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Ectopic pregnancy: Incidence, risk factors, and pathology

Togas Tulandi, MD, MHCM
Section Editor
Robert L Barbieri, MD
Deputy Editor
Sandy J Falk, MD, FACOG


Ectopic pregnancy occurs when the developing blastocyst becomes implanted at a site other than the endometrium of the uterine cavity. The most common extra-uterine location is the fallopian tube, which accounts for 98 percent of all ectopic gestations (picture 1A-B). Management of these pregnancies has changed dramatically over the years [1]. The guiding principle has become a medical treatment, rather than surgery. However, it is important to remember that hemorrhage from ectopic pregnancy is still the leading cause of pregnancy related maternal death in the first trimester and accounts for 4 to 10 percent of all pregnancy related deaths, despite improved diagnostic methods leading to earlier detection and treatment [2,3].

The incidence, risk factors, and pathology of ectopic pregnancy will be reviewed here. The clinical presentation, diagnosis, and treatment (medical and surgical) of this disorder are discussed separately. (See "Ectopic pregnancy: Clinical manifestations and diagnosis" and "Ectopic pregnancy: Methotrexate therapy" and "Ectopic pregnancy: Surgical treatment".)


The prevalence of ectopic pregnancy among women who go to an emergency department with first trimester bleeding, pain, or both ranges from six to 16 percent [4]. The overall incidence of ectopic pregnancy increased during the mid twentieth century, plateauing at approximately almost 20 per 1000 pregnancies in the early 1990s, the last time national data were reported by the Centers for Disease Control [2]. This rising incidence is strongly associated with an increased incidence of pelvic inflammatory disease [5].

The current incidence of ectopic pregnancy is difficult to estimate from available data (hospitalizations, insurance billing records) because inpatient hospital treatment of ectopic pregnancy has decreased and multiple health care visits for a single ectopic pregnancy have increased [6]. Furthermore, since the incidence is expressed as the number of ectopic pregnancies/1000 pregnancies, the denominator is difficult to determine accurately since early pregnancy failures that do not result in delivery or hospitalization are often not counted.

Ectopic pregnancy occurs with some seasonal variation and is most common in June and December [7]. The reason is unclear; the authors postulated that reproduction is seasonal, depends on photoperiod and temperature, and varies with different latitudes. Therefore, depending on the location of the investigation, ectopic pregnancy may show different seasonal rhythmicities. An altered maturation of the follicle and oocyte may negatively influence reproductive outcome in the transition between two reproductive steady states of high and low overall fecundity.

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Literature review current through: Sep 2017. | This topic last updated: Apr 13, 2016.
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  1. Yao M, Tulandi T. Current status of surgical and nonsurgical management of ectopic pregnancy. Fertil Steril 1997; 67:421.
  2. Centers for Disease Control and Prevention (CDC). Ectopic pregnancy--United States, 1990-1992. MMWR Morb Mortal Wkly Rep 1995; 44:46.
  3. Fylstra DL. Tubal pregnancy: a review of current diagnosis and treatment. Obstet Gynecol Surv 1998; 53:320.
  4. Murray H, Baakdah H, Bardell T, Tulandi T. Diagnosis and treatment of ectopic pregnancy. CMAJ 2005; 173:905.
  5. 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; 76:28.
  6. Zane SB, Kieke BA Jr, Kendrick JS, Bruce C. Surveillance in a time of changing health care practices: estimating ectopic pregnancy incidence in the United States. Matern Child Health J 2002; 6:227.
  7. Cagnacci A, Landi S, Volpe A. Rhythmic variation in the rate of ectopic pregnancy throughout the year. Am J Obstet Gynecol 1999; 180:1067.
  8. 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.
  9. Ankum WM, Mol BW, Van der Veen F, Bossuyt PM. Risk factors for ectopic pregnancy: a meta-analysis. Fertil Steril 1996; 65:1093.
  10. Bouyer J, Coste J, Shojaei T, et al. Risk factors for ectopic pregnancy: a comprehensive analysis based on a large case-control, population-based study in France. Am J Epidemiol 2003; 157:185.
  11. 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.
  12. Goldberg JM, Falcone T. Effect of diethylstilbestrol on reproductive function. Fertil Steril 1999; 72:1.
  13. Hillis SD, Owens LM, Marchbanks PA, et al. Recurrent chlamydial infections increase the risks of hospitalization for ectopic pregnancy and pelvic inflammatory disease. Am J Obstet Gynecol 1997; 176:103.
  14. Shaw JL, Wills GS, Lee KF, et al. Chlamydia trachomatis infection increases fallopian tube PROKR2 via TLR2 and NFκB activation resulting in a microenvironment predisposed to ectopic pregnancy. Am J Pathol 2011; 178:253.
  15. Sivin I. Dose- and age-dependent ectopic pregnancy risks with intrauterine contraception. Obstet Gynecol 1991; 78:291.
  16. Backman T, Rauramo I, Huhtala S, Koskenvuo M. Pregnancy during the use of levonorgestrel intrauterine system. Am J Obstet Gynecol 2004; 190:50.
  17. Mol BW, Ankum WM, Bossuyt PM, Van der Veen F. Contraception and the risk of ectopic pregnancy: a meta-analysis. Contraception 1995; 52:337.
  18. 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.
  19. Furlong LA. Ectopic pregnancy risk when contraception fails. A review. J Reprod Med 2002; 47:881.
  20. 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.
  21. Gemzell C, Guillome J, Wang CF. Ectopic pregnancy following treatment with human gonadotropins. Am J Obstet Gynecol 1982; 143:761.
  22. 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.
  23. Saraiya M, Berg CJ, Kendrick JS, et al. Cigarette smoking as a risk factor for ectopic pregnancy. Am J Obstet Gynecol 1998; 178:493.
  24. Nazari A, Askari HA, Check JH, O'Shaughnessy A. Embryo transfer technique as a cause of ectopic pregnancy in in vitro fertilization. Fertil Steril 1993; 60:919.
  25. Perkins KM, Boulet SL, Kissin DM, et al. Risk of ectopic pregnancy associated with assisted reproductive technology in the United States, 2001-2011. Obstet Gynecol 2015; 125:70.
  26. Wølner-Hanssen P, Eschenbach DA, Paavonen J, et al. Association between vaginal douching and acute pelvic inflammatory disease. JAMA 1990; 263:1936.
  27. Pisarska MD, Carson SA, Buster JE. Ectopic pregnancy. Lancet 1998; 351:1115.
  28. Nybo Andersen AM, Wohlfahrt J, Christens P, et al. Maternal age and fetal loss: population based register linkage study. BMJ 2000; 320:1708.
  29. 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.
  30. Bouyer J, Coste J, Fernandez H, et al. Sites of ectopic pregnancy: a 10 year population-based study of 1800 cases. Hum Reprod 2002; 17:3224.
  31. Lopez HB, Micheelsen U, Berendtsen H, Kock K. Ectopic pregnancy and its associated endometrial changes. Gynecol Obstet Invest 1994; 38:104.
  32. Senterman M, Jibodh R, Tulandi T. Histopathologic study of ampullary and isthmic tubal ectopic pregnancy. Am J Obstet Gynecol 1988; 159:939.
  33. Kutluay L, Vicdan K, Turan C, et al. Tubal histopathology in ectopic pregnancies. Eur J Obstet Gynecol Reprod Biol 1994; 57:91.
  34. Attar E. Endocrinology of ectopic pregnancy. Obstet Gynecol Clin North Am 2004; 31:779.
  35. Timor-Tritsch IE, Yeh MN, Peisner DB, et al. The use of transvaginal ultrasonography in the diagnosis of ectopic pregnancy. Am J Obstet Gynecol 1989; 161:157.
  36. Coste J, Fernandez H, Joyé N, et al. Role of chromosome abnormalities in ectopic pregnancy. Fertil Steril 2000; 74:1259.
  37. Goddijn M, van der Veen F, Schuring-Blom GH, et al. Cytogenetic characteristics of ectopic pregnancy. Hum Reprod 1996; 11:2769.
  38. Gaudoin MR, Coulter KL, Robins AM, et al. Is the incidence of ovarian ectopic pregnancy increasing? Eur J Obstet Gynecol Reprod Biol 1996; 70:141.
  39. Raziel A, Golan A, Pansky M, et al. Ovarian pregnancy: a report of twenty cases in one institution. Am J Obstet Gynecol 1990; 163:1182.
  40. Spiegelberg, O. Zur casvistik des ovarials schwangerschaft. Arch Gynack 1878; 13:73.
  41. Lau S, Tulandi T. Conservative medical and surgical management of interstitial ectopic pregnancy. Fertil Steril 1999; 72:207.
  42. Jansen RP, Elliott PM. Angular intrauterine pregnancy. Obstet Gynecol 1981; 58:167.
  43. Tulandi T, Al-Jaroudi D. Interstitial pregnancy: results generated from the Society of Reproductive Surgeons Registry. Obstet Gynecol 2004; 103:47.
  44. Larraín D, Marengo F, Bourdel N, et al. Proximal ectopic pregnancy: a descriptive general population-based study and results of different management options in 86 cases. Fertil Steril 2011; 95:867.
  45. Baldawa PS, Chaudhari HK. Angular ectopic pregnancy presenting as rupture of lateral wall of the uterus. J Hum Reprod Sci 2008; 1:33.
  46. Rotas MA, Haberman S, Levgur M. Cesarean scar ectopic pregnancies: etiology, diagnosis, and management. Obstet Gynecol 2006; 107:1373.
  47. Ash A, Smith A, Maxwell D. Caesarean scar pregnancy. BJOG 2007; 114:253.
  48. Hassiakos D, Bakas P, Pistofidis G, Creatsas G. Heterotopic pregnancy at 16 weeks of gestation after in-vitro fertilization and embryo transfer. Arch Gynecol Obstet 2002; 266:124.
  49. Strafford JC, Ragan WD. Abdominal pregnancy. Review of current management. Obstet Gynecol 1977; 50:548.
  50. Martin JN Jr, Sessums JK, Martin RW, et al. Abdominal pregnancy: current concepts of management. Obstet Gynecol 1988; 71:549.