Ectopic Pregnancy: A Clinical Casebook

1. Identification of Risk Factors of Ectopic Pregnancy

Ali Ardehali Ishwari Casikar1 and George Condous1


Acute Gynaecology, Early Pregnancy and Advanced Endosurgery Unit, Nepean Centre for Perinatal Care, Nepean Clinical School, Nepean Hospital, University of Sydney, Penrith, Sydney, Australia

Ali Ardehali



Ectopic pregnancyRisk factorsRecurrent ectopic pregnancy

Case Study

The patient was a 29-year-old African-descent woman who presented to the emergency department (ED) with low abdominal pain and nausea. Her pain started 20 h prior to her presentation. The pain had gradually become worse and had radiated to her shoulder tip and was associated with increasing nausea. She had also experienced some per vaginal (PV) spotting and a few episodes of diarrhea during the previous 2–3 days. She initially thought she was starting to menstruate as she also had some breast tenderness. She had no history of abnormal PV discharge.

She smoked approximately 30 cigarettes per day and was a social drinker. She was currently not on any contraception as she was trying to conceive. She had commenced sexual activity at age of 16, with her first husband. She had had two vaginal births at 17 and 20 years of age. She admitted to having had multiple sexual partners from the age of 21 to 26 while she was divorced from her first husband. She had also had two surgical terminations for unwanted pregnancies during that time. She had a laparoscopy at 23 years of age for a right-sided dermoid cyst and there had been evidence of pelvic inflammatory disease (PID). A vaginal swab taken at time confirmed chlamydia infection and she had been appropriately treated. She migrated to Australia from Africa, at the age of 21, as a refugee with her husband and two children.

On examination, she was noted to be pale, and appeared to be in moderate discomfort with a pulse of 102 beats per minute, blood pressure 98/54, afebrile, and saturating at 97 % on room air. Her body mass index (BMI) was 19. Apart from the three laparoscopic scars on her abdomen, she had tenderness, guarding, and rebound pain in the right iliac fossa. Speculum examination demonstrated small amount of blood at the cervical os. Bimanual examination revealed a significant right adnexal tenderness; she was uncomfortable with cervical excitation.

Her hemoglobin (Hgb) was 100 g/L with microcytic and hypochromic picture, white blood cell (WBC) 11.6 × 109/L, and platelet count 286 × 109/L. A urinalysis was positive for blood, ketones, and human chorionic gonadotropin (hCG) .

My Management




Diagnosis and Assessment

In the last three decades, we have witnessed significant changes in the diagnosis and management of EP . The key factors contributing to this change are increased awareness of EPs, tertiary-level early pregnancy units (EPUs), introduction of high-resolution transvaginal ultrasound probes and availability of accurate and rapid serum hCG assays [1]. However, EP is still the most common cause of pregnancy-related deaths and morbidity worldwide, and accounts for 54 % of first-trimester maternal deaths in the UK, and 3–4 % of all mortalities related to pregnancy [23]. This is despite the fact that the mortality from EP has significantly dropped over the past few decades [4].

About 6–16 % of all women who present to an emergency department with first-trimester bleeding or pain or both have EP [5]. Due to the nature of pathology of EP and the absence of a single diagnostic test, early diagnosis can be challenging in emergency and general practice settings. In the most recent confidential enquiry into maternal deaths in the UK during 2006–2008, gastrointestinal symptoms, particularly diarrhea and dizziness in early gestation, are important indicators of EP. These features need to be emphasized to all clinical staff in the primary-care setting [1]. Although transvaginal ultrasound scans (TVS) and the rapid availability of quantitative hCG levels have significantly improved the early diagnosis and optimal management of EP [68], a high index of suspicion of this condition in the first presentation remains the key to early diagnosis and achieving the best outcome.


A detailed history along with a focused physical examination and a quick office test can guide the clinician toward early diagnosis of EP. Detailed TVS performed by an experienced operator can then confirm the diagnosis [910].

The gradual onset of and progressive abdominal pain, and subsequent radiation to the shoulder tip, in addition to mild tachycardia, pallor, and abdominal examination findings, indicate intraperitoneal bleeding . More importantly, the occurrence of diarrhea in the preceding 2–3 days is an important historical factor [2]. The patient’s past medical and surgical history revealed several risk factors, which suggested EP in the list of differential diagnoses. These risk factors are smoking, multiple sexual partners, laparoscopic evidence of PID and confirmed chlamydia swab, and two surgical terminations of pregnancy (Fig. 1.1).


Fig. 1.1

a Ultrasonographic image of tubal ectopic pregnancy (EP) with both embryonic pole and yolk sac visible within the gestational sac. b Same tubal EP demonstrating cardiac activity using M-Mode (viable EP)

Differential Diagnosis

·               Ectopic pregnancy

·               Threatened or incomplete miscarriage

·               Appendicitis

·               Urinary tract infection

·               Ovarian torsion

·               Pelvic inflammatory disease

·               Urinary calculus

·               Gastroenteritis

·               Ruptured or hemorrhagic ovarian cyst

Our patient had been trying to conceive for the last 6 months and now had a positive urine pregnancy test. Therefore, all the complications of early pregnancy including ectopic and early miscarriage should be considered. A quantitative serum hCG would be helpful to confirm the urine test and also as a tool to estimate the age of pregnancy along with the TVS. More importantly, serial serum hCG levels can be measured as well as TVS examination during the conservative management and follow up of patients diagnosed with EP.

The mild tachycardia and relatively low blood pressure, in addition to abdominal tenderness, peritonitis, blood in vagina, and adnexal tenderness, are indicative of clinical instability and potential rupture of EP and the urgency of diagnosis and management.

Risk Factors for EP

There are several studies published regarding EP and its risk factors. However, only about 50 % of women diagnosed with an EP have identifiable risk factors . Recognition of these risk factors can assist the clinicians not only in the early diagnosis of EP but also in reducing the risk of morbidity and mortality of massive intra-abdominal hemorrhage . Most papers have categorized the risk factors to high, medium, and low risks, although there are variations depending on the epidemiology of the study. Below, we have reviewed the most widely accepted factors for EP. [1112].

Previous EP and Tubal Surgery

Previous EP is one of the high risk factors and the incidence increases among people who have had a history of an EP. A woman who has had two prior EPs has a tenfold increased in future EP. This could be due to the tubal dysfunction as the main pathology or secondary to the treatment of EP. The recurrence rate of EP after surgical or nonsurgical management has been reported from 8 to 15 % and 15 % after conservative management [1314]. The risk of EP also increases in women who have had a history of any type of pelvic surgery. For example, previous appendectomy increases the risk of EP by twofold [15]. Among the group of women for whom tubal sterilization has failed, pregnancy can result in an EP rate as high as 33 %. Among these patients, the risk of EP is higher in those less than 30 years of age [13].

PID, Infections, and Multiple Sexual Partners

The growing rate of EP is strongly associated with the increasing rate of PID. The incidence of EP increased by more than twofold from 1970 to 1985 from 7 to 16 per 1000 and then declined by 30 % from 1985 to 1997. This was explained by the increase and decline of PID within those periods [16]. It has also been proven that having multiple sexual partners is a strong risk factor for EP with the odds ratio of 2.1 [17]; but the association between PID and number of sexual partners has to be considered [1819].

In a European study, 65 % of women with EP had suffered from tubal salpingitis. A history of tubal pathology or tubal surgery has been shown to increase the risk of EP with the odds ratio of 3.8–21.0 and 21.0, respectively [20]. Overall, the history of genital infections, including sexually transmitted disease, PID, and/or any tubal pathology or surgery, is a high risk factor for tubal EP.


There are several studies which have confirmed the increased risk of EP in smokers. The risk of EP increases by threefold to fourfold in women who smoke more than one packet of cigarettes per day. The level of risk has been proven to be variable depending on the number of cigarettes smoked. Smoking more than 20 cigarettes a day increases the risk of EP more than smoking 1–5 cigarettes a day with the odds ratio 1.7–3.5 [1421].


It has been proven that the duration of infertility is associated with increased risk of EP with an adjusted odd ratio of 2.7 for more than 2 years of infertility [21]. The rate of EP is 2–3 % higher in patients undergoing an in vitro fertilization (IVF) [20]. In addition, treatment with gonadotropin and other drugs such as clomiphene in IVF pregnancy increases the incidence of EP. This can also be due to dysfunction of the fallopian tubes [2326]. The rate of heterotopic pregnancy in the assisted reproductive population could be up to 1 in 100 to 1 in 45 [2728].

Other Causes

There are other proven risk factors for EP such as diethylstilbestrol (DES) exposure, intrauterine contraceptive devices, surgical termination of pregnancy, and age. In utero exposure to DES increases the relative risk of EP by 3.84. Intrauterine contraceptive devices (IUCD) such as copper IUCD and Mirena intra-uterine system (IUS) decrease the risk of an EP, but if pregnancy does occur with the device in situ, the risk of EP is higher. Of the 0.5 per 100 Mirena IUS users who become pregnant in 5 years (cumulatively), half are EPs. Regular vaginal douching three to four times per month can increase the risk of PID as a high risk factor for EP by three to four times. Women aged 35–44 years have three times risk of EP compared to younger women. Surgical terminations of pregnancy, spontaneous miscarriages, and older age have all also been shown to increase the risk of EP [11212935].

Types of EP

More than 90–98 % of EPs are tubal pregnancies. EP can also be found in the cervix, ovaries, interstitial tube, cesarean scar, the horn of a bicornuate pregnancy (cornual), or abdomen. About 2–3 % of EPs are implanted in the interstitial portion of the tube (interstitial EP). If the ectopic is implanted in one horn of bicornuate uterus, it is called cornual. Of all EPs, 1 % is cervical, 1–3 % is ovarian, and 1–2 % is abdominal pregnancies. Cesarean scar EP is another rare type of EP, the incidence of which is increasing. [3640] (Fig. 1.2).


Fig. 1.2

Laparoscopic image of right tubal ectopic pregnancy with significant hemoperitoneum


A TVS confirmed the diagnosis of a right-sided ruptured right tubal EP with blood noted in the pouch of Douglas and Morison’s pouch for which the patient had urgent laparoscopic salpingectomy.

Clinical Pearls/Pitfalls

·               Failure to recognize the symptoms of an EP can result in increased morbidity and even mortality.

·               Identification of risk factors for EP allows early detection and treatment.

·               High risk factors include previous EP, previous tubal surgery, tubal damage, and current IUD use.



Casikar I, Condous G. How to effectively diagnose ectopic pregnancy using ultrasound? Expert Rev Obstet Gynecol. 2013;8(6):493–5.CrossRef


Cantwell R, Clutton-Brock T, Cooper G, Dawson A, Drife J, Garrod D, et al. Saving mothers’ lives: reviewing maternal deaths to make motherhood safer: 2006–2008. The eighth report of the confidential enquiries into maternal deaths in the United Kingdom. BJOG. 2011;118:1–203.PubMed


Centers for Disease Control and Prevention (CDC). Ectopic pregnancy—United States, 1990–1992. JAMA 1995;7:533


Creanga AA, Shapiro-Mendoza CK, Bish CL, et al. Trends in ectopic pregnancy mortality in the United States: 1980–2007. Obstet Gynecol. 2011;117:837–43CrossRefPubMed


Murray H, Baakdah H, Bardell T, Tulandi T. Diagnosis and treatment of ectopic pregnancy. CMAJ. 2005;173:905.CrossRefPubMedCentralPubMed


Condous G. The management of early pregnancy complications. Best Pract Res Clin Obstet GynaecoI. 2004;lB:37–57.CrossRef


Condous G, Okaro E, Bourne T. The conservative management of early pregnancy complications: a review of the literature. Ultrasound Obstet GynecoI. 2003;22:420–30.CrossRef


Condous G, Okaro E, Bourne T. The management ofectopic pregnancies and pregnancies of unknown location. Gynecol Surg. 2004;1:81–6.CrossRef


Condous G, Okaro E, Khalid A, et al. The accuracy of transvaginal ultra- sonography for the diagnosis of ectopic pregnancy prior to surgery. Hum Reprod. 2005;20:1404–9.CrossRefPubMed


Condous, G. Ectopic pregnancy: risk factors and diagnosis [online]. Aust Fam Physician. 2006 Nov;35(11):854–7.PubMed


Farquhar CM. Ectopic pregnancy. Lancet 2005;366:583–91.


Ankum WM, Mol BW, van der Veen F, Bossuyt PM. Risk factors for ectopic pregnancy: a meta-analysis. Fertil Steril. 1996;65:1093–9. (Comment in Fertil Steril 1997;67:791–2).PubMed


Michalas S, Minaretzis D, Tsionou C, Maos G, Kioses E, Aravantinos D. Pelvic surgery, reproductive factors and risk of ectopic pregnancy: a case controlled study. Int J Gynaecol Obstet. 1992;38:101–5.CrossRefPubMed


Bouyer J, Coste J, Shojaei T, Pouly J, Fernandez H, Gerbaud L, Job-Spira N. Risk factors for ectopic pregnancy: a comprehensive analysis based on a large case-control, population-based study in France. Am J Epidemiol. 2003;157(3):185.CrossRefPubMed


Yao M, Tulandi T. Current status of surgical and nonsurgical management of ectopic pregnancy. Fertil Steril. 1997;67:421.CrossRefPubMed


Peterson HB, Xia Z, Hughes JM, et al. The risk of ectopic pregnancy after tubal sterilization. U.S. Collaborative Review of Sterilization Working Group. N Engl J Med. 1997;336:762.CrossRefPubMed


Kamwendo F, Forslin L, Bodin L, Danielsson D. Epidemiology of ectopic pregnancy during a 28-year period and the role of pelvic inflammatory disease. Sex Transm Infect. 2000;76:28CrossRefPubMedCentralPubMed


Kriebs JM, Fahey JO. Ectopic pregnancy. J Midwifery Womens Health. 2006;51:431–9.CrossRefPubMed


Coste J, Job-Spira N, Fernandez H, et al. Risk factors for ectopic pregnancy: a case-control study in France, with special focus on infectious factors. Am J Epidemiol. 1991;133:839–49.PubMed


Weström L. Influence of acute pelvic inflammatory disease on fertility. Am J Obstet Gynecol. 1975;121:707–13.PubMed


Pisarska MD, Carson SA, Buster JE. Ectopic pregnancy. Lancet. 1998;351:1115–20.CrossRefPubMed


Saraiya M, Berg CJ, Kendrick JS, et al. Cigarette smoking as a risk factor for ectopic pregnancy. Am J Obstet Gynecol.1998;178:493.CrossRefPubMed


Chow WH, Daling JR, Cates W Jr, et al. Epidemiology of ectopic pregnancy. Epidemiol Rev. 1987;9:70–94.PubMed


Job-Spira N, Bouyer J, Pouly JL, et al. Fertility after ectopic pregnancy: first results of a population-based cohort study in France. Hum Reprod. 1996;11:99–104.CrossRefPubMed


Cohen J, Mayaux MJ, Guihard-Moscato ML, Schwartz D. In-vitro fertilization and embryo transfer: a collaborative study of 1163 pregnancies on the incidence and risk factors of ectopic pregnancies. Hum Reprod. 1986;1:255.PubMed


Gemzell C, Guillome J, Wang CF. Ectopic pregnancy following treatment with human gonadotropins. Am J Obstet Gynecol. 1982;143:761.PubMed


McBain JC, Evans JH, Pepperell RJ, et al. An unexpectedly high rate of ectopic pregnancy following the induction of ovulation with human pituitary and chorionic gonadotrophin. Br J Obstet Gynaecol. 1980;87:5.CrossRefPubMed


Molloy D, Deambrosis W, Keeping D, Hynes J, Harrison K, Hennessey J. Multiple-sited (heterotopic) pregnancy after in vitro fertilization and gamete intrafallopian transfer. Fertil Steril. 1990;53:1068–71.PubMed


Talbot K, Simpson R, Price N, Jackson SR. Heterotopic pregnancy. J Obstet Gynaecol. 2011;31(1):7–12CrossRefPubMed


Goldberg JM, Falcone T. Effect of diethylstilbestrol on reproductive function. Fertil Steril. 1999;72:1.CrossRefPubMed


Backman T, Rauramo I, Huhtala S, Koskenvuo M. Pregnancy during the use of levonorgestrel intrauterine system. Am J Obstet Gynecol. 2004;190:50.CrossRefPubMed


Xiong X, Buekens P, Wollast E. IUD use and the risk of ectopic pregnancy: a meta-analysis of case-control studies. Contraception. 1995;52:23.CrossRefPubMed


Wølner-Hanssen P, Eschenbach DA, Paavonen J, et al. Association between vaginal douching and acute pelvic inflammatory disease. JAMA. 1990;263:1936.CrossRefPubMed


Nybo Andersen AM, Wohlfahrt J, Christens P, et al. Maternal age and fetal loss: population based register linkage study. BMJ. 2000;320:1708.CrossRefPubMed


Storeide O, Veholmen M, Eide M, et al. The incidence of ectopic pregnancy in Hordaland County, Norway 1976–1993. Acta Obstet Gynecol Scand. 1997;76:345.CrossRefPubMed


Backman T. Levonorgestrel-releasing intrauterine system in contraception. Expert Rev Obstet Gynecol. 2009;4(3):239–44.CrossRef


Fylstra DL. Ectopic pregnancy within a cesarean scar: a review. Obstet Gynecol Survey. 2002;57:537–43.CrossRef


Flystra DL. Ectopic pregnancy not within the (distal) fallopian tube: etiology, diagnosis, and treatment. Am J Obstet Gynecol. 2012;206(4):289–99.CrossRef


Zhang Y, Chen YS, Wang JJ, Lu ZY, Hua KQ. Analysis of 96 cases with cesarean scar pregnancy. Zhonghua Fu Chan Ke Za Zhi. 2010;45:664–8.PubMed


Bouyer J, Coste J, Fernandez H, Pouly JL, Job-Spira N. Site of ectopic pregnancy: a 10-year population-based study of 1800 cases. Hum Reprod. 2002;17:3224–30.CrossRefPubMed