Download PDF
CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2018; 78(01): 70-77
DOI: 10.1055/s-0043-122151
GebFra Science
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Comparison of Four Methods of Treating Ectopic Pregnancy: A Retrospective Cohort Study

Vergleich von 4 Methoden zur Behandlung der ektopen Schwangerschaft: eine retrospektive Kohortenstudie
Zeynep Ozturk Inal
Konya Education and Research Hospital, Department of Gynecology, Konya, Turkey
,
Hasan Ali Inal
Konya Education and Research Hospital, Department of Gynecology, Konya, Turkey
› Author Affiliations
Further Information

Publication History

received 23 September 2017
revised 29 October 2017

accepted 01 November 2017

Publication Date:
22 January 2018 (online)

Also available at
   Permissions and Reprints

Abstract

Objective To compare the results of expectant management, single and multidose methotrexate (MTX) and surgical management of ectopic pregnancy (EP).

Materials and Methods In this retrospective cohort study, the original files of 233 patients who were treated for EP between May 2009 and December 2016 were analyzed. The patients were assigned to the following groups based on the applied treatment methods: Group 1, expectant management (n = 24), Group 2, single-dose MTX (n = 144), Group 3, multiple-dose MTX (n = 25), and Group 4, surgical intervention (n = 40). The following parameters were recorded and assessed: sociodemographic characteristics, pelvic ultrasonography findings (gestational sac, ectopic mass appearance, positive fetal cardiac activity), serum beta-human chorionic gonadotropin (β-hCG) levels on Day 0, Day 4, and Day 7, and surgical procedures in women that underwent surgical interventions.

Results The sociodemographic characteristics were similar in all four groups. The percentage of ectopic mass and positive fetal cardiac activity was greater and the diameter of the mass was larger in Group 4 than in the other groups. The β-hCG values on Day 0, Day 4, and Day 7 were statistically different between the groups (p < 0.001). The cutoff value for the β-hCG change for EP resolution was 18% between Day 0 and Day 4 (AUC = 0.726, p < 0.001) and 15% between Day 4 and Day 7 (AUC = 0.874, p < 0.001). The probability of the requirement for an additional dose of MTX was 0.78 (95% CI 0.71 – 0.87; p < 0.001) times lower in patients who had a > 18% decrease in β-hCG levels from Day 0 to Day 4 in comparison to those who had a decrease < 18% from Day 0 to Day 4. The probability of the requirement for an additional dose of MTX was 1.64 (95% CI 1.25 – 2.16; p < 0.001) times greater in patients whose reduction in β-hCG levels from Day 4 to Day 7 was < 15% in comparison to those who had > 15% reduction from Day 4 to Day 7.

Conclusions Additional dose requirements for patients with EP may be predicted early in the changes in β-hCG levels between Day 0 and Day 4. Further prospective studies are required to elucidate this issue.

Zusammenfassung

Ziel Ziel dieser Studie war es, 4 Methoden zur Behandlung einer ektopen Schwangerschaft (ES) miteinander zu vergleichen: das aktive Beobachten und Warten, die Behandlung mit Methotrexat (MTX), entweder als einmalige Gabe oder in mehrfachen Dosen, und der operative Eingriff.

Material und Methoden In dieser retrospektiven Kohortenstudie wurden die originalen Patientenakten von 233 Patientinnen ausgewertet, die zwischen Mai 2009 und Dezember 2016 wegen einer ES behandelt wurden. Je nach Behandlung wurden die Patientinnen in eine der folgenden Gruppen eingeteilt: Gruppe 1 (aktives Beobachten und Warten; n = 24), Gruppe 2 (einmalige Gabe von MTX; n = 144), Gruppe 3 (mehrfache Gabe von MTX; n = 25) und Gruppe 4 (operativer Eingriff; n = 40). Die folgenden Kenngrößen wurden erfasst und ausgewertet: soziodemografische Merkmale, Ergebnisse der Beckensonografie (Fruchtsack, Erscheinungsbild der extrauterinen Masse, fetale Herztätigkeit), Serumspiegel von beta-humanem Choriongonadotropin (β-hCG) am Tag 0 sowie am 4. und 7. Tag, und Art des operativen Eingriffs bei denjenigen Frauen, die sich einem operativen Eingriff unterzogen.

Ergebnisse Die soziodemografischen Merkmale waren in allen 4 Gruppen ähnlich. In der Gruppe 4 waren die Prozentsätze der ektopen Masse und der fetalen Herztätigkeit höher verglichen mit den anderen 3 Gruppen. Die β-hCG-Werte der Gruppen am Tage 0, am 4. Tag und am 7. Tag unterschieden sich statistisch signifikant (p < 0,001). Der Cut-off-Wert für β-hCG-Veränderungen, die auf eine Beendigung der ES hinwiesen, betrug 18% zwischen dem Tag 0 und dem 4. Tag (AUC = 0,726, p < 0,001) und 15% zwischen dem 4. und dem 7. Tag (AUC = 0,874, p < 0,001). Die Wahrscheinlichkeit, dass eine weitere Dosis MTX benötigt wurde, war 0,78-mal (95%-KI 0,71 – 0,87; p < 0,001) niedriger bei Patientinnen, bei denen ein Rückgang von > 18% der β-hCG-Werte zwischen dem Tag 0 und dem 4. Tag gemessen wurde, verglichen mit den Patientinnen, bei denen ein Rückgang von < 18% zwischen dem Tag 0 und dem 4. Tag verzeichnet wurde. Die Wahrscheinlichkeit, dass eine weitere Dosis MTX benötigt wurde, war 1,64-mal (95%-KI 1,25 – 2,16; p < 0,001) höher bei Patientinnen, bei denen ein Rückgang der β-hCG-Werte zwischen dem 4. und dem 7. Tag von < 15% verzeichnet wurde, verglichen mit den Frauen, bei denen der Rückgang zwischen dem 4. und dem 7. Tag > 15% betrug.

Schlussfolgerungen Veränderungen der β-hCG-Werte zwischen dem Tag 0 und dem 4. Tag bei Patientinnen mit ES könnten ein frühzeitiger Hinweis auf einen zusätzlichen Bedarf an MTX-Gaben sein. Weitere prospektive Studien werden zur Klärung dieser Frage benötigt.

Key words

ectopic pregnancy - human chorionic gonadotropin - methotrexate - single dose - multiple dose - gynecology - infertility

Schlüsselwörter

ektope Schwangerschaft - humanes Choriongonadotropin - Methotrexat - Einzeldosis - mehrfache Dosen - Gynäkologie - Infertilität
 

  • References

  • 1 Centers for Disease Control (CDC). Ectopic pregnancy–United States, 1988-1989. MMWR Morb Mortal Wkly Rep 1992; 41: 591-594
    PubMedGoogle Scholar
  • 2 Farquhar CM. Ectopic pregnancy. Lancet 2005; 366: 583-591
    CrossrefPubMedGoogle Scholar
  • 3 Buckley RG, King KJ, Disney JD. et al. History and physical examination to estimate the risk of ectopic pregnancy: validation of a clinical prediction model. Ann Emerg Med 1999; 34: 589-594
    CrossrefPubMedGoogle Scholar
  • 4 Guvendag Guven ES, Dilbaz S, Dilbaz B. et al. Comparison of single and multiple dose methotrexate therapy for unruptured tubal ectopic pregnancy: a prospective randomized study. Acta Obstet Gynecol Scand 2010; 89: 889-895
    CrossrefPubMedGoogle Scholar
  • 5 Fylstra DL. Tubal pregnancy: a review of current diagnosis and treatment. Obstet Gynecol Surv 1998; 53: 320-328
    CrossrefPubMedGoogle Scholar
  • 6 Dart RG, Kaplan B, Varaklis K. Predictive value of history and physical examination in patients with suspected ectopic pregnancy. Ann Emerg Med 1999; 33: 283-290
    CrossrefPubMedGoogle Scholar
  • 7 Mol BW, Hajenius PJ, Engelsbel S. et al. Serum human chorionic gonadotropin measurement in the diagnosis of ectopic pregnancy when transvaginal sonography is inconclusive. Fertil Steril 1998; 70: 972-981
    CrossrefPubMedGoogle Scholar
  • 8 Lipscomb GH, Givens VM, Meyer NL. et al. Comparison of multidose and single-dose methotrexate protocols for the treatment of ectopic pregnancy. Am J Obstet Gynecol 2005; 192: 1844-1847
    CrossrefPubMedGoogle Scholar
  • 9 Dorfman SF, Grimes DA, Gates W. et al. Ectopic pregnancy mortality, United States 1979–1980: clinical aspects. Obstet Gynecol 1984; 64: 386-389
    PubMedGoogle Scholar
  • 10 Jurkovic D, Memtsa M, Sawyer E. et al. Single-dose systemic methotrexate vs expectant management for treatment of tubal ectopic pregnancy: a placebo-controlled randomized trial. Ultrasound Obstet Gynecol 2017; 49: 171-176
    CrossrefPubMedGoogle Scholar
  • 11 Dogan A, Gulhan I, Uyar I. et al. Methotrexate treatment in progressive tubal ectopic pregnancies and hCG-related clinicosurgical implications. Kaohsiung J Med Sci 2016; 32: 317-322
    CrossrefPubMedGoogle Scholar
  • 12 Tanaka T, Hayashi H, Kutsuzawa T. et al. Treatment of interstitial ectopic pregnancy with methotrexate: report of a successful case. Fertil Steril 1982; 37: 851-852
    CrossrefPubMedGoogle Scholar
  • 13 Ustunyurt E, Duran M, Coskun E. et al. Role of initial and day 4 human chorionic gonadotropin levels in predicting the outcome of single-dose methotrexate treatment in women with tubal ectopic pregnancy. Arch Gynecol Obstet 2013; 288: 1149-1152
    CrossrefPubMedGoogle Scholar
  • 14 Yıldırım A, Cırık DA, Altay M. et al. Early prediction for the requirement of second or third dose methotrexate in women with ectopic pregnancy, treated with single-dose regimen. Arch Gynecol Obstet 2015; 291: 1327-1332
    CrossrefPubMedGoogle Scholar
  • 15 Barnhart KT, Gosman G, Ashby R. et al. The medical management of ectopic pregnancy: a meta-analysis comparing ‘single dose’ and ‘multidose’ regimens. Obstet Gynecol 2003; 101: 778-784
    PubMedGoogle Scholar
  • 16 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: 1661-1666
    CrossrefPubMedGoogle Scholar
  • 17 Lipscomb GH, Bran D, McCord ML. et al. Analysis of three hundred fifteen ectopic pregnancies treated with single-dose methotrexate. Am J Obstet Gynecol 1998; 178: 1354-1358
    CrossrefPubMedGoogle Scholar
  • 18 Levin I, Tsafrir Z, Saʼar N. et al. “Watchful waiting” in ectopic pregnancies: a balance between reduced success rates and less methotrexate. Fertil Steril 2011; 95: 1159-1160
    CrossrefPubMedGoogle Scholar
  • 19 Kirk E, Van Calster B, Condous G. et al. Ectopic pregnancy: using the hCG ratio to select women for expectant or medical management. Acta Obstet Gynecol Scand 2011; 90: 264-272
    PubMedGoogle Scholar
  • 20 Elson J, Tailor A, Banerjee S. et al. Expectant management of tubal ectopic pregnancy: prediction of successful outcome using decision tree analysis. Ultrasound Obstet Gynecol 2004; 23: 552-556
    CrossrefPubMedGoogle Scholar
  • 21 Korhonen J, Stenman UH, Ylostalo P. Serum human chorionic gonadotrophin dynamics during spontaneous resolution of ectopic pregnancy. Fertil Steril 1994; 61: 632-636
    CrossrefPubMedGoogle Scholar
  • 22 Sagiv R, Debby A, Feit H. et al. The optimal cutoff serum level of human chorionic gonadotropin for efficacy of methotrexate treatment in women with extrauterine pregnancy. Int J Gynaecol Obstet 2012; 116: 101-104
    CrossrefPubMedGoogle Scholar
  • 23 Gamzu R, Almog B, Levin Y. et al. Efficacy of methotrexate treatment in extrauterine pregnancies defined by stable or increasing human chorionic gonadotropin concentrations. Fertil Steril 2002; 77: 761-765
    CrossrefPubMedGoogle Scholar
  • 24 Nowak-Markwitz E, Michalak M, Olejnik M. et al. Cutoff value of human chorionic gonadotropin in relation to the number of methotrexate cycles in the successful treatment of ectopic pregnancy. Fertil Steril 2009; 92: 1203-1207
    CrossrefPubMedGoogle Scholar
  • 25 Natale A, Busacca M, Candiani M. et al. Human chorionic gonadotropin patterns after a single dose of methotrexate for ectopic pregnancy. Eur J Obstet Gynecol Reprod Biol 2002; 100: 227-230
    CrossrefPubMedGoogle Scholar
  • 26 Practice Committee of American Society for Reproductive Medicine. Medical treatment of ectopic pregnancy: a committee opinion. Fertil Steril 2013; 100: 638-644
    CrossrefPubMedGoogle Scholar
  • 27 Potter MB, Lepine LA, Jamieson DJ. Predictors of success with methotrexate treatment of tubal ectopic pregnancy at Grady Memorial Hospital. Am J Obstet Gynecol 2003; 188: 1192-1194
    CrossrefPubMedGoogle Scholar
  • 28 Agostini A, Blanc K, Ronda I. et al. Prognostic value of human chorionic gonadotropin changes after methotrexate injection for ectopic pregnancy. Fertil Steril 2007; 88: 504-506
    CrossrefPubMedGoogle Scholar
  • 29 Bottin P, Gnisci A, Crochet P. et al. [Prognostic value of early hCG changes after methotrexate injection for ectopic pregnancy]. Gynecol Obstet Fertil 2014; 42: 3-7
    CrossrefPubMedGoogle Scholar
  • 30 Atkinson M, Gupta S, Mcgee T. βhCG monitoring after single-dose methotrexate treatment of tubal ectopic pregnancy: is the Day 4 βhCG necessary? A retrospective cohort study. Aust N Z J Obstet Gynaecol 2014; 54: 475-479
    CrossrefPubMedGoogle Scholar