eMedicine Specialties > Emergency Medicine > Obstetrics & Gynecology

Pregnancy, Ectopic: Treatment & Medication

Author: Thomas J Chi, MD, Assistant Clinical Professor, Emergency Medicine, State University of New York Downstate Medical Center; Attending Physician, Emergency Medicine, Kings County Hospital Center, New York
Contributor Information and Disclosures

Updated: Nov 9, 2009

Treatment

Prehospital Care

Patients in shock require prehospital care to treat hypotension.

Emergency Department Care

The most critical step in beginning the workup is to have a high clinical suspicion for ectopic pregnancy (eg, in any woman of childbearing age). After a positive urine pregnancy test, any necessary initial resuscitation, and physical examination (including pelvic examination to rule out an open cervical os or completed abortion), a transabdominal pelvic ultrasonography, followed by a transvaginal ultrasonography if needed, should be performed to identify a definitive intrauterine pregnancy (yolk sac or fetal pole) or definitive ectopic pregnancy (extrauterine yolk sac or fetal pole).
 
This initial sonogram should be obtained at bedside by an emergency physician, where feasible. A protocol using bedside emergency physician-performed transvaginal ultrasonography showed a large reduction in the incidence of discharged patients who later had ruptured ectopic pregnancies.55 Emergency physician-performed ultrasonography has been shown to speed time to diagnosis compared to ultrasonography performed by an OB/GYN consult56 or by the radiology department57 . Experienced emergency physicians are sometimes able to correctly diagnose ectopic pregnancies initially missed by OB/GYN consults.58 The only lawsuit found in a search of the WESTLAW nationwide litigation database concerning emergency physicians and ultrasonography was filed for failure to perform ED ultrasonography in an ectopic pregnancy that ruptured several days later.59  
 
Hemodynamically unstable patients should first be scanned in the right upper quadrant of the abdomen, as the finding of free fluid in Morison's pouch in the right clinical setting by the emergency physician has been shown to decrease time to the operating room.60 Attention should be paid to the adnexa, even when an intrauterine pregnancy (IUP) is visualized, to rule out the rare heterotopic pregnancy, especially in patients with a history of assisted reproduction.

Ultrasonographic findings suggestive of ectopic pregnancy (empty uterus with a tubal ring, complex adnexal mass, or a moderate-to-large amount of free fluid), or a definite extrauterine pregnancy, warrant an immediate GYN consult for medical or surgical treatment. Patients with evidence of a failed IUP should be followed up in consultation with GYN for either repeat ultrasonography and serial beta-HCG, D&C, or expectant management.

Patients with indeterminate sonogram findings (empty uterus, gestational sac <8 mm without yolk sac) should have a beta-HCG level drawn, and follow up closely with GYN to monitor serial beta-HCG levels and ultrasonography. Although a certain percentage of pregnancies of unknown location (PULs) (15% in one study) will eventually be diagnosed with an ectopic pregnancy, these are much less likely than those diagnosed on the initial sonogram to require surgical treatment.61 Patients with a live IUP on sonogram are essentially ruled out for ectopic pregnancy, have a low risk of eventually aborting (about 9% in one study, higher if associated with vaginal bleeding62 ), and can be discharged from the ED after routine further care.

Consultations

OB/GYN should be consulted as needed for ectopic pregnancies, and follow-up care of patients with failing/failed IUPs or pregnancies of unknown location. Any patient who is clinically unstable should have the consultation in the emergency department.

OB/GYN or radiology should also be consulted for transvaginal sonography as needed, according to institutional policy.

Medication

The current standard medical treatment of unruptured ectopic pregnancy is methotrexate (MTX) therapy.63 This decision should be made in conjunction with, if not by, the consulting OB/GYN. The ideal candidate for medical treatment should have (1) hemodynamic stability, (2) no severe or persisting abdominal pain, (3) ability to follow-up multiple times, and (4) normal baseline liver and renal function tests. Absolute contraindications include existence of intrauterine pregnancy (IUP), immunodeficiency, moderate-to-severe anemia, leucopenia, or thrombocytopenia, sensitivity to MTX, active pulmonary or peptic ulcer disease, clinically important hepatic or renal dysfunction, or breastfeeding. 

Sonogram findings of an ectopic gestational sac greater than 4 cm in size, (or 3.5 cm if the ectopic pregnancy has fetal heart motion), an initial beta-HCG concentration of greater than 5000 mIU/mL, or significant free fluid are indicators of likely failure of MTX therapy and therefore relative contraindications.

The multiple-dose regimen of methotrexate consists of daily doses of 1 mg/kg IM, given on alternating days with leucovorin (folinic acid, which reduces side effects), until there is a 15% decline in beta-HCG over 2 days. The single-dose regimen consists of one dose of methotrexate 50 mg/m2, followed by a repeat beta-HCG at day 4, and another dose of MTX 50 mg/m2 if the beta-HCG has declined less than 15% between days 4 and 7. Both treatment regimens show an efficacy similar to surgical management for unruptured ectopic pregnancies in the ideal patient population. Common side effects include increase in abdominal girth, vaginal bleeding or spotting, abdominal pain, GI symptoms, stomatitis, dizziness. Rare side effects include severe neutropenia, reversible alopecia, or pneumonitis.63

Anti-Metabolite

These agents are used to terminate pregnancy.


Methotrexate (Folex, PFS)

Used for treatment of unruptured tubal pregnancy and for persistent disease after salpingostomy.

Adult

1 mg/kg IM qod with leucovorin 0.1 mg/kg IM between doses; not to exceed 4 doses

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Oral aminoglycosides may decrease absorption and blood levels of concurrent oral methotrexate (MTX); charcoal lowers levels; coadministration with etretinate may increase hepatotoxicity of MTX; folic acid or its derivatives contained in some vitamins may decrease response; coadministration with NSAIDs may be fatal; indomethacin and phenylbutazone can increase MTX plasma levels; may decrease phenytoin serum levels; probenecid, salicylates, procarbazine, and sulfonamides (including TMP-SMZ) may increase effects and toxicity of MTX; may increase plasma levels of thiopurines

Documented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia)

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Toxic hematologic, renal, GI, pulmonary, and neurologic effects

More on Pregnancy, Ectopic

Overview: Pregnancy, Ectopic
Differential Diagnoses & Workup: Pregnancy, Ectopic
Treatment & Medication: Pregnancy, Ectopic
Follow-up: Pregnancy, Ectopic
Multimedia: Pregnancy, Ectopic
References
[ CLOSE WINDOW ]

References

  1. Farquhar CM. Ectopic pregnancy. Lancet. Aug 13-19 2005;366(9485):583-91. [Medline].

  2. 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. Dec 2002;17(12):3224-30. [Medline].

  3. 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. [Medline].

  4. 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].

  5. Goldner TE, Lawson HW, Xia Z, Atrash HK. Surveillance for ectopic pregnancy--United States, 1970-1989. MMWR CDC Surveill Summ. Dec 17 1993;42(6):73-85. [Medline].

  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. Dec 2002;6(4):227-36. [Medline].

  7. Calderon JL, Shaheen M, Pan D, Teklehaimenot S, Robinson PL, Baker RS. Multi-cultural surveillance for ectopic pregnancy: California 1991-2000. Ethn Dis. 2005;15(4 Suppl 5):S5-20-4. [Medline].

  8. Van Den Eeden SK, Shan J, Bruce C, Glasser M. Ectopic pregnancy rate and treatment utilization in a large managed care organization. Obstet Gynecol. May 2005;105(5 Pt 1):1052-7. [Medline].

  9. Goyaux N, Leke R, Keita N, Thonneau P. Ectopic pregnancy in African developing countries. Acta Obstet Gynecol Scand. Apr 2003;82(4):305-12. [Medline].

  10. 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. 2007:92, 93.

  11. Grimes DA. Estimation of pregnancy-related mortality risk by pregnancy outcome, United States, 1991 to 1999. Am J Obstet Gynecol. Jan 2006;194(1):92-4. [Medline].

  12. Chang J, Elam-Evans LD, Berg CJ, Herndon J, Flowers L, Seed KA, et al. Pregnancy-related mortality surveillance--United States, 1991--1999. MMWR Surveill Summ. Feb 21 2003;52(2):1-8. [Medline].

  13. Khan KS, Wojdyla D, Say L, Gülmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: a systematic review. Lancet. Apr 1 2006;367(9516):1066-74. [Medline].

  14. Bouyer J, Coste J, Shojaei T, Pouly JL, Fernandez H, Gerbaud L, et al. Risk factors for ectopic pregnancy: a comprehensive analysis based on a large case-control, population-based study in France. Am J Epidemiol. Feb 1 2003;157(3):185-94. [Medline].

  15. Alsuleiman SA, Grimes EM. Ectopic pregnancy: a review of 147 cases. J Reprod Med. Feb 1982;27(2):101-6. [Medline].

  16. Stovall TG, Kellerman AL, Ling FW, Buster JE. Emergency department diagnosis of ectopic pregnancy. Ann Emerg Med. Oct 1990;19(10):1098-103. [Medline].

  17. 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. Jul 2006;86(1):36-43. [Medline].

  18. Kaplan BC, Dart RG, Moskos M, et al. Ectopic pregnancy: prospective study with improved diagnostic accuracy. Ann Emerg Med. Jul 1996;28(1):10-7. [Medline].

  19. Anderson FW, Hogan JG, Ansbacher R. Sudden death: ectopic pregnancy mortality. Obstet Gynecol. Jun 2004;103(6):1218-23. [Medline].

  20. Abbott J, Emmans LS, Lowenstein SR. Ectopic pregnancy: ten common pitfalls in diagnosis. Am J Emerg Med. Nov 1990;8(6):515-22. [Medline].

  21. Dart RG, Kaplan B, Varaklis K. Predictive value of history and physical examination in patients with suspected ectopic pregnancy. Ann Emerg Med. Mar 1999;33(3):283-90. [Medline].

  22. Ankum WM, Mol BW, Van der Veen F, Bossuyt PM. Risk factors for ectopic pregnancy: a meta-analysis. Fertil Steril. Jun 1996;65(6):1093-9. [Medline].

  23. Strandell A, Thorburn J, Hamberger L. Risk factors for ectopic pregnancy in assisted reproduction. Fertil Steril. Feb 1999;71(2):282-6. [Medline].

  24. Furlong LA. Ectopic pregnancy risk when contraception fails. A review. J Reprod Med. Nov 2002;47(11):881-5. [Medline].

  25. 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. Mar 13 1997;336(11):762-7. [Medline].

  26. Vinson DR. Emergency contraception and risk of ectopic pregnancy: is there need for extra vigilance?. Ann Emerg Med. Aug 2003;42(2):306-7. [Medline].

  27. Fylstra DL. Ectopic pregnancy after hysterectomy: a review and insight into etiology and prevention. Fertil Steril. Apr 24 2009;[Medline].

  28. Cohen HL, Moore WH. History of emergency ultrasound. J Ultrasound Med. Apr 2004;23(4):451-8. [Medline].

  29. Gracia CR, Barnhart KT. Diagnosing ectopic pregnancy: decision analysis comparing six strategies. Obstet Gynecol. Mar 2001;97(3):464-70. [Medline].

  30. Kalinski MA, Guss DA. Hemorrhagic shock from a ruptured ectopic pregnancy in a patient with a negative urine pregnancy test result. Ann Emerg Med. Jul 2002;40(1):102-5. [Medline].

  31. Grynberg M, Teyssedre J, Andre C, Graesslin O. Rupture of ectopic pregnancy with negative serum beta-hCG leading to hemorrhagic shock. Obstet Gynecol. Feb 2009;113(2 Pt 2):537-9. [Medline].

  32. Kohn MA, Kerr K, Malkevich D, O'Neil N, Kerr MJ, Kaplan BC. Beta-human chorionic gonadotropin levels and the likelihood of ectopic pregnancy in emergency department patients with abdominal pain or vaginal bleeding. Acad Emerg Med. Feb 2003;10(2):119-26. [Medline].

  33. Marill KA, Ingmire TE, Nelson BK. Utility of a single beta HCG measurement to evaluate for absence of ectopic pregnancy. J Emerg Med. May-Jun 1999;17(3):419-26. [Medline].

  34. 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. Jul 2004;104(1):50-5. [Medline].

  35. Silva C, Sammel MD, Zhou L, Gracia C, Hummel AC, Barnhart K. Human chorionic gonadotropin profile for women with ectopic pregnancy. Obstet Gynecol. Mar 2006;107(3):605-10.

  36. Dart RG, Mitterando J, Dart LM. Rate of change of serial beta-human chorionic gonadotropin values as a predictor of ectopic pregnancy in patients with indeterminate transvaginal ultrasound findings. Ann Emerg Med. Dec 1999;34(6):703-10. [Medline].

  37. Mol BW, Lijmer JG, Ankum WM, van der Veen F, Bossuyt PM. The accuracy of single serum progesterone measurement in the diagnosis of ectopic pregnancy: a meta-analysis. Hum Reprod. Nov 1998;13(11):3220-7. [Medline].

  38. Valley VT, Mateer JR, Aiman EJ, Thoma ME, Phelan MB. Serum progesterone and endovaginal sonography by emergency physicians in the evaluation of ectopic pregnancy. Acad Emerg Med. Apr 1998;5(4):309-13. [Medline].

  39. Cabar FR, Fettback PB, Pereira PP, Zugaib M. Serum markers in the diagnosis of tubal pregnancy. Clinics (Sao Paulo). Oct 2008;63(5):701-8. [Medline].

  40. DeWitt C, Abbott J. Interstitial pregnancy: a potential for misdiagnosis of ectopic pregnancy with emergency department ultrasonography. Ann Emerg Med. Jul 2002;40(1):106-9. [Medline].

  41. Gun M, Mavrogiorgis M. Cervical ectopic pregnancy: a case report and literature review. Ultrasound Obstet Gynecol. Mar 2002;19(3):297-301. [Medline].

  42. Dighe M, Cuevas C, Moshiri M, Dubinsky T, Dogra VS. Sonography in first trimester bleeding. J Clin Ultrasound. Jul-Aug 2008;36(6):352-66. [Medline].

  43. Patel MD. "Rule out ectopic": Asking the right questions, getting the right answers. Ultrasound Q. Jun 2006;22(2):87-100. [Medline].

  44. Brown DL, Doubilet PM. Transvaginal sonography for diagnosing ectopic pregnancy: positivity criteria and performance characteristics. J Ultrasound Med. Apr 1994;13(4):259-66. [Medline].

  45. Stein MW, Ricci ZJ, Novak L, Roberts JH, Koenigsberg M. Sonographic comparison of the tubal ring of ectopic pregnancy with the corpus luteum. J Ultrasound Med. Jan 2004;23(1):57-62. [Medline].

  46. Hertzberg BS, Kliewer MA, Bowie JD. Adnexal ring sign and hemoperitoneum caused by hemorrhagic ovarian cyst: pitfall in the sonographic diagnosis of ectopic pregnancy. AJR Am J Roentgenol. Nov 1999;173(5):1301-2. [Medline].

  47. Frates MC, Brown DL, Doubilet PM, Hornstein MD. Tubal rupture in patients with ectopic pregnancy: diagnosis with transvaginal US. Radiology. Jun 1994;191(3):769-72. [Medline].

  48. Blaivas M. Color doppler in the diagnosis of ectopic pregnancy in the emergency department: is there anything beyond a mass and fluid?. J Emerg Med. May 2002;22(4):379-84. [Medline].

  49. Dart R, McLean SA, Dart L. Isolated fluid in the cul-de-sac: how well does it predict ectopic pregnancy?. Am J Emerg Med. Jan 2002;20(1):1-4. [Medline].

  50. Nyberg DA, Laing FC, Filly RA, Uri-Simmons M, Jeffrey RB Jr. Ultrasonographic differentiation of the gestational sac of early intrauterine pregnancy from the pseudogestational sac of ectopic pregnancy. Radiology. Mar 1983;146(3):755-9. [Medline].

  51. Dart RG, Dart L, Mitchell P, Berty C. The predictive value of endometrial stripe thickness in patients with suspected ectopic pregnancy who have an empty uterus at ultrasonography. Acad Emerg Med. Jun 1999;6(6):602-8. [Medline].

  52. Seeber B, Sammel M, Zhou L, Hummel A, Barnhart KT. Endometrial stripe thickness and pregnancy outcome in first-trimester pregnancies with bleeding, pain or both. J Reprod Med. Sep 2007;52(9):757-61. [Medline].

  53. Filhastre M, Dechaud H, Lesnik A, Taourel P. Interstitial pregnancy: role of MRI. Eur Radiol. Jan 2005;15(1):93-5. [Medline].

  54. Kirk E, Condous G, Van Calster B, Van Huffel S, Timmerman D, Bourne T. Rationalizing the follow-up of pregnancies of unknown location. Hum Reprod. Jun 2007;22(6):1744-50. [Medline].

  55. Mateer JR, Valley VT, Aiman EJ, Phelan MB, Thoma ME, Kefer MP. Outcome analysis of a protocol including bedside endovaginal sonography in patients at risk for ectopic pregnancy. Ann Emerg Med. Mar 1996;27(3):283-9. [Medline].

  56. Burgher SW, Tandy TK, Dawdy MR. Transvaginal ultrasonography by emergency physicians decreases patient time in the emergency department. Acad Emerg Med. Aug 1998;5(8):802-7. [Medline].

  57. Blaivas M, Sierzenski P, Plecque D, Lambert M. Do emergency physicians save time when locating a live intrauterine pregnancy with bedside ultrasonography?. Acad Emerg Med. Sep 2000;7(9):988-93. [Medline].

  58. Adhikari S, Blaivas M, Lyon M. Diagnosis and management of ectopic pregnancy using bedside transvaginal ultrasonography in the ED: a 2-year experience. Am J Emerg Med. Jul 2007;25(6):591-6. [Medline].

  59. Blaivas M, Pawl R. 269: Analysis of Lawsuits Filed Against Emergency Physicians Over Bedside Emergency Ultrasound Examination Performance or Interpretation Over a 20-Year Period. Ann Emerg Med. Sept 2007;50(3):S85.

  60. Rodgerson JD, Heegaard WG, Plummer D, Hicks J, Clinton J, Sterner S. Emergency department right upper quadrant ultrasound is associated with a reduced time to diagnosis and treatment of ruptured ectopic pregnancies. Acad Emerg Med. Apr 2001;8(4):331-6. [Medline].

  61. Tayal VS, Cohen H, Norton HJ. Outcome of patients with an indeterminate emergency department first-trimester pelvic ultrasound to rule out ectopic pregnancy. Acad Emerg Med. Sep 2004;11(9):912-7. [Medline].

  62. Juliano M, Dabulis S, Heffner A. Characteristics of women with fetal loss in symptomatic first trimester pregnancies with documented fetal cardiac activity. Ann Emerg Med. Aug 2008;52(2):143-7. [Medline].

  63. [Guideline] Practice Committee of American Society for Reproductive Medicine. Medical treatment of ectopic pregnancy. Fertil Steril. Nov 2008;90(5 Suppl):S206-12. [Medline]. [Full Text].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Thomas J Chi, MD, Assistant Clinical Professor, Emergency Medicine, State University of New York Downstate Medical Center; Attending Physician, Emergency Medicine, Kings County Hospital Center, New York
Thomas J Chi, MD is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, and Medical Society of the State of New York
Disclosure: Nothing to disclose.

Medical Editor

Assaad J Sayah, MD, Chief, Department of Emergency Medicine, Cambridge Health Alliance
Assaad J Sayah, MD is a member of the following medical societies: National Association of EMS Physicians
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Mark Zwanger, MD, MBA, Assistant Professor, Department of Emergency Medicine, Thomas Jefferson University
Mark Zwanger, MD, MBA is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and American Medical Association
Disclosure: Medicines Company Consulting fee Consulting; Pfizer Salary Employment

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Pamela L Dyne, MD, Professor of Clinical Medicine/Emergency Medicine, David Geffen School of Medicine at UCLA; Attending Physician, Department of Emergency Medicine, Olive View-UCLA Medical Center
Pamela L Dyne, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

RELATED EMEDICINE ARTICLES
RELATED MEDSCAPE ARTICLES
 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.