Keywords :
Biochemical markers, Color and pulsed Doppler ultrasound, Ectopic pregnancy, Three-dimensional ultrasound, Transvaginal ultrasound
Citation Information :
Plavsic SK, Panchal S, Honemeyer U. Ectopic Pregnancy: Diagnosing and Treating the Challenge. Donald School J Ultrasound Obstet Gynecol 2024; 18 (3):261-281.
Ectopic pregnancy remains a significant clinical challenge, with early and accurate diagnosis being critical for effective management and reducing morbidity. This review article discusses the combined use of advanced ultrasound techniques alongside biochemical markers to enhance the detection and treatment of ectopic pregnancies. Transabdominal and transvaginal ultrasounds provide initial assessment, with transvaginal imaging offering superior resolution for early detection. Doppler ultrasound, particularly color and pulsed Doppler, is instrumental in evaluating blood flow, helping to distinguish between viable and nonviable pregnancies. Three-dimensional ultrasound further enhances diagnostic precision by offering detailed spatial imaging, which aids in localization and assessment of ectopic sites. Additionally, biochemical markers, particularly serum β human chorionic gonadotropin (beta hCG) levels, complement imaging by providing crucial insights into pregnancy viability and progression. By integrating these modalities, this approach aims to improve diagnostic accuracy, facilitate timely intervention, and optimize patient outcomes in cases of ectopic pregnancy.
Speroff L, Glass RH, Kase NG, editors. Ectopic pregnancy. In: Clinical Gynecologic Endocrinology and Infertility. London: Williams and Wilkins; 1999. pp. 1149–1167.
Timor-Tristch IE, Monteagudo A. Ectopic pregnancy. In: Kupesic S, de Ziegler D, editors. Ultrasound and Infertility. UK: Parthenon Publishing Group; 2000. pp. 215–239.
Kurjak A, Kupesic S. Ectopic pregnancy. In: Kurjak A, editor. Ultrasound in Obstetrics and Gynecology. Boston: CRC Press; 1990. pp. 225–235.
Kupesic S, Kurjak A. Color Doppler assessment of ectopic pregnancy. In: Kurjak A, Kupesic S, editors. An Atlas of Transvaginal Color Doppler. London: Parthenon Publishing; 2000. pp. 137–147.
Boufous S, Quartararo M, Mohsin M, et al. Trends in the incidence of ectopic pregnancy in New South Wales between 1990-1998. Aust N Z J Obstet Gynaecol 2001;41:436–468. DOI: 10.1111/j.1479-828x.2001.tb01325.x
Rajkhowa M, Glass MR, Rutherford AJ, et al. Trends in the incidence of ectopic pregnancy in England and Wales from 1966 to 1996. BJOG 2000;107:369–374. DOI: 10.1111/j.1471-0528.2000.tb13233.x
Nederlof KP, Lawson HW, Saftlas AF, et al. Ectopic pregnancy surveillance. MMWR CDC Surveill Summ 1990;39:9. PMID: 2124330.
Strandell A, Thorburn J, Hamberger L. Risk factors for ectopic pregnancy in assisted reproduction. Fertil Steril 1999;2:282–286. DOI: 10.1016/s0015-0282(98)00441-5
Kamwendo F, Forslin L, Bodin L, et al. Epidemiology of ectopic pregnancy during a 28 year period and the role of pelvic inflammatory disease. Sex Transm Infect 2000;76:28–32. DOI: 10.1136/sti.76.1.28
Barlow RE, Cooke ID, Odukoya O, et al. The prevalence of Chlamydia trachomatis in fresh tissue specimens from patients with ectopic pregnancy or tubal factor infertility as determined by PCR and in-situ hybridisation. J Med Microbiol 2001;50:902–908. DOI: 10.1099/0022-1317-50-10-902
Brown WD, Burrows L, Todd CS. Ectopic pregnancy after cesarean hysterectomy. Obstet Gynecol 2002;99:933–934. DOI: 10.1016/s0029-7844(02)01932-4
Bouyer J, Rachou E, Germain E, et al. Risk factors for extrauterine pregnancy in women using an intrauterine device. Fertil Steril 2000;74:899–908. DOI: 10.1016/s0015-0282(00)01605-8
Bouyer J, Coste J, Fernandez H, et al. Sites of ectopic pregnancy: a 10 year population-based study of 1800 cases. Hum Reprod 2002;17:3224–3230. DOI: 10.1093/humrep/17.12.3224
Mol BW, van der Veen F, Bossuyt PM. Symptom-free women at increased risk of ectopic pregnancy: should we screen? Acta Obstet Gynecol Scand 2002;81:661–672. DOI: 10.1034/j.1600-0412.2002.810713.x
Kalinski MA, Guss DA. Hemorrhagic shock from a ruptured ectopic pregnancy in a patient with a negative urine pregnancy test result. Ann Emerg Med 2002;40:102–105. DOI: 10.1067/mem.2002.125446
Mertz HL, Yalcinkaya TM. Early diagnosis of ectopic pregnancy. Does use of a strict algorithm decrease the incidence of tubal rupture? Reprod Med 2001;46:29–33. PMID: 11209628.
Sagaster P, Zojer N, Dekan G, et al. Paraneoplastic syndrome mimicking extrauterine pregnancy. Ann Oncol 2002;13:170–172. DOI: 10.1093/annonc/mdf011
Hick JL, Rodgerson JD, Heegaard WG, et al. Vital signs fail to correlate with hemoperitoneum from ruptured ectopic pregnancy. Am J Emerg Med 2001;19:488–491. DOI: 10.1053/ajem.2001.27133
Birkhahn RH, Gaeta TJ, Bei R, et al. Shock index in the first trimester of pregnancy and its relationship to ruptured ectopic pregnancy. Acad Emerg Med 2002;9:115–119. DOI: 10.1111/j.1553-2712.2002.tb00226.x
Wong E, Suat SO. Ectopic pregnancy-a diagnostic challenge in the emergency department. Eur J Emerg Med 2000;7:189–194. DOI: 10.1097/00063110-200009000-00005
Dart R, McLean SA, Dart L. Isolated fluid in the cul-de-sac: how well does it predict ectopic pregnancy? Am J Emerg Med 2002;20:1–4. DOI: 10.1053/ajem.2002.30101
Barnhart KT, Katz I, Hummel A, et al. Presumed diagnosis of ectopic pregnancy. Obstet Gynecol 2002;100:505–510. DOI: 10.1016/s0029-7844(02)02142-7
Sheppard RW, Patton PE, Novy MJ. Serial beta hCG measurements in the early detection of ectopic pregnancy. Obstet Gynecol 1990;7:417–420. PMID: 1689477.
Levsky ME, Handler JA, Suarez RD, et al. False-positive urine beta-HCG in a woman with a tubo-ovarian abscess. J Emerg Med 2001;21:407–409. DOI: 10.1016/s0736-4679(01)00387-0
Dumps P, Meisser A, Pons D, et al. Accuracy of single measurements of pregnancy-associated plasma protein-A, human chorionic gonadotropin and progesterone in the diagnosis of early pregnancy failure. Eur J Obstet Gynecol Reprod Biol 2002;100:174–180. DOI: 10.1016/s0301-2115(01)00470-5
Poppe WA, Vandenbussche N. Eur Postoperative day 3 serum human chorionic gonadotropin decline as a predictor of persistent ectopic pregnancy after linear salpingotomy. J Obstet Gynecol Reprod Biol 2001;99:249–252. DOI: 10.1016/s0301-2115(01)00397-9
Timor-Tristch IE, Rottem S, Thale I. Review of transvaginal ultrasonography: description with clinical application. Ultrasound Q 1988;6:1–32.
Peisner DB, Timor-Tritsch IE. The discriminatory zone of beta hCG for vaginal probes. J Clin Ultrasound 1990;18:280–285. DOI: 10.1002/jcu.1870180411
Fossum GT, Dvajan V, Kletzky DA. Early detection of pregnancy with transvaginal ultrasound. Fertil Steril 1988;49:788–791. DOI: 10.1016/s0015-0282(16)59884-7
Bernascheck G, Euaelstorfer R, Csaicsich P. Vaginal sonography versus serum human chorionic gonadotropin in early detection of pregnancy. Am J Obstet 1988;158:608–612. DOI: 10.1016/0002-9378(88)90039-7
Kurjak A, Zalud I, Volpe G. Conventional B-mode and transvaginal color Doppler on ultrasound assessment of ectopic pregnancy. Acta Med 1990;44:91–103. PMID: 2191540.
Rubin GL, Petersin HB, Dorfman SF. Ectopic pregnancy in the United States 1970-1978. J Am Med Assoc 1983;249:1725–1729.
Bolton G, Cohen F. Detecting and treating ectopic pregnancy. Contemp Obstet Gynecol 1981;18:101–104. PMID: 6827760.
Hopp H, Schaar P, Entezami M. Diagnostic reliability of vaginal ultrasound in ectopic pregnancy. Geburtshilfe Frauen 1995;55:666–670. DOI: 10.1055/s-2007-1022310
Hertzberg BS, Kliewer MA. Ectopic pregnancy: ultrasound diagnosis and interpretive pitfalls. South Med J 1995;88:1191–1198. PMID: 7502109.
Thoma ME. Early detection of ectopic pregnancy visualizing the presence of a tubal ring with ultrasonography performed by emergency physicians. Am J Emerg Med 2000;18:444–448. DOI: 10.1053/ajem.2000.7345
Nyberg D. Ectopic pregnancy. In: Nyberg DA, Hill LM, Bohm-Velez M, editors. Transvaginal Sonography. St. Louis: Mosby Year Book; 1992. pp. 105–135.
Wojak JC, Clayton MJ, Nolan TE. Outcomes of ultrasound diagnosis of ectopic pregnancy. Dependence on observer experience. Invest Radiol 1995;30:115–117. DOI: 10.1097/00004424-199502000-00010
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;161:157–161. DOI: 10.1016/0002-9378(89)90255-x
Pellerito JS, Taylor KJW, Quedens-Case C, et al. Ectopic pregnancy: evaluation with endovaginal color flow imaging. Radiology 1992;183:407–411. DOI: 10.1148/radiology.183.2.1561341
Fleischer AC, Pennell RG, McKee MS. Ectopic pregnancy: features at transvaginal sonography. Radiology 1990;174:375–378. DOI: 10.1148/radiology.174.2.1688662
Bernhart K, Mennuti MT, Benjamin D, et al. Prompt diagnosis of ectopic pregnancy in an emergency department setting. Obstet Gynecol 1994;84:1010–1015. PMID: 7970455.
Leung TY, Ng PS, Fung TY. Ectopic pregnancy diagnosed by laparoscopic ultrasound scan. Ultrasound Obstet Gynecol 1999;13:281–282. DOI: 10.1046/j.1469-0705.1999.13040281.x
Kurjak A, Zalud I, Shulman H. Ectopic pregnancy: transvaginal color Doppler of trophoblastic flow in questionable adnexa. J Ultrasound Med 1991;10:685–689. DOI: 10.7863/jum.1991.10.12.685
Zalud I, Kurjak A. The assessment of luteal blood flow in pregnant and non-pregnant women by transvaginal color Doppler. J Perinat Med 1990;18:215–221. DOI: 10.1515/jpme.1990.18.3.215
Jurkovic D, Bourne TH, Jauniaux E, et al. Transvaginal color Doppler study of blood flow in ectopic pregnancies. Fertil Steril 1992;57:68–73. PMID: 1730333.
Wherry KL, Dubinsky TJ, Waitches GM, et al. Low-resistance endometrial arterial flow in the exclusion of ectopic pregnancy revisited. J Ultrasound Med 2001;20:335–342. DOI: 10.7863/jum.2001.20.4.335
Dillon EH, Feyock AL, Taylor KJW. Pseudogestational sacs: Doppler US differentiation from normal or abnormal intrauterine pregnancies. Radiology 1990;176:359–364. DOI: 10.1148/radiology.176.2.2195591
Orden MR, Gudmundsson S, Helin HL, et al. Intravascular contrast agent in the ultrasonography of ectopic pregnancy. Ultrasound Obstet Gynecol 1999;14:348–352. DOI: 10.1046/j.1469-0705.1999.14050348.X
Pellerito JS, Troiano RN, Quedens-Case C, et al. Common pitfalls of endovaginal color Doppler flow imaging. Radiographics 1995;15:37–47. DOI: 10.1148/radiographics.15.1.7899612
Lurie S, Katz Z. Where a pendulum of expectant management of ectopic pregnancy should rest? Gynecol Obstet Invest 1996;45:145. DOI: 10.1159/000291929
Stovall TG, Link WF. Expectant management of ectopic pregnancy. Obstet Gynecol Clin North Am 1991;18:135–144. PMID: 1923253.
Laurie S, Insler V. Can the serum beta hCG level reliably predict likelihood of a ruptured tubal pregnancy? Isr J Obstet Gynecol 1992;3:152–544.
Budowich M, Johnson Jr TR, Genadry R, et al. The histopathology of developing tubal ectopic pregnancy. Fertil Steril 1980;34:169–171. DOI: 10.1016/s0015-0282(16)44902-2
Kemp B, Funk A, Hauptmann S, et al. Doppler sonographic criteria for viability in symptomless ectopic pregnancies. Lancet 1997;349:1220–1221. DOI: 10.1016/S0140-6736(05)62412-9
Baba K, Stach K, Sakamoto S, et al. Development of an ultrasonic system for three dimensional reconstruction of the fetus. J Perinat Med 1989;17:19–24. DOI: 10.1515/jpme.1989.17.1.19
Rempen A. The shape of the endometrium evaluated with three-dimensional ultrasound: an additional predictor of extrauterine pregnancy. Hum Reprod 1998;13:450–454. DOI: 10.1093/humrep/13.2.450
Harika G, Gabriel R, Carre-Pigeon F, et al. Primary application of three-dimensional ultrasonography to early diagnosis of ectopic pregnancy. Eur J Obstet Gynecol Reprod Biol 1995;60:117–120. DOI: 10.1016/0028-2243(95)02088-a
Shih JC, Shyu MK, Cheng WF, et al. Arteriovenous malformation of mesosalpinx associated with a vanishing ectopic pregnancy: diagnosis with three-dimensional color power angiography. Ultrasound Obstet Gynecol 1999;13:63–66. DOI: 10.1046/j.1469-0705.1999.13010063.x
Mancino D, Carbone L, Ragucci V, et al. Angular pregnancy at 6th week of pregnancy treated with minimally invasive surgery preceded by systemic and local medical therapy with methotrexate. Case Report Giorn It Ostet Gin 2013;35(3):462–465.
Agarwal SK, Wisot AL, Garzo G, et al. Cornual pregnancies in patients with prior salpingectomy undergoing in vitro fertilization and embryo transfer. Fertil Steril 1996;65:659–660. DOI: 10.1016/s0015-0282(16)58171-0
Timor-Tritsch IE, Monteagudo A, Matera C, et al. Sonographic evaluation of cornual pregnancies treated without surgery. Obstet Gynecol 1992;79:1044–1049. PMID: 1579304.
Honemeyer U, Kupesic Plavsic S, Kurjak A. Interstitial ectopic pregnancy: the essential role of ultrasound diagnosis. DSJUOG 2010;4(3):321–325.
Hafner T, Aslam N, Ros JA, et al. The effectiveness of non-surgical management of early interstitial pregnancy: a report of ten cases and review of the literature. Ultrasound Obstet Gynecol 1999;13:131–136. DOI: 10.1046/j.1469-0705.1999.13020131.x
Jurkovic D, Geipel A, Gruboeck K, et al. Three-dimensional ultrasound for the assessment of uterine anatomy and detection of congenital uterine anomalies. A comparison with hysterosalpingography and two dimensional sonography. Ultrasound Obstet Gynecol 1995;5:233–237. DOI: 10.1046/j.1469-0705.1995.05040233.x
Lawrence A, Jurkovic D. Three-dimensional ultrasound diagnosis of interstitial pregnancy. Ultrasound Obstet Gynecol 1999;14:292–293. DOI: 10.1046/j.1469-0705.1999.14040292.X
Ben-Sholmo I, Eliyahu S, Yanai N, et al. Methotrexate as a possible cause of ovarian cyst formation: experience with women treated for ectopic pregnancies. Fertil Steril 1997;67:786–788. DOI: 10.1016/s0015-0282(97)81385-4
Schiff E, Tsabari A, Shalev E, et al. Pharmacokinetics of methotrexate after local tubal injection for conservative treatment of ectopic pregnancy. Fertil Steril 1992;57:688–690. DOI: 10.1016/s0015-0282(16)54923-1
Timor-Tritsch IE, Monteagudo A, Mandeville EO, et al. Successful management of viable cervical pregnancy by local injection of methotrexate guided by transvaginal ultrasonography. Am J Obstet Gynecol 1994;170:737–739. DOI: 10.1016/s0002-9378(94)70273-x
Jurkovic D, Hacket E, Campbell S. Diagnosis and treatment of early cervical pregnancy: a review and a report of two cases treated conservatively. Ultrasound Obstet Gynecol 1996;8:373–380. DOI: 10.1046/j.1469-0705.1997.08060373.x
Jauniaux E, Taidi J, Jurkovic D, et al. Comparison of color Doppler features and pathological findings in complicated early pregnancy. Hum Reprod 1994;9:2432–2437. DOI: 10.1093/oxfordjournals.humrep.a138465
Morita Y, Tsutsumi O, Kurmochi K, et al. Successful laparoscopic management of primary abdominal pregnancy. Hum Reprod 1996;11:2546–2547. DOI: 10.1093/oxfordjournals.humrep.a019157
Ahmed B, Fawzi HW, Abushama M. Advanced abdominal pregnancy in the developing countries. J Obstet Gynecol 1996;16:400–405. DOI: 10.3109/01443619609030058
Angtuaco TL, Shah HR, Meal MR, et al. Ultrasound evaluation of abdominal pregnancy. Crit Rev Diagn Imaging 1994;35:1–59. PMID: 8185834.
Bajo JM, Garcia FA, Huertas MA. Sonographic follow-up of a placenta left in situ after delivery of the fetus in abdominal pregnancy. Ultrasound Obstet Gynecol 1996;7:285–288. DOI: 10.1046/j.1469-0705.1996.07040285.x
Zaki ZMS. An unusual presentation of ectopic pregnancy. Ultrasound Obstet Gynecol 1998;11:456–458. DOI: 10.1046/j.1469-0705.1998.11060456.x
Rheinbolt M, Osborn D, Delprosto Z. Cesarean section scar ectopic pregnancy: a clinical case series. J Ultrasound 2015;18(2):191–195. DOI: 10.1007/s40477-015-0162-5
Riaz RM, Williams TR, Craig BM, et al. Cesarean section ectopic pregnancy: imaging features, current treatment options and clinical outcomes. Abdom Imaging 2015;40(7):2589–2599. DOI: 10.1007/s00261-015-0472-2
Qian ZD, Guo QY, Huang LL. Identifying risk factors for recurrent cesarean scar pregnancy: a case control study. Fertil Steril 2014;102(1):129–134. DOI: 10.1016/j.fertnstert.2014.04.003
Wang Z, Le A, Shan L, et al. Assessment of transvaginal hysterotomy combined with medication for Cesarean Scar ectopic pregnancy. J Minim Invasive Gynecol 2012;19(5):639–642. DOI: 10.1016/j.jmig.2012.06.006
Thoen LD, Crenin MD. Medical treatment of ectopic pregnancy with methotrexate. Fertil Steril 1997;68:727–730. DOI: 10.1016/s0015-0282(97)00284-7
Lipscomb GH, Meyer NL, Flynn DE, et al. Oral methotrexate for treatment of ectopic pregnancy. Am J Obstet Gynecol 2002;186:1192–1195. DOI: 10.1067/mob.2002.123825
Haimov-Kochman R, Sciaky-Tamir Y, Yanai N, et al. Conservative management of two ectopic pregnancies implanted in previous uterine scars. Ultrasound Obstet Gynecol 2002;19:616–619. DOI: 10.1046/j.1469-0705.2002.00719.x
El-Lamie IK, Shehata NA, Kamel HA. Intramuscular methotrexate for tubal pregnancy. J Reprod Med 2002;47:144–150. PMID: 11883354.
Yao M, Tulandi T. Current status of surgical and non-surgical management of ectopic pregnancy. Fertil Steril 1997;67:421–433. DOI: 10.1016/s0015-0282(97)80064-7
Powell MP, Spellman JR. Medical management of the patient with an ectopic pregnancy. J Perinat Neonat Nurs 1997;9:31–43. DOI: 10.1097/00005237-199603000-00005
Luciano AA, Roy G, Solima E, et al. Ectopic pregnancy from surgical emergency to medical management. Acad Sci 2001;943:235–254. DOI: 10.1111/j.1749-6632.2001.tb03805.x
Morlock RJ, Lafata JE, Eisenstein D. Cost-effectiveness of single-dose methotrexate compared with laparoscopic treatment of ectopic pregnancy. Obstet Gynecol 2000;95:407–412. DOI: 10.1016/s0029-7844(99)00548-7
Tulandi T, Sammour A. Evidence-based management of ectopic pregnancy. Curr Opin Obstet Gynecol 2000;12:289–292. DOI: 10.1097/00001703-200008000-00004
Stovall TG, Ling FW, Carson SA, et al. Serum progesterone and uterine curettage in differential diagnosis of ectopic pregnancy. Fertil Steril 1992;57(2):456–457. DOI: 10.1016/s0015-0282(16)54866-3
Kirk E, Condous G, van Calster B, et al. A validation of the most commonly used protocol to predict the success of single dose metotrexate in the treatment of ectopic pregnancy. Hum Reprod 2004;19:1900–1910. DOI: 10.1093/humrep/del433
Van Den Eeden SK, Shan J, Bruce C, et al. Ectopic pregnancy rate and treatment utilization in a large managed care organization. Obstet Gynecol 2005;105:1052–1057. DOI: 10.1097/01.AOG.0000158860.26939.2d
Barnhart KT, Sammel MD, Hummel A, et al. A novel “two dose” regimen of methotrexate to treat ectopic pregnancy. Fertil Steril 2005;84(Suppl):S130. DOI: 10.1016/j.fertnstert.2006.06.054
Alleyassin A, Khademi A, Aghahosseini M, et al. 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;85(6):1661–1666. DOI: 10.1016/j.fertnstert.2005.11.055