Talk:Abnormal Development - Ectopic Implantation
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Cite this page: Hill, M.A. (2024, April 19) Embryology Abnormal Development - Ectopic Implantation. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Abnormal_Development_-_Ectopic_Implantation |
2012
Comparison of double- and single-dose methotrexate protocols for treatment of ectopic pregnancy
Int 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
2011
2010
Expression of the repulsive SLIT/ROBO pathway in the human endometrium and Fallopian tube
Mol 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
2009
Attenuated sex steroid receptor expression in fallopian tube of women with ectopic pregnancy
J 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
2008
CB1 expression is attenuated in Fallopian tube and decidua of women with ectopic pregnancy
PLoS 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.
2000
Interventions for tubal ectopic pregnancy
Cochrane 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 Interventions
Tubal Pregnancy
The most recent Cochrane review of tubal pregnancy interventions was carried out in 2000. PMID10796710
- diagnosis of ectopic pregnancy can now often be made by using diagnostic algorithms combining non-invasive methods
- sensitive pregnancy tests (in urine and serum)
- high resolution transvaginal sonography
Treatment options include
- surgical treatment - performed radically or conservatively, either laparoscopically or by an open surgical procedure.
- medical treatment - variety of drugs administered systemically and/or locally (transvaginally under sonographic guidance or under laparoscopic guidance)
Cervical Pregnancy
Ultrasound 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
Historic
Tubal Pregnancy showing Foetus undergoing Dissolution
Purslow CE. Proc R Soc Med. 1915;8(Obstet Gynaecol Sect):68. No abstract available. PMID: 19978839
J Natl Med Assoc. 1982 Aug;74(8):785-8.
Pathogenesis of tubal pregnancy
Clark JF, Verly GP, Johnson HD.
PMID: 7131577
