A salpingostomy is the removal of the ectopic pregnancy, by dissecting it out of the tube, leaving the Fallopian tube in situ in an attempt to preserve fertility on that side. Centre for Maternal and Child Enquiries (CMACE). Human chorionic gonadotropin profile for women with ectopic pregnancy. An official website of the United States government. Improved fertility following conservative surgical treatment of ectopic pregnancy. The aetiology of ectopic pregnancy remains uncertain although a number of risk factors have been identified.4 Its diagnosis can be difficult. Front Med (Lausanne). In one study, 2 of 44 (4.5%) women reported to have no evidence of an ectopic pregnancy at the time of laparoscopy were subsequently diagnosed with one.55 An alternative to diagnostic laparoscopy may involve a repeat ultrasound examination, particularly when -hCG concentrations are close to 1500 IU/l. In the absence of an intrauterine gestation sac, an ectopic pregnancy can be diagnosed by the presence of an adnexal mass, often visible within the Fallopian tube. Kirk E, Bourne T. Diagnosis of ectopic pregnancy with ultrasound. Risk factors for ectopic pregnancy: a comprehensive analysis based on a large case-control, population-based study in France. The managed care of early pregnancy problems. Although the incidence in the developed world has remained relatively static in recent years, between 1972 and 1992 there was an estimated six-fold rise in the incidence of ectopic pregnancy.8 This increase was attributed to three factors: an increase in risk factors such as pelvic inflammatory disease and smoking in women of reproductive age, the increased use of assisted reproductive technology (ART) and increased awareness of the condition, facilitated by the development of specialised early pregnancy units (EPUs). Accurate diagnosis of early ectopic pregnancy. Creative Commons Attribution-NonCommercial 4.0 International License. Ultrasound evaluation of first trimester pregnancy complications. A number of systematic reviews have examined reproductive outcomes following the two procedures in patients with a healthy contralateral tube. 1997 Aug;9(4):262-6. Evidence levels for the recommendations are given in italics in square brackets. In current practice most units use a minimum value of between 50% and 66% for the acceptable 48-hour increase in -hCG in a normal pregnancy.53 Some non-viable IUPs will also demonstrate an exponential increase in serum -hCG, so normal -hCG changes do not necessarily confirm viability. Clinical presentation can be highly variable and ranges from no symptoms to cardiovascular collapse. Progesterone may be no different. Novel studies focusing on the functional consequences of smoking and infection on Fallopian tube physiology and pathobiology are required. Federal government websites often end in .gov or .mil. government site. In: Cantwell R, Clutton-Brock T, Cooper G, et al., editors. Chlamydia trachomatis has been linked to 30-50% of all ectopic pregnancies.12 The exact mechanism of this association is not known but it has been proposed that in addition to distortion of tubal architecture, it may to be due to an effect on the tubal microenvironment.13, Previous tubal surgery (including female sterilisation) and pelvic surgery including Caesarean section and ovarian cystectomy, Previous abdominal surgery including appendicectomy and bowel surgery, Confirmed genital infection and pelvic inflammatory disease, commonly caused by chlamydial infection, Ectopic pregnancy is more common in women attending infertility clinics14 even in the absence of tubal disease. official website and that any information you provide is encrypted Epub 2021 Dec 16. The https:// ensures that you are connecting to the Shalev E, Peleg D, Tsabari A, et al. Previous spontaneous abortion or induced abortion, Positive identification of an ectopic pregnancy mass: inhomogenous mass, empty adnexal gestation sac or adnexal sac containing yolk sac or fetal pole, Free fluid (i.e. Ahmed AA, Tom BD, Calabrese P. Ectopic pregnancy diagnosis and the pseudo-sac. (A) An IUP at 6 weeks. Indeed, if treatment was started 9 weeks of gestation, there was no effect of progesterone supplementation (RR: 0.98, 95% CI: 0.941.03). Condous G, Okaro E, Khalid A, et al. Horne AW, Duncan WC, Critchley HO. Close treatment surveillance, and staff and patient awareness of potential treatment failure, are vital. Linear salpingostomy for ectopic pregnancy. Combined intra-uterine and extra-uterine pregnancy more frequently in IVF pregnancies, depending on the number of embryos transferred). Using transabdominal ultrasound examination, it was reported then that the absence of an intrauterine gestational sac at a -hCG concentration over 6500 IU/l had a sensitivity of 100%, specificity of 96%, positive predictive value of 87% and negative predictive value of 100% for the prediction of ectopic pregnancy. Federal government websites often end in .gov or .mil. There is further evidence from the PROMISE trial where vaginal micronised progesterone (400 mg twice daily) was given from a positive pregnancy test until 12 weeks of gestation in those with recurrent miscarriage (Coomarasamy et al. Weckstein LN, Boucher AR, Tucker H, et al. EUROPEAN GUIDELINES AND GOOD PRACTICE RECOMMENDATIONS FOR CONTRAST ENHANCED ULTRASOUND (CEUS) Please click here to view the guidelines prepared by EFSUMB. NICE have made a considered call about the utility of progesterone supplementation in threatened miscarriage with those with a previous miscarriage based on post hoc analysis. In vitro fertilisation (IVF) is associated with an ectopic pregnancy risk of 2-5% and it may be higher than this where there is tubal disease. This guideline covers diagnosing and managing ectopic pregnancy and miscarriage in women with complications, such as pain and bleeding, in early pregnancy (that is, up to 13 completed weeks of pregnancy). 21). W Colin Duncan is an Associate Editor of Reproduction and Fertility. Barnhart K, van Mello NM, Bourne T, et al. It aims to improve how early pregnancy loss is diagnosed, and the support women are given, to limit the psychological impact of their loss. In the PRISM trial (Coomarasamy et al. Shalev E, Yarom I, Bustan M, et al. Which management is most appropriate depends on ongoing assessment and on numerous clinical factors. (A) Left tubal ectopic pregnancy at laparoscopy. Cotinine exposure increases Fallopian tube PROKR1 expression via nicotinic AChRalpha-7: a potential mechanism explaining the link between smoking and tubal ectopic pregnancy. Disclaimer. Colin Duncan holds a Scottish Senior Clinical Fellowship and has grant support from The Cunningham Trust. New biomarkers with clinical utility would be helpful in improving the diagnosis of ectopic pregnancy, with the potential benefits of greater safety and reduced diagnostic costs.5,32, In cases where an ectopic pregnancy is suspected and ultrasound is inconclusive, a diagnostic laparoscopy may be required. J Fam Plann Reprod Health Care. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). PMC This guideline was developed with complete independence from RCOG governance. 4 UNI | 4.95 per 1UNI. This guideline covers diagnosing and managing ectopic pregnancy and miscarriage in women with complications, such as pain and bleeding, in early pregnancy (that is, up to 13 completed weeks of pregnancy). Recommendations This guideline includes new and updated recommendations on: management of miscarriage It also includes recommendations on: using ultrasound scans for diagnosis of tubal ectopic pregnancy expectant management support and information giving early pregnancy assessment services symptoms and signs of ectopic pregnancy Bethesda, MD 20894, Web Policies The site is secure. Bangsgaard N, Lund CO, Ottesen B, et al. Would you like email updates of new search results? Coomarasamy A, Harb HM, Devall AJ, Cheed V, Roberts TE, Goranitis I, Ogwulu CB, Williams HM, Gallos ID, Eapen A, Daniels JP, Ahmed A, Bender-Atik R, Bhatia K, Bottomley C, Brewin J, Choudhary M, Crosfill F, Deb S, Duncan WC, Ewer A, Hinshaw K, Holland T, Izzat F, Johns J, Lumsden MA, Manda P, Norman JE, Nunes N, Overton CE, Kriedt K, Quenby S, Rao S, Ross J, Shahid A, Underwood M, Vaithilingham N, Watkins L, Wykes C, Horne AW, Jurkovic D, Middleton LJ. The https:// ensures that you are connecting to the National register data are of value in studies on miscarriage-Validation of the healthcare register data in Finland. There are theoretical risks impacting offspring health in later life after maternal pharmaceutical progesterone treatment. 2021 exceptional surveillance of ectopic pregnancy and miscarriage: diagnosis and initial management (NICE guideline NG126) Surveillance report London: National Institute for Health and Care Excellence (NICE); 2021 Oct 21. Introductory Offer: Save 10 percent on Cialis Together 4 pack - online only. It's very important that the diagnosis of ectopic pregnancy is certain before receiving this treatment. National Library of Medicine Their absence in the presence of a static -hCG is suggestive of an ectopic pregnancy. The 1997-1999 and 2003-2005 Confidential Enquiries into Maternal Deaths reports highlighted that most of the women who died from ectopic pregnancy were misdiagnosed in the primary care or accident and emergency settings.28,29 It was therefore recommended that all clinicians should be made aware of the atypical clinical presentations of ectopic pregnancy. It is the PRISM trial protocol, which required a scan-confirmed intrauterine pregnancy and treatment with 400 mg twice daily vaginal micronised progesterone up until 16 weeks of pregnancy, that informed the NICE guidance. Clayton HB, Schieve LA, Peterson HB, et al. 17 April 2019 This site needs JavaScript to work properly. Gilman A, Goodman LS, Goodman A, Calabresi P, Chabner BA. 2020 Jun;24(33):1-70. doi: 10.3310/hta24330. Scenario: Follow up after an ectopic pregnancy: Covers how to follow up a woman after treatment for an ectopic pregnancy. This guideline will cover the following ectopic pregnancies: tubal, cervical, caesarean scar, interstitial, cornual, ovarian, abdominal and heterotopic. the contents by NLM or the National Institutes of Health. They recognised that this was an off-label use of vaginal micronised progesterone. The source of progesterone support for pregnancy is endocrine, coming from the corpus luteum of the maternal ovary, until 9 weeks of gestation and uterine, coming from the fetal placenta, after 9 weeks of gestation (Duncan 2021). Royal College of Obstetricians and Gynaecologists and Royal College of Radiologists Faculty of Clinical Radiology . The commonly used single-dose methotrexate treatment regimen involves a deep intramuscular injection at a dose of 50 mg/m2 of the calculated body surface area. Sometimes, an ectopic pregnancy occurs in other areas of the body, such as the ovary, abdominal cavity or the lower part of the uterus (cervix), which connects to the vagina. Risk factors for ectopic pregnancy: a meta-analysis. As ectopic pregnancy affects young, fit women they are often able to mount remarkable haemodynamic compensation. The site is secure. Nama V, Manyonda I. Tubal ectopic pregnancy: diagnosis and management. As the effect of progesterone seems to be complete by 12 weeks of gestation, we should consider carefully whether to follow the guidance and treat up to 16 weeks of pregnancy. The committee felt that the important size effect and post hoc subgroup analysis were robust enough to inform the recommendation (https://www.nice.org.uk/guidance/ng126/evidence/evidence-review-c-pdf-10889099534). Chez RA, Moore JG. Diagnosis of ectopic pregnancy has improved significantly due to advances in ultrasound technology, rapid and sensitive serum hormone assays, the development of EPUs and an increased awareness and understanding of the associated risk factors. The multi-dose regimen consists of methotrexate treatment on Days 1, 3, 5 and 7 to a maximum of four doses and leucovorine rescue-therapy at a dose of 0.1 mg/kg on alternate Days 2, 4, 6 and 8. There have been major advances in the diagnosis and management of ectopic pregnancies during the last 20 years. 4 Its diagnosis can be difficult. It is not known whether methotrexate treatment has better fertility outcomes than surgery but this is likely to be the case when the ectopic gestation occurs in the only functioning tube. GK has received funding from the Public Services Ombudsman for Wales. When minimal evidence is available, recommendations are based on the Guideline Development Groups experience and opinion of what constitutes good practice. London: National Institute for Health and Care Excellence (NICE); 2021 Mar 31. blood): suggestive of ectopic pregnancy in the absence of IUP, but not diagnostic (small amount may be physiological), Serum beta-human chorionic gonadotrophin (-hCG) concentrations. Follow-up should be between one and three times weekly with -hCG measurement and ultrasonography as required. If the contralateral tube is healthy, the preferred option is salpingectomy, where the entire Fallopian tube, or the affected segment containing the ectopic gestation, is removed (Figure 3). Chang J, Elam-Evans LD, Berg CJ, et al. In selected cases of PUL, an endometrial biopsy may be taken and analysed for the presence or absence of chorionic villi. Human chorionic gonadotrophin and progesterone levels in pregnancies of unknown location. A ruptured ectopic pregnancy should be strongly suspected if a woman has a positive pregnancy test and presents with syncope and signs of shock including tachycardia, pallor and collapse. In a clinically realistic ovine study, administration of natural progesterone to the mother, until the equivalent developmental stage of 1516 weeks in humans, increased male fetal progesterone concentrations (Siemienowicz et al. This site needs JavaScript to work properly. Overview. References. Of the women who died during 200608, half were from minority ethnic groupsand so may have accessed care later or experienced difficulty in communicationand most deaths were associated with substandard care due to failure to consider ectopic pregnancy when presentation was atypical.2 Therefore, it is vital that healthcare professionals in all specialties are alert to the possibility of ectopic pregnancy in order to avoid missed opportunities for diagnosis. 2019). Expectant management is reported to be most useful when the initial -hCG is <1000 IU/l.58 A rapidly declining -hCG level also appears to predict a favourable outcome.77 Success rates between 47% and 82% are reported, depending on the patients initial status.78. NICE now recommend to offer vaginal micronised progesterone 400 mg twice daily to women with an intrauterine pregnancy confirmed by a scan, if they have vaginal bleeding and have previously had a miscarriage and if a fetal heartbeat is confirmed, continue progesterone until 16 completed weeks of pregnancy. The major change in this guideline was in the management of threatened miscarriage. Indeed the first IVF pregnancy, before the first IVF live birth, was a tubal ectopic pregnancy.15, Some types of contraception, such as progestogen-only contraception and the intrauterine contraceptive device, are associated with an increased incidence of ectopic pregnancy when there is contraceptive failure, without necessarily increasing the absolute risk of ectopic pregnancy.16, One third of all cases of ectopic pregnancy are thought to be associated with smoking.17 There is a doseeffect relationship, with the highest adjusted odds ratio (OR) (3.9) when more than 20 cigarettes are smoked a day.18 Several mechanisms for this association have been suggested, including one or more of the following: delayed ovulation, altered tubal and uterine motility and microenvironment, or altered immunity.19,20, The risk of ectopic pregnancy increases with advancing maternal age, with age over 35 years being a significant risk factor.6 Hypotheses for this association include the higher probability of exposure to most other risk factors with advancing age, increase in chromosomal abnormalities in trophoblastic tissue and age-related changes in tubal function delaying ovum transport, resulting in tubal implantation.18, Women with a previous history of ectopic pregnancy also have an increased risk, which increases further in proportion to the number of previous ectopic pregnancies. National Library of Medicine government site. -hCG, beta-human chorionic gonadotrophin. These factors include any previous pelvic or abdominal surgery, and pelvic infection.11 Conservative versus radical surgery for tubal pregnancy. Barnhart KT, Gosman G, Ashby R, et al. Quality standard - Ectopic pregnancy and miscarriage, Finding more information and committee details, using ultrasound scans for diagnosis of tubal ectopic pregnancy, diagnosis of viable intrauterine pregnancy and ectopic pregnancy, assess and reduce the environmental impact of implementing NICE recommendations, Women with complications in early pregnancy (up to 13 completed weeks of pregnancy), their families and carers. The authors thank Ronnie Grant for graphics support and Dr Graeme Walker for images. Before In a recent study of 287 patients with pain or bleeding, the minimum rise in -hCG for a viable IUP was 24% at 24 hours and 53% at 48 hours.51 In addition, Seeber et al.52 produced data with a 99% CI that suggested a more conservative minimum rise of 35% over 2 days. The NICE guideline (NG126) Ectopic pregnancy and miscarriage: diagnosis and initial management was updated on 24 November 2021 (https://www.nice.org.uk/guidance/ng126). If -hCG concentrations are falling but an ectopic has not been excluded, consideration should be given to performing serial -hCG measurements until levels become undetectable, as rupture can still occur.40. There is thought to be a 5-20% risk of a recurrence of ectopic pregnancy with one previous ectopic pregnancy and a risk of 32% or more following more than one previous ectopic.79 However, the risk is reduced after each subsequent IUP.80 Even when there has been a bilateral salpingectomy there is still a risk of ectopic pregnancy in the interstitial tube or in tubal remnants following IVF. The 20062008 CMACE report drew attention to a maternal death secondary to ruptured ectopic pregnancy where a diagnosis of PUL had been made.30 Although most patients with a PUL will subsequently be diagnosed with either a failed IUP (a spontaneous abortion) or viable IUP, the report highlights that 7-20% will be diagnosed with an ectopic pregnancy. Clinicians should be suspicious of pregnancy in any such woman who presents with abdominal or pelvic symptoms and should always bear in mind the possibility of ectopic pregnancy in any woman of reproductive age who presents with any of the symptoms mentioned above. Inclusion in an NLM database does not imply endorsement of, or agreement with, Around 80% of ectopic pregnancies will be on the same side as the ovarian corpus luteum, the identification of which can help in the search for an adnexal mass. If someone who has had a previous miscarriage starts bleeding, they should now be treated with progesterone as this slightly reduces the chance of miscarriage. Many women will experience complications in early pregnancy. FOIA Shaw JL, Dey SK, Critchley HO, et al. This work did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector. The UK is the first country to allow OTC access to Sanofi's tadalafil-based erectile dysfunction drug Cialis following a successful switch. Royal College of Obstetricians and Gynaecologists . NICE recommends dedicated NHS service for women with miscarriage or ectopic pregnancy. AWH receives grant support from UK Medical Research Council (2009-13) (G0802808), IKTF (2009-2011) and an Albert McKern Bequest (2010-11). American Institute of Ultrasound in Medicine AIUM practice guideline for the performance of obstetric ultrasound examinations. Other strategies include alternative diagnostic tests, such as serum progesterone or an endometrial biopsy, or empirical medical treatment as the patient may well have an ectopic pregnancy. FOIA 2013 Jan 22;346:f197. The medication is given by injection. Please note: your email address is provided to the journal, which may use this information for marketing purposes. Robson SJ, OShea RT. Overall, there was a 75% live birth at 34 weeks in the progesterone arm and a 72% live birth at 34 weeks in the placebo arm. The clinician should be certain that the pregnancy, if intrauterine, is non-viable and appropriate consent obtained, as this procedure could potentially interrupt a continuing pregnancy. This is believed by many to be the gold standard investigation in ectopic pregnancy. Laparoscopic surgery in ectopic pregnancy. Accessibility It is notable that it is unique to humans, and perhaps the higher apes, so that there are no good animal models that could be used to further our understanding.21 However, it is thought that tubal implantation occurs as a result of a combination of arrest of the embryo in the Fallopian tube and changes in the tubal microenvironment that allow early implantation to occur.4 Inflammation within the tube, resulting from infection or smoking, may affect embryo-tubal transport by disrupting smooth muscle contractility and ciliary beat activity and may also provide pro-implantation signals. The .gov means its official. Prompt diagnosis of ectopic pregnancy in an emergency department setting. National Library of Medicine Careers, Unable to load your collection due to an error. Competing interests: We declare the following interests based on NICE's policy on conflicts of interests (https://www.nice.org.uk/Media/Default/About/Who-we-are/Policies-and-procedures/declaration-of-interests-policy.pdf): SF has received funding from NICE, National Institute for Health Research, Royal College of Obstetricians and Gynaecologists, and Mott MacDonald. Molecular research generally involves studying Fallopian tube biopsies taken from women with ectopic pregnancies. Interpretation is limited as comparable Fallopian tube samples are not available from women with an intrauterine pregnancy (IUP) or in advance of an ectopic pregnancy occurring. While the short-term costs of postoperative follow-up and treatment of persistent trophoblast are greater following a salpingostomy,69 the potential avoidance of the subsequent need for assisted conception will make it more cost effective compared with salpingectomy.66. Curr Opin Obstet Gynecol. W Colin Duncan was not involved in the review or editorial process for this paper, on which he is listed as an author. and transmitted securely. The effect of progesterone on neural function is well recognised although its effect on the developing brain is not well researched. Laparoscopic procedures are associated with shorter operative times, less intraoperative blood loss, shorter hospital stays and lower analgesia requirements.59-61 Laparotomy should be reserved for patients who present with rupture and are in a state of hypovolaemic shock and compromise. 5705185. Goldner TE, Lawson HW, Xia Z, et al. A randomised trial comparing single dose systemic methotrexate and laparoscopic surgery for the treatment of unruptured tubal pregnancy. Endometrial inhibin/activin beta-B subunit expression is related to decidualization and is reduced in tubal ectopic pregnancy. NICE guidance on ectopic pregnancy and miscarriage restricts access and choice and may be clinically unsafe. Korhonen J, Stenman UH, Ylstalo P. Serum human chorionic gonadotropin dynamics during spontaneous resolution of ectopic pregnancy. An official website of the United States government. Approximately 10% of women will require surgical intervention,75 although most of these are for slowly falling -hCG levels rather than for acute tubal rupture. The central dark area is the intrauterine gestational sac and within the sac is a circular ringed structure that is the yolk sac. Although there are no definitive values that demarcate an ectopic pregnancy from an IUP, the measurement of serum progesterone levels is a potentially useful adjunct in the assessment of PULs.55 Serum progesterone concentrations in a viable IUP are >50 ng/ml. 2019 Nov 13;367:l6283. Unauthorized use of these marks is strictly prohibited. WCD holds a Scottish Senior Clinical Fellowship and has grant support from The Cunningham Trust. Lipscomb GH, Bran D, McCord ML, et al. Perriera L, Reeves MF. 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