1. OVERVIEW AND DIAGNOSIS OF ECTOPIC PREGNANCY C. KIM 3.25.15

2. Learning Objectives  To describe the epidemiology of ectopic pregnancy  To list risk factors for ectopic pregnancy  To describe how an ectopic pregnancy is diagnosed  Prerequisites:  NONE  Closely related topics:  MEDICAL MANAGEMENT OF ECTOPIC PREGNANCY  SURGICAL MANAGEMENT OF ECTOPIC PREGNANCY

3. DEFINITION  An ectopic pregnancy is an EXTRAUTERINE pregnancy–one in which the BLASTOCYST implants anywhere other than the endometrial lining of the uterine cavity  95% of ectopic pregnancies implant in the fallopian tube 1

5. EPIDEMIOLOGY  Accounts for 1-2% of pregnancies in U.S.  Accounts for 9% of pregnancy-related mortality (3 rd most common cause) 1  1/200,000 are bilateral 2  Since 1970, the frequency has increased 4X 3-4, however mortality has decreased 10X  Risk of mortality 3.4X higher in non-white women 2/2 issues with access to care 3

6. RISK FACTORS  Tubal factors 1   prevalence of PID/STIs, especially chlamydia 2 which may damage the tube   use of ART (artificial reproductive technologies)  Prior pelvic surgery, especially surgery on fallopian tube for previous ectopic, restorative purposes, or tubal sterilization

7. RISK FACTORS  Other risk factors:  Advanced maternal age  Smoking  STERILIZATION & IUDS   the risk of having an ectopic if a patient gets pregnant, HOWEVER, because they reduce the overall chance of even becoming pregnant to begin with… the overall risk of ectopic is decreased

8. RISK FACTORS 1-2 ODDS RATIO (95% CI) Prior ectopic pregnancy12.5 (7.5-20.9) Prior tubal surgery4.0 (2.6-6.1) Smoking 20+ cigarettes/day3.5 (1.4-8.6) Confirmed PID via laparoscopy and/or positive test for C. trachomatis 3.4 (2.4-5.0) 3+ prior spontaneous miscarriages3.0 (1.3-6.9) 40+ years of age2.9 (1.4-6.1) Prior medical or surgical abortion2.8 (1.1-7.2) 12+ months of Infertility2.6 (1.6-4.2) 5+ sexual partners over lifetime1.6 (1.2-2.1) Previous IUD-use1.3 (1.0-1.8)

9. CLINICAL PRESENTATION  Approximately 50% of women diagnosed with ectopic have no identifiable risk factors  Classic symptoms include:  Abdominal pain  Nausea / vomiting  Missed period  Vaginal bleeding  Other symptoms may include: syncope, dizziness, pregnancy symptoms, referred shoulder pain (due to blood in the abdomen irritating the diaphragm)

10. DIFFERENTIAL DIAGNOSIS  Tubal abortion  Obstetric complications of an intrauterine pregnancy:  Threatened / Missed / Complete/ Incomplete abortion  Molar pregnancy / Gestational trophoblastic neoplasia  Non-pregnant gynecologic causes:  PID, follicular or corpus luteum cyst rupture, endometriosis, ovarian torsion  Common non-gynecologic causes:  Appendicitis, gastroenteritis, UTI, kidney stones,

11. CLINICAL EVALUATION  Physical exam  Can range from totally normal to hypovolemic shock and acute abdomen; abdominal/pelvic tenderness is found in 50-90% of patients  CMT (cervical motion tenderness) is also common  Labs: CBC, b-HCG, Blood type and screen, +/- Progesterone  Beta HCG:  The "discriminatory zone" of hCG is ~1,500–2,000 mIU/mL, which when reached, is associated with the appearance of a normal singleton intrauterine gestation on TVUS 1  Further, if the serum hCG is not rising > 53% over 48 hours, this confirms an abnormal pregnancy (99% sensitive)  Serum progesterone: > 20 normal IUP, 5-20 equivocal, <5 abnl pregnancy  MUCH less specific, rarely used

12. DIAGNOSIS  Imaging: Transvaginal ultrasound (TVUS)  If the hCG level is higher than the discriminatory zone, and the TVUS shows no IUP, ectopic pregnancy is likely (about 2/3)  An adnexal mass is found in ~1/3 of patients, however the absence of an adnexal mass DOES NOT rule out ectopic  Other concerning signs on TVUS include: free fluid in the pelvis or evidence of a pseudo-sac in the uterus  Other diagnostic tools  Dilation & curettage - to check for products of conception (used in cases of confirmed abnormal pregnancy or in cases where even if a threatened abortion of an early IUP was possible, that the pregnancy would NOT be desired)  Culdocentesis - using a needle to check for blood in the posterior cul- de-sac which would be present if the ectopic pregnancy ruptured  Rarely used, given modern ultrasound availability

13. TVUS: WHAT DO YOU SEE? #1 (Wikipedia commons) #2#3

14. TVUS: WHAT DO YOU SEE? Ectopic in the adnexa (Wikipedia commons) Free fluid in posterior cul-de-sac Ring of fire

15. IMPORTANT LINKS  PRACTICE BULLETIN 94 – Medical Management of Ectopic PregnanciesMedical Management of Ectopic Pregnancies

16. OTHER SOURCES  Barnhart KT. Ectopic Pregnancy. N Engl J Med. 2009; 261:379-387Ectopic Pregnancy  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 157:185, 2003 [PubMed: 12543617] [PubMed: 12543617]  Lipscomb, G. Obstetrics & Gynecology: 2010 - Volume 115 - Issue 3 – p 487-488  al-Awwad MM, al Daham N, Eseet JS: Spontaneous unruptured bilateral ectopic pregnancy: conservative tubal surgery. Obstet Gynecol Surv 54:543, 1999 [PubMed: 10481854] [PubMed: 10481854]  Centers for Disease Control and Prevention: Ectopic pregnancy—United States, 1990-1992. MMWR Morb Mortal Wkly Rep 44:46, 1995  Van Den Eeden SK, Shan J, Bruce C, et al: Ectopic pregnancy rate and treatment utilization in a large managed care organization. Obstet Gynecol 105:1052, 2005  Ankum WM, Mol BW, Van der Veen F, et al: Risk factors for ectopic pregnancy: a meta-analysis. Fertil Steril 65:1093, 1996 [PubMed: 8641479] [PubMed: 8641479]  Rajkhowa M, Glass MR, Rutherford AJ, et al: Trends in the incidence of ectopic pregnancy in England and Wales from 1966 to 1996. BJOG 107:369, 2000 [PubMed: 10740334] [PubMed: 10740334]  Mol BW, Ankum WM, Bossuyt PM, et al: Contraception and the risk of ectopic pregnancy: a meta-analysis. Contraception 52:337, 1995 [PubMed: 8749596] [PubMed: 8749596]  Buster JE, Pisarska MD: Medical management of ectopic pregnancy. Clin Obstet Gynecol 42:23, 1999 [PubMed: 10073296] [PubMed: 10073296]  Doubilet et al. Diagnostic criteria for nonviable pregnancy in the early first trimester. N Engl J Med 2013;369:1443-51. DOI: 10.1056/NEJMra1302417