Ectopic pregnancy and miscarriage

What are the signs and symptoms associated with ectopic pregnancy?

Bibliographic details Participants Tests Methods Outcomes and results Comments

Full citation Sample size Tests Methods Results Limitations

Barnhart,K.T., N=452 Index test The Department of Obstetrics Frequency of symptoms Retrospective Rinaudo,P., and Gynaecology at the (number with Hummel,A., Pena,J., Characteristics History taking and physical University of Pennsylvania symptom/total ectopics Unclear who entered the Sammel,M.D., examination Medical Centre has an electronic (%)) data of symptoms in to the Chittams,J., Acute data management system. All database originally. and chronic Age/years (mean): 28.6 Reference test patients at risk for an ectopic Pain as primary complaint: presentation of pregnancy are entered into a 329/452 (72.8) Type or location of pain is ectopic pregnancy Gravida (mean): 3.6 Unclear, however it is database and followed until not defined may be two clinical reported that some patients definitive diagnosis. This study Bleeding as primary entities, Fertility and Parity (mean): 1.2 were managed surgically and evaluates the database and complaint: 336/452 (74.3) Exclusion criteria not Sterility, 80, 1345- some medically; therefore medical records of 452 patients reported 1351, 2003 Duration of ectopic pregnancy is likely to diagnosed with ectopic Severity of bleeding at amenorrhea/days have been diagnosed pregnancy during the study presentation: Other information Ref Id (mean): 45.0 through ultrasound or period. Historic risk factors and - No bleeding: 116/452 laparoscopy. findings at presentation were (25.7) 68010 Duration of evaluated. - Mild bleeding: 270/452 60/452 (13.3%) of the bleeding/days (mean): (59.7) ectopics were ruptured. Country/ies where 8.5 Data were taken from operative - Moderate bleeding: 60/452 the study was records, outpatient charts and (13.3) Site of ectopic carried out Race (% African inpatient charts using a uniform - Severe bleeding: 6/452 American): 377/452 (83.4) data collection sheet. Data were (1.3) Cornual: 40/452 (8.8) USA then entered into an Excel Isthmic: 74/452 (16.4) database. Frequency of signs on Ampullary/distal: 269/452 Study type Inclusion Criteria examination (number with (59.5) Fimbriae or aborting: Case-series Diagnosed with ectopic sign/total ectopics (%) 22/452 (4.9) pregnancy Entire tube: 48/452 (10.6) Aim of the study Orthostasis on presentation: 21/452 (4.6) Cervical, ovarian or Exclusion Criteria abdominal: 8/452 (1.8) To compare women Ultrasound report at with "early" or acute Not reported presentation: Note: this study is presentation with - Definitive EP: 90/452 conducted in the same those with "late" or (19.9) location and time period as chronic presentations - Suspicious for EP: another included study of ectopic pregnancy 152/452 (33.6) (Barnhart et al. 2006);

52 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments to look for differences - Nondiagnostic: 195/452 therefore they are likely to in the patient (43.1) be the same population of characteristics and - Non-viable IUP: 14/452 ectopic pregnancies. short-term sequelae (3.1) Presenting symptoms are of the disease. reported in more detail in Positive cervical cultures this study and therefore are Study dates (Neisseria gonorrheae or detailed here. Risk factors Chlamydia trachomatis): are analysed in more detail 22/452 (4.9) in the other study, and are 1993 to 1998 detailed in that study.

Source of funding

National Institutes of Health Full citation Sample size Tests Methods Results Limitations

Banerjee,S., N=127 Index test This is a prospective (Note: where possible, ORs Type or location of pain is Aslam,N., Zosmer,N., observational study of women were calculated by the not reported Woelfer,B., attending an EPAU. Women were technical team, comparing Jurkovic,D., The (However only 64 were History taking diagnosed as referred for ultrasound by their odds of the risk factor or Incidence of risk factors is expectant GP or A&E. A full history was symptom in those with EP management of spontaneously resolving Reference test not reported (except PID), and 18 as ectopic taken, and physical examination vs. odds in all other therefore it is impossible to women with early performed in all cases. All women outcomes (i.e. spontaneous pregnancy of pregnancy, therefore the judge what % of women Ectopic pregnancy: had a positive pregnancy test. resolution, miscarriage and unknown location, population of interest is presented with the risk diagnosed using laparoscopy The diagnosis of PUL was made normal pregnancy) Ultrasound in N=82) factor. or ultrasound at the initial visit in all women with Obstetrics and no evidence of an intrauterine or Gynecology, 14, 231- Characteristics Spontaneous resolution: extrauterine pregnancy on Frequency of possible Unclear who collected the 236, 1999 decrease of serum hCG transvaginal scan. risk factors for ectopic initial signs and symptoms Final outcome levels to below 20 IU/l and pregnancy data Ref Id (number/total (%)) complete resolution of Women with PUL were managed symptoms without n=18 for ectopic 69257 expectantly on an outpatient a. Number of previous Ectopic pregnancy: 18/127 intervention basis. They were advised not to elective abortions pregnancies. (14.2) Country/ies where travel, to avoid sexual (median (range)) Spontaneous resolution: the study was intercourse, and to return Other information 64/127 (50.4) carried out immediately if their pain Ectopic pregnancy: 0 (0-2) Miscarriage: 11/127 (8.7) increased significantly. Follow-up Spontaneous resolution: 0 Normal pregnancy: 34/127

53 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

UK (26.8) appointments were arranged for (0-4) PUL population 2-3 days later, and continued until Miscarriage: 0 (0-3) Study type a final diagnosis was reached. Normal pregnancy: 0 (0-5) Note: the following are only None of the ectopics were reported for spontaneously Prospective cohort ruptured; location is not resolving pregnancies and Diagnosis of final outcome b. Number of previous study reported. ectopic pregnancies, as miscarriages (median they are the population of (range)) Aim of the study Normal pregnancy: diagnosed in interest for this review women with a normally growing question. intrauterine gestational sac and Ectopic pregnancy: 0 (0-3) To assess the results detectable live embryo on follow- Spontaneous resolution: 0 of expectant Age/years (mean (95% up scans (0-3) management in CI)) Miscarriage: 1 (0-3) women with Normal pregnancy: 0 (0-5) pregnancy of Miscarriage: diagnosed Ectopic pregnancy: 29.8 unknown location and histologically, following surgical (18.9-40.8) c. Number of previous to identify diagnostic evacuation, or by ultrasound Spontaneous resolution: caesareans (median parameters that are 29.6 (15.5-43.7) (range)) predictive of Ectopic pregnancy: diagnosed at spontaneous laparoscopy or at ultrasound in Ectopic pregnancy: 0.5 (0-2) pregnancy resolution. Duration of women that received medical Spontaneous resolution: 0 amenorrhea/days (mean treatment (95% CI)) (0-2) Study dates Miscarriage: 0 (0-1) Ectopic pregnancy: 52.1 Spontaneous resolution: defined Normal pregnancy: 0 (0-0) August 1997 to March (22.4-81.9) as a decrease of serum hCG to 1998 Spontaneous resolution: below 20 IU/l and complete d. Number of previous 51.3 (24.3-78.3) resolution without need for any ectopic therapeutic intervention Source of funding pregnancies (median Gravida (median (range)) (range)) Data regarding past obstetric and Not reported Ectopic pregnancy: 3.5 (1- gynaecological history were Ectopic pregnancy: 0 (0-1) 6) recorded in a database. Spontaneous resolution: 0 Spontaneous resolution: (0-1) 2.5 (1-10) This papers aims to identify Miscarriage: 0 (0-1) parameters that predict Normal pregnancy: 0 (0-1) Inclusion Criteria spontaneous resolution by creating a logistic model. e. Past history of PID However this is not relevant to (number/total (%)) Pregnancy of unknown this review question, and location (defined as no

54 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

evidence of an intrauterine therefore methodological details Ectopic pregnancy: 3/18 or ectopic pregnancy on have not been reported here. (16.7) transvaginal scan) Only prevalence of risk factors Spontaneous resolution: and signs and symptoms will be 9/64 (14.1) Exclusion Criteria reported here. Similarly, only data Miscarriage: 2/11 (18.2) for ectopic pregnancies and Normal pregnancy: 6/34 spontaneous resolving (17.6) Early pregnancy sac-like pregnancies (whose location is structure in the uterine not reported, and hence could be OR (95% CI): 1.08 (0.28 - cavity that needed follow- ectopics) will be reported. 4.15) up for verification Frequency of symptoms Adnexal mass believed to (number with be ectopic pregnancy symptoms/total (%))

Clinically unstable patients a. Pain

Indirect signs of a specific Ectopic pregnancy: 11/18 pregnancy location (61.1) Spontaneous resolution: 45/64 (70.3) Products of conception Miscarriage: 6/11 (54.5) visualised on speculum Normal pregnancy: 27/34 examination (79.4)

OR (95% CI): 0.62 (0.22 - 1.76)

b. Bleeding

Ectopic pregnancy: 13/18 (72.2) Spontaneous resolution: 61/64 (95.3) Miscarriage: 5/11 (45.5) Normal pregnancy: 6/34 (17.6)

OR (95% CI): 1.34 (0.44 -

55 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

4.03)

Full citation Sample size Tests Methods Results Limitations

Makinen,J., N=168 Index test During the study period, 168 Frequency of possible Retrospective Nikkanen,V., consecutive patients with a risk factors (number with Kivikoski,A., Characteristics History taking histologically confirmed diagnosis risk factor/total ectopics Unclear who initially Problems and of ectopic pregnancy were (%)) recorded the signs and benefits in early Reference test operated on at the Central symptoms data, and who diagnosis of ectopic Age/years (mean Hospital of Paijat-Hame, Finland. Abdominal surgery: 82/168 extracted the data from the pregnancy, European (range)): 29.7 (15-44) Surgical confirmation This study is a retrospective (48.8) records. Journal of Obstetrics, review of available records. Gynecology, and Inclusion Criteria Tubal surgery: 27/168 Exclusion criteria are not Reproductive Biology, The diagnostic procedures used (16.1) reported. 16, 381-391, 1984 Histologically confirmed in reaching the final diagnosis include pregnancy tests, grey Appendectomy: 27/168 Ref Id diagnosis of ectopic Other information pregnancy scale and real-time ultrasound, (16.1) curettage, culdocentesis, 69499 laparoscopy and laparotomy. IUCD in situ: 56/168 (33.3) Type of ectopic Exclusion Criteria pregnancy (number/total Country/ies where Low-dose progestogen: (%)) the study was 1/168 (0.6) carried out Not reported Tubal: 163/168 (97.0) PID: 20/168 (11.9) Ovarian: 3/168 (1.8) Finland Tubo-ovarian: 2/168 (1.2) Ectopic pregnancy: 21/168 Study type (12.5) Note: rupture of the oviduct had occurred in 79/165 Case-series Infertility: 21/168 (12.5) (47.9%) cases

Aim of the study Induced abortion: 25/168 81/168 (48.2%) of patients (14.9) had a positive pregnancy To show certain test (unclear if this is features and trends Miscarriage: 19/168 (11.3) because of negative test characteristic of results or tests not ectopic pregnancy Endometriosis: 6/168 (3.6) performed). and it's early

56 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments diagnosis, and their Sterilisation: 1/168 (0.6) relation to diagnostic delay. No predisposing factors: 40/168 (23.8) Study dates Frequency of symptoms (number with January 1977 to symptom/total ectopics December 1981 (%))

Source of funding Abdominal pain: 151/168 (89.9) Not reported Shoulder pain: 21/168 (12.5)

Spotting: 108/168 (64.3)

Profuse bleeding: 20/168 (11.9)

No clear amenorrhea: 60/168 (35.7)

Nausea: 26/168 (15.5)

Breast tenderness: 43/168 (25.6)

Note: signs and symptoms were also analysed separately for those with and without an IUCD in situ. There were no significant differences except in the % of each group with no clear amenorrhea (51.8% in those with an IUCD, compared to 27.7% in those without an IUCD).

57 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Full citation Sample size Tests Methods Results Limitations

Hutton,J.D., N=177 Index test The records of all tubal ectopic Frequency of risk factors Retrospective Narayan,R., Is ectopic pregnancies diagnosed at the (number with risk pregnancy too often Characteristics History taking and physical National Women's Hospital in factor/total ectopics (%)) Unclear who collected the diagnosed too late?, examination 1979 and 1980 were reviewed data in the first place. New Zealand Medical retrospectively. The diagnosis History of previous pelvic Journal, 99, 3-5, 1986 The race, age and parity Reference test was established by laparotomy or infection: 44/177 (24.9) Unclear who reviewed the distributions showed no laparoscopy in all but two cases. records.

Ref Id predominance when Visualisation of extrauterine The interrelationships of various Contraceptive use at point compared with patients gestation at laparotomy or predisposing factors, presenting of conception 69774 Other information delivering at the same laparoscopy, in all but 2 signs and symptoms, diagnostic - No contraception: 144/177 hospital, except that 12% cases (where it was felt that investigations, treatment and (81.4) Country/ies where of women were aged over expulsion was complete) outcomes were analysed using - IUCD: 19/177 (10.7) 68/177 (38.4%) of the the study was 35 years old. SPSS. Statistical analysis was - Oral contraceptive: 7/177 ectopics were ruptured. carried out performed using chi-squared (4.0) Gestational age tests or Pearson's rank - Mini-pill: 5/177 (2.8) A urinary pregnancy test New Zealand - <6 weeks: 60/177 (34) correlation coefficient. - Barrier methods: 2/177 was done on admission in - 6-7 weeks: 64/177 (36) (11.3) 121 women, of which 87 Study type - 8-9 weeks: 39/177 (22) (72%) tested positive. Case-series History of infertility - At least 2 years: 67/177 Aim of the study (37.9) - At least 5 years: 24/177 Inclusion Criteria (13.6) To report the predisposing factors Tubal ectopic pregnancy and presenting Frequency of symptoms symptoms and signs Exclusion Criteria (number of all women admitted with symptom/total with an ectopic ectopics (%)) Not reported pregnancy during the study period, and Lower abdominal pain: 99 relate these to their outcomes, including Vaginal bleeding: 82 the time to definitive diagnosis, type of Fainting: 28 surgery and need for Shoulder-tip pain: 23

58 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments a blood transfusion. Frequency of signs at Study dates examination (%)

Shock: 10 1979-1980 Pelvic tenderness: 91 Source of funding Rebound abdominal 86 Not reported tenderness:

Palpable pelvic mass: 19

(Note: the authors report that fainting, shoulder-tip pain and shock commonly occurred together, p<0.01) Full citation Sample size Tests Methods Results Limitations

Jiao,L.Z., Zhao,J., N=28 Index test During the study, 2663 ectopic Medical history linked to Retrospective Wan,X.R., Liu,X.Y., pregnancies were diagnosed at previous caesareans Feng,F.Z., Ren,T., Characteristics History taking Peking Union Medical College Unclear who collected Xiang,Y., Diagnosis Hospital. 28 of them were Number of previous medical history in the first and treatment of Reference test diagnosed as caesarean scar caesareans (number/total place, and who extracted it cesarean scar Age/years (mean pregnancies and constitute the (%)): from the files. pregnancy, Chinese (range)): 31.4 (26 - 42) Ultrasound, MRI study population. 1: 26/28 (92.9) Medical Sciences >1: 2/28 (7.1) Exclusion criteria not Journal, 23, 10-15, Gravidity (mean (range)): The clinical data of the patients reported. 2008 3.3 (2 - 7) were obtained from medical files, Interval from last and analysed retrospectively. The caesarean section to Many of the participants

Ref Id Parity (mean (range)): 1.2 following information was delivery/years (mean had undergone prior (1 - 2) collected: age, gravidity, parity, (range)): 5.5 (0.3 - 15) treatment for a 69926 previous history of caesarean, misdiagnosis. Duration of interval from last caesarean to Frequency of symptoms Country/ies where amenorrhea/days diagnosis, clinical presentation, (number with the study was Other information (range): 39 - 80 results of auxiliary examination, symptoms/total ectopics carried out location of pregnancy, diagnosis, (%)) treatment and follow-up. CAESAREAN SCAR China Amenorrhea: 27/28 (96.4) PREGNANCIES ONLY

59 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Study type Inclusion Criteria Severe vaginal bleeding: Clinical presentations Case-series Caesarean scar pregnancy 11/28 (39.3) (number/total (%))

Aim of the study (It is reported that these Persistent vaginal bleeding Exclusion Criteria were the most common after intrauterine pregnancy To investigate the symptoms; no details of interruption: 10/28 (35.7) early diagnosis and Not reported other presenting signs and treatment of symptoms are given) Failure of medical abortion: caesarean scar 6/28 (21.4) pregnancy. Amenorrhea followed by irregular vaginal bleeding: Study dates 5/28 (17.9)

January 1994 to April Amenorrhea without 2007 vaginal bleeding: 3/28 (10.7) Source of funding Slow rise or fall in hCG after suction curettage: Not reported 3/28 (10.7)

Irregular vaginal bleeding with no amenorrhea: 1/28 (3.6)

Note: 19/28 were primarily diagnosed as other diseases (early intrauterine pregnancies, gestational trophoblastic tumours). Therefore, 16 of them had undergone medical abortion, curettage or chemotherapy in other facilities before admission. 9/28 were definitely diagnosed of caesarean scar pregnancies before

60 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

treatment, using ultrasound (n=8) or MRI (n=1). Full citation Sample size Tests Methods Results Limitations

Buckley,R.G., N=486 Index test This study was conducted in the Frequency of clinical Only includes women with King,K.J., emergency department of a large findings (number with pain and/or bleeding. Disney,J.D., (however only 39 were History taking and physical tertiary care teaching hospital of finding/total ectopics (%)) Ambroz,P.K., ectopic pregnancies, and examination the US Navy. All patients are Other information Gorman,J.D., hence constitute the seen under the direct supervision a. Absence of fetal heart Klausen,J.H., population of interest for Reference test of residency-trained, board- tones: 39/39 (100) Derivation of a clinical this review question) eligible, or board certified Note: 12/39 ectopics were prediction model for Visualisation of extrauterine emergency physicians. b. Absence of tissue at ruptured the emergency Characteristics gestation at laparotomy or Ultrasound is available 24 hours cervical os: 39/39 (100) department diagnosis laparoscopy, or ultrasound a day, performd in the radiology of ectopic pregnancy, visualisation. department and interpreted by a c. Pain other than midline Academic Emergency Characteristics of radiologist. cramping: 38/39 (97.4) Medicine, 5, 951-960, patients with ectopic 1998 pregnancy This study included all d. Any abdominal pain: haemodynamically stable patients 38/39 (97.4)

Ref Id Age/years (mean (SD)): presenting with abdominal pain or 26.1 (6.1) vaginal bleeding during the study e. Absence of tissue 70825 period. Patients were included in passed by history: 38/39 Estimated gestational a prospective clinical registry. 104 (97.4) Country/ies where age/years (mean (SD)): patients were excluded (see the study was 39 (18) (p<0.001 when exclusion criteria) and 7 were lost f. Absence of open carried out compared to non-ectopic to follow-up, leaving 486 patients cervical os: 38/39 (97.4) pregnancies) available for analysis. A USA templated clinical data collection g. Estimated gestational hCG <2000 mIU/ml: 22/39 form was completed, and a age <70 days: 37/39 (94.9) Study type (56%) (p<0.001 when standard blood panel (including compared to non-ectopic CBC, urinalysis, blood typing, h. Any abdominal Prospective cohort pregnancies) study serum hCG and progesterone) tenderness: 33/39 (84.6) was ordered. To facilitate data Ultrasonography during Aim of the study collection and encourage the i. Any pelvic abnormality: ED visit: 23/39 (59%) inclusion of all eligible patients, 30/39 (76.9) the data forms were approved by To assess the value Inclusion Criteria the hospital to be used as a j. Any adnexal and limitations of substitute for the written or tenderness: 27/39 (69.2) individual clinical Presenting with first dictated history and physical

61 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments findings to predict the trimester abdominal pain examination. To encourage k. Any vaginal bleeding: presence or absence or vaginal bleeding blinding, physicians were 27/39 (69.2) of ectopic pregnancy. encouraged to complete the Exclusion Criteria history and physical examination l. Any cervical motion To derive a clinical portions of the form before tenderness: 13/39 (33.3) prediction model that obtaining lab or ultrasound could potentially help Prior documentation of an results. m. Any ectopic risk clinicians estimate the intrauterine pregnancy on factors: 9/39 (23.1) probability of ectopic ultrasound All patients were followed pregnancy. longitudinally until a diagnosis n. Abdominal peritoneal Enrolled on a previous was reached. The criteria for signs: 9/39 (23.1) emergency department Study dates diagnosis of an ectopic visit pregnancy was as follows: o. Definite cervical motion - Direct visualisation of an tenderness: 9/39 (23.1) August 1994 to Gestational age of ≥ 13 extrauterine gestation on September 1995 weeks (based on first day laparoscopy or laparotomy p. Discrete adnexal mass: of last normal period and - For non-surgical cases, an 2/29 (5.1) Source of funding uterine size) empty uterine cavity on ultrasound accompanied by Not reported visualisation of an adnexal mass Other diagnostic accuracy with significant free peritoneal measures for each clinical fluid, adnexal ring, or an adnexal finding sac that contains a yolk sac or fetal pole a. Absence of fetal heart tones: The association between clinical Specificity: 5.8 variables and the presence or PPV: 8.5 absence of ectopic pregnancy NPV: 100 was assessed. Sensitivity, LR+: 1.06 specificity, PPV and NPV with LR-: 0.00 95% CI were calculated. b. Absence of tissue at cervical os: Specificity: 2.0 PPV: 8.2 NPV: 100 LR+: 1.02 LR-: 0.00

c. Pain other than midline

62 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

cramping: Specificity: 21.3 PPV: 9.7 NPV: 99.0 LR+: 1.24 LR-: 0.12

d. Any abdominal pain: Specificity: 15.3 PPV: 9.1 NPV: 98.5 LR+: 1.15 LR-: 0.17

e. Absence of tissue passed by history: Specificity: 6.9 PPV: 8.4 NPV: 96.9 LR+: 1.05 LR-: 0.38

f. Absence of open cervical os: Specificity: 6.5 PPV: 8.3 NPV: 96.7 LR+: 1.04 LR-: 0.40

g. Estimated gestational age <70 days: Specificity: 26.6 PPV: 10.1 NPV: 98.3 LR+: 1.29 LR-: 0.19

h. Any abdominal tenderness:

63 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Specificity: 50.1 PPV: 12.9 NPV: 97.4 LR+: 1.70 LR-: 0.31

i. Any pelvic abnormality: Specificity: 53.5 PPV: 12.7 NPV: 96.4 LR+: 1.66 LR-: 0.43

j. Any adnexal tenderness: Specificity: 62.0 PPV: 13.7 NPV: 95.8 LR+: 1.82 LR-: 0.50

k. Any vaginal bleeding: Specificity: 26.2 PPV: 7.6 NPV: 90.7 LR+: 0.94 LR-: 1.18

l. Any cervical motion tenderness: Specificity: 90.8 PPV: 24.1 NPV: 94.0 LR+: 3.62 LR-: 0.73

m. Any ectopic risk factors: Specificity: 83.4 PPV: NR

64 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

NPV: 92.6 LR+: 1.39 LR-: 0.92

n. Abdominal peritoneal signs: Specificity: 94.9 PPV: 28.1 NPV: 93.4 LR+: 4.52 LR-: 0.81

o. Definite cervical motion tenderness: Specificity: 97.3 PPV: 42.9 NPV: 93.5 LR+: 8.56 LR-: 0.79

p. Discrete adnexal mass: Specificity: 96.4 PPV: 11.1 NPV: 92.1 LR+: 1.42 LR-: 0.98 Full citation Sample size Tests Methods Results Limitations

Condous,G., N=376 Index test Women were seen in an EPAU Frequency of signs and No details of individual risk Van,Calster B., during the study period. Women symptoms (number/total factors are reported. Kirk,E., Haider,Z., classified as having a PUL (see (%)) Timmerman,D., (however, only 27 were Ultrasound, history taking diagnosed as ectopic inclusion criteria) were followed Location of the ectopics is Van,Huffel S., up using hCG, ultrasound and/or (Note: the odds ratios (OR) Bourne,T., Clinical pregnancy, and hence Reference test not reported. constitute the main laparoscopy until final clinical reported have been information does not outcomes were established. The calculated by the technical improve the population of interest for Ectopic pregnancy: outcomes were defined as team, for the odds of the Other information performance of this review) diagnosed using transvaginal follows: symptom in diagnosed EP mathematical models ultrasound and/or vs. the odds in any other PUL population in predicting the - Failing PUL: serum outcome (i.e. failing PUL

65 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments outcome of Characteristics laparoscopy progesterone at presentation <20 and IUP)) Training and test data sets pregnancies of nmol/l, with a subsequent drop in have been combined, as unknown location, Final outcome Failing PUL: serum hCG to below 5 IU/l and location a. Abdominal pain this dichotomy is not Fertility and Sterility, (number/total (%)) progesterone at presentation remaining unknown relevant to this review 88, 572-580, 2007 <20 nmol/l, with a - Intrauterine pregnancy: made Any question. Failing PUL: 203/376 subsequent drop in hCG to using transvaginal ultrasound EP: 20/27 (74.1) Ref Id (54.0) below 5 IU/l and location when a gestational sac was Failing PUL: 134/203 (66.0) EP: 17/376 (4.5) remaining unknown visualised within the endometrial IUP: 98/140 (70) 70932 IUP: 140/376 (3.7) cavity Persisting PUL: 6/376 (1.6) - EP: diagnosed using ultrasound, OR (95% CI): 1.37 (0.56 - Country/ies where and/or laparoscopy with 3.33) the study was confirmatory histology of the carried out Inclusion Criteria chorionic villi. Left iliac fossa EP: 4/27 (14.8) UK Pregnancy of unknown Risk factors, and the presence of Failing PUL: 17/203 (8.4) location, diagnosed with pain/bleeding on entry to the IUP: 24/140 (17.1) Study type transvaginal ultrasound as study were recorded. However, no signs of an intra- or risk factors were only reported as OR (95% CI): 1.28 (0.42 - Prospective cohort extra-uterine pregnancy or a sum (i.e. the total number of 3.89) study RPOC in a woman with a risk factors in a given woman). positive pregnancy test Right iliac fossa Aim of the study The risk factors investigated were: PID, STI, previous EP, EP: 3/27 (11.1) Exclusion Criteria endometriosis, infertility, fertility Failing PUL: 8/203 (3.9) To see if the treatment, past surgical history IUP: 18/140 (12.9) incorporation of and contraceptive use. clinical variables can Any evidence of an OR (95% CI): 1.52 (0.43 - improve the intrauterine sac at first 5.40) diagnostic scan This data was used to create a performance of model to predict the outcome of Central lower abdominal logistic regression Adnexal mass thought to PULs. However, this model is not pain models in the be an ectopic pregnancy at relevant to this review question, EP: 13/27 (48.1) prediction of pregancy initial scan and methodological details and Failing PUL: 109/203 (53.7) of unknown location results will not be reported here. IUP: 56/140 (40) Only data on presenting outcome. Endometrial thickness of signs/symptoms will be reported. OR (95% CI): 1.00 (0.46 - >15 mm on transvaginal 2.19) Study dates scan, with the presence of heterogenous irregular b. Vaginal bleeding March 2002 to July tissues within the uterus (thought to be an Any

66 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

2003 incomplete miscarriage) EP: 20/27 (74.1) Failing PUL: 179/203 (88.2) Source of funding Clinical instability or signs IUP: 34/140 (24.3) of intra-abdominal bleeding OR (95% CI): 1.74 (0.72 - Research Council of or haemoperitoneum on scans 4.24) the Katholieke Universiteit Leuven Without clots EP: 14/27 (51.9) Flemish Government Failing PUL: 78/203 (38.4) IUP: 31/140 (22.1) Research communities ICCoS OR (95% CI): 2.31 (1.05 - and ANMMM 5.09)

With clots Belgian Federal EP: 6/27 (22.2) Government Failing PUL: 101/203 (49.8) IUP: 3/140 (2.1) EU OR (95% CI): 0.66 (0.26 - 1.67)

c. Abdominal tenderness

EP: 2/27 (7.4) Failing PUL: 24/203 (11.8) IUP: 21/140 (15)

OR (95% CI): 0.53 (0.12 - 2.31) Full citation Sample size Tests Methods Results Limitations

Tsai,H.D., Chen,H.Y., N=681 Index test 681 ectopic pregnancies were Frequency of risk factors Retrospective Yeh,L.S., A 12-year encountered at the China Medical for ectopic pregnancy survey of 681 ectopic Characteristics History taking and physical College Hospital during the study (number of women/total Unclear who extracted the pregnancies, Chung examination period. In all cases, the diagnosis (%)) data and how the cases Hua i Hsueh Tsa Chih was confirmed by were identified - Chinese Medical Age/years (range): 16 – 43 Reference test histopathological examinations. Previous PID: 196/681

67 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Journal, 55, 457-462, (28.8) Exclusion criteria not 1995 Nulliparous (number/total Histopathological Analysis was confined to known (Note: this is defined as reported (%)): 81/681 (11.9) examination risk factors of ectopic pregnancy previous antibiotic therapy Ref Id recorded during the hospital stay. for PID) % of ruptured EP not Inclusion Criteria Clinical management in terms of reported 72121 diagnostic procedures and Previous pelvic operation: surgical treatment was analysed. 138/681 (20.3) Other information Country/ies where Ectopic pregnancy the study was Previous D&C: 106/681 carried out Exclusion Criteria (15.6) Location of ectopic (number (%)) Taiwan, Republic of Not reported IUCD in situ: 63/681 (9.3) China Tubal: 647 (95.0) Frequency of symptoms Cornual: 11 (1.6) Study type (number of women/total Ovarian: 10 (1.5) (%)) Cervical: 5 (0.7) Case-series Abdominal: 4 (0.6) Abdominal pain: 667/681 Rudimentary horn: 4(0.6) Aim of the study (97.9)

Not stated Amenorrhea: 613/681 (90.0)

Vaginal bleeding: 436/681 Study dates (64.0)

January 1981 to Pregnancy symptoms: December 1992 279/681 (41.0) (Note: includes nausea, Source of funding vomiting, breast engorgement and colostrum) Not reported

Fainting and syncope: 32/681 (4.7)

Back pain: 18/681 (2.6) (Note: all of these patients had ruptured EP with a large amount of

68 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

haemoperitoneum)

Full citation Sample size Tests Methods Results Limitations

Jabbar,F.A., Al- N=68 Index test At the Riyadh Maternity Hospital, Frequency of possible Retrospective Wakeel,M., A study of the medical records of 68 cases risk factors (number with 45 cases of ectopic of suspected ectopic pregnancy risk factor/total ectopics pregnancy, (however only 45 of these History taking and physical Unclear who was were diagnosed as ectopic examination were reviewed. Only 45 of the 68 (%)) responsible for recording International Journal were finally diagnosed as ectopic of Gynaecology and pregnancies, and hence signs and symptoms in the constitute the population of pregnancies, and constitute the History of pelvic infection: first place. Obstetrics, 18, 214- Reference test study population. 217, 1980 interest for this review 20/45 (44.4) question) Visualisation of extrauterine Unclear who extracted the Ref Id gestation at laparoscopy History of pelvic or data from the medical Characteristics and/or laparotomy. abdominal surgery: 18/45 records. 77352 (40) Age/years (number/total Other information Country/ies where (%)) History of infertility: 21/45 the study was (46.7) carried out 21/40 (52.5%) of the tubal 15-20: 5/45 (11.1) pregnancies had ruptured Saudia Arabia 20-30: 27/45 (60) IUD in situ: 1/45 (2.2) by the time of laparotomy. 30-40: 13/45 (28.9) Study type Recurrent ectopic Type of ectopic Parity pregnancy: 1/45 (2.2) pregnancy (number/total Case-series (%)) Aim of the study 0: 1/45 (2.2) 1-5: 39/45 (86.7) >5: 5/45 (11.1) To discuss the clinical Frequency of symptoms presentation of (number with Tubal: 40/45 (88.9) ectopic pregnancy symptom/total ectopics Cervical: 2/45 (4.4) and explore the most (%)) Ovarian: 1/45 (2.2) common predisposing Rudimentary horn factors among Saudi Amenorrhea: 43/45 (95.6) pregnancy: 2/45 (4.4) women. Inclusion Criteria Lower abdominal pain:

Study dates Diagnosed ectopic

69 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

1977-1979 pregnancy 42/45 (93.3)

Exclusion Criteria Vaginal bleeding: 23/45 (51.1)

(Note: this is reported Not reported in Islamic calendar Fainting attacks: 4/45 (8.9) years in the paper, 1397-1399) Shoulder tip pain: 14/45 (31.1)

Frequency of signs at Source of funding physical examination (number with sign/total ectopics (%)) Not reported Acute collapse: 5/45 (11.1)

Tachycardia (100 bpm): 34/45 (75.6)

Hypotension (<100/60 mmHg): 12/45 (26.7)

Full citation Sample size Tests Methods Results Limitations

Michelas,S., N=152 Index test This study reports the ectopic Frequency of risk factors for Retrospective Creatsas,G., pregnancies occurring during the ectopic pregnancy (n (%)) Fakas,G., Characteristics History taking study period at the Alexandra Method of data collection Kaskarelis,D., Ectopic State and University Maternity Previous ectopic pregnancy: not reported pregnancy: outcome Reference test Hospital, Athens, Greece. 19 (13) of 152 cases, Primigravida (n (%)): 20 Unclear who was International Surgery, (13) Culdocentesis or laparoscopy Previous miscarriage: 50 responsible for collecting (33)

70 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

65, 355-358, 1980 At least one previous data in the first place delivery (n (%)): 92 (61) Previous induced abortion: Ref Id 72 (47) Other information Age/years (range): 16 - 48 77452 Previous caesarean: 18 (12) The % of ruptured ectopics Country/ies where Duration of amenorrhea (n History of appendectomy at is not reported. the study was (%)) least one year before carried out pregnancy: 68 (45) Location of pregnancy (n < 4: 9 (6) (%)) Greece 6 - 10: 80 (53) Laparotomy for 11 - 14: 60 (39) gynaecological reasons: 3 Tubal: 141 (93) Study type 28 - 40: 3 (2) (2) Fimbrial: 3 (2) Interstitial: 3 (2) Case-series Inclusion Criteria Chronic inflammation of Abdominal: 3 (2) fallopian tubes: 50 (33) Cervical: 2 (1) Aim of the study Ectopic pregnancy Not stated Frequency of symptoms (n Exclusion Criteria (%))

Study dates Not reported Pelvic pain: 152 (100)

January 1976 to Vaginal bleeding: 120 (79) December 1978 Weakness, syncope, Source of funding dizziness: 74 (49)

Nausea: 28 (18) Not reported

Frequency of signs (n (%))

Shock: 35 (23) Full citation Sample size Tests Methods Results Limitations

Raziel,A., N=19 Index test This study reviewed the medical Frequency of possible Retrospective Schachter,M., records of 19 patients with risk factors (number with Mordechai,E., History taking and physical ovarian pregnancy at Assaf risk factor/total ectopics Unclear who was collected Friedler,S., Panski,M., Harofeh Medical Centre, Zerifin,

71 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Ron-El,R., Ovarian Characteristics examination Israel during the study period. (%)) data on signs and pregnancy-a 12-year The medical centre is a major symptoms in the first place. experience of 19 Age/years (mean Reference test medical facility for obstetrics and a. Previous abdominal cases in one (range)): 32.3 (24-43) gynaecology in the surrounding surgery: 2/19 (10.5) Unclear who extracted the institution, European area. During the time period there Laparoscopy (n=18) or (Note: one appendectomy, data from the charts. Journal of Obstetrics, were 63330 deliveres and 694 one diagnostic laparoscopy) Gynecology, and Gravidity (mean): 2.8 ultrasound (n=1) ectopic pregnancies at the Reproductive Biology, institution. 19 were ovarian Other information 114, 92-96, 2004 Parity (mean): 2.1 pregnancies. b. Previous caesarean section: 2/19 (10.5) OVARIAN PREGNANCIES Ref Id (Note: 1 of these patients hCG/mIU/l (range): 256 - All records coded as "ectopic also had previous other 12834 pregnancy" during the same abdominal surgery) 77529 period were also reviewed to Inclusion Criteria ensure that all the diagnoses of Country/ies where ovarian pregnancy were correctly c. IUD present: 13/19 the study was assigned. Diagnosis of ovarian (68.4) carried out Ovarian pregnancy pregnancy was confirmed by review of the pathological reports Israel d. History of elective Exclusion Criteria from surgical material in all abortion: 3/19 (15.8) ectopic pregnancies. In cases in Study type which ovarian tissue was Not reported e. History of miscarriage: available, the final diagnosis was Case-series 3/19 (15.8) established by histo-pathologic examination showing that the Aim of the study pregnancy was limited to the ovary. To report the Frequency of signs and prevalence, symptoms (number with presentation, sign or symptom/total diagnostic modalities, ectopics (%)) and treatment of ovarian pregnancy in one institution. a. Abdominal pain: 17/19 (89.5) Study dates b. Menstrual irregularities: 14/19 (73.7) 1990 to 2001 c. Circulatory collapse:

72 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Source of funding 4/19 (21.1)

Not reported Full citation Sample size Tests Methods Results Limitations

Al-Suleiman,S.A., N=104 Index test The case records of 104 patients Frequency of possible Retrospective Khwaja,S.S., Ectopic with ectopic pregnancies during risk factors (number with pregnancy, Journal of Characteristics History taking and physical the study period were studied. All risk factor/total ectopics Unclear who initially Obstetrics and patients underwent laparotomy (%)) Gynaecology, 12, examination collected history, and and the operative diagnosis of unclear who extracted data 254-257, 1992 Ethnic origin ectopic gestation was confirmed (number/total (%)) Reference test History of infertility: 25/104 from the medical records. by histological examination of the (24.0) Ref Id specimens. Saudi: 45/104 (43.3) Surgical confirmation and Exclusion criteria not 90845 History of PID: 22/104 reported. Other Arabs: 35/104 (33.7) histological examination of The hospital is a referral hospital Non-Arabs: 24/104 (23.1) specimen (21.2) Country/ies where that receives patients from Other information the study was primary health care centres and IUCD in situ: 3/104 (2.9) carried out Age/years (number/total other hospitals in the area, in (%)) addition to emergency cases 39% of the ectopic Saudia Arabia brought straight to the emergency Prior use of IUCD: 3/104 pregnancies were ruptured. department. The population <19: 7/104 (6.7) (2.9) Study type 20-24: 27/104 (26.0) includes patients of all 25-29: 31/104 (29.8) nationalities, but the majority are Prior EP and Case-series 30-34: 31/104 (29.8) Arab. salpingectomy: 3/104 (2.9) >35: 8/104 (7.7) Aim of the study Real time transabdominal Prior tubal or ovarian Parity (number/total (%)) ultrasound was available from surgery: 5/104 (4.8) To determine the 1982 onwards on a limited scale, incidence of ectopic and since 1988, resident pregnancy in the 0: 23/104 (22.1) obstetricians were trained and Appendicectomy: 7/104 hospital population 1-2: 46/104 (44.2) scanning was possible at any (6.7) and to assess the 3-5: 26/104 (25) time. The ultrasound findings possible risk factors >5: 9/104 (8.7) suggestive of ectopic pregnancy Prior caesarean: 7/104 (6.7) and clinical features included absence of an of ectopic pregnancy. intrauterine gestation sac, Inclusion Criteria Prior caesarean and tubal presence of an adnexal mass, sterilisation: 1/104 (1.0) Study dates and presence of fluid in the cul- de-sac. hCG assay kits were

73 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

1981 to 1989 Ectopic gestation available twice a week. Specimens were stored for testing if sent on other days. Source of funding Exclusion Criteria Frequency of symptoms (number with symptom/total ectopics Not reported Not reported (%))

Abdominal pain: 98/104 (94.2)

Abnormal uterine bleeding: 77/104 (74.0)

Amenorrhoea: 67/104 (64.4)

Dizziness: 20/104 (19.2)

Syncope: 19/104 (18.3)

Nausea or vomiting: 17/104 (16.3)

Passage of tissue: 13/104 (12.5)

Diarrhoea: 2/104 (1.9)

Urinary symptoms: 9/104 (8.7)

Frequency of signs at physical examination (number with sign/total ectopics (%))

74 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Abdominal tenderness: 86/104 (82.7)

Rebound tenderness: 38/104 (36.5)

Cervical excitation: 90/104 (86.5)

Adnexal tenderness: 88/104 (84.6)

Enlarged uterus: 34/104 (32.7)

Adnexal mass: 28/104 (26.9)

Full citation Sample size Tests Methods Results Limitations

Dimitry,E.S., A ten N=193 Index test The study is based on the case Frequency of possible Retrospective year survey of 193 records of patients with ectopic risk factors (number with ectopic pregnancies, pregnancy seen and treated in risk factor/total ectopics Journal of Obstetrics Characteristics History taking and physical Only includes women who examination the Medway District Hospital. (%)) underwent surgery to treat and Gynaecology, 9, Cases were identified from 309-313, 1989 Age/years (number/total an ectopic registers kept in the Previous appendicectomy: (%)) Reference test histopathology department, 47/193 (24.4) Ref Id operating theatre and Unclear who extracted data 15-19: 7/193 (3.6) Surgical confirmation. gynaecological ward, and the from records, and who 91199 20-24: 42/193 (21.7) Hospital Activity Analysis records. Previous investigations for made the records in the 25-29: 66/193 (34.2) Every woman who underwent infertility: 36/193 (18.7) first place. Country/ies where 30-34: 58/193 (30.1) surgery for ectopic pregnancy the study was 35-39: 16/193 (8.3) during the study period was Use of an IUD at time of Other information carried out 40-44: 4/193 (2.1) identified, which was a total of diagnosis: 29/193 (15.0) 193 cases. 66/193 (34%) had a negative pregnancy test.

75 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

UK Parity (number/total (%)) Previous PID: 24/193 (12.4) 61% were unruptured. Study type 0 + 0: 43/193 (22.3) Previous abdominal surgery 0 + >=1: 25/193 (13.0) (excluding Type of ectopic Case-series >=1 + 0: 52/193 (26.9) appendicectomy): 17/193 pregnancy (number/total >=1 + >= 1: 73/193 (37.8) (8.8) (%)) Aim of the study

Inclusion Criteria Previous ectopic pregnancy: Tubal: 184/193 (95.3) To review the 14/193 (7.3) Ovarian: 4/193 (2.1) incidence, trend, Abdominal: 4/193 (2.1) diagnosis and Undergoing surgery for Cervical: 1/193 (0.5) management of ectopic pregnancy Previous reconstructive ectopic pregnancy. tubal surgery: 10/193 (5.2) Exclusion Criteria Study dates Previous tubal sterilisation: Not reported 8/193 (4.1) 1977-1986 Use of progestagen-only contraception: 8/193 (4.1) Source of funding

No risk factors: 32% Not reported

Frequency of symptoms (%)

Abnormal vaginal bleeding: 82

Amenorrhea: 73

Abdominal pain: 96

Dizziness: 23

76 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Shoulder pain: 19

Rectal pressure: 9

Frequency of signs at physical examination (%)

Abdominal tenderness: 91

Adnexal tenderness: 82

Cervical excitation pain: 48

Rebound abdominal tenderness: 46

Adnexal mass: 40

Enlarged uterus: 24

Tachycardia >100 bpm or hypotension <90/60 mmHg: 21

Full citation Sample size Tests Methods Results Limitations

Easley,H.A., N=119 Index test The records of 119 patients (Note: the stated odds ratios Retrospective Olive,D.L., undergoing surgery for suspected (OR) have been calculated Holman,J.F., ectopic pregnancy were reviewed by the technical team, for Contemporary (Note: this is the History taking and physical Unclear who extracted the population of the entire examination retrospectively. Each patient was those with ectopic data from the charts. evaluation of evaluated in either the pregnancy (n=68) vs. those suspected ectopic study, however only 68 were finally diagnosed with emergency room or the outpatient without an ectopic pregnancy, Journal of Reference test gynaecology clinic. Histories were pregnancy (n=51)) Exclusion criteria not Reproductive an ectopic pregnancy and hence constitute the taken and recorded by obstetrics

77 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Medicine, 32, 901- main population of interest Surgical confirmation. and gynaecology residents. reported. 906, 1987 for this review question) Physical examinations were Frequency of symptoms initially performed by first year (number with Other information Ref Id Characteristics residents, and then repeated by symptom/total ectopics more advanced clinicians. If there (%)) 91220 were differences in findings, TUBAL ECTOPICS Final diagnosis those recorded by the most (indirectly reported in the (number/total (%)) Abdominal pain only: 22/68 discussion) Country/ies where advanced resident were used. (32.4) the study was OR (95% CI): 0.54 (0.25 - carried out Ectopic pregnancy: 68/119 This study included both patients 1.14) Unclear why a total of 68 (57.1) who did and did not undergo ectopics were reported, but USA Non-ectopic: 51/119 (42.9) serum pregnancy tests. Vaginal bleeding only: 6/68 it is reported that 27 were - Ruptured ovarian cyst: Culdocentesis was performed (8.8) ruptured and 40 were Study type 13/119 (10.9) usually by first and second year OR (95% CI): 1.14 (0.30 - unruptured. - Unruptured ovarian cyst: residents. Patients were selected 4.26) Case-series 8/119 (6.7) for the procedure without a - Miscarriage: 11/119 (9.2) Aim of the study specific protocol. Ultrasound Abdominal pain and vaginal - PID: 7/119 (5.9) scanning of the pelvis was bleeding: 37/68 (54.4) - IUP: 1/119 (0.8) performed by trained ultrasound OR (95% CI): 1.34 (0.65 - To identify the factors - Other: 11/119 (9.2) technicians or radiology residents 2.78) that might be using realy time scanning, and important in the was reviewed by an attending Frequency of signs at differential diagnosis radiologist. Ultrasound was physical examination of ectopic pregnancy. ordered without any specific Characteristics of those (number with sign/total protocol. with ectopic pregnancy ectopics (%)) Study dates (n=68) Test results in women with Rebound: 24/68 (35.3) June 1981 to June a. Time since last ectopic pregnancy (N=68) were OR (95% CI): 2.55 (1.06 - 1983 menstrual period/weeks compared to those without 6.11) (mean): 6.8 ectopic pregnancy, and those with a ruptured ectopic were Source of funding Abdominal tenderness: compared to those with an b. Duration of pain/days 24/68 (35.3) unruptured pregnancy. Results OR (95% CI): 0.57 (0.27 - Not reported (mean): 8.0 were analysed using chi-squared 1.19) and student's t-tests. c. Duration of bleeding/days (mean): 8.0 Unilateral abdominal tenderness: 40/68 (58.8) OR (95% CI): 0.54 (0.25 - d. Presence of

78 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

haemoperitoneum: 52/119 1.18) (43.7) Adnexal mass: 33/68 (48.5) Inclusion Criteria OR (95% CI): 0.66 (0.32 - 1.37) Patients undergoing surgery with a pre- Orthostatic hypotension: operative diagnosis of 12/68 (17.6) suspected ectopic OR (95% CI): 3.43 (0.91 - pregnancy 12.87)

Exclusion Criteria Signs and symptoms, split by ruptured status Not reported (number with sign or symptom/total ectopics (%))

a. Abdominal pain only

Ruptured: 13/27 (48.1) Unruptured: 9/40 (22.5) (p<0.05)

b. Vaginal bleeding only

Ruptured: 2/27 (7.4) Unruptured: 4/40 (10) (NS)

c. Abdominal pain and vaginal bleeding

Ruptured: 12/27 (44.4) Unruptured: 24/40 (60) (NS)

79 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

d. Rebound

Ruptured: 16/27 (59.3) Unruptured: 7/40 (17.5) (P<0.001)

e. Abdominal tenderness

Ruptured: 6/27 (22.2) Unruptured: 18/40 (45) (NS)

f. Unilateral abdominal tenderness

Ruptured: 14/27 (51.9) Unruptured: 25/40 (62.5) (NS)

g. Adnexal mass

Ruptured: 12/27 (44.4) Unruptured: 20/40 (50) (NS)

Full citation Sample size Tests Methods Results Limitations

Wong,E., Suat,S.O., N=207 Index test This study is a retrospective Frequency of possible Retrospective Ectopic pregnancy--a descriptive study of 207 cases of risk factors (number with diagnostic challenge ectopic pregnancy seen at a risk factor/total on whom in the emergency Characteristics History taking and physical Exclusion criteria not examination tertiary teaching hospital. The data is available (%)) reported department, cases were identified from the European Journal of Age/years (mean (range)): hospital's computer database Emergency Medicine, 30.6 (18 - 43) Reference test Previous elective abortion: Unclear who collected using the ICD coding. The cases 34/183 (18.6) 7, 189-194, 2000 were then traced by the Medical signs and symptoms data in the first place, and who

80 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Ref Id Gravidity (mean): 2.68 Ultrasound (n=123), Records Office, and information Previous miscarriage: then extracted it from laparoscopy (n=37), or was extracted from the admission 30/183 (16.4) medical records. 92207 Parity (mean): 1.04 laparotomy (n=47) and clerking notes. Subfertility: 26/179 (14.5) Data is missing on certain Country/ies where Duration of risk factors and the study was Previous ectopic pregnancy: signs/symptoms; carried out amenorrhea/weeks 16/183 (8.7) (mean): 6.3 sometimes up to 192/207 have missing data Singapore History of tubal ligation: 10/205 (4.9) Study type Other information Inclusion Criteria Ovarian induction agents: Case-series 8/162 (4.9) 84/199 (42.2%) of the ectopics were ruptured. Aim of the study Ectopic pregnancy, IUCD: 6/89 (6.7) classified by ICD coding in hospital records Site of ectopics is not To investigate the History of PID: 3/15 (20) reported. clinical presentation of ectopic pregnancy Exclusion Criteria With risk factors: 105/182 in the emergency (57.7) department, and Not reported highlight the atypical presentations and pitfalls in its diagnosis. Frequency of symptoms (number with symptom/total on whom Study dates data is available (%))

1992 to 1995 Abdominal pain: 171/196 (87.2) Source of funding Amenorrhea: 169/195 (86.7)

Not reported Vaginal bleeding: 144/188 (76.6)

Vomiting: 22/64 (34.4)

Diarrhoea: 22/60 (36.7)

81 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Non-specific dizziness: 16/19 (84.2)

Syncope: 14/53 (26.4)

Shoulder tip pain: 13/37 (35.1)

Urinary symptoms: 10/43 (23.3)

Rectal bleeding: 1 (denominator or % not reported)

Epigastric/central abdominal pain: 3 (denominator or % not reported)

Frequency of signs at examination (number with sign/total ectopics (%))

Abdominal tenderness: 140/200 (70)

Positive cervical motion tenderness: 94/148 (63.5)

Haemoglobin <11 g%: 77/192 (40.1)

Rebound tenderness: 74/145 (51.0)

Adnexal tenderness: 71/83 (85.5)

82 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Blood in the vagina: 51/76 (67.1)

Guarding: 50/158 (31.6)

Hypotension (systolic BP <100mmHg): 46/200 (23)

Pallor: 43/97 (44.3)

Shifting dullness: 34/61 (55.7)

Abdominal distension: 31/55 (56.4)

Tachycardia (>100 bpm): 20/193 (10.4)

Palpable pelvic mass: 8/65 (12.3)

Shock: 46/200 (23)

Frequency of combinations of abdominal pain, amenorrhea and bleeding in 174 cases (number/total (%))

a. Pain + Amenorrhea + Bleeding: 98/174 (56.3) b. Amenorrhea + Pain only: 35/174 (20.1) c. Amenorrhea + Bleeding only: 20/174 (11.5) d. Pain + Bleeding only:

83 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

12/174 (6.9) e. Pain alone: 6/174 (3.4) f. Amenorrhea alone: 2/174 (1.2) g. Bleeding alone: 1/174 (0.6) Full citation Sample size Tests Methods Results Limitations

Gonzalez,F.A., N=501 Index test This was a retrospective review Frequency of risk factors for Retrospective Waxman,M., Ectopic of all 501 patients with an ectopic ectopic pregnancy (n (%)) pregnancy. A Characteristics History taking and physical pregnancy treated at Kings Abdominal tenderness and retrospective study of examination County Hospital during the study Previous induced abortion: rebound abdominal 501 consecutive period. Complete information was 149 (29.7) tenderness refer to at least patients, Diagnostic Age/years (mean (range)): Reference test available on 448 patients, and moderate tenderness. Gynecology and 28.1 (15 - 45) incomplete data was available on Previous miscarriage: 93 Obstetrics, 3, 181- Culdocentesis, ultrasound, 53 patients from the files of (18.6) Unclear who extracted 186, 1981 Previous pregnancy (mean laparoscopy Surgical Pathology. data, or was responsible for (range)): 2.5 (1 - 8) Previous ectopic: 34 (6.8) collecting data originally.

Ref Id The following data were recorded Ethnicity (% black): 80.6 and analysed: age, race, History of pelvic infection: Some signs and symptoms 95822 gravidity, parity, past health, 71 (14.2) have only reported a value Duration of history of present illness, physical for n, without a Country/ies where amenorrhea/weeks (mean exam on admission, and Abdominal surgery: 71 denominator or %. the study was (range)): 7.8 (0 - 22) diagnostic and therapeutic (14.2) However, as denominators carried out procedures performed. Histologic differing from 501 are slides of the tubes were reviewed Use of birth control pills: 75 reported for some findings, USA Inclusion Criteria for 394 patients, in an effort to (15.0) the technical team have identify tubal pathology such as assumed that those without Study type Diagnosis of ectopic pregnancy during the study salpingitis, diverticula, Use of an IUCD: 47 (9.4) a stated different value Case-series period endometriosis, or tumour. have a denominator Tuboplasty: 24 (4.8) of 501.

Aim of the study Exclusion Criteria Tubal ligation: 10 (2.0) Other information To examine Not reported retrospectively the Frequency of presenting 339/501 (67.6%) of anamnestic, clinical symptoms (number/total ectopics were ruptured at and pathologic data in (%)) the point of laparotomy. patients with known Amenorrhea: 98%

84 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments ectopic pregnancy (denominator NR) Location of ectopic pregnancy (n (%)) Study dates Abdominal pain: 439/449 (98) Fimbria: 49 (9.8) Ampulla: 260 (51.9) January 1st 1973 to Vaginal bleeding: 230/438 Isthmus: 68 (13.6) December 31st 1977 (52.5) Cornua: 42 (8.4) Ovary: 1 (0.2) Source of funding Nausea and vomiting: 141 Unknown: 81 (16.1) (denominator NR, 28% Not reported assuming N=501)

Dizziness: 184 (denominator NR, 37% assuming N=501)

Fainting: 128 (denominator NR, 26% assuming N=501)

Dysuria: 26/441 (5.9)

Tenesmus: 35/500 (7)

Breast tenderness: 39/438 (8.9)

Frequency of signs on physical examination (number/total (%))

Systolic BP < 90 mmHg: 68/501 (13.6)

Moderate to severe abdominal tenderness: 342/439 (77.9)

Moderate rebound abdominal tenderness: 249/401 (62.1)

85 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Cyanotic cervix: 177/458 (38.6)

Cervical motion pain: 321/448 (71.6)

Adnexal fullness: 268/481 (55.7)

Enlarged uterus: 39/253 (15.4)

Full citation Sample size Tests Methods Results Limitations

Powers,D.N., Ectopic N=204 Index test During a five year period, 204 Frequency of possible Retrospective pregnancy: a five- patients with ectopic pregnancies risk factors (number with year experience, were treated at Fairfax Hospital. risk factor/total ectopics Southern Medical Characteristics History taking and physical Exclusion criteria not examination The charts of these patients were (%)) reported Journal, 73, 1012- reviewed, and data were 1015, 1980 Age/years (minimum- analysed as to incidence, age, Previous elective abortion: maximum): 17 - 45 Reference test parity, etiology, medical history, Unclear who initially 64/204 (31.4) Ref Id symptoms, physical findings, collected signs and Parity (number/total (%)) Ultrasound or laparoscopy diagnosis and treatment, symptoms data, and who 101705 0: 77/204 (37.7) pathologic findings and morbidity. Previous ectopic: 14/204 was responsible for 1: 66/204 (32.4) (6.9) extracting it from the Country/ies where >=2: 61/204 (29.9) charts. the study was Past pelvic surgery: 46/204 carried out Duration of (22.5) Other information USA amenorrhea/weeks (average): 7.4 Tubal ligation: 8/204 (3.9) Location of ectopic Study type (number/total (%)) Duration of History or record of Case-series bleeding/days (minimum- salpingitis: 27/204 (13.2) Tubal: 200/204 (98.0) Ovarian: 1/204 (0.5)

86 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Aim of the study maximum): 1 - 84 Past use of IUCD: 18/204 Abdominal: 2/204 (1.0) (8.8) Heterotopic: 1/204 (0.5) To review historic and Inclusion Criteria physical findings, IUCD in situ: 21/204 (10.3) Status of ectopic at time diagnostic Ectopic pregnancy of surgery (number/total procedures. (%)) etiological factors and Exclusion Criteria treatment in patients Ruptured: 150/204 (73.5) presenting with an Frequency of symptoms (number with Unruptured: 48/204 (23.5) ectopic gestation at Not reported Aborting: 6/204 (2.9) Fairfax Hospital. symptom/total ectopics (%)) Study dates Abdominal pain: 194/204 (95.1) January 1974 to December 1978 Nausea and/or vomiting: 56/204 (27.5) Source of funding Syncope: 20/204 (9.8) Not reported Amenorrhea: 146/204 (71.6)

No missed period: 52/204 (25.5)

Atypical uterine bleeding: 130/204 (63.7)

Frequency of signs at examination (number with sign/total ectopics (%))

Abdominal tenderness: 186/204 (91.2)

87 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

- Unilateral: 69/204 (33.8) - Bilateral: 117/204 (57.4)

Rebound tenderness: 92/204 (45.1)

Abdominal distention: 35/204 (17.2)

Diminished bowel sounds: 40/204 (19.6)

Absent bowel sounds: 4/204 (2.0)

Cullen's sign: 0/204 (0)

Adnexal tenderness: 193/204 (94.6)

Cervical tenderness: 107/204 (52.5)

Adnexal fullness: 101/204 (49.5)

Adnexal mass: 52/204 (25.5)

Uterine enlargement: 36/204 (17.6)

Shock: 36/204 (17.6) Full citation Sample size Tests Methods Results Limitations

Diamond,M.P., Wiser-

88 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Estin,M., Jones,E.E., N=60 Index test Data collection Frequency of symptoms at Retrospective study DeCherney,A.H., presentation (number of Failure of standard women and %) (N=60) Unclear who reviewed criteria to diagnose Characteristics History taking Retrospective analysis of patients' records. The population patients' records nonemergency ectopic pregnancies Not reported Reference test included women from the Asymptomatic: 5 (8.3) Reproductive Endocrinology and Unclear who collected data in a noninfertility on symptoms in the first patient population, Infertility Clinic (n=38), and those Abdominal pain: 40 (66.7) Inclusion Criteria Laparoscopy or laparoscopy from the Obstetrics and place Journal of the American Association Gynaecology Clinic (n=22). Spotting/bleeding > 3 days: 63% of the study of Gynecologic Surgically proved ectopic pregnancy treated in the 16 (26.7) population are patients at Laparoscopists, 1, Diagnostic tests an infertility clinic, although 131-134, 1994 same hospital (either at the infertility clinic or Dizziness: 4 (6.7) it is unclear whether they Clinically stable patients were conceived as a result of Ref Id the residents' clinic) followed with serial β-hCG titres infertility treatment until the titre reached 6500mIU/ml Shoulder pain: 3 (5.0) 101769 A minimum of two β-hCG at which point they had an Specific characteristics of measurements ultrasound. Abdominal ultrasound abdominal pain not Country/ies where Frequency of signs (number was supplemented with vaginal recorded the study was of women and %) (N=60) ultrasound if the first one failed to carried out Exclusion Criteria identify an intrauterine Orthostasis: 2 (3.3) Other information USA Ectopic pregnancy pregnancy. With the exception of haemodynamically unstable managed by private 11/60 (18.3%) of Study type practitioner patients, ectopic pregnancies were identified definitely by ectopic pregnancies were ruptured. Case-series laparoscopy. Where possible, Women who were first treatment was also by evaluated in the Aim of the study laparoscopy. The two populations in the emergency room and were study have been grouped diagnosed at that time to and reported as one case To examine the utility have an ectopic pregnancy series for the purposes of of the same this review. diagnostic criteria for identifying and ectopic pregnancy in different patient populations in the same institution (women in an infertility clinic and a

89 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments residents' Obstetrics and Gynaecology clinic)

Study dates

May 1988 to July 1990

Source of funding

Not stated Full citation Sample size Tests Methods Results Limitations

Aboud,E., Chaliha,C., N=138 Index tests Data collection Frequency of possible Retrospective study Nine year survey of risk factors (number of 138 ectopic women and %) (N=138) pregnancies, Archives Characteristics History taking and physical This is a retrospective review of Unclear who reviewed the of Gynecology and examination the case records of patients case records Obstetrics, 261, 83- Not stated treated for ectopic pregnancy Past investigations for 87, 1998 Reference tests during the study period. Cases infertility: 24 (17) Unclear who collected data were identified from Registers in Inclusion Criteria on risk factors and signs Ref Id the Histopathology Department, Previous use of IUCD: 18 and symptoms in the first Unclear, however all patients operating theatres and had a laparotomy. (13) place 102060 Patients treated for ectopic Gynaecology ward. pregnancy at a North Previous ectopic pregnancy: Unclear how many patients Country/ies where London Hospital 15 (11) had an ultrasound, and the study was what kind of carried out Exclusion Criteria Previous appendectomy: 13 ultrasound was used UK (9.5) Not stated Pyrexia not defined Study type Previous PID: 11 (8)

Case-series

90 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Aim of the study Previous tubal surgery: 8 (6) Other information

Not stated Endometriosis: 7 (5) At laparotomy, 64% of the ectopics were intact and Study dates Use of progesterone only had not ruptured. 35% of pill: 6 (4) the ectopics had ruptured. 1986 to 1994 Past history of tubal ligation: Asymptomatic patients 2 (1) were diagnosed by pelvic Source of funding ultrasound scan carried out for early pregnancy dating Not stated Frequency of symptoms at presentation (number of women and %) (N=138) The majority of patients were referred to hospital by their GP (62%). 32% were Abdominal pain: 132 (96) self referrals into A&E and 6% were referred to the Vaginal bleeding preceding Gynaecology Department pain: 82 (59.4) from other specialties within the hospital Nausea and vomiting: 30 (22) 11 patients (8%) had a negative urine pregnancy Dizziness: 22 (16) test and in 39 patients (28.3%) it was inconclusive or not documented Shoulder tip pain: 11 (8) Serum β hCG was Asymptomatic: 4 (2.9) performed on 21 patients and only two of them Frequency of signs on required quantitative serial examination (number of measurements women and %) (N=138) 134 pregancies were tubal, Abdominal tenderness: 121 3 ovarian and 1 cervical (88)

91 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Adnexal tenderness: 79 (57)

Cervical excitation: 58 (42)

Abdominal tenderness with rebound and guarding: 57 (41)

Enlarged uterus: 46 (33)

Adnexal mass: 14 (10)

Tachycardia over 100 beats/min: 21 (15)

Hypotension (< 90/60 mmHg): 20 (14.5)

Pyrexia: 10 (7)

Full citation Sample size Tests Methods Results Limitations

Barnhart,K.T., N=2026 Index test A database of all women who Frequency of possible Retrospective Sammel,M.D., present with pain and/or bleeding risk factors in cases Gracia,C.R., at the University of Pennsylvania only (number with risk Chittams,J., (367 cases of ectopic History taking Only includes women pregnancy, 1659 controls) is maintained, with data entered factor (%)) presenting with pain and/or Hummel,A.C., directly by clinical staff caring for Shaunik,A., Risk Reference tests bleeding the patients. Potential risk factors Prior elective abortion factors for ectopic Characteristics for ectopic pregnancy were pregnancy in women - Spontaneous miscarriage: identified from the history, clinical with symptomatic 0: 294 (82.4) Age/years histopathology of products of presentation and diagnostic tests. first-trimester 1: 33 (9.2) conception on suction D & C Other information pregnancies, Fertility 2 or more: 30 (8.4) < 20: 43 (11.8) or spontanous decline of and Sterility, 86, 36- Women were followed in the 20 - 25: 87 (23.8) hCG level to ≤5 mIU/mL 43, 2006 database until they were Note: this study was 25 - 30: 112 (30.7) History of miscarriage definitely diagnosed with either conducted during the same

92 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Ref Id ≥ 35: 39 (10.7) - Normal intrauterine an ectopic pregnancy or an 0: 269 (83.8) time period in the same pregnancy: ongoing intrauterine pregnancy (either 1: 36 (11.2) hospital as another 102279 Race progression of the pregnancy viable ongoing pregnancy or 2 or more: 16 (5) included study (Barnhart et by ultrasound visualisation of miscarriage). See "tests" section al. 2003). This paper has Country/ies where African-American: 229 an intrauterine yolk sac, fetal for diagnostic criteria. History of ectopic more details on risk factors the study was (62.6) pole or the presence of pregnancy but less on presenting carried out Other: 12 (3.3) heartbeat Data were analysed as a nested symptoms; therefore details case-control study. The cases 0: 306 (83.4) of risk factors have been USA reported here, and details Prior live births: 192 - Ectopic pregnancy: were defined as women who 1: 48 (13.1) confirmed by the presence of were definitively diagnosed with 2 or more: 13 (3.5) of prevalence of symptoms Study type (52.3) chorionic viili in the fallopian an ectopic pregnancy. Controls are reported for the other tube, or by visualisation of an were defined as those presenting paper (with the exception of Case-control study Parity History of pelvic surgery the odds ratios for pain and extrauterine gestational sac with the same symptoms but who (excluding CS): 88 (24) (with yolk sac or cardiac were eventually diagnosed with bleeding, which have been Aim of the study 0: 174 (47.4) activity) for those treated an intrauterine pregnancy (Note: reported in this study) 1: 94 (25.6) medically, or by a rise in hCG the controls consist of 1659 History of prior caesarean To evaluate the 2: 45 (12.3) level after dilatation and women diagnosed with an IUP (of association between 3: 29 (7.9) evacuation, with no evidence which 467 had an ongoing 0: 342 (93.2) ectopic pregnancy 4 or more: 25 (6.8) of chorionic villi in the pregnancy and 1192 had a 1: 16 (4.4) and clinical and endometrial curettage miscarriage) 2 or more: 9 (2.4) historical factors Inclusion Criteria samples. among women Firstly, univariate associations Past use of IUCD: 20 (5.5) presenting with pain were evaluated using student's t- and/or bleeding in All women in their first early pregnancy trimester of pregnancy test or chi-squared. Stratified History of PID: 90 (24.5) (positive pregnancy test or analyses were then performed to test for confounding and effect history of a missed period) History of outpatient Study dates modification. Historical and presenting with pain and/or treatment for gonorrhea bleeding clinical presentation variables and/or chlamydia January 1st 1990 to were first tested to check for interaction. For the purposes of July 31st 1999 Exclusion Criteria 0: 289 (79) analysis of categorial variables, 1: 60 (16.4) one category was chosen as the Source of funding Not stated 2: 18 (4.9) reference standard. Reference 3 or more: 0 (0) categories included age 25 - 29 National Institutes of years and hCG of < 500 mIU/l. Health (Bethesda, When no interaction was noted, Current gonorrhea and/or MD) grant R01: HD- both historical and clinical chlamydia cervical 36455-05 variables were combined. A infection: 22 (6.9) logistic regression model was

93 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

then generated using manual selection of confounding variables and backward stepwise Risk factors associated selection of variables. At each with ectopic pregnancy step, the largest p value variable (adjusted odds ratio (95% was removed from the table and CI), p value) this process was repeated until alll variables had a p value of ≤ 0.05. A variable was retained in a. Age/years the model as a confounder if it significantly affected the < 20: 0.34 (0.22 - 0.52), coefficient estimates of other p<0.0001 variables by at least 15%. 20 - 24: 0.59 (0.41 - 0.85), p=0.01 25 - 29: Reference 30 - 34: 1.18 (0.79 - 1.76), p=0.42 ≥ 35: 1.00 (0.61 - 1.64), p=0.99

b. Prior elective abortion

0: Reference 1: 0.58 (0.38 - 0.90), p=0.02 2 or more: 0.99 (0.61 - 1.6), p=0.96

c. History of ectopic pregnancy

0: Reference 1: 2.98 (1.88 - 4.73), p<0.0001 2 or more: 16.04 (5.39 - 47.72), p<0.0001

d. History of PID

Yes: 1.50 (1.11 - 2.05),

94 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

p=0.01

e. Parity

0: Reference 1: 1.71 (1.21 - 2.42), p=0.003 2: 1.13 (0.72 - 1.78), p=0.60 3: 0.95 (0.56 - 1.59), p=0.83 4 or more: 1.26 (0.68 - 2.36), p=0.46

f. hCG at presentation

0 - 500: Reference 501 - 2000: 1.73 (1.24 - 2.42), p=0.001 2001 - 4000: 1.38 (0.88 - 2.16), p=0.16 ≥ 4000: 0.97 (0.67 - 1.39), p=0.86

Note: History of 2 treatments for gonorrhea and/or chlamydia and current gonorrhea/chlamydia infection were significantly associated in the univariate analysis but not in the adjusted analysis. The remaining risk factors were not significant in either univariate or adjusted analyses.

Association of symptoms with ectopic pregnancy

95 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

vs. controls (OR (95% CI))

a. Pain as the presenting symptom

Unadjusted OR: 1.16 (0.92 - 1.48) Adjusted OR: 1.42 (1.06 - 1.92)

b. Bleeding (moderate to severe) at presentation

Unadjusted OR: 1.34 (1.04 - 1.78) Adjusted OR: 1.42 (1.04 - 1.93) Full citation Sample size Tests Methods Results Limitations

Menon,S., N=2721 Index test A database of all pregnant Frequency of possible Retrospective Sammel,M.D., women presenting with risk factors in those with Vichnin,M., (However, only 509 of History taking and physical complaints of pain or bleeding is ectopic pregnancy, split Unclear what type of Barnhart,K.T., Risk kept at the University of by age (% (n for whom factors for ectopic these were diagnosed with examination surgery is reported as a ectopic pregnancy and Pennsylvania. The database data was available) risk factor pregnancy: a contains information on women comparison between hence constitute the Reference test population of interest for since 1990. Only women a. Prior ectopic pregnancy adults and adolescent requiring a follow-up ultrasound Only includes women with women, Journal of this review question. No Ectopic pregnancy: or hCG measurements were Adolescents: 1.61 (n=62) pain and/or bleeding Pediatric and data or outcomes have Diagnosed if products of included in the database. Adults: 20.22 (n=445) Adolescent been reported for the conception were detected Information about women (p < 0.01) Unclear what was adjusted Gynecology, 20, 181- remaining 2212 women) within the fallopian tube, undergoing a salpingostomy for for to calculate adjusted 185, 2007 ultrasound documeneted an ectopic pregnancy treatment was b. Prior surgery ORs Characteristics extra uterine gestational sac, entered into the database; those Ref Id or a rise in hCG was seen undergoing emergency Adolescents: 1.59 (n=63) Breakdown of final following dilation and salpingectomy were excluded. Adults: 24.44 (n=446) 102281 diagnosis by age evacuation. 2721 presented to the emergency (p < 0.01) (number (%)) department during the first Other information Country/ies where Viable pregnancy: Diagnosed trimester of pregnancy, of which c. Prior PID the study was Total by ultrasound visualisation of 649 were adolescents. A total of This study population has

96 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments carried out Adolescents: 649 a yolk sac, fetal pole or fetal 509 patients were eventually Adolescents: 22.22 (n=63) also been reported in other Adult: 2072 cardiac activity within the diagnosed with an ectopics Adults: 19.73 (n=446) included studies (Barnhart USA uterus pregnancy, of which 63 were in (p=0.64) et al. 2003, Barnhart et al. Ectopic pregnancy adolescents and 446 were in 2006). However, it has Study type Adolescents: 63 (9.7) Miscarriage: Diagnosed adults. d. Prior gonorrhea or been included here due to Adults: 446 (21.7) when hCG fell to <5 mIU/ml chlamydia infection its consideration of the Case-series or by pathologic confirmation Transvaginal ultrasounds were differing presentations of Intrauterine pregnancy of products of conception routinely performed at initial Adolescents: 30.65 (n=62) ectopic pregnancy in Aim of the study Adolescents: 172 (26.5) after suction dilation and presentation. Results were Adults: 26.68 (n=446) adolescents and adults. Adults: 505 (24.4) curettage categorised as likely IUP, non- (p=0.51) To compare the diagnostic, suspicious for EP, prevalence of Miscarriage definite EP, and non-viable e. Use of an IUCD classical risk factors Adolescents: 414 (63.8) IUP. Age, obstetric history, and presenting signs Adults: 1121 (53.9) previous STIs and surgical history Adolescents: 0 (n=62) and symptoms were recorded in the database. Adults: 4.93 (n=446) between adolescents 95% of the population Symptoms at time of presentation (p=0.07) and adults with were black, with no to the emergency room were also ectopic pregnancy. difference between recorded. Both research and f. Parous adolescent and adult clinical staff caring for the patient Adolescents: 22.22 (n=62) Study dates populations. were responsible for entry of information in to the database. Adults: 62.33 (n=446) (p < 0.01) Inclusion Criteria Diagnoses were confirmed for 1990 onwards (no each woman (see "Tests" further details given) section). Pregnant women in the Frequency of symptoms Source of funding first trimester presenting in those with ectopic with pain or bleeding A retrospective cross-sectional study was designed to analyse pregnancy, split by age Not reported the incidence of ectopic (% (n for whom data was Requirement for follow-up pregnancies in a teenage available)) ultrasound or serial hCG population. The database was measurements first split into adolescent (<20 a. Bleeding years old) and adult (≥20 years Adolescents: 77.42 (n=62) Exclusion Criteria old). Descriptive statistics were used to compare the presentation Adults: 75.36 (n=418) (p=0.72) Emergency salpingectomy and risk factor association of ectopics in adults versus adolescents. b. Pain

Adolescents: 79.37 (n=63) Adults: 66.82 (n=446)

97 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

(p=0.045)

c. Current gonorrhea or chlamydia infection

Adolescents: 22.22 (n=63) Adults: 4.07 (n=393) (p < 0.01)

d. Pain among those without gonorrhea/chlamydia

Adolescents: 83.3 (n=42) Adults: 68.2 (n=377) (p=0.043)

e. Pain among those with gonorrhea/chlamydia

Adolescents: 58.3 (n=12) Adults: 81.3 (n=16) (p=0.183)

Adjusted associations comparing risk factors and symptoms between adolescents and adults (OR (95% CI), p value)

(Note: OR < 1 indicates that the risk factor or symptom is less prevalent in adolescents compared to adults)

Parous: 0.35 (0.206 - 0.577), p<0.0001

98 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Previous ectopic: 0.11 (0.013 - 0.859), p=0.035

History of surgery: 0.10 (0.013 - 0.791), P=0.029

Neither pain or infection: 1.00 (Reference) Pain only: 2.55 (6.562 - 402.676), p=0.035 (Note: it is unclear why reported OR is not within 95% CI) Infection only: 0.08 (0.007 - 0.800), p=0.0002 Pain and infection: 3.94 (1.271 - 12.186), p=0.018 Full citation Sample size Tests Methods Results Limitations

Bouyer,J., Coste,J., N=1679 Index test Data collection Frequency of potential risk Other information Fernandez,H., factors (number of women Pouly,J.L., Job- Characteristics History taking An ectopic pregnancy register and %) (n=1679) 259/1679 (15.4%) of Spira,N., Sites of was established in three districts ectopics had tubal rupture. ectopic pregnancy: A Reference test of the Auvergne region. In each Smoker: 767 (48.1) 10 year population- Age/years (number of medical centre in the recruitment Only 4.5% extratubal EPs based study of 1800 women and %) Surgical visualisation area (15 public or private Current IUCD: 424 (25.5) (ovarian (n=54) and cases, Human (unclear whether laparoscopy maternity hospitals and 12 abdominal (n=22)) were Reproduction, 17, < 25: 210 (12.5) or laparotomy) surgical units) a trained Prior spontaneous observed and about three- 3224-3230, 2002 25 - 34: 977 (58.2) investigator, either a midwife or a miscarriage: 428 (25.6) quarters of the tubal ≥ 35: 490 (29.2) physician, was responsible for pregnancies Ref Id case identification, follow-up and Prior EP: 210 (12.6) (1175/1603=73%) were Prior delivery (n (%)): 1164 data collection. 102345 ampullary. No cervical (69.7) Prior STI: 318 (19.7) pregnancies were observed

Country/ies where Inclusion Criteria Prior tubal surgery: 312 the study was (18.7) carried out All women between 15 and France 44 years of age who live permanently in the target area and who had

99 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Study type had surgical treatment for ectopic pregnancy Case-series Exclusion Criteria Aim of the study

Women who had medical To investigate the treatment only because the distribution of ectopic site of implantation could pregnancy sites in a not be determined with population-based certainty. sample and its variation over time Women who had surgical treatment but for whom To study the precise information immediate concerning the distribution complications and of ectopic factors determining pregnancy implantation the site of ectopic was not provided pregnancy (this data was not extracted, as it is not relevant to this review question).

Study dates

January 1992 to December 2001

Source of funding

National Institute Committee (Comite National des Registres-INSERM- InVS), France

100 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Full citation Sample size Tests Methods Results Limitations

Clancy,M.J., N=60 Index test Patient's discharged from St. Frequency of possible Retrospective Illingworth,R.N., The James's University Hospital risk factors (number with diagnosis of ectopic Characteristics History taking and physical Leeds with a diagnosis of ectopic risk factor/total ectopics Unclear who extracted the pregnancy in an examination pregnancy were identified from (%)) data from the records, or accident and hospital computer records. The who exactly was emergency Age/years (mean Reference test notes of the patients who had Investigations for infertility: responsible for reporting department, Archives (range)): 28 (17-45) initially attended the A&E 10/60 (16.7) signs and symptoms in the of Emergency All patients had laparotomy. department were analysed for first place. Medicine, 6, 205-210, Previous, recent contact factors associated with ectopic Previous abdominal 1989 with medical facilities pregnancy, presenting signs and surgery: 9/60 (15) The location of the ectopic (number/total (%)) symptoms, initial diagnosis and pregnancies is not

Ref Id - Referred from GP: 26/60 investigations, and subsequent IUCD used within previous reported. (43.3) outcome. The notes of 60 year: 8/60 (13.3) 102446 - Recently seen in another patients were available. Other information A&E: 2/60 (3.3) Previous ectopic pregnancy: Country/ies where - Recently seen in 4/60 (6.7) the study was gynaecology departments: 45 patients had results of a carried out 8/60 (13.3) Previous pelvic infection: pregnancy test reported, of 4/60 (6.7) which 20/45 (44%) were UK negative. Progestogen-only Study type contraceptive pill: 4/60 (6.7) Inclusion Criteria Case-series Tubal ligation or diathermy: Discharged with a Aim of the study 3/60 (5) diagnosis of ectopic pregnancy None of these risk factors: To determine the 31/60 (51.7) accuracy of ectopic Initially attended A&E pregnancy in an department accident and Frequency of symptoms emergency Exclusion Criteria (number with department and symptom/total ectopics consider how it could (%)) Not reported (however be improved they state that 2 patients' Abdominal pain: 57/60 (95) records could not be

Study dates traced) Amenorrhea: 41/60 (68.3)

101 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

1983 to 1986 Vaginal bleeding: 45/60 (75) - Vaginal bleeding for more Source of funding than a week: 21/60 (35)

Not reported Nausea and vomiting: 29/60 (48.3)

Breast tenderness: 19/60 (31.7)

Faintness, dizziness or vomiting: 18/60 (30)

Chest or shoulder pain: 9/60 (15)

Pain on defecation: 4/60 (6.7)

Frequency of signs at physical examination (number with sign/total ectopics (%))

Abdominal tenderness: 42/60 (70)

Adnexal tenderness: 32/60 (53.3)

Cervical excitation: 25/60 (41.7)

Adnexal mass: 11/60 (18.3)

Uterine enlargement: 22/60 (36.7)

102 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Hypovolaemic shock: 7/60 (11.7)

Pyrexia (37.5° or higher): 6/60 (10) Full citation Sample size Tests Methods Results Limitations

Larrain,D., N = 86 Index test Data collection Frequency of risk factors There is missing data for a Marengo,F., for ectopic pregnancy lot of the risk factors (more Bourdel,N., Characteristics History taking In the Auvergne region, all (number/total (%)) than 50% for in utero Jaffeux,P., ublet- women aged 15 to 45 who are diethylstilbestrol Cuvelier,B., Reference test treated for ectopic pregnancy are Smoking: 47/79 (59.5) exxposure) and the Pouly,J.L., Mage,G., Age/years (mean (range)): registered on the Auvergne denominator is not reported Rabischong,B., 31 (18 - 44) Transvaginal ultrasound Ectopic Pregnancy Registry, and History of PID: 27/83 (32.5) for the symptoms. Proximal ectopic (44%), abdominal ultrasound then followed up prospectively pregnancy: a Gestational age at (8%), laparoscopy (45%), until the age of 45. The authors Previous surgery: 59/86 Other information descriptive general diagnosis/days (mean emergency laparotomy identified all of the women (68.6) population-based (range)): 48.2 (12 - 89) diagnosed with a proximal ectopic (Note: type of surgery is not study and results of prengancy, located either in the reported) This study population is different management hCG level (mean): 10759 intramyometrial portion of the likely to partially options in 86 cases, (95% CI 6189 - 15328) fallopian tube (interstitial) or in the History of adhesiolysis: incorporate the interstitial Fertility and Sterility, uterine horns (cornual). 11/82 (13.4) pregnancies reported in 95, 867-871, 2011 Inclusion Criteria Bouyer et al., 2002; (Note: the authors also report Previous salpingectomy: however, this only affects Ref Id risk factors. It is not Proximal ectopic details around the management 15/82 (18.2) of the ectopics, but the data is not possible to deal with 118771 pregnancy, defined as the cross over, as Bouyer either cornual or interstitial relevant to this review question Previous tubal surgery: 3/82 and therefore will not be reported (3.7) et al. does not report Country/ies where here) proximal pregnancies in the study was Aged 15 - 45 History of endometriosis: this way. carried out Treated for ectopic 3/84 (3.6)

France pregnancy In utero diethylstilbestrol exposure: 2/38 (5.2) Study type Exclusion Criteria Population-based History of oral study None reported contraception: 42/65 (64.6)

History of IUCD use: 16/65

103 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Aim of the study (24.6)

To summarise the Previous EP: 24/86 (27.9) presence of pre- disposing faactors for proximal ectopic Frequency of symptoms pregnancy and (%) outcomes of different treatments among Abdominal pain: 87 patients with proximal ectopic pregnancy in Vaginal bleeding: 56 the population

Study dates

January 1992 to December 2008

Source of funding

None stated Full citation Sample size Tests Methods Results Limitations

Kazandi,M., Turan,V., N = 254 Index test Data collection Frequency of risk factors Retrospective Ectopic pregnancy; reported (%) risk factors and Characteristics Clinical history taking 254 ectopic pregnancies were Exclusion criteria not comparison of retrospectively reviewed. The a. History of pelvic surgery: reported intervention success Reference test presenting symptoms of the 12 rates in tubal ectopic None reported patients, the location of the Unclear whether there was pregnancy, Clinical Combination of transvaginal ectopic and the management of b. Previous ectopic: 6% any missing data, and and Experimental Inclusion Criteria ultrasound and quantitative the patient were evaluated. therefore what the Obstetrics and serum hCG levels (However, any outcomes relating c. Use of IUCD: 6% denominator was for each Gynecology, 38, 67- Ectopic pregnancy to treatment are not relevant to of these symptoms and risk 70, 2011 this review and therefore will not d. History of infertility: 5.5% factors be reported here)

Ref Id Exclusion Criteria e. History of PID: 4% Not reported how the data

104 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

123280 None reported Frequency of symptoms was collected and who by reported (%) Country/ies where Other information the study was a. Abdominopelvic pain: carried out 77% 243 (95%) ectopics were Turkey b. Vaginal bleeding: 14% tubal; with the remainder split among cornual (n=3), Study type c. Vaginal bleeding and cervical (n=3), rudimentary pelvic pain: 7% horn (n=3), ovarian (n=1) Case-series and abdominal (n=1)

Aim of the study

The assessment of ectopic pregnancy, its risk factors, and a comparison of the treatment modes

Study dates

January 2002 to July 2009

Source of funding

None stated Full citation Sample size Tests Methods Results Limitations

Shaunik,A., Kulp,J., N = 173 Index test Data collection Frequency of symptoms Type or location of pain is Appleby,D.H., reported (n/total (%)) not reported Sammel,M.D., (However, only 107 of Clinical history This was a cohort study including Barnhart,K.T., Utility these were ultimately all women with a non-viable PUL a. Pain: 58/107 (54.2%) Exclusion criteria is not of dilation and diagnosed with an ectopic Reference test meeting the inclusion criteria. reported curettage in the pregnancy and therefore Potential predictors of clinical b. Bleeding: 68/107 (63.6%) diagnosis of form the population of Unclear, but women seem to outcome were identified from pregnancy of

105 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments unknown location, interest for this review) have received a uterine medical and surgical history, Other information American Journal of evacuation (the authors state clinical presentation, and Obstetrics and Characteristics that this was standard clinical diagnostic tests. Women were Gynecology, 204, practice before beginning followed up in the clinical 130-130, 2011 medical treatment for a database until the were Median initial hCG presumed ectopic) definitively diagnosed with an Ref Id (mIU/ml): 344 (range 142 - ectopic or non-viable IUP. 926) 130830 Inclusion Criteria Country/ies where the study was Women with a non-viable carried out PUL

USA Clinically stable with either: - initial hCG ≥ 2000 and a Study type non-diagnostic ultrasound Prospective cohort - initial hCG < 2000 and an study abnormal rise/fall/plateau of levels Aim of the study Exclusion Criteria To determine the usefulness of None reported dilatation and curettage for diagnosis of non viable pregnancy of unknown location (PUL)

Study dates

December 2003 to July 2007

Source of funding

106 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Grant from National Institutes of Health Full citation Sample size Tests Methods Results Limitations

Choi,H.J., Im,K.S., N = 49 Index test Data collection Frequency of risk factors Retrospective Jung,H.J., Lim,K.T., reported (n/total (%)) Mok,J.E., Kwon,Y.S., Characteristics Clinical history taking The authors retrospectively Exclusion criteria not Clinical analysis of reviewed the medical records of a. Previous ectopic: 6/49 reported ovarian pregnancy: a Reference test 49 cases of ovarian pregnancy (12.2) report of 49 cases, Age/years (mean (SD)): diagnosed and treated in one Other information European Journal of 30.7 (4.4) Review of pathology reports hospital during the study period. b. Present IUD use: 2/49 Obstetrics, They collected data on patient (4.1) Gynecology, and Inclusion Criteria characteristics, as well as All ovarian pregnancies Reproductive Biology, complaints, risk factors, and c. History of abdominal 158, 87-89, 2011 Ovarian pregnancy diagnosis. surgery: 19/49 (38.8)

Ref Id d. Endometriosis: 16/49

Exclusion Criteria (32.7) 152753

None reported e. PID: 4/49 (8.2) Country/ies where the study was f. Ovulation induction: 4/49 carried out (8.2)

South Korea g. IVF: 8/49 (16.3)

Study type h. No risk factors: 12/49 Case-series (24.5)

Aim of the study Frequency of symptoms reported (n/total (%)) To clinically analyse cases of ectopic a. Abdominal pain: 21/49 ovarian pregnancy (42.9) and to generate data regarding the b. Vaginal bleeding: 14/49 evaluation and (28.6) management of

107 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments suspected ectopic c. Adnexal mass: 3/49 (6.1) ovarian pregnancies d. Shock: 1 (2.0) Study dates e. Vomiting: 1/49 (2.0)

January 1996 to f. Asymptomatic: 9/49 (18.4) December 2009 g. Skipped menstruation: Source of funding 4/49 (8.2)

None stated Full citation Sample size Tests Methods Results Limitations

Downey,L.V., N = 187 Index test Data collection and analysis Frequency of risk factors Retrospective Zun,L.S., Indicators of (%) potential for rupture Characteristics Medical history, physical A retrospective chart review was Only includes women with for ectopics seen in examination and lab values conducted of all women with an Previous ectopic pregnancy: pain or bleeding the emergency Inclusion Criteria ectopic who presented to the ED 16.0 department, Journal Reference test during the study period. Data was Unclear what gold standard of Emergencies collected from the ED, Frequency of symptoms (%) was used to confirm the Trauma and Shock, 4, Women aged at least 18 Unclear hospitalisation records, and diagnosis of ectopic 374-377, 2011 years old outpatient clinics, using a data Abdominal pain: 75.7 pregnancy collection sheet that included

Ref Id Presenting with abdominal basic demographic information, Vaginal bleeding: 51.9 Individual denominators for pain or vaginal bleeding to history of the patient (medical, each symptom or sign are 152776 the emergency department surgical, obstetric, gynecological, Nausea: 20.6 not reported; therefore only (ED) sexual, social), findings on % can be calculated Country/ies where physical examination and lab Vomiting: 16.4 the study was Determined to have an values (urine pregnancy test, Unclear who collected the carried out ectopic pregnancy beta-hCG values and complete Frequency of signs on data blood count). clinical examination (%) USA Exclusion Criteria Other information The data was entered into SPSS Abdominal tenderness: 60.8 Study type and multivariate regression and < 18 years old Out of those presenting to Case-series frequency distributions were performed. Out of 249 patients the ED: 49% had rupture, Presenting with complaints 26% did not, 4% were not other than abdominal pain with ectopic, 187 had complete data available for analysis. recorded, and 17% were

108 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

Aim of the study or vaginal bleeding not diagnosed with an EP at the ED visit. To evaluate the Found to have other indicators for rupture diagnosis Risk factors were reported; in patients who however, their prevalence present to the Significant data missing was not reported (only emergency from charts association with rupture), department with an and therefore they cannot ectopic pregnancy be reported here

Study dates

2000 to 2005

Source of funding

The authors state that they did not receive any support Full citation Sample size Tests Methods Results Limitations

Goksedef,B.P., N = 232 Index test Data collection Frequency of risk factors, Retrospective Kef,S., Akca,A., overall and split by Bayik,R.N., Cetin,A., Characteristics Clinical history This was a retrospective review rupture status (n/total (%)) 38% of ectopics were Risk factors for of diagnosed ectopic ruptured rupture in tubal Reference test pregnancies, and risk factors a. IUD use ectopic pregnancy: Status of ectopic (n/total were identified and recorded. - All women: 16/232 (6.9) Unclear what the source of definition of the (%)) Laparotomy or laparoscopy Patients with tubal rupture who - Ruptured: 6/88 (6.8) the data was (i.e. who clinical findings, needed emergency laparotomy - Unruptured: 10/144 (6.9) collected it and retrieved it) European Journal of Ruptured: 88/232 (37.9%) and blood transfusion were (p = 0.97) and how cases were Obstetrics, Unruptured: 144/232 identified. identified Gynecology, and (62.1%) b. Smoking Reproductive Biology, Analysis - All women: 44/232 (19.0) Other information 154, 96-99, 2011 Age (mean (SD)) - Ruptured: 18/88 (20.5) Student's t-test, Mann-Whitney- - Unruptured: 26/144 (18.1)

Ref Id Ruptured: 29.6 (5.6) Wilcoxon test for independent (p = 0.61) Unruptured: 28.9 (5.6) samples, Pearson's chi-square (p = 0.97)

109 Ectopic pregnancy and miscarriage

Bibliographic details Participants Tests Methods Outcomes and results Comments

152810 and Fisher's exact test were c. Previous ectopic Gestational age (mean applied for the comparison of - All women: 23/232 (9.9) Country/ies where (SD)) groups, where appropriate. - Ruptured: 10/88 (11.4) the study was Multivariate logistic regression - Unruptured: 13/144 (9.0)* carried out Ruptured: 7.8 (1.09) analysis was used to identify (p = 0.33) Unruptured: 6.4 (1.2) predictors of the outcome of the Turkey (p < 0.0001) EP (variables with a p-value of < d. History of PID 0.05 from the univariate analysis - All women: 17/232 (7.3) Study type hCG levels/IU/ml (mean were entered into the multivariate - Ruptured: 9/88 (10.2) (SD)) analysis) - Unruptured: 8/144 (5.6) Case-series (p = 0.18) Ruptured: 8735.3 Aim of the study (11317.8) e. Endometriosis Unruptured: 4506 (5673.7) - All women: 11/232 (4.7) To determine risk - Ruptured: 4/88 (4.5) factors for rupture of Inclusion Criteria - Unruptured: 7/144 (4.9) an ectopic pregnancy (p = 0.91) and therefore identify Cases of tubal ectopic those at greatest risk *this % does not match that pregnancy operated on by stated in the paper, and it is laparotomy or laparoscopy unclear why, because to get Study dates a denominator of 8.6% (as Exclusion Criteria stated), you would need a January 2003 to larger study population than September 2009 None stated that which is reported.

Source of funding Note: in the multivariate analysis, only gestational age and hCG were None stated important risk factors for tubal rupture.

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