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Hum. Reprod. Advance Access originally published online on September 13, 2007
Human Reproduction 2007 22(11):2824-2828; doi:10.1093/humrep/dem283
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

The diagnostic effectiveness of an initial transvaginal scan in detecting ectopic pregnancy

Emma Kirk1,5, Aris T. Papageorghiou1,2, George Condous1,3, Linda Tan1, Shabana Bora1 and Tom Bourne1,4

1 Early Pregnancy and Gynaecological Ultrasound Unit, Department of Obstetrics and Gynaecology, St George's, University of London, Cranmer Terrace, London SW17 0RE, UK 2 Fetal Medicine Unit, Department of Obstetrics and Gynaecology, St George's, University of London, London, UK 3 Early Pregnancy and Advanced Endosurgery Unit, Nepean Clinical School, Nepean Hospital, University of Sydney, Sydney, Australia 4 Department of Obstetrics and Gynaecology, University Hospitals, KU Leuven, Belgium

5 Correspondence address. Tel: +44-208-725-0050; Fax: +44-208-725-0094; E-mail: ejkirk{at}hotmail.co.uk


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
 References
 
BACKGROUND: To determine the effectiveness of an initial transvaginal ultrasound scan (TVS) in the detection of ectopic pregnancy in consecutive women attending an early pregnancy unit (EPU).

METHODS: This was a prospective observational study. Unselected women attending a dedicated EPU underwent a TVS. Women were classified as having an intrauterine pregnancy (IUP), ectopic pregnancy or pregnancy of unknown location (PUL). Women with a PUL were followed up until the final location of the pregnancy was determined. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) with 95% confidence intervals (CIs) for the initial TVS in the diagnosis of ectopic pregnancy were calculated.

RESULTS: During a one-year study period, 5318 consecutive women attended the EPU. Outcome data were available for 5240 (98.5%) women. Of these, the initial TVS showed an IUP in 4693 (89.6%) cases and an ectopic pregnancy in 91 (1.7%) cases. The remaining 456 (8.7%) women were classified as PUL, and of these 31 (6.8%) were subsequently found to have ectopic pregnancies. The overall sensitivity of the initial TVS in the diagnosis of ectopic pregnancy was 73.9% (95% CI: 65.1–81.6) with a specificity of 99.9% (95% CI: 99.8–100), a PPV of 96.7% (95% CI: 90.7–99.3) and an NPV of 99.4% (95% CI: 99.2–99.6).

CONCLUSIONS: In unselected women attending an EPU, pregnancy location can be diagnosed accurately in over 90% of all pregnancies and in 73.9% of ectopic pregnancies with a single TVS.

Key words: transvaginal ultrasound/ectopic pregnancy/intrauterine pregnancy/pregnancy of unknown location


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Conclusions
 References
 
Ectopic pregnancy is a common problem, occurring in about 11 in 1000 pregnancies (Lewis and Drife, 2004Go), and over 10 000 are diagnosed annually in the United Kingdom. Early diagnosis may prevent tubal rupture, and enables elective or non-surgical treatment to be offered (Cacciatore et al., 1994Go; Kirk and Bourne, 2006Go). The use of transvaginal ultrasonography (TVS) to screen for early pregnancy complications has been studied in certain patient populations. In one study of 140 women undergoing a TVS in a termination of pregnancy clinic, 1 woman (0.7%) was correctly diagnosed with an ectopic pregnancy and in total 56 women (40%) benefited from a TVS, leading to a change in management plan: of these 27% had a non-viable pregnancy, 36% did not remember their last menstrual period (LMP), 13% had discrepancy between the scan and LMP and 25% had significant incidental findings (Sinha et al., 2004Go). Another study examined the effectiveness of TVS or transabdominal ultrasound examination in the detection of ectopic pregnancy in women attending an emergency department with a serum human chorionic gonadotrophin (hCG) level >1500 IU/l (Braffman et al., 1994Go). The sensitivity and specificity of screening for ectopic pregnancy were 99% and 84%, respectively. The results of screening programmes involving TVS and the measurement of serum hCG levels in asymptomatic women with recognized risk factors for ectopic pregnancy have been variable, due to different prevalence rates. One study, in which 24.4% of the women were subsequently diagnosed with an ectopic pregnancy, concluded that early surveillance reduced the risk of complications, facilitated treatment and should therefore be offered to all at-risk women (Cacciatore et al., 1994Go). Conversely another study, in which the prevalence of ectopic pregnancy in the screened population was 5.6%, concluded that it was questionable whether the possible benefits outweigh possible detriments including a false-positive diagnosis, financial costs and emotional stress (Mol et al., 1997Go).

TVS has been shown to be an acceptable diagnostic procedure for women attending an early pregnancy unit (EPU) with problems such as pain and bleeding in early pregnancy (Dutta and Economides, 2003Go; Basama et al., 2004Go). It has been shown to be an accurate diagnostic test for ectopic pregnancy with a high sensitivity (87.0–99.0%) and specificity (94.0–99.9%) (Braffman et al., 1994Go; Shalev et al., 1998Go; Atri et al., 2003Go; Condous et al., 2005aGo). However, these studies examined women using TVS prior to laparoscopy, and correlated sonographic features to surgical findings. Therefore, they do not give us good information about overall test performance in the EPU population.

To date there are no data on the overall performance of an initial TVS in the EPU setting. The aim of this study was to assess the effectiveness of an initial TVS in detecting ectopic pregnancy in an unselected population of women attending an EPU.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Conclusions
 References
 
This was a prospective observational study including all women attending the EPU with a positive pregnancy test over a one-year period. The EPU is open 6 days a week and receives referrals from General Practitioners, the Accident and Emergency Department, Midwives and other health care professionals, as well as accepting self-referrals. Over 7000 ultrasound examinations are performed in the unit each year. Women attended for a number of reasons, including abdominal pain, vaginal bleeding (or both), uncertain menstrual dates, maternal anxiety or a history of a previous pregnancy complication. All women underwent TVS using a 5 MHz transducer for B mode imaging (Aloka SSD 900, 2000 or 4000, Aloka Co. Japan) by experienced sonographers. Ultrasound findings were entered onto an electronic database (Viewpoint PIA database, LB Systems, Vienna, Austria) at the time of the ultrasound examination. Pregnancy outcomes were entered onto the same database when these became available.

Women were diagnosed with either an intrauterine pregnancy (IUP) or an ectopic pregnancy using pre-defined criteria (Table 1). Women with no evidence of an intrauterine or ectopic pregnancy on TVS were classified as having a pregnancy of unknown location (PUL). These women were followed up with serum human chorionic gonadotrophin (hCG) and progesterone levels, repeat TVS examinations and, if necessary, laparoscopy or uterine curettage, until the final location of the pregnancy was known. In some pregnancies serum hCG levels failed to rise or decline over three or more serial measurements over at least two weeks, and in addition no pregnancy was ever located on TVS, laparoscopy or uterine curettage. These were termed persisting PUL, and they may represent undiagnosed ectopic pregnancies (Condous et al., 2005bGo). Women lost to follow-up and those in whom the final location of the pregnancy was unknown (persisting PUL) were excluded from the analysis.


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  		Table 1: Diagnostic criteria used for pregnancy location on TVS

 
Women diagnosed with tubal ectopic pregnancies were managed expectantly, medically or surgically. The type of management depended on clinical signs and symptoms, TVS findings and serum hCG levels. Surgical management was by laparoscopy or laparotomy. Medical management was in the form of a single systemic dose of methotrexate (50 mg/m2). Non-tubal ectopic pregnancies were either managed surgically, with systemic methotrexate, or with ultrasound-guided injection of intra-amniotic methotrexate.

The primary outcome measure of this study was ectopic pregnancy. This was defined as the ultrasonographic visualization of an ectopic pregnancy mass or the finding of an ectopic pregnancy at the time of a laparoscopy or laparotomy and confirmed histologically. The secondary outcome measure was IUP, which was diagnosed on ultrasound using predefined ultrasound criteria (Table 1), or by histological confirmation of products of conception after a surgical evacuation of the uterus.

Statistical analysis
The sensitivity, specificity, positive predictive value (PPV), negative predictive value and (NPV) with 95% confidence intervals (CI) for the initial USS to diagnose ectopic pregnancy were calculated. After testing for normality using the Shapiro–Wilk test, the Mann–Whitney U test was used to compare continuous non-parametric variables between the two groups, and chi-squared or Fisher's exact test were used as appropriate to compare dichotomous variables. Two sided P-values are reported. Statistical analysis was performed using MS Excel 2000 and StatsDirect Version 2.6.2.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Conclusions
 References
 
Between February 2005 and February 2006, 5318 women attended the EPU for an initial scan. Of these, 78 (1.5%) were excluded from analysis: 71 women who were lost to follow-up and 7 women with persisting PULs. A total of 5240 women undergoing an initial TVS in the EPU were therefore included in the analysis.

At the initial TVS, 91.3% (4784/5240) of women had the location of their pregnancy diagnosed: 89.6% (4693/5240) were diagnosed with IUPs and 1.7% (91/5240) were diagnosed with ectopic pregnancies. The remaining 8.7% (456/5240) were initially classified as PULs.

Of the 91 women diagnosed as having an ectopic pregnancy on the initial TVS, 86 were diagnosed as a tubal ectopic pregnancy, 3 were interstitial pregnancies and 2 were caesarean section scar pregnancies. There were three false-positive diagnoses of tubal ectopic pregnancy. In one case, the diagnosis of ectopic pregnancy was subsequently excluded: a laparoscopy revealed an inflamed appendix, which was the mass seen on TVS. An appendicetomy was performed and histology showed acute suppurative appendicitis. A viable IUP was visualized on TVS two weeks later. In another two cases, the diagnosis of ectopic pregnancy could not be confirmed as although a mass was seen on ultrasound, no abnormality was found at laparoscopy. In one of these, the serum hCG level spontaneously decreased, while in the other, systemic methotrexate was administered for persistently raised serum hCG levels despite uterine curettage, which failed to show any trophoblastic tissue.

Of the remaining 88 women with ectopic pregnancy, surgical management was undertaken in 74 (84%) cases, and the diagnosis was confirmed histologically in all of these. The remaining 14 (16%) women had successful non-surgical management in the form of systemic methotrexate (n = 11) or expectant management (n = 3).

The initial TVS failed to locate the pregnancy in 456 cases, and these were classified as PUL. Of these, 6.8% (31/456) were subsequently diagnosed with ectopic pregnancies. Therefore, 31 cases of ectopic pregnancy were not visualized on the initial TVS; these comprised 27 tubal ectopic pregnancies, 1 interstitial ectopic pregnancy and 3 caesarean section scar pregnancies. Although not visualized on the original scan, 29 out of 31 (93.5%) of the ectopic pregnancies in the PUL population were visualized on subsequent follow-up TVS prior to treatment, while the remaining two cases were diagnosed at the time of laparoscopy. Of the 31 cases of ectopic pregnancy that were not visualized on the initial TVS, 15 (48%) underwent successful non-surgical management: 11 tubal pregnancies were managed with systemic methotrexate (n = 8) or expectant management (n = 3), and 4 non-tubal pregnancies were managed with systemic methotrexate (n = 2) or local methotrexate (n = 2). The other 16 (52%) ectopic pregnancies were managed laparoscopically without any complications (14 salpingectomies, 1 salpingostomy and 1 laparoscopy where a tubal miscarriage was diagnosed and required no further treatment).

At presentation, serum hCG levels in those tubal ectopic pregnancies missed on the initial TVS (i.e. those initially classified as PULs) were significantly lower than those in tubal ectopic pregnancies visualized on the initial TVS (Table 2).


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  		Table 2: Serum hCG levels and characteristics of TVS in tubal ectopic pregnancies visualized on initial TVS, and those initially classified as PULs

 
The sensitivity of the initial TVS to diagnose ectopic pregnancy was 73.9% (95% CI: 65.1–81.6) with a specificity of 99.9% (95% CI: 99.8–100), a PPV of 96.7% (95% CI: 90.7–99.3) and an NPV of 99.4% (95% CI: 99.2–99.6, Table 3). If follow-up scans are included, the overall sensitivity of TVS to diagnose ectopic pregnancy was 98.3% (95% CI: 94.1–99.8) with a specificity of 99.9% (95% CI: 99.8–100), a PPV of 97.5% (95% CI: 92.9–99.5) and an NPV of 100% (95% CI: 99.9–100) (Table 4).


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  		Table 3: 2x2 tables for the use of the initial TVS performed in the EPU to diagnose ectopic pregnancy

 

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  		Table 4: 2x2 table for the overall performance of TVS performed in the EPU to diagnose ectopic pregnancy

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Conclusions
 References
 
We have shown that a single TVS is an effective test for the detection of ectopic pregnancy in the population of women attending an EPU. This single scan will detect ~75% of all ectopic pregnancies with a high specificity (99.9%). In addition, the high NPV of this initial ultrasound also means that the majority of women (~90%) can be reassured that the pregnancy is intrauterine. Finally, the scan identified 9% of women as having a PUL. This group appears to benefit from close follow-up as it will contain within it 25% of all ectopic pregnancies. The use of such follow-up ultrasound scans means that the sensitivity of TVS overall in the diagnosis of ectopic pregnancies is much higher (98.3%) as some ectopic pregnancies subsequently visualized on TVS were classified as PULs on the initial examination.

The overall sensitivity of TVS to diagnose ectopic pregnancy in our study is high and similar to the rates of 87.0–99.0% that are published in other studies (Braffman et al., 1994Go; Shalev et al., 1998Go; Atri et al., 2003Go; Condous et al., 2005aGo). An important limitation of previous studies is that they did not assess a single admission scan as the test, but rather report on the detection of ectopic pregnancies visualized using subsequent scans also. In addition, most only relate to selected populations of women and some are retrospective reviews of women with histologically confirmed ectopic pregnancies only (Table 5). We therefore believe our study gives a more realistic idea of what standards should be expected when an unselected group of women attend an EPU for the first time. It should also be emphasized that most ectopic pregnancies will be visualized on follow-up scans and certainly prior to surgery.


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  		Table 5: Summary of studies assessing performance of TVS to diagnose ectopic pregnancy

 
One limitation of this study is that it is possible that women with an ultrasound diagnosis of ectopic pregnancy who were managed non-surgically may have been misdiagnosed, as there was no histological confirmation. In the current study, we have shown that using a single TVS examination correctly diagnosed ectopic pregnancy in 96.1% (74/77) of those undergoing surgical management. One could extrapolate this and assume misdiagnosis in 3.9% of all the non-surgically managed ectopic pregnancies. This would leave us with the same sensitivity of the initial TVS in detecting ectopic pregnancy (74%), but would reduce the PPV of the test from 97% to around 94%.

One interesting finding in our study is that serum hCG levels were significantly higher in women diagnosed with ectopic pregnancy at the time of the initial TVS than in those with PUL who were subsequently diagnosed with ectopic pregnancy (P < 0.001). Interestingly, the serum hCG at diagnosis was similar between the two groups. This may suggest that there is a level of serum hCG at which visualization of ectopic pregnancy becomes more likely. However, the relatively small number of ectopic pregnancies in this population may mean that this difference in hCG behaviour is a chance finding due to multiple comparisons between the groups (i.e. a type I error), and examination of hCG levels in a larger population are needed to confirm this.

We have shown that TVS is an effective test for the detection of ectopic pregnancy in women presenting to the EPU. This included symptomatic and asymptomatic women, and this raises the question of whether we should be offering screening for ectopic pregnancy. Studies from the Netherlands have shown that screening of asymptomatic high-risk women, with an ectopic pregnancy rate of 6%, compared with 2% in our study, might be justified for psychological reasons, but the medical and economic benefits of such a policy seem to be limited. Further studies in asymptomatic women are needed to assess whether the potential benefits such as prevention of complications and reassurance outweigh the possible detriments such as false-positive diagnosis, financial costs and emotional stress (Mol et al., 1997Go, 2002Go).


   Conclusions
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
References
 
In unselected women attending the EPU, almost 75% of ectopic pregnancies will be visualized on the initial scan. Overall, pregnancy location can be diagnosed accurately in over 90% of women with a single TVS examination. About 9% will have a PUL on this initial scan, and this group contains within it all remaining ectopic pregnancies.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
 References
 
Atri M, Valenti DA, Bret PM, Gillett P. Effect of transvaginal sonography on the use of invasive procedures for evaluating patients with a clinical diagnosis of ectopic pregnancy. J Clin Ultrasound (2003) 31:1–8.[CrossRef][Web of Science][Medline]

Basama FM, Crosfill F, Price A. Women's perception of transvaginal sonography in the first trimester; in an early pregnancy assessment unit. Arch Gynecol Obstet (2004) 269:117–120.[CrossRef][Medline]

Bottomley C. Caesarean scar pregnancy. In: Handbook of Early Pregnancy Care—Bourne T, Condous G, eds. (2006) Abingdon, Oxon: Informa Healthcare. 117–129.

Braffman BH, Coleman BG, Ramchandani P, Arger PH, Nodine CF, Dinsmore BJ, Louie A, Betsch SE. Emergency department screening for ectopic pregnancy: a prospective US study. Radiology (1994) 190:797–802.[Abstract/Free Full Text]

Cacciatore B, Stenman UH, Ylostalo P. Early screening for ectopic pregnancy in high-risk symptom-free women. Lancet (1994) 343:517–518.[CrossRef][Web of Science][Medline]

Condous G, Okaro E, Khalid A, Lu C, Van Huffel S, Timmerman D, Bourne T. The accuracy of transvaginal ultrasonography for the diagnosis of ectopic pregnancy prior to surgery. Hum Reprod (2005a) 20:1404–1409.[Abstract/Free Full Text]

Condous G, Okaro E, Bourne T. Pregnancies of unknown location: diagnostic dilemmas and management. Curr Opin Obstet Gynecol (2005b) 17:568–573.[Web of Science][Medline]

Dutta RL, Economides DL. Patient acceptance of transvaginal sonography in the early pregnancy unit setting. Ultrasound Obstet Gynecol (2003) 22:503–507.[CrossRef][Web of Science][Medline]

Farquharson RG, Jauniaux E, Exalto N. Updated and revised nomenclature for description of early pregnancy events. Hum Reprod (2005) 20:3008–3011.[Abstract/Free Full Text]

Jermy K, Thomas J, Doo A, Bourne T. The conservative management of interstitial pregnancy. Br J Obstet Gynecol (2004) 111:1283–1288.

Jurkovic D, Hacket E, Campbell S. Diagnosis and treatment of early cervical pregnancy: a review and a report of two cases treated conservatively. Ultrasound Obstet Gynecol (1996) 8:373–380.[CrossRef][Web of Science][Medline]

Kirk E, Bourne T. The nonsurgical management of ectopic pregnancy. Curr Opin Obstet Gynecol (2006) 18:587–593.[Web of Science][Medline]

Lewis G, Drife J. Why mothers die. Triennial Report 2000–2002. In: Confidential Enquiry into Maternal Deaths, UK (2004) London: RCOG Press.

Mol BW, Hajenius PJ, Ankum WM, Bossuyt PM, van der Veen F. Screening for ectopic pregnancy in symptom-free women at increased risk. Obstet Gynecol (1997) 85:704–707.[CrossRef]

Mol BW, van der Veen F, Bossuyt PM. Symptom-free women at increased risk of ectopic pregnancy: should we screen? Acta Obstet Gynecol Scand (2002) 81:661–672.[CrossRef][Web of Science][Medline]

Royal College of Obstetricians and Gynaecologists. Green-top Guideline No. 25. The Management of Early Pregnancy Loss (2006) London: RCOG Press.

Royal College of Radiologists/Royal College of Obstetricians and Gynaecologists. Guidance and Ultrasound Procedures in Early Pregnancy (1995) London: RCOG Press.

Shalev E, Yarom I, Bustan M, Weiner E, Ben-Shlomo I. Transvaginal sonography as the ultimate diagnostic tool for the management of ectopic pregnancy: experience with 840 cases. Fertil Steril (1998) 69:62–65.[CrossRef][Web of Science][Medline]

Sinha P, Pradhan A, Chowdhury V. Value of routine transvaginal ultrasound scan in women requesting early termination of pregnancy. J Obstet Gynaecol (2004) 24:426–428.[CrossRef][Medline]

Timor-Tritsch IE, Monteagudo A, Mandeville EO, Peisner DB, Anaya GP, Pirrone EC. Successful management of viable cervical pregnancy by local injection of methotrexate guided by transvaginal ultrasonography. Am J Obstet Gynecol (1994) 170:737–739.[Web of Science][Medline]

Submitted on April 15, 2007; resubmitted on June 15, 2007; accepted on June 20, 2007.


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