Diagnostic Considerations

Only 50% of patients with an ectopic pregnancy present with the classic triad of pain, amenorrhea, and vaginal bleeding. Numerous conditions may have a presentation similar to an extrauterine pregnancy. The most common of these include the following:

Appendicitis
Salpingitis
Ruptured corpus luteum cyst or ovarian follicle
Spontaneous abortion or threatened abortion
Ovarian torsion
Urinary tract disease

Intrauterine pregnancies with other abdominal or pelvic problems, such as degenerating fibroids, must also be included in the differential diagnosis.

A study by Huchon et al found that the following 4 symptoms independently contributed to the diagnosis of tubal rupture:

Vomiting during pain
Diffuse abdominal pain
Acute pain for longer than 30 minutes
Flashing pain

The sensitivity was 93% in the presence of 1 or more of these items, and the specificity was 44%, with a negative likelihood ratio for ruling out tubal rupture of 0.16.^[55]

The following conditions should also be considered in the differential diagnosis of ectopic pregnancy:

Postabortion bleeding
Retained products of abortion
Molar pregnancy
Cornual myoma or abscess
Ovarian tumor
Endometrioma
Cervical phase of uterine abortion

Differential Diagnoses

Workup

Farquhar CM. Ectopic pregnancy. Lancet. 2005 Aug 13-19. 366(9485):583-91. [QxMD MEDLINE Link].
Kadar N, Bohrer M, Kemmann E, Shelden R. The discriminatory human chorionic gonadotropin zone for endovaginal sonography: a prospective, randomized study. Fertil Steril. 1994 Jun. 61(6):1016-20. [QxMD MEDLINE Link].
Stein JC, Wang R, Adler N, et al. Emergency physician ultrasonography for evaluating patients at risk for ectopic pregnancy: a meta-analysis. Ann Emerg Med. 2010 Dec. 56(6):674-83. [QxMD MEDLINE Link].
Hoover KW, Tao G, Kent CK. Trends in the diagnosis and treatment of ectopic pregnancy in the United States. Obstet Gynecol. 2010 Mar. 115(3):495-502. [QxMD MEDLINE Link].
Lipscomb GH. Medical therapy for ectopic pregnancy. Semin Reprod Med. 2007 Mar. 25(2):93-8. [QxMD MEDLINE Link].
Stovall TG, Ling FW, Gray LA. Single-dose methotrexate for treatment of ectopic pregnancy. Obstet Gynecol. 1991 May. 77(5):754-7. [QxMD MEDLINE Link].
Riaz RM, Williams TR, Craig BM, Myers DT. Cesarean scar ectopic pregnancy: imaging features, current treatment options, and clinical outcomes. Abdom Imaging. 2015 Oct. 40 (7):2589-99. [QxMD MEDLINE Link].
Bouyer J, Coste J, Fernandez H, Pouly JL, Job-Spira N. Sites of ectopic pregnancy: a 10 year population-based study of 1800 cases. Hum Reprod. 2002 Dec. 17(12):3224-30. [QxMD MEDLINE Link].
Saito M, Koyama T, Yaoi Y, Kumasaka T, Yazawa K. Site of ovulation and ectopic pregnancy. Acta Obstet Gynecol Scand. 1975. 54(3):227-30. [QxMD MEDLINE Link].
Nkusu Nunyalulendho D, Einterz EM. Advanced abdominal pregnancy: case report and review of 163 cases reported since 1946. Rural and Remote Health 8 (online). 2008;1087. [Full Text].
Ankum WM, Mol BW, Van der Veen F, Bossuyt PM. Risk factors for ectopic pregnancy: a meta-analysis. Fertil Steril. 1996 Jun. 65(6):1093-9. [QxMD MEDLINE Link].
Strandell A, Thorburn J, Hamberger L. Risk factors for ectopic pregnancy in assisted reproduction. Fertil Steril. 1999 Feb. 71(2):282-6. [QxMD MEDLINE Link].
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 Feb 1. 157(3):185-94. [QxMD MEDLINE Link].
Fylstra DL. Ectopic pregnancy after hysterectomy: a review and insight into etiology and prevention. Fertil Steril. 2010 Jul. 94(2):431-5. [QxMD MEDLINE Link].
Peterson HB, Xia Z, Hughes JM, Wilcox LS, Tylor LR, Trussell J. The risk of ectopic pregnancy after tubal sterilization. U.S. Collaborative Review of Sterilization Working Group. N Engl J Med. 1997 Mar 13. 336(11):762-7. [QxMD MEDLINE Link].
Furlong LA. Ectopic pregnancy risk when contraception fails. A review. J Reprod Med. 2002 Nov. 47(11):881-5. [QxMD MEDLINE Link].
Williams S, Peipert J, Buckel C, Zhao Q, Madden T, Secura G. Contraception and the risk of ectopic pregnancy. Contraception. 2014 Sept. 90(3):326.
[Guideline] National Collaborating Centre for Women’s and Children’s Health (UK). Long-acting reversible contraception: the effective and appropriate use of long-acting reversible contraception. National Institute for Health and Care Excellence: Guidance. 2005 Oct. [QxMD MEDLINE Link]. [Full Text].
Vinson DR. Emergency contraception and risk of ectopic pregnancy: is there need for extra vigilance?. Ann Emerg Med. 2003 Aug. 42(2):306-7. [QxMD MEDLINE Link].
Dor J, Seidman DS, Levran D, Ben-Rafael Z, Ben-Shlomo I, Mashiach S. The incidence of combined intrauterine and extrauterine pregnancy after in vitro fertilization and embryo transfer. Fertil Steril. 1991 Apr. 55(4):833-4. [QxMD MEDLINE Link].
Svare JA, Norup PA, Thomsen SG, et al. [Heterotopic pregnancy after in vitro fertilization]. Ugeskr Laeger. 1994 Apr 11. 156(15):2230-3. [QxMD MEDLINE Link].
Rombauts L, McMaster R, Motteram C, Fernando S. Risk of ectopic pregnancy is linked to endometrial thickness in a retrospective cohort study of 8120 assisted reproduction technology cycles. Hum Reprod. 2015 Dec. 30 (12):2846-52. [QxMD MEDLINE Link].
Majmudar B, Henderson PH 3rd, Semple E. Salpingitis isthmica nodosa: a high-risk factor for tubal pregnancy. Obstet Gynecol. 1983 Jul. 62(1):73-8. [QxMD MEDLINE Link].
Hoover RN, Hyer M, Pfeiffer RM, et al. Adverse health outcomes in women exposed in utero to diethylstilbestrol. N Engl J Med. 2011 Oct 6. 365(14):1304-14. [QxMD MEDLINE Link].
Goldner TE, Lawson HW, Xia Z, Atrash HK. Surveillance for ectopic pregnancy--United States, 1970-1989. MMWR CDC Surveill Summ. 1993 Dec 17. 42(6):73-85. [QxMD MEDLINE Link].
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 Dec. 6(4):227-36. [QxMD MEDLINE Link].
Calderon JL, Shaheen M, Pan D, Teklehaimenot S, Robinson PL, Baker RS. Multi-cultural surveillance for ectopic pregnancy: California 1991-2000. Ethn Dis. 2005 Autumn. 15(4 Suppl 5):S5-20-4. [QxMD MEDLINE Link].
Van Den Eeden SK, Shan J, Bruce C, Glasser M. Ectopic pregnancy rate and treatment utilization in a large managed care organization. Obstet Gynecol. 2005 May. 105(5 Pt 1):1052-7. [QxMD MEDLINE Link].
Mann LM, Kreisel K, Llata E, Hong J, Torrone EA. Trends in Ectopic Pregnancy Diagnoses in United States Emergency Departments, 2006-2013. Matern Child Health J. 2020 Feb. 24 (2):213-21. [QxMD MEDLINE Link]. [Full Text].
Goyaux N, Leke R, Keita N, Thonneau P. Ectopic pregnancy in African developing countries. Acta Obstet Gynecol Scand. 2003 Apr. 82(4):305-12. [QxMD MEDLINE Link].
Lewis G, ed. Saving Mothers’ Lives: Reviewing maternal deaths to make motherhood safer - 2003-2005. The Seventh Report of the Confidential Enquiries into Maternal Deaths in the United Kingdom. London, UK: The Confidential Enquiry into Maternal and Child Health (CEMACH). 2007:92-3.:
Chang J, Elam-Evans LD, Berg CJ, et al. Pregnancy-related mortality surveillance--United States, 1991--1999. MMWR Surveill Summ. 2003 Feb 21. 52(2):1-8. [QxMD MEDLINE Link].
Yao M, Tulandi T. Current status of surgical and nonsurgical management of ectopic pregnancy. Fertil Steril. 1997 Mar. 67(3):421-33. [QxMD MEDLINE Link].
Dubuisson JB, Morice P, Chapron C, De Gayffier A, Mouelhi T. Salpingectomy - the laparoscopic surgical choice for ectopic pregnancy. Hum Reprod. 1996 Jun. 11(6):1199-203. [QxMD MEDLINE Link].
Clausen I. Conservative versus radical surgery for tubal pregnancy. A review. Acta Obstet Gynecol Scand. 1996 Jan. 75(1):8-12. [QxMD MEDLINE Link].
Maymon R, Shulman A, Halperin R, Michell A, Bukovsky I. Ectopic pregnancy and laparoscopy: review of 1197 patients treated by salpingectomy or salpingotomy. Eur J Obstet Gynecol Reprod Biol. 1995 Sep. 62(1):61-7. [QxMD MEDLINE Link].
Parker J, Bisits A. Laparoscopic surgical treatment of ectopic pregnancy: salpingectomy or salpingostomy?. Aust N Z J Obstet Gynaecol. 1997 Feb. 37(1):115-7. [QxMD MEDLINE Link].
Ory SJ, Nnadi E, Herrmann R, O'Brien PS, Melton LJ 3rd. Fertility after ectopic pregnancy. Fertil Steril. 1993 Aug. 60(2):231-5. [QxMD MEDLINE Link].
Rulin MC. Is salpingostomy the surgical treatment of choice for unruptured tubal pregnancy?. Obstet Gynecol. 1995 Dec. 86(6):1010-3. [QxMD MEDLINE Link].
Stovall TG, Ling FW, Carson SA, Buster JE. Serum progesterone and uterine curettage in differential diagnosis of ectopic pregnancy. Fertil Steril. 1992 Feb. 57(2):456-7. [QxMD MEDLINE Link].
Xu Z, Yan L, Liu W, Xu X, Li M, Ding L, et al. Effect of treatment of a previous ectopic pregnancy on in vitro fertilization-intracytoplasmic sperm injection outcomes: a retrospective cohort study. Fertil Steril. 2015 Dec. 104 (6):1446-51.e1-3. [QxMD MEDLINE Link].
Barnhart KT, Gosman G, Ashby R, Sammel M. The medical management of ectopic pregnancy: a meta-analysis comparing "single dose" and "multidose" regimens. Obstet Gynecol. 2003 Apr. 101(4):778-84. [QxMD MEDLINE Link].
Alleyassin A, Khademi A, Aghahosseini M, Safdarian L, Badenoosh B, Hamed EA. Comparison of success rates in the medical management of ectopic pregnancy with single-dose and multiple-dose administration of methotrexate: a prospective, randomized clinical trial. Fertil Steril. 2006 Jun. 85(6):1661-6. [QxMD MEDLINE Link].
Barnhart KT, Sammel MD, Hummel AC, Jain JK, Chakhtoura N, Strauss III J. A novel "two dose" regimen of methotrexate to treat ectopic pregnancy. Fertil Steril. 2005 Sept. 84(Suppl):S1:S130-S131. [Full Text].
Ectopic pregnancy mortality - Florida, 2009-2010. MMWR Morb Mortal Wkly Rep. 2012 Feb 17. 61(6):106-9. [QxMD MEDLINE Link].
Anderson FW, Hogan JG, Ansbacher R. Sudden death: ectopic pregnancy mortality. Obstet Gynecol. 2004 Jun. 103(6):1218-23. [QxMD MEDLINE Link].
Grimes DA. Estimation of pregnancy-related mortality risk by pregnancy outcome, United States, 1991 to 1999. Am J Obstet Gynecol. 2006 Jan. 194(1):92-4. [QxMD MEDLINE Link].
Khan KS, Wojdyla D, Say L, Gulmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: a systematic review. Lancet. 2006 Apr 1. 367(9516):1066-74. [QxMD MEDLINE Link].
Alsuleiman SA, Grimes EM. Ectopic pregnancy: a review of 147 cases. J Reprod Med. 1982 Feb. 27(2):101-6. [QxMD MEDLINE Link].
Stovall TG, Kellerman AL, Ling FW, Buster JE. Emergency department diagnosis of ectopic pregnancy. Ann Emerg Med. 1990 Oct. 19(10):1098-103. [QxMD MEDLINE Link].
Barnhart KT, Sammel MD, Gracia CR, Chittams J, Hummel AC, Shaunik A. Risk factors for ectopic pregnancy in women with symptomatic first-trimester pregnancies. Fertil Steril. 2006 Jul. 86(1):36-43. [QxMD MEDLINE Link].
Kaplan BC, Dart RG, Moskos M, et al. Ectopic pregnancy: prospective study with improved diagnostic accuracy. Ann Emerg Med. 1996 Jul. 28(1):10-7. [QxMD MEDLINE Link].
Abbott J, Emmans LS, Lowenstein SR. Ectopic pregnancy: ten common pitfalls in diagnosis. Am J Emerg Med. 1990 Nov. 8(6):515-22. [QxMD MEDLINE Link].
Dart RG, Kaplan B, Varaklis K. Predictive value of history and physical examination in patients with suspected ectopic pregnancy. Ann Emerg Med. 1999 Mar. 33(3):283-90. [QxMD MEDLINE Link].
Huchon C, Panel P, Kayem G, et al. Is a standardized questionnaire useful for tubal rupture screening in patients with ectopic pregnancy?. Acad Emerg Med. 2012 Jan. 19(1):24-30. [QxMD MEDLINE Link].
Mol F, van den Boogaard E, van Mello NM, et al. Guideline adherence in ectopic pregnancy management. Hum Reprod. 2011 Feb. 26(2):307-15. [QxMD MEDLINE Link].
Pereira N, Bender JL, Hancock K, et al. Routine monitoring of liver, renal, and hematologic tests after single- or double-dose methotrexate treatment for ectopic pregnancies after in vitro fertilization. J Minim Invasive Gynecol. 2015 Nov-Dec. 22 (7):1266-70. [QxMD MEDLINE Link].
Shepherd RW, Patton PE, Novy MJ, Burry KA. Serial beta-hCG measurements in the early detection of ectopic pregnancy. Obstet Gynecol. 1990 Mar. 75(3 Pt 1):417-20. [QxMD MEDLINE Link].
Barnhart KT, Sammel MD, Rinaudo PF, Zhou L, Hummel AC, Guo W. Symptomatic patients with an early viable intrauterine pregnancy: HCG curves redefined. Obstet Gynecol. 2004 Jul. 104(1):50-5. [QxMD MEDLINE Link].
Condous G, Kirk E, Lu C, et al. Diagnostic accuracy of varying discriminatory zones for the prediction of ectopic pregnancy in women with a pregnancy of unknown location. Ultrasound Obstet Gynecol. 2005 Dec. 26(7):770-5. [QxMD MEDLINE Link].
Taran FA, Kagan KO, Hubner M, Hoopmann M, Wallwiener D, Brucker S. The diagnosis and treatment of ectopic pregnancy. Dtsch Arztebl Int. 2015 Oct 9. 112 (41):693-704. [QxMD MEDLINE Link].
Barclay L. Transvaginal sonogram may be best test for ectopic pregnancy. Medscape News from WebMD. April 23, 2013. Available at http://www.medscape.com/viewarticle/802998. Accessed: April 29, 2013.
Crochet JR, Bastian LA, Chireau MV. Does this woman have an ectopic pregnancy?: the rational clinical examination systematic review. JAMA. 2013 Apr 24. 309(16):1722-9. [QxMD MEDLINE Link].
Barnhart K, Mennuti MT, Benjamin I, Jacobson S, Goodman D, Coutifaris C. Prompt diagnosis of ectopic pregnancy in an emergency department setting. Obstet Gynecol. 1994 Dec. 84(6):1010-5. [QxMD MEDLINE Link].
Verma U, English D, Brookfield K. Conservative management of nontubal ectopic pregnancies. Fertil Steril. 2011 Dec. 96(6):1391-1395.e1. [QxMD MEDLINE Link].
Stovall TG, Ling FW, Carson SA, Buster JE. Serum progesterone and uterine curettage in differential diagnosis of ectopic pregnancy. Fertil Steril. 1992 Feb. 57(2):456-7. [QxMD MEDLINE Link].
Bonin L, Pedreiro C, Moret S, Chene G, Gaucherand P, Lamblin G. Predictive factors for the methotrexate treatment outcome in ectopic pregnancy: A comparative study of 400 cases. Eur J Obstet Gynecol Reprod Biol. 2017 Jan. 208:23-30. [QxMD MEDLINE Link].
Menon S, Colins J, Barnhart KT. Establishing a human chorionic gonadotropin cutoff to guide methotrexate treatment of ectopic pregnancy: a systematic review. Fertil Steril. 2007 Mar. 87(3):481-4. [QxMD MEDLINE Link].
Thurman AR, Cornelius M, Korte JE, Fylstra DL. An alternative monitoring protocol for single-dose methotrexate therapy in ectopic pregnancy. Am J Obstet Gynecol. 2010 Feb. 202(2):139.e1-6. [QxMD MEDLINE Link].
Ozcan MCH, Wilson JR, Frishman GN. A Systematic Review and Meta-analysis of Surgical Treatment of Ectopic Pregnancy with Salpingectomy versus Salpingostomy. J Minim Invasive Gynecol. 2021 Mar. 28 (3):656-67. [QxMD MEDLINE Link].
Medical treatment of ectopic pregnancy. Fertil Steril. 2008 Nov. 90(5 Suppl):S206-12. [QxMD MEDLINE Link].
Douglas D. Salpingectomy may often have edge in ectopic pregnancy. Medscape News from WebMD. 2014 Feb 27. Available at http://www.medscape.com/viewarticle/821131. Accessed: February 27, 2014.
Mol F, van Mello NM, Strandell A, et al. Salpingotomy versus salpingectomy in women with tubal pregnancy (ESEP study): an open-label, multicentre, randomised controlled trial. Lancet. 2014 Apr 26. 383(9927):1483-9. [QxMD MEDLINE Link].
Sivin I. Dose- and age-dependent ectopic pregnancy risks with intrauterine contraception. Obstet Gynecol. 1991 Aug. 78(2):291-8. [QxMD MEDLINE Link].
Rombauts L, McMaster R, Motteram C, Fernando S. Risk of ectopic pregnancy is linked to endometrial thickness in a retrospective cohort study of 8120 assisted reproduction technology cycles. Hum Reprod. 2015 Dec. 30 (12):2846-52. [QxMD MEDLINE Link].
ACOG Practice Bulletin No. 193: Tubal Ectopic Pregnancy. Obstet Gynecol. 2018 Mar. 131 (3):e91-e103. [QxMD MEDLINE Link].

Media Gallery

Sites and frequencies of ectopic pregnancy. By Donna M. Peretin, RN. (A) Ampullary, 80%; (B) Isthmic, 12%; (C) Fimbrial, 5%; (D) Cornual/Interstitial, 2%; (E) Abdominal, 1.4%; (F) Ovarian, 0.2%; and (G) Cervical, 0.2%.
Laparoscopic picture of an unruptured right ampullary tubal pregnancy; bleeding out of the fimbriated end has resulted in hemoperitoneum.
A 12-week interstitial gestation, which eventually resulted in a hysterectomy. Courtesy of Deidra Gundy, MD, Department of Obstetrics and Gynecology at Medical College of Pennsylvania and Hahnemann University (MCPHU).
A 12-week interstitial gestation, which eventually resulted in a hysterectomy. Courtesy of Deidra Gundy, MD, Department of Obstetrics and Gynecology at Medical College of Pennsylvania and Hahnemann University (MCPHU).
An endovaginal sonogram reveals an intrauterine pregnancy at approximately 6 weeks. A yolk sac (ys), gestational sac (gs), and fetal pole (fp) are depicted.
Linear incision being made at the antimesenteric side of the ampullary portion of the fallopian tube.
Laparoscopic picture of an ampullary ectopic pregnancy protruding out after a linear salpingostomy was performed.
Schematic of a tubal gestation being teased out after linear salpingostomy.

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Author

Vicken P Sepilian, MD, MSc Medical Director, Reproductive Endocrinology and Infertility, CHA Fertility Center

Vicken P Sepilian, MD, MSc is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Ellen Wood, DO, FACOG Voluntary Assistant Professor, University of Miami, Leonard M Miller School of Medicine

Ellen Wood, DO, FACOG is a member of the following medical societies: American Society for Reproductive Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Frances E Casey, MD, MPH Associate Professor, Director of Family Planning Services, Department of Obstetrics and Gynecology, VCU Medical Center

Frances E Casey, MD, MPH is a member of the following medical societies: American College of Obstetricians and Gynecologists, Association of Reproductive Health Professionals, National Abortion Federation, Physicians for Reproductive Health, Society of Family Planning

Disclosure: Nothing to disclose.

Chief Editor

Michel E Rivlin, MD Former Professor, Department of Obstetrics and Gynecology, University of Mississippi School of Medicine

Michel E Rivlin, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Medical Association, Mississippi State Medical Association, Royal College of Surgeons of Edinburgh, Royal College of Obstetricians and Gynaecologists

Disclosure: Nothing to disclose.

Acknowledgements

A David Barnes, MD, PhD, MPH, FACOG Consulting Staff, Department of Obstetrics and Gynecology, Mammoth Hospital (Mammoth Lakes, California), Pioneer Valley Hospital (Salt Lake City, Utah), Warren General Hospital (Warren, Pennsylvania), and Mountain West Hospital (Tooele, Utah)

A David Barnes, MD, PhD, MPH, FACOG is a member of the following medical societies: American College of Forensic Examiners, American College of Obstetricians and Gynecologists, American Medical Association, Association of Military Surgeons of the US, and Utah Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Robert K Zurawin, MD Associate Professor, Director of Baylor College of Medicine Program for Minimally Invasive Gynecology, Director of Fellowship Program, Minimally Invasive Surgery, Department of Obstetrics and Gynecology, Baylor College of Medicine

Robert K Zurawin, MD is a member of the following medical societies: American Association of Gynecologic Laparoscopists, American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine, Association of Professors of Gynecology and Obstetrics, Central Association of Obstetricians and Gynecologists, Harris County Medical Society, North American Society for Pediatric and Adolescent Gynecology, and Texas Medical Association

Disclosure: Johnson and Johnson Honoraria Speaking and teaching; Conceptus Honoraria Speaking and teaching; ConMed Consulting fee Consulting

Ectopic Pregnancy Differential Diagnoses

Diagnostic Considerations

Differential Diagnoses

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