Today on the emDOCs cast with Brit Long (@long_brit), we cover myths and misconceptions in ectopic pregnancy, focusing on risk factors, history, and exam.
Episode 135: Ectopic Pregnancy Myths Part 1
Background
- Ectopic pregnancy is a fertilized ovum that implants outside of the uterine cavity. Most occur in the fallopian tubes.
- Account for less than 2% of pregnancies overall, but in patients who present to the ED who are pregnant with vaginal bleeding/pain, numbers are higher (6-18%).
- Ectopic pregnancy is decreasing in incidence.
- Mortality has also decreased, but ectopic pregnancy is life-threatening if rupture occurs.
- Patients do not always have the classic presentation of positive pregnancy test, pain and vaginal bleeding, and mass in the adnexa on imaging.
Myth 1: Majority of Patients with EP Have at Least One Risk Factor That Predisposes to the Condition
- Major risk factors (primarily associated with damage to the fallopian tubes): prior ectopic pregnancy, history of tubal surgery or congenital tube abnormalities, assisted reproductive technology, history of induced abortion, PID, older pregnancy age, and smoking (Saxon, Shaw, Hoover).
- Problem: Literature suggests up to 50% of women with an ectopic pregnancy will not have a risk factor (Marion, Brown, Dart, Saxon).
- A study with over 690 ectopic pregnancies found 57% had no risk factors. 33% had one risk factor, approximately 10% had two risk factors, just over 2% had three, and less than 1% had four of these risk factors (Saxon).
- Two other retrospective studies found that between 40-53% of patients with confirmed ectopic pregnancy had no risk factors (Shah, Shah).
- Takeaway: Patients with risk factors are at higher risk for ectopic pregnancy, but the absence of these factors is not protective. Patients can have ectopic pregnancy with no known risk factors or known issues with the fallopian tubes.
Myth 2: Contraceptives, Including Tubal Ligation, Intrauterine Devices, and Emergency Methods Are Associated with More Ectopic Pregnancies Than Those in the General Population.
- There have been case reports of ectopic pregnancy after using emergency contraception like levonorgestrel, ulipristal acetate, and mifepristone.
- Many associate these factors as something that increases the risk of ectopic pregnancy (Marion, Bartz).
- However, if taken properly, they do not themselves increase a woman’s risk of EP.
- Systematic review with over 130 studies that evaluated pregnancy rates after either mifepristone or levonorgestrel (Cleland).
- Of all cases of failed contraception, authors found a rate of 0.6% of ectopic pregnancy in the mifepristone group and 1% in the levonorgestrel group (Cleland). For ulipristal, the rate of ectopic pregnancy is around 1% (Barnhart).
- Those rates are no different from the average rate of ectopic pregnancy.
- 2015 case-control study found levonorgestrel to be an effective contraceptive, and it did not increase the overall risk of ectopic pregnancy. Authors found that if pregnancy did occur, the risk of ectopic pregnancy increased (odds ratio 2.79) (Zhang).
- There is literature suggesting that if the patient becomes pregnant and they have an IUD in place, the risk of ectopic pregnancy is over 50%.
- Takeaway: Overall, compared to no contraception, these devices reduce the overall risk of ectopic pregnancy because they reduce the chance of pregnancy. If the method fails, then there is potentially a higher risk of ectopic pregnancy. If the patient presents with concerning signs and symptoms, obtain serum pregnancy test.
Myth 3: Patients with Ectopic Pregnancy Always Present with Pain or Adnexal Tenderness on Examination.
- Classic presentation is abdominal or pelvic pain, vaginal bleeding, and amenorrhea, and these are the most common presentations (Weckstein).
- Problem: these are not sensitive or specific; less than half of cases have all three signs/symptoms (Condous, National Institute, Kaplan, Ayim, MacKintosh, Dart).
- Case reports describe patients with ectopic pregnancy having no signs, no symptoms.
- Abdominal pain or tenderness: majority of studies report over 90% have some form of pain or tenderness, but there are several studies that report somewhere between 9% up to even 62% of patients have no abdominal or pelvic pain (this study was performed in a pregnancy clinic though (Coundous)) (Condous, National Institute, Kaplan, Ayim, MacKintosh, Dart).
- If pain is present, it can be sharp and stabbing, dull and throbbing or colicky. It is usually unilateral due to distension of the fallopian tube and can become more generalized and severe if it ruptures.
- There is no pattern or characteristic of the pain that can rule in or out the disease. Some form of abdominal pain or tenderness is usually present in most patients.
- Pelvic exam: cervical motion tenderness +LR of 4.9, adnexal mass +LR of 2.4. Slightly increase the likelihood of ectopic pregnancy (Robertson).
- Vaginal bleeding: present in 50-60%. Volume and pattern of bleeding vary.
- Bleeding may be scant brown to large volume blood loss; may be one episode or continuous.
- Up to 75% report amenorrhea prior to bleeding if it occurs (many will mistake this for a normal menstrual period).
- Another issue is that abdominal pain and bleeding can occur in women with normal IUPs (Abott, Stovall).
- Ectopic pregnancy can also present with nausea and vomiting, lightheadedness or even syncope, dizziness, rectal pressure, pain with defecation, shoulder pain.
- Takeaway: Consider ectopic pregnancy in the patient with abdominal or pelvic pain, abdominal or pelvic symptoms, or if they have vaginal bleeding. Do not use the absence of the classic triad to rule out the disease.
Stay tuned for Part 2, where we’ll cover urine pregnancy testing, serum β-hCG, and ultrasound.
References:
- Jeffers K, Koyfman A, Long B. Updates in emergency medicine: Ectopic pregnancy. Am J Emerg Med 2024 Nov;85:90-97.
- Robertson JJ, Long B, Koyfman A. Emergency Medicine Myths: Ectopic Pregnancy Evaluation, Risk Factors, and Presentation. J Emerg Med 2017 Dec;53(6):819-828.
- Hendriks E, Rosenberg R, Prine L. Ectopic Pregnancy: Diagnosis and Management. Am Fam Physician 2020 May 15;101(10):599-606.
- Brady PC. New Evidence to Guide Ectopic Pregnancy Diagnosis and Management. Obstet Gynecol Surv 2017 Oct;72(10):618-625.
- Saxon D, Falcone T, Mascha EJ, et al. A study of ruptured tubal ectopic pregnancy. Obstet Gynecol 1997;90(1):46-9.
- Shah R, Darawade S, Potdar J, Naphade P. Study of Risk Factors of Ectopic Pregnancy and its Management. Global Journal For Research Analysis 2016; 5(3). X129.
- Hoover KW, Tao G, Kent CK. Trends in the diagnosis and treatment of ectopic pregnancy in the United States. Obstet Gynecol 2010;115(3):495-502.
- Dart RG, Kaplan B, Varaklis K. Predictive value of history and physical examination in patients with suspected ectopic pregnancy. Ann Emerg Med 1999;33(3):283-90.
- Marion LL, Meeks GR. Ectopic pregnancy: history, incidence, epidemiology, and risk factors. Clin Obstet Gynecol 2012;55(2):376-86.
- Brown MD, Byyny R, Diercks DB, et al. Clinical Policy: Critical Issues in the Initial Evaluation and Management of Patients Presenting to the Emergency Department in Early Pregnancy. Annals of Emergency Medicine 2017;69(2):241-50.
- Shah N, Khan NH. Ectopic pregnancy: presentation and risk factors.
J Coll Physicians Surg Pak: JCPSP 2005;15(9):535-8. - Bartz D, Greenberg JA. Sterilization in the United States. Rev Obstet Gynecol 2008;1(1):23-32.
- Cleland K, Raymond EG, Westley E, Trussell J. Emergency contraception review: evidence-based recommendations for clinicians. Clin Obstet Gynecol 2014;57(4):741.
- Barnhart KT, Sammel MD, Gracia CR, et al. Risk factors for ectopic pregnancy in women with symptomatic first-trimester pregnancies. Fertil Steril 2006;86(1):36-43.
- Zhang J, Li C, Zhao WH, et al. Association between levonorgestrel emergency contraception and the risk of ectopic pregnancy: a multicenter case-control study. Scientific reports 2015;5.
- Weckstein LN, Boucher AR, Tucker H, et al. Accurate diagnosis of early ectopic pregnancy. Obstet Gynecol 1985;65(3):393-7.
- National Institute for Health and Clinical Excellence. Ectopic Pregnancy and Miscarriage: Diagnosis and Initial Management in Early Pregnancy of Ectopic Pregnancy and Miscarriage (Clinical Guideline 154) 2012. http://www.nice.org.uk/CG154
- Kaplan BC, Dart RG, Moskos M, et al. Ectopic pregnancy: prospective study with improved diagnostic accuracy. Ann Emerg Med 1996;28(1):10-7.
- Ayim F, Tapp S, Guha S, et al. Can risk factors, clinical history and symptoms be used to predict risk of ectopic pregnancy in women attending an early pregnancy assessment unit? Ultrasound Obstet Gynecol 2016;48(5):656-62.
- MacKintosh M, Elkattan E, Mahendran M, Basama F. An asymptomatic ectopic pregnancy in a caesarean section scar. J Obstet Gynaecol 2010;30(8):868-9.
- Dart RG, Kaplan B, Varaklis K. Predictive value of history and physical examination in patients with suspected ectopic pregnancy. Ann Emerg Med 1999;33(3):283-90.
- 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;26(7):770-5.
- Abbott J, Emmans LS, Lowenstein SR. Ectopic pregnancy: ten common pitfalls in diagnosis. Am J Emerg Med 1990;8(6):515-22.
- Stovall TG, Kellerman AL, Ling FW, Buster JE. Emergency department diagnosis of ectopic pregnancy. Ann Emerg Med 1990;19(10):1098-103.
- Griffey RT, Trent CJ, Bavolek RA, et al. “Hook-like effect” causes false-negative point-of-care urine pregnancy testing in emergency patients. J Emerg Med 2013;44(1):155-60.
- Gronowski AM, Cervinski M, Stenman UH, et al. False-negative results in point-of-care qualitative human chorionic gonadotropin (hCG) devices due to excess hCGβ core fragment. Clin Chem 2009;55(7):1389-94.
- Maccato ML, Estrada R, Faro S. Ectopic pregnancy with undetectable serum and urine [beta]-hCG levels and detection of [beta]-hCG in the ectopic trophoblast by immunocytochemical evaluation. Obstet Gynecol 1993;81(5):878-9.
- Nerenz RD, Song H, Gronowski AM. Screening method to evaluate point-of-care human chorionic gonadotropin (hCG) devices for susceptibility to the hook effect by hCG β core fragment: evaluation of 11 devices. Clin Chem 2014;60(4):667-74.
- Sheele, MJ, Bernstein R, Counselman FL. A Ruptured Ectopic Pregnancy Presenting with a Negative Urine Pregnancy Test. Case Rep Emerg Med 2016;2016.
- Brennan DF, Kwatra S, Kelly M, Dunn M. Chronic ectopic pregnancy—two cases of acute rupture despite negative βhCG. J Emerg Med 2000;19(3):249-54.
- Kamer SM, Foley KF, Schmidt RL, Greene DN. Analytical sensitivity of four commonly used hCG point of care devices. Clin Biochem 2015;48(6):448-52.
- Greene DN, Schmidt RL, Kamer SM, et al. Limitations in qualitative point of care hCG tests for detecting early pregnancy. Clin Chim Acta 2013;415:317-21.
- Butler SA, Khanlian SA, Cole LA. Detection of early pregnancy forms of human chorionic gonadotropin by home pregnancy test devices. Clin Chem 2001;47(12):2131-6.
- Kadar N, DeVore E GR, Romero R. Discriminatory hCG zone: its use in the sonographic evaluation for ectopic pregnancy. Obstet Gynecol 1981;58(2):156-61.
- American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 94: Medical management of ectopic pregnancy. Obstet Gynecol 2008;111(6):1479.
- Seeber BE, Sammel MD, Guo W, et al. Application of redefined human chorionic gonadotropin curves for the diagnosis of women at risk for ectopic pregnancy. Fertil Steril 2006;86(2):454-9.
- Morse CB, Sammel MD, Shaunik A, et al. Performance of human chorionic gonadotropin curves in women at risk for ectopic pregnancy: exceptions to the rules. Fertil Steril 2012;97(1):101-6.
- Silva C, Sammel MD, Zhou L, et al. Human chorionic gonadotropin profile for women with ectopic pregnancy. Obstet Gynecol 2006;107(3):605-10.
- Barnhart KT. Ectopic pregnancy. N Engl J Med 2009;361(4):379-87.
- Dillon KE, Sioulas VD, Sammel MD, et al. How and when human chorionic gonadotropin curves in women with an ectopic pregnancy mimic other outcomes: differences by race and ethnicity. Fertil Steril 2012;98(4):911-6.
- Connolly A, Ryan DH, Stuebe AM, et al. Reevaluation of discriminatory and threshold levels for serum β-hCG in early pregnancy. Obstet Gynecol 2013;121(1):65-70.
- Barnhart K, Mennuti MT, Benjamin I, et al. Prompt diagnosis of ectopic pregnancy in an emergency department setting. Obstet Gynecol 1994; 84(6):1010-5.
- Mehta TS, Levine D, Beckwith B. Treatment of ectopic pregnancy: is a human chorionic gonadotropin level of 2,000 mIU/mL a reasonable threshold? Radiol 1997;205(2):569-73.
- 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 2007;25(6):591-6.
- Simsek Y, Ay MO. Analysis of ectopic pregnancies admitted to emergency department. Turk J Emerg Med 2015;15(4):151-4.
- Fu J, Henne MB, Blumstein S, Lathi RB. Rupture of ectopic pregnancy with minimally detectable beta-human chorionic gonadotropin levels: a report of 2 cases. J Reprod Med 2007;52(6):541-2.
- Hochner-Celnikier D, Ron M, Goshen R, et al. Rupture of ectopic pregnancy following disappearance of serum beta subunit of hCG. Obstet Gynecol 1992;79(5 (Pt 2)):826-7.
- Grynberg M, Teyssedre J, Andre C, Graesslin O. Rupture of ectopic pregnancy with negative serum β-hCG leading to hemorrhagic shock. Obstet Gynecol 2009;113(2, Part 2):537-9.
- Resta S, Fuggetta E, D’Itri F, et al. Rupture of ovarian pregnancy in a woman with low beta-HCG levels. Case Rep Obstet Gynecol 2012;2012.
- Galstyan K, Kurzel RB. Serum beta-hCG titers do not predict ruptured ectopic pregnancy. Int J Fertil Womens Med 2005;51(1):14-6.
