(2+)](i) responses were monitored in ciliated and non-ciliated oviductal cells isolated from wild-type and MR subtypes 1 and 3 gene deficient mice. KEY FINDINGS: Transcripts for all MR subtypes (M1-M5) are constantly expressed whereas there is some variability in nAChR expression from individual to individual. The qualitative expression pattern is independent from the hormonal status of the animal, except for nAChR α7, which is less present during pregnancy. The epithelium expresses M1, M3, nAChR α7 (data from laser-assisted microdissection) and nAChR α3 (ultrastructural investigation of reporter mice). MR dominate over nAChR in increasing [Ca(2+)](i) with being M3 the major, but not sole subtype driving this effect. The general nAChR inhibitor mecamylamine enhances muscarinic and purinergic responses. SIGNIFICANCE: In conclusion, the murine oviduct is endowed with a multiplicity of muscarinic and nicotinic receptors subtypes that, with respect to regulation of [Ca(2+)](i), are inversely linked to each other. The major, but not sole, cholinergic receptor driving increase in [Ca(2+)](i) is M3. Copyright © 2012 Elsevier Inc. All rights reserved. PMID 22480510
The paracrinology of tubal ectopic pregnancyMol Cell Endocrinol. 2012 Jul 25;358(2):216-22. doi: 10.1016/j.mce.2011.07.037. Epub 2011 Jul 30. Shaw JL, Horne AW. Source Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8. Abstract As part of successful human reproduction, the Fallopian tube must provide a suitable environment for pre-implantation development of the embryo and for efficient transport of the embryo to the uterus for implantation. These functions are coordinated by paracrine interactions between tubal epithelial, smooth muscle and immune cells and the cells of the developing embryo. Alterations in these signals can lead to a tubal microenvironment encouraging of embryo implantation and to dysregulated tubal motility, ultimately resulting in inappropriate and early implantation of the embryo in the Fallopian tube. Here, we highlight novel and emerging concepts in tubal physiology and pathobiology, such as the induction of a receptive phenotype within the Fallopian tube, leading to ectopic implantation. Chlamydia trachomatis infection is a risk factor for tubal ectopic pregnancy. Activation of toll-like receptor 2 (TLR-2) in the Fallopian tube epithelium, by C. trachomatis has recently been demonstrated, leading to the dysregulation of factors involved in implantation and smooth muscle contractility, such as prokineticins (PROK), activin A and interleukin 1 (IL-1). The Fallopian tube has also recently been shown to harbour a unique population of immune cells, compared to the endometrium. In addition, the complement of immune cells in the Fallopian tube has been reported to be altered in Fallopian tube from women with ectopic pregnancy. There are increasing data suggesting that vascularisation of the Fallopian tube, by the embryo during ectopic pregnancy, differs from that initiated in the uterus during normal pregnancy. This too, is likely the result of paracrine signals between the embryo and the tubal microenvironment. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved. PMID 21827822 Ectopic molar pregnancy: a case reportPan Afr Med J. 2012;11:63. Epub 2012 Apr 4. Bousfiha N, Erarhay S, Louba A, Saadi H, Bouchikhi C, Banani A, El Fatemi H, Sekkal M, Laamarti A. Source Department of gynecology obstetric I, Teaching Hospital, Hassan II, Fez, Morocco. Abstract The incidence of hydatidiform moles is 1 per 1,000 pregnancies. Ectopic pregnancy occurs in 20 per 1,000 pregnancies. Thus, the incidence of the ectopic molar gestation is very rare. We report a case of tubal molar pregnancy diagnosed at the systematic histology exam of an ectopic pregnancy. We report the case of 32 years old nulliparus women who presented a vaginal bleeding, lower abdominal pain and 6 weeks amenorrhea corresponding to the last menstrual period. At the clinical examination, the arterial pressure was 100/60 mmHG. The gynecological examination was difficult because of lower abdominal pain. Serum gonadotropin activity was 3454 ui/l. Pelvic ultrasound revealed an irregular echogenic mass in the left adnexa. Diagnostic laparoscopy revealed a left-sided unruptured ampullary ectopic pregnancy. A left laparoscopic salpingectomy was performed. The systematic histologic test identified an ectopic partial molar pregnancy, which was confirmed by DNA ploidy image analysis. The patient was followed with weekly quantitative B-hCG titers until three successive B-hCG levels were negative. It is pertinent that clinicians take routine histological examination of tubal specimens in ectopic pregnancy very seriously in order to diagnose cases of ectopic molar gestations early and mount appropriate post treatment surveillance. PMID 22655097 http://www.panafrican-med-journal.com/content/article/11/63/full/ © Najoua Bousfiha et al. The Pan African Medical Journal - ISSN 1937-8688. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Images in clinical medicine. Abdominal ectopic pregnancyN Engl J Med. 2012 Dec 13;367(24):2334. doi: 10.1056/NEJMicm1111814. Gabriela Gayer, M.D. Stanford Medical Center, Palo Alto, CA ggayer@stanford.edu Source Stanford Medical Center, Palo Alto, CA, USA. ggayer@stanford.edu A 30-year-old woman who had a history of two pregnancies and one birth presented with an uncomplicated pregnancy until routine ultrasonography at 19 weeks revealed severe oligohydramnios and a fetus that appeared to be extrauterine. PMID 23234516 http://www.nejm.org/doi/full/10.1056/NEJMicm1111814 Indicators of potential for rupture for ectopics seen in the emergency departmentJ Emerg Trauma Shock. 2011 Jul;4(3):374-7. Downey LV, Zun LS. Source School of Policy Studies, Roosevelt University, Chicago, IL, USA. Abstract BACKGROUND: Emergency departments (ED) frequently evaluate patients with probable ectopic pregnancies who go home and may rupture. It would be beneficial to know which patient factors are associated with rupture and which are not. OBJECTIVES: The purpose of this study was to determine which ED patients with ectopic pregnancies are at risk for rupture. MATERIALS AND METHODS: This study was a retrospective chart review of all women aged ≥18 years during a 5-year period who were diagnosed with ectopic pregnancy to a level I ED. Data collected included basic demographic information, medical, surgical, obstetric and gynecologic history, social and sexual history, findings on physical examination, and laboratory values such as urine pregnancy test, β-hCG, and complete blood count. RESULTS: There was a significant difference using a multivariate regression analysis with 95% CI in history findings of abdominal pain, nausea, vomiting, and urinary tract symptoms. There was a significant difference in physical examination of pulse, diastolic pressure, abdominal tenderness, peritoneal signs, cervical motion tenderness, and adnexal tenderness. There was also a significant difference in β-hCG, hemoglobin and hematocrit results and ultrasound findings of free peritoneal fluid, intrauterine pregnancy and cardiac findings between those who ruptured and those who did not. None of these tests was able to differentiate those that would go on to rupture. CONCLUSION: The result of the study did not find any single sign, symptom, or test that could reliably differentiate patients who have a ruptured ectopic from those who do not. However, β-hCG over 1500 mIU was the best variable in explaining the variation between those who would or would not go on to rupture after their ED visit. PMID 21887029 [PubMed] PMCID: PMC3162708 Reporting rates of ectopic pregnancy: Are we any closer to achieving consensus?J Obstet Gynaecol. 2012 Jan;32(1):64-7. de Rosnay P, Irvine LM. Source Department of Obstetrics and Gynaecology, West Middlesex University Hospita l, Isleworth. Abstract Calculating rates of ectopic pregnancy in a reliable and reproducible way can be challenging. To date, there is no consensus as to which denominators to use but the authors suggest using the total number of deliveries as a benchmark. In many developing countries where ectopic pregnancy is a major cause of maternal morbidity and mortality, standardisation of epidemiological data is arguably even more important. Using the number of deliveries is probably the most pragmatic and reliable way of quoting ectopic pregnancy rates in developing countries, as structures are usually already in place to record births/deliveries. This would ensure greater consistency and allow more meaningful comparisons to be made, both within individual units over time as well as globally. Using additional denominators is more labour intensive and lends itself to inaccuracy but may nevertheless be useful depending on the issues being addressed. Ultimately, the correct denominator(s) to use should be determined by the clinical question(s) of interest. The authors acknowledge that the statistical analysis used in this paper is based on one retrospective study alone and that further work is required in this area before definitive conclusions can be made. PMID 22185541 Comparison of double- and single-dose methotrexate protocols for treatment of ectopic pregnancyInt J Gynaecol Obstet. 2012 Jan;116(1):67-71. Epub 2011 Oct 28. Hamed HO, Ahmed SR, Alghasham AA. Source Department of Obstetrics and Gynecology, Qassim University, Burraidah, Saudi Arabia; Women's Health Center, Assiut University, Assiut, Egypt. Abstract OBJECTIVE: To compare efficacy between double-dose methotrexate and single-dose methotrexate for treatment of tubal ectopic pregnancy (EP). METHODS: Between March 2008 and February 2011,157 patients who had tubal EP diagnosed by a non-laparoscopic approach and were hemodynamically stable were enrolled in a prospective study in Qassim, Saudi Arabia. The participants were randomized to receive either double-dose (50mg/m(2) intramuscularly on days 0 and 4; group 1) or single-dose (50mg/m(2) intramuscularly on day 0; group 2) methotrexate. Serum human chorionic gonadotropin (β-hCG) levels were followed until negative. RESULTS: The overall success rate was comparable between groups 1 and 2 (88.6% versus 82.0%, P=0.1). The duration of follow up until negative β-hCG was shorter in group 1 (P=0.001). Receiver operative characteristics showed that higher cut-off levels of β-hCG and gestational mass diameter were associated with successful outcome in group 1. Among participants with initial β-hCG of 3600-5500mIU/mL, the success rate was higher in group 1 (P=0.03). There was no significant difference between groups in adverse effects. CONCLUSION: For treatment of EP, double-dose methotrexate had efficacy and safety comparable to that of single-dose methotrexate; it had better success among patients with moderately high β-hCG and led to a shorter follow up. Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. PMID 22035883 Management of ectopic pregnancies with poor prognosis through ultrasound guided intrasacular injection of methotrexate, series of 14 casesArch Gynecol Obstet. 2012 Feb;285(2):529-33. Epub 2011 Aug 12. Andrés MP, Campillos JM, Lapresta M, Lahoz I, Crespo R, Tobajas J. Source Department of Obstetrics, Miguel Servet University Hospital, C/Monasterio Ntra. Sra. De los Angeles 3, P4, 2ºA, 50012, Zaragoza, Spain. Abstract PURPOSE: The purpose of this study is to describe our experience in cases of tubal ectopic pregnancy with heartbeat, abdominal, interstitial (corneal) and cervical ectopic pregnancies treated with intrasacular injection of methotrexate (MTX) administered under ultrasound guidance associated with a single systemic dose of MTX. METHODS: Descriptive retrospective study of 14 cases of extrauterine pregnancies treated with intrasacular injection of MTX under ultrasound control, attended in the Maternal-Fetal Medicine Unit of the Miguel Servet University Hospital, in Zaragoza, Spain, between January of 2009 and June of 2010. RESULTS: Of the 14 ectopic pregnancies, 7 were tubal with heartbeat, 3 cornual, 2 cervical and 2 abdominal. The average gestational age was 7 + 3 weeks and the average β-hCG value on the date of puncture was 22,885.69 mIU/mL. Surgical treatment was required in two cases, the first due to post-puncture haemoperitoneum and the second as a consequence of the rupture of the corneal ectopic pregnancy. In post-treatment monitoring, an asymptomatic increase of β-hCG on the seventh day post-puncture was observed in two cases. The success rate of the treatment was 92.96%. CONCLUSIONS: Ultrasound guided intrasacular injection of MTX associated with a systemic dose adjusted to the body surface of the patient is a minimally invasive, safe and effective treatment in the cases of tubal ectopic pregnancy with heartbeat, abdominal, cornual or cervical ectopic pregnancy. PMID 21837423 2011Molecular diagnosis of ectopic pregnancyExpert Rev Mol Diagn. 2011 Nov;11(8):759-62. Barnhart K, Speicher DW. A number of EP biomarkers have been proposed include markers of:
Gene-expression microarray analysis of the endometrium - identified activin B as a potential target as it is secreted by the decidua and is found in greater quantities in the serum of women with an intrauterine pregnancy (IUP). Immunohistochemisty and quantitative real time-PCR, followed by serum assay, has been used to identify PGF-1 as a novel EP marker. Immunohistochemistry of the fallopian tubes has been used to identify mucin-1 as a possible marker. PMID 22022935
Development of a multiple marker test for ectopic pregnancyObstet Gynecol. 2011 Mar;117(3):573-82. doi: 10.1097/AOG.0b013e31820b3c61. Rausch ME, Sammel MD, Takacs P, Chung K, Shaunik A, Barnhart KT. Source Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Abstract OBJECTIVE: Many serum markers have been proposed to aid in the identification of an ectopic pregnancy, but few have been validated. Most studies have been limited by sample size and design. The goal of this study was to assess putative markers to identify which can be optimally combined. METHODS: We conducted a case-control study using sera from 100 patients with ectopic pregnancy and 100 patients with intrauterine pregnancy who presented to three urban academic centers between September 2000 and April 2009 with first-trimester pain or bleeding. Samples were analyzed for 12 promising biomarkers. Classification tree analysis was used to examine markers simultaneously with the goal of optimizing the accuracy of ectopic pregnancy diagnosis, and validation was performed using bootstrapping. RESULTS: Six of the 12 markers were differentially expressed between those with ectopic pregnancy and intrauterine pregnancy (P<.001) with fair diagnostic properties (area under the curve greater than 0.6) when examined individually (inhibin A, progesterone, activin A, vascular endothelial growth factor [VEGF], pregnancy-specific β-1-glycoprotein, and pregnancy-associated plasma protein-A). Six additional markers were found to have limited value. Using a two-step diagnostic algorithm with four markers (progesterone, VEGF, inhibin A, activin A), we diagnosed 42% of the sample with perfect specificity and 98% (93-100%) sensitivity. Overall, a single ectopic pregnancy was misclassified, achieving 99% (96-100%) accuracy. CONCLUSION: Evaluating a large number of biomarkers simultaneously demonstrates that most of the putative markers of ectopic pregnancy are not useful. However, a select few can distinguish ectopic pregnancy from intrauterine pregnancy with superior accuracy as part of a multiple marker test. CLINICAL TRIAL REGISTRATION:
PMID 21343760 Full-term extrauterine abdominal pregnancy: a case reportJ Med Case Reports. 2011 Oct 31;5:531. Dahab AA, Aburass R, Shawkat W, Babgi R, Essa O, Mujallid RH. Source Department of Anesthesia, Maternity and Children Hospital, Jeddah, Saudi Arabia. rmujallid@gmail.com. Abstract ABSTRACT: INTRODUCTION: Extrauterine abdominal pregnancy is extremely rare and is frequently missed during antenatal care. This is a report of a full-term extrauterine abdominal pregnancy in a primigravida who likely had a ruptured ectopic pregnancy with secondary implantation and subsequently delivered a healthy baby. CASE PRESENTATION: A 23-year-old, Middle Eastern, primigravida presented at 14 weeks gestation with intermittent suprapubic pain and dysuria. An abdominal ultrasound examination showed a single viable fetus with free fluid in her abdomen. A follow-up examination at term showed a breech presentation and the possibility of a bicornute uterus with the fetus present in the left horn of her uterus. Our patient underwent Cesarean delivery under general anesthesia and was found to have a small intact uterus with the fetus lying in her abdomen and surrounded by an amniotic fluid-filled sac. The baby was extracted uneventfully, but the placenta was implanted in the left broad ligament and its removal resulted in massive intraoperative bleeding that necessitated blood and blood products transfusion and the administration of Factor VII to control the bleeding. Both the mother and newborn were discharged home in good condition. CONCLUSIONS: An extrauterine abdominal pregnancy secondary to a ruptured ectopic pregnancy with secondary implantation could be missed during antenatal care and continue to term with good maternal and fetal outcome. An advanced extrauterine pregnancy should not result in the automatic termination of the pregnancy. PMID 22040324 [PubMed] PMCID PMC3216095 http://www.jmedicalcasereports.com/content/5/1/531 2010Expression of the repulsive SLIT/ROBO pathway in the human endometrium and Fallopian tubeMol Hum Reprod. 2010 Dec;16(12):950-9. Epub 2010 Jul 22. Duncan WC, McDonald SE, Dickinson RE, Shaw JL, Lourenco PC, Wheelhouse N, Lee KF, Critchley HO, Horne AW. Source Centre for Reproductive Biology, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4SB, UK. w.c.duncan@ed.ac.uk Abstract We investigated whether the repulsive SLIT/ROBO pathway is expressed in the endometrium and is negatively regulated during implantation. We also examined whether deficient expression in the Fallopian tube (FT) may predispose to ectopic pregnancy (EP). Endometrium (n = 21) and FT (n = 17) were collected across the menstrual cycle from fertile women with regular cycles. Decidualized endometrium (n = 6) was obtained from women undergoing termination, and FT (n = 6) was obtained from women with EP. SLIT/ROBO expression was quantified by reverse transcription-PCR and protein localized by immunohistochemistry. The regulation of SLIT/ROBO expression in vitro, by sex steroids and hCG, was assessed in endometrial (hTERT-EEpC) epithelial cells, and the effects of Chlamydia trachomatis infection and smoking were studied in oviductal (OE-E6/E7) epithelial cells. Endometrial SLIT3 was highest in the mid-secretory phase (P = 0.0003) and SLIT1,2 and ROBO1 showed a similar trend. ROBO2 was highest in proliferative phase (P = 0.027) and ROBO3,4 showed a similar trend. SLIT2,3 and ROBO1, 4 were lower in decidua compared with mid-secretory endometrium (P < 0.05). SLITs and ROBOs, excepting ROBO2, were expressed in FT but there were no differences across the cycle or in EP. SLIT/ROBO proteins were localized to endometrial and FT epithelium. Treatment of hTERT-EEpC with a combination of estradiol and medroxyprogesterone acetate inhibited ROBO1 expression (P < 0.01) but hCG had no effect. Acute treatment of OE-E6/E7 with smoking metabolite, cotinine, and C. trachomatis had no effect. These findings imply a regulated role for the endometrial SLIT/ROBO interaction during normal development and pregnancy but that it may not be important in the aetiology of EP. PMID: 20651036 http://www.ncbi.nlm.nih.gov/pubmed/20651036 2009Attenuated sex steroid receptor expression in fallopian tube of women with ectopic pregnancyJ Clin Endocrinol Metab. 2009 Dec;94(12):5146-54. Epub 2009 Oct 28. Horne AW, King AE, Shaw E, McDonald SE, Williams AR, Saunders PT, Critchley HO. Source Division of Reproductive and Developmental Sciences, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom. Abstract CONTEXT: Sex steroid hormone receptor (SHR) dynamics are well-documented in human endometrium but have not been comprehensively studied in Fallopian tube (FT). OBJECTIVE: The aim of the study was to compare expression patterns and hormonal regulation of SHR in FT with that described in endometrium and to determine whether SHR expression is altered in FT of women with ectopic pregnancy (EP). DESIGN: Tissue was analyzed and cultured. PATIENTS OR OTHER PARTICIPANTS: Women undergoing surgery for benign gynecological conditions (n = 14) and EP (n = 6) participated in the study. INTERVENTIONS: Quantitative RT-PCR and immunohistochemistry were used to determine SHR mRNA expression and protein localization, respectively. SHR levels were measured in tubal explant cultures stimulated with estrogen and progestogen. RESULTS: ERalpha and ERbeta mRNAs were constitutively expressed in FT during the menstrual cycle. PR-AB and PR-B mRNAs were decreased in midluteal phase compared to follicular phase. ERalpha, PR-AB, and PR-B mRNAs were down-regulated in human FT in vitro by treatment with progestogen. ERalpha, ERbeta1, ERbeta2, PR, and AR proteins localized to cell nuclei of epithelium, stroma, and smooth muscle of nonpregnant FT. In FT from women with EP, PR-B mRNA was decreased when compared to midluteal FT, and ERalpha protein was not detected. CONCLUSIONS: SHR expression in FT is different from that observed in endometrium recovered at similar stages of the menstrual cycle, and expression in FT from women with EP is also altered compared with normal FT. These data are an important benchmark for furthering the understanding of normal human FT physiology, changes in expression of SHR in FT in response to progesterone, and disorders of FT function, such as EP. PMID: 19864448 J Clin Endocrinol Metab. 2009 Dec;94(12):5146-54. Epub 2009 Oct 28. Attenuated sex steroid receptor expression in fallopian tube of women with ectopic pregnancy. Horne AW, King AE, Shaw E, McDonald SE, Williams AR, Saunders PT, Critchley HO. Source Division of Reproductive and Developmental Sciences, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom. Abstract CONTEXT: Sex steroid hormone receptor (SHR) dynamics are well-documented in human endometrium but have not been comprehensively studied in Fallopian tube (FT). OBJECTIVE: The aim of the study was to compare expression patterns and hormonal regulation of SHR in FT with that described in endometrium and to determine whether SHR expression is altered in FT of women with ectopic pregnancy (EP). DESIGN: Tissue was analyzed and cultured. PATIENTS OR OTHER PARTICIPANTS: Women undergoing surgery for benign gynecological conditions (n = 14) and EP (n = 6) participated in the study. INTERVENTIONS: Quantitative RT-PCR and immunohistochemistry were used to determine SHR mRNA expression and protein localization, respectively. SHR levels were measured in tubal explant cultures stimulated with estrogen and progestogen. RESULTS: ERalpha and ERbeta mRNAs were constitutively expressed in FT during the menstrual cycle. PR-AB and PR-B mRNAs were decreased in midluteal phase compared to follicular phase. ERalpha, PR-AB, and PR-B mRNAs were down-regulated in human FT in vitro by treatment with progestogen. ERalpha, ERbeta1, ERbeta2, PR, and AR proteins localized to cell nuclei of epithelium, stroma, and smooth muscle of nonpregnant FT. In FT from women with EP, PR-B mRNA was decreased when compared to midluteal FT, and ERalpha protein was not detected. CONCLUSIONS: SHR expression in FT is different from that observed in endometrium recovered at similar stages of the menstrual cycle, and expression in FT from women with EP is also altered compared with normal FT. These data are an important benchmark for furthering the understanding of normal human FT physiology, changes in expression of SHR in FT in response to progesterone, and disorders of FT function, such as EP. PMID: 19864448 http://www.ncbi.nlm.nih.gov/pubmed/19864448 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989877
2008CB1 expression is attenuated in Fallopian tube and decidua of women with ectopic pregnancyPLoS One. 2008;3(12):e3969. Epub 2008 Dec 18. Horne AW, Phillips JA 3rd, Kane N, Lourenco PC, McDonald SE, Williams AR, Simon C, Dey SK, Critchley HO. Source Department of Reproductive and Developmental Sciences, University of Edinburgh, Centre for Reproductive Biology, Queen's Medical Research Institute, Edinburgh, UK. Abstract BACKGROUND: Embryo retention in the Fallopian tube (FT) is thought to lead to ectopic pregnancy (EP), a considerable cause of morbidity. In mice, genetic/pharmacological silencing of cannabinoid receptor Cnr1, encoding CB1, causes retention of embryos in the oviduct. The role of the endocannabinoids in tubal implantation in humans is not known. METHODS AND FINDINGS: Timed FT biopsies (n = 18) were collected from women undergoing gynecological procedures for benign conditions. Endometrial biopsies and whole blood were collected from women undergoing surgery for EP (n = 11); management of miscarriage (n = 6), and termination of pregnancy (n = 8). Using RT-PCR and immunohistochemistry, CB1 mRNA and protein expression levels/patterns were examined in FT and endometrial biopsies. The distribution of two polymorphisms of CNR1 was examined by TaqMan analysis of genomic DNA from the whole blood samples. In normal FT, CB1 mRNA was higher in luteal compared to follicular-phase (p<0.05). CB1 protein was located in smooth muscle of the wall and of endothelial vessels, and luminal epithelium of FT. In FT from women with EP, CB1 mRNA expression was low. CB1 mRNA expression was also significantly lower (p<0.05) in endometrium of women with EP compared to intrauterine pregnancies (IUP). Although of 1359G/A (rs1049353) polymorphisms of CNR1 gene suggests differential distribution of genotypes between the small, available cohorts of women with EP and those with IUP, results were not statistically significant. CONCLUSIONS: CB1 mRNA shows temporal variation in expression in human FT, likely regulated by progesterone. CB1 mRNA is expressed in low levels in both the FT and endometrium of women with EP. We propose that aberrant endocannabinoid-signaling in human FT leads to EP. Furthermore, our finding of reduced mRNA expression along with a possible association between polymorphism genotypes of the CNR1 gene and EP, suggests a possible genetic predisposition to EP that warrants replication in a larger sample pool. PMID: 19093002 PLoS One. 2008;3(12):e3969. Epub 2008 Dec 18. 2000Interventions for tubal ectopic pregnancyCochrane Database Syst Rev. 2000;(2):CD000324. Hajenius PJ, Mol BW, Bossuyt PM, Ankum WM, Van Der Veen F. Source Department of Obstetrics and Gynecology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, PO Box 22700, Amsterdam, The Netherlands, 1100 DE. p.hajenius@amc.uva.nl Update in Cochrane Database Syst Rev. 2007;(1):CD000324. Abstract BACKGROUND: The diagnosis of ectopic pregnancy can now often be made by non-invasive methods due to sensitive pregnancy tests (in urine and serum) and high resolution transvaginal sonography, which have been integrated in diagnostic algorithms. These algorithms, in combination with the increased awareness and knowledge of risk factors among both clinicians and patients, have enabled an early and accurate diagnosis of ectopic pregnancy. As a consequence, the clinical presentation of ectopic pregnancy has changed from a life threatening disease to a more benign condition. This in turn has resulted in major changes in the options available for therapeutic management. Many treatment options are now available to the clinician in the treatment of tubal pregnancy: surgical treatment, which can be performed radically or conservatively, either laparoscopically or by an open surgical procedure; medical treatment, with a variety of drugs, that can be administered systemically and/or locally by different routes (transvaginally under sonographic guidance or under laparoscopic guidance); expectant management. The choice of a treatment modality should be based on short-term outcome measures (primary treatment success and reinterventions for clinical symptoms or persistent trophoblast) and on long-term outcome measures (tubal patency and future fertility). OBJECTIVES: In the treatment of tubal pregnancy various types of treatments are available: surgical treatment, medical treatment and expectant management. In this review the effects of various treatments are summarized in terms of treatment success, need for reinterventions, tubal patency and future fertility. SEARCH STRATEGY: The Cochrane Menstrual Disorders and Subfertility Group trials register and MEDLINE were searched. SELECTION CRITERIA: Randomized controlled trials comparing treatments in women with ectopic pregnancy. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data extracted independently by two reviewers. Differences were resolved by discussion with all reviewers. MAIN RESULTS: Laparoscopic conservative surgery is significantly less successful than the open surgical approach in the elimination of tubal pregnancy due to a higher persistent trophoblast rate of laparoscopic surgery. Long term follow-up shows similar tubal patency rates, whereas the number of subsequent intrauterine pregnancies is comparable, and the number of repeat ectopic pregnancies lower, although these differences are not statistically significant. The laparoscopic approach is less costly as a result of significantly less blood loss and analgesic requirement, and a shorter duration of operation time, hospital stay, and convalescence time. Compared to laparoscopic conservative surgery (salpingostomy) local methotrexate is not a treatment option. Injection of this drug, both under laparoscopic guidance and under ultrasound guidance, is significantly less successful in the elimination of tubal pregnancy. Systemic methotrexate in a single dose intramuscular regimen is not effective enough in eliminating the tubal pregnancy compared to laparoscopic salpingostomy. This as a result of inadequately declining serum hCG concentrations after one single dose of methotrexate necessitating additional methotrexate injections or surgical interventions. If methotrexate primarily given in a multiple dose intramuscular regimen is compared with laparoscopic salpingostomy no large differences are found in medical outcomes, both short term and long term. However, this treatment regimen is associated with a greater impairment of health related quality of life and is more expensive, due to surgical interventions for clinical signs of tubal rupture, generating additional direct costs due to prolonged hospital stay. Furthermore, indirect costs due to productivity loss are higher. Only in patients with low initial serum hCG concentrations systemic methotrexate leads to costs savings compared to laparoscopic salpingostomy. PMID: 10796710 http://www.ncbi.nlm.nih.gov/pubmed/10796710 Ectopic InterventionsTubal PregnancyThe most recent Cochrane review of tubal pregnancy interventions was carried out in 2000. PMID10796710
Treatment options include
Cervical PregnancyUltrasound Obstet Gynecol. 2006 Apr;27(4):430-7. The conservative management of cervical ectopic pregnancies. Kirk E, Condous G, Haider Z, Syed A, Ojha K, Bourne T. Source Early Pregnancy, Gynaecological Ultrasound and MAS Unit, St George's Hospital Medical School, London, UK. ejkirk@hotmail.co.uk Abstract OBJECTIVE: To evaluate the role of conservative management in the treatment of cervical ectopic pregnancies. METHODS: This was a retrospective analysis of all cervical ectopic pregnancies diagnosed in women attending our early pregnancy unit between April 1997 and September 2004 inclusive. The diagnosis of cervical ectopic pregnancy was made using transvaginal ultrasound. Clinical and demographic data were recorded in all cases. Serum human chorionic gonadotropin levels were measured at presentation and monitored subsequently to determine the rate of successful resolution. Conservative management was in the form of medical or expectant management. Medical management involved administration of systemic or intra-amniotic methotrexate, with or without intra-amniotic potassium chloride. Systemic methotrexate was either a single dose of 50 mg/m2 or an alternate-day regimen of methotrexate at 1 mg/kg (days 1,3,5) with folinic acid rescue (days 2,4,6). If intra-amniotic treatment was required, this was either 50 mg methotrexate or 5 mmol/L potassium chloride. RESULTS: Seven cervical ectopic pregnancies were diagnosed during the study period. Three cases were managed successfully with a single dose of methotrexate. One case was managed successfully using a multiple-dose methotrexate regimen. Another case failed medical management with both the single- and multiple-dose regimens but was successfully treated after potassium chloride was given intra-amniotically under ultrasound guidance. One case was successfully treated with intra-amniotic methotrexate and another was managed expectantly. There was no associated morbidity or mortality during the study period. We also performed a review of the current literature. CONCLUSION: The conservative management of cervical ectopic pregnancy is effective and safe. Copyright 2006 ISUOG. PMID: 16514619 HistoricTubal Pregnancy showing Foetus undergoing DissolutionPurslow CE. Proc R Soc Med. 1915;8(Obstet Gynaecol Sect):68. No abstract available. PMID: 19978839
Pathogenesis of tubal pregnancyClark JF, Verly GP, Johnson HD. PMID 7131577 Activin and Inhibin
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