Logo
homeHome

Koomesh

Journal of Semnan University of Medical Sciences

Koomesh

homeHome
lightbulbInstructions
euroAPC
Authors GuideSubmit Manuscript
koomesh

Image Credit:koomesh

Outlines

https://doi.org/10.69107/koomesh-153590

Comparison of Methotrexate and Actinomycin D in the Treatment of Patients with Cesarean Scar Pregnancy, a Randomized Clinical Trial

Author(s):
Setareh NasiriSetareh NasiriSetareh Nasiri ORCID1, Soudabeh JamaliSoudabeh JamaliSoudabeh Jamali ORCID2, Elham SaffariehElham SaffariehElham Saffarieh ORCID3,*
1Department of Obstetrics and Gynecology, Endometriosis Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
2Department of Obstetrics and Gynecology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
3Abnormal Uterine Bleeding Research Center, Semnan University of Medical Sciences, Semnan, Iran
*Corresponding Author: Abnormal Uterine Bleeding Research Center, Semnan University of Medical Sciences, Semnan, Iran. Email:[email protected]
Koomesh:Vol. 27, issue 1; e153590
Published online:Mar 15, 2025
Article type:Research Article
How to Cite:Nasiri S, Jamali S, Saffarieh E. Comparison of Methotrexate and Actinomycin D in the Treatment of Patients with Cesarean Scar Pregnancy, a Randomized Clinical Trial. koomesh. 2025;27(1):e153590. doi: https://doi.org/10.69107/koomesh-153590

Abstract

Background: Cesarean scar pregnancy (CSP) is a rare type of ectopic pregnancy which causes severe complications such as uterine rupture, massive bleeding, and even, hysterectomy. Therapeutic steps in CSP are controversial. 

Objectives: In this study, we compare the rate of success, failure and possible complications of methotrexate (MTX) and actinomycin D in the treatment of CSP, in order to determine the efficacy of actinomycin D as an alternative for MTX. 

Materials and methods: In a single-blind, randomized clinical trial, 39 patients with ectopic pregnancy in the caesarean scar were assigned to two groups, the first group received MTX (50 mg) and the other group received Actinomycin D (0.5 mg). Mass size and β-Human chorionic gonadotropin (β-HCG) levels were recorded before and after intervention. The prescribed dose was repeated after 7 days if there was no therapeutic result. If the beta level did not decrease or increased after the intervention, it was interpreted as treatment failure and patient referred for surgical treatment. 

Results: Two groups were matched in terms of age, parity, and gestational age. Hemoglobin drop (P=0.192), alterations in β-HCG levels (P=0.411), and duration of lowering the β-HCG level and reaching to negative range as an indicator of success treatment (P=0.749) were not significantly different between two groups. In the regression analysis, the initial β-HCG level less than 4700, reduced the need to surgery and treatment failure to one fifth (Exp(β)= 0.222, P=0.033). 

Conclusion: In terms of treatment failure, methotrexate and actinomycin D are not superior to each other in the treatment of ectopic pregnancy in cesarean scar, and actinomycin D can be a suitable alternative to methotrexate. The pre-treatment β-HCG level was an important factor in predicting the success of medical treatment.

Highlights

Keywords
Actinomycin D
Cesarean scar pregnancy (CSP)
Ectopic pregnancy
Methotrexate

References

  • 1.
    Baradwan S, Khan F, Al-Jaroudi D. Successful management of a spontaneous viable monochorionic diamniotic twin pregnancy on cesarean scar with systemic methotrexate: A case report. Medicine. 2018;97(37):e12343. [PubMed ID:30212987]. [PubMed Central ID:PMC6155970]. https://doi.org/10.1097/MD.0000000000012343.
  • 2.
    Maymon R, Halperin R, Mendlovic S, Schneider D, Herman A. Ectopic pregnancies in a Caesarean scar: review of the medical approach to an iatrogenic complication. Hum Reprod Update. 2004;10(6):515-23. [PubMed ID:15375087]. https://doi.org/10.1093/humupd/dmh042.
  • 3.
    Wang S, Beejadhursing R, Ma X, Li Y. Management of Caesarean scar pregnancy with or without methotrexate before curettage: human chorionic gonadotropin trends and patient outcomes. BMC Pregnancy Childbirth. 2018;18(1):289. [PubMed ID:29973177]. [PubMed Central ID:PMC6032533]. https://doi.org/10.1186/s12884-018-1923-x.
  • 4.
    Barghdoust HR, Taghavi Zahed Kolaie A, Saeednia S. [Risk factors assoicated with increased the chance of ectopic pregnancy]. Koomesh J. 2021;23(4):502-9. Persian. https://doi.org/10.52547/koomesh.23.4.502.
  • 5.
    Jameel K, Abdul Mannan G-e-r, Niaz R, Hayat D-e-s. Cesarean Scar Ectopic Pregnancy: A Diagnostic and Management Challenge. Cureus. 2021(13). https://doi.org/10.7759/cureus.14463.
  • 6.
    Xiao J, Zhang S, Wang F, Wang Y, Shi Z, Zhou X, et al. Cesarean scar pregnancy: noninvasive and effective treatment with high-intensity focused ultrasound. Am J Obstet Gynecol. 2014;211(4):356 e1-7. [PubMed ID:24769010]. https://doi.org/10.1016/j.ajog.2014.04.024.
  • 7.
    Moradan S. [Spontaneous bilateral ectopic pregnancy: A case report]. Koomesh J. 2014;15:265. Persian.
  • 8.
    Glenn TL, Bembry J, Findley AD, Yaklic JL, Bhagavath B, Gagneux P, et al. Cesarean Scar Ectopic Pregnancy: Current Management Strategies. Obstet Gynecol Surv. 2018;73(5):293-302. [PubMed ID:29850919]. https://doi.org/10.1097/OGX.0000000000000561.
  • 9.
    Timor-Tritsch I, Buca D, Di Mascio D, Cali G, D'Amico A, Monteagudo A, et al. Outcome of cesarean scar pregnancy according to gestational age at diagnosis: A systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2021;258:53-9. [PubMed ID:33421811]. https://doi.org/10.1016/j.ejogrb.2020.11.036.
  • 10.
    Hong T, Chai Z, Liu M, Zheng L, Qi F. The Efficacy and Health Economics of Different Treatments for Type 1 Cesarean Scar Pregnancy. Front Pharmacol. 2022;13:822319. [PubMed ID:35153794]. [PubMed Central ID:PMC8831712]. https://doi.org/10.3389/fphar.2022.822319.
  • 11.
    Huo S, Shen L, Ju Y, Liu K, Liu W. Treatments for cesarean scar pregnancy: 11-year experience at a medical center. J Matern Fetal Neonatal Med. 2023;36(1):2162818. [PubMed ID:36597830]. https://doi.org/10.1080/14767058.2022.2162818.
  • 12.
    Hameed MSS, Wright A, Chern BSM. Cesarean Scar Pregnancy: Current Understanding and Treatment Including Role of Minimally Invasive Surgical Techniques. Gynecol Minim Invasive Ther. 2023;12(2):64-71. [PubMed ID:37416110]. [PubMed Central ID:PMC10321345]. https://doi.org/10.4103/gmit.gmit_116_22.
  • 13.
    Di Spiezio Sardo A, Zizolfi B, Saccone G, Ferrara C, Sglavo G, De Angelis MC, et al. Hysteroscopic resection vs ultrasound-guided dilation and evacuation for treatment of cesarean scar ectopic pregnancy: a randomized clinical trial. Am J Obstet Gynecol. 2023;229(4):437 e1- e7. [PubMed ID:37142075]. https://doi.org/10.1016/j.ajog.2023.04.038.
  • 14.
    Leziak M, Zak K, Frankowska K, Ziolkiewicz A, Perczynska W, Abramiuk M, et al. Future Perspectives of Ectopic Pregnancy Treatment-Review of Possible Pharmacological Methods. Int J Environ Res Pub Health. 2022;19(21). [PubMed ID:36361110]. [PubMed Central ID:PMC9656791]. https://doi.org/10.3390/ijerph192114230.
  • 15.
    Allegrini M, Legendre G, Dabi Y, Thubert T, Joste M, Lavoue V, et al. Local injection of methotrexate ultrasound guided-transvaginal. J Gynecol Obstet Hum Reprod. 2022;51(7):102419. [PubMed ID:35667587]. https://doi.org/10.1016/j.jogoh.2022.102419.
  • 16.
    Hao J, Zhou W, Zhang M, Yu H, Zhang T, An R, et al. Direct comparisons of efficacy and safety between actinomycin-D and methotrexate in women with low-risk gestational trophoblastic neoplasia: a meta-analysis of randomized and high-quality non-randomized studies. BMC Cancer. 2021;21(1):1122. [PubMed ID:34663255]. [PubMed Central ID:PMC8524874]. https://doi.org/10.1186/s12885-021-08849-7.
  • 17.
    Jiang F, Mao MY, Xiang Y, Lu X, Guan CL, Jiao LZ, et al. Comparing biweekly single-dose actinomycin D with multiday methotrexate therapy for low-risk gestational trophoblastic neoplasia (FIGO Score 0-4): study protocol for a prospective, multicentre, randomized trial. BMC Cancer. 2023;23(1):784. [PubMed ID:37612621]. [PubMed Central ID:PMC10464396]. https://doi.org/10.1186/s12885-023-11225-2.
  • 18.
    Bethesda MD. Dactinomycin. In: Bethesda MD, editor. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. USA: National Institute of Diabetes and Digestive and Kidney Diseases;; 2012.
  • 19.
    Buskmiller C. The Ethics of Interstitial and Cesarean Scar Ectopic Pregnancies: Four Case Studies and a Review of the Literature. Linacre Q. 2018;85(3):252-69. [PubMed ID:30275610]. [PubMed Central ID:PMC6161235]. https://doi.org/10.1177/0024363918788858.
  • 20.
    Salari N, Kazeminia M, Shohaimi S, Nankali AA, Mohammadi M. Evaluation of treatment of previous cesarean scar pregnancy with methotrexate: a systematic review and meta-analysis. Reprod Biol Endocrinol. 2020;18(1):108. [PubMed ID:33168010]. [PubMed Central ID:PMC7650162]. https://doi.org/10.1186/s12958-020-00666-0.
  • 21.
    Bodur S, Ozdamar O, Kilic S, Gun I. The efficacy of the systemic methotrexate treatment in caesarean scar ectopic pregnancy: A quantitative review of English literature. J Obstet Gynaecol. 2015;35(3):290-6. [PubMed ID:25259651]. https://doi.org/10.3109/01443615.2014.954101.
  • 22.
    Huang Y, Zhou T, Li Y, Gao X, Zhu Q, Wu M. Primary cesarean scar choriocarcinoma: A case series and literature review. Int J Gynaecol Obstet. 2023;162(2):433-9. [PubMed ID:36710632]. https://doi.org/10.1002/ijgo.14702.
  • 23.
    Schink JC, Filiaci V, Huang HQ, Tidy J, Winter M, Carter J, et al. An international randomized phase III trial of pulse actinomycin-D versus multi-day methotrexate for the treatment of low risk gestational trophoblastic neoplasia; NRG/GOG 275. Gynecol Oncol. 2020;158(2):354-60. [PubMed ID:32460997]. [PubMed Central ID:PMC7432963]. https://doi.org/10.1016/j.ygyno.2020.05.013.
  • 24.
    Aminimoghaddam S, Omranipoor A. Successful treatment using Actinomycin D in a case of methotrexate-resistant ectopic pregnancy: A case report. Med J Islam Repub Iran. 2019;33:100. [PubMed ID:31696094]. [PubMed Central ID:PMC6825387]. https://doi.org/10.34171/mjiri.33.100.
  • 25.
    Tam LM, Kotani T, Linh TM, Thu PTM, Khanh TV, Anh NTK, et al. Outcome of cesarean scar pregnancy treated with local methotrexate injection. Nagoya J Med Sci. 2020;82(1):15-23. [PubMed ID:32273628]. [PubMed Central ID:PMC7103867]. https://doi.org/10.18999/nagjms.82.1.15.
  • 26.
    Lipscomb GH, Givens VM, Meyer NL, Bran D. Comparison of multidose and single-dose methotrexate protocols for the treatment of ectopic pregnancy. Am J Obstet Gynecol. 2005;192(6):1844-7; discussion 7-8. [PubMed ID:15970826]. https://doi.org/10.1016/j.ajog.2004.12.061.
  • 27.
    Elsalam A, Soliman M, Ibrahim M, Abdelwahab A. The Effect of Using Local Injection of Methotrexate in Management of Cesarean Scar Pregnancy in Minia University Maternity Hospital. Minia J Med Res. 2023;0(0):0-. https://doi.org/10.21608/mjmr.2023.185780.1284.
  • 28.
    Uludag SZ, Kutuk MS, Ak M, Ozgun MT, Dolanbay M, Aygen EM, et al. Comparison of systemic and local methotrexate treatments in cesarean scar pregnancies: time to change conventional treatment and follow-up protocols. Eur J Obstet Gynecol Reprod Biol. 2016;206:131-5. [PubMed ID:27693933]. https://doi.org/10.1016/j.ejogrb.2016.09.010.
  • 29.
    Heidar Z, Zadeh Modarres S, Abediasl Z, Khaghani A, Salehi E, Esfidani T. Cesarean scar pregnancy treatment: a case series. J Med Case Rep. 2021;15(1):506. [PubMed ID:34625100]. [PubMed Central ID:PMC8501523]. https://doi.org/10.1186/s13256-021-03081-0.
  • 30.
    Levin G, Zigron R, Dior UP, Gilad R, Shushan A, Benshushan A, et al. Conservative management of Caesarean scar pregnancies with systemic multidose methotrexate: predictors of treatment failure and reproductive outcomes. Reprod Biomed Online. 2019;39(5):827-34. [PubMed ID:31530445]. https://doi.org/10.1016/j.rbmo.2019.05.015.
  • 31.
    Menon S, Colins J, Barnhart KT. Establishing a human chorionic gonadotropin cutoff to guide methotrexate treatment of ectopic pregnancy: a systematic review. Fertil Steril. 2007;87(3):481-4. [PubMed ID:17173905]. https://doi.org/10.1016/j.fertnstert.2006.10.007.
  • 32.
    Timor-Tritsch IE, Monteagudo A, Santos R, Tsymbal T, Pineda G, Arslan AA. The diagnosis, treatment, and follow-up of cesarean scar pregnancy. Am J Obstet Gynecol. 2012;207(1):44 e1-13. [PubMed ID:22607667]. https://doi.org/10.1016/j.ajog.2012.04.018.
  • 33.
    Saraj AJ, Wilcox JG, Najmabadi S, Stein SM, Johnson MB, Paulson RJ. Resolution of hormonal markers of ectopic gestation: a randomized trial comparing single-dose intramuscular methotrexate with salpingostomy. Obstet Gynecol. 1998;92(6):989-94. [PubMed ID:9840564]. https://doi.org/10.1016/s0029-7844(98)00324-x.
  • 34.
    Yamaguchi M, Honda R, Uchino K, Tashiro H, Ohba T, Katabuchi H. Transvaginal methotrexate injection for the treatment of cesarean scar pregnancy: efficacy and subsequent fecundity. J Minim Invasive Gynecol. 2014;21(5):877-83. [PubMed ID:24743111]. https://doi.org/10.1016/j.jmig.2014.03.024.
  • 35.
    Tan KL, Chen YM, Zeng W, Meng Y, Jiang L. Local Methotrexate Injection Followed by Dilation and Curettage for Cesarean Scar Pregnancy: A Prospective Non-randomized Study. Front Med (Lausanne). 2021;8:800610. [PubMed ID:35127758]. [PubMed Central ID:PMC8815728]. https://doi.org/10.3389/fmed.2021.800610.
  • 36.
    Tanigaki S, Nagata C, Ueno K, Ozawa N, Nagaoka S, Tanaka K, et al. Successful Treatment of Caesarean Scar Pregnancies by Local Treatment Only. Obstet Gynecol Int. 2017;2017:9543570. [PubMed ID:28396687]. [PubMed Central ID:PMC5371214]. https://doi.org/10.1155/2017/9543570.
  • 37.
    Howard SC, McCormick J, Pui CH, Buddington RK, Harvey RD. Preventing and Managing Toxicities of High-Dose Methotrexate. Oncologist. 2016;21(12):1471-82. [PubMed ID:27496039]. [PubMed Central ID:PMC5153332]. https://doi.org/10.1634/theoncologist.2015-0164.

Copyright

© 2025, Author(s). This open-access article is available under the Creative Commons Attribution 4.0 (CC BY 4.0) International License (https://creativecommons.org/licenses/by/4.0/), which allows for unrestricted use, distribution, and reproduction in any medium, provided that the original work is properly cited.

Similar Articles

31
Jan
2010

Misoprostol Alone or in Combination with Methotrexate for Termination of Pregnancy at First Trimester

Fatemeh Vahid Roudsari,
Sedigheh Ayati,
Nafiseh Saghafy,
Mohamadtaghi Shakeri

Vahid Roudsari F, Ayati S, Saghafy N, Shakeri M. Misoprostol Alone or in Combination with Methotrexate for Termination of Pregnancy at First Trimester. Iran J Pharm Res. 2010;9(1):e126037. doi: https://doi.org/10.22037/ijpr.2010.841

11
Nov
2023
Iran J Pharm Res

Micronized Progesterone or Dydrogesterone? A Comparative Study on the Effects of Two Forms of Progesterone on Pregnancy Outcomes After Threatened Abortion

Iman Ansari,
Ezzatalsadat Hajiseid Javadi,
Hamideh Pakniat,
Ali Emami,
Fatemeh Ranjkesh,
Simindokht Molaverdikhani

Ansari I, Hajiseid Javadi E, Pakniat H, Emami A, Ranjkesh F, et al. Micronized Progesterone or Dydrogesterone? A Comparative Study on the Effects of Two Forms of Progesterone on Pregnancy Outcomes After Threatened Abortion. Iran J Pharm Res. 2023;22(1):e136320. doi: https://doi.org/10.5812/ijpr-136320

31
Oct
2014

Comparison of therapeutic abortion efficacy by suction curettage and misoprostol vaginally in the first trimester of pregnancy

2
Jan
2019
Image credit: pxhere

Variations of Cesarean Scar Pregnancy in Practice

Mojgan Barati,
Farideh Moramezi,
Sara Masihi,
Razieh Mohamad Jafari

Barati M, Moramezi F, Masihi S, Mohamad Jafari R. Variations of Cesarean Scar Pregnancy in Practice. Jentashapir J Cell Mol Biol. 2018;9(6):e86355. doi: https://doi.org/10.5812/jjhr.86355

31
Oct
2021

The Effective Role of Adding Letrozole to Methotrexate in the Management of Tubal Ectopic Pregnancies, a Randomized Clinical Trial

Zahra Rezaei,
Marjan Ghaemi,
Elham Feizabad,
Behnaz Ghavami,
Firoozeh Akbari Asbagh,
Fatemeh Davari Tanha
,et al.

Rezaei Z, Ghaemi M, Feizabad E, Ghavami B, Akbari Asbagh F, et al. The Effective Role of Adding Letrozole to Methotrexate in the Management of Tubal Ectopic Pregnancies, a Randomized Clinical Trial. Iran J Pharm Res. 2021;20(4):e124537. doi: https://doi.org/10.22037/ijpr.2021.115659.15461

Download PDF786.23 KB
Import into EndNoteImport into BibTex
Indexed in
logoScopus
Crossmark

Crossmark

Checking

Share on
Comments
Number of Comments:0
Cited by
Metrics
Licensing and reuse information

Ordering Reprints

Articles are published under the Creative Commons license stated on each article. No permission or royalty fee is required for uses permitted by that license. CCC handles optional bulk and customized reprint orders. Any quotation covers production and delivery services only, not copyright permission. > Request Reprints from CCC 

Search Relations

Author(s):

Related Articles

Related Article in PubMed

Related Article in Google Scholar

Create Citation Alert via Google Reader