The fertility sparing therapy in ectopic pregnancy

Authors: B. Sehnal 1 ;  J. Hanáček 2 ;  J. Matěcha 1 ;  M. Fanta 3
Authors‘ workplace: Gynekologicko-porodnická klinika 1. LF UK a FN Bulovka, Praha 1;  Ústav pro péči o matku a dítě, 3. LF UK, Praha 2;  Gynekologicko-porodnická klinika 1. LF UK a VFN v Praze 3
Published in: Ceska Gynekol 2023; 88(1): 20-26
Category: Review Article


Objective: A review of current knowledge on the possibilities of fertility sparing therapy in case of ectopic pregnancy. Methods and results: Ectopic pregnancy is defined as implantation of an embryo outside the endometrial cavity, most often in the fallopian tube. This dia­gnosis is very common among young women. Ectopic pregnancies can be treated using the following three approaches, which can be combined: expectantly, pharmacologically or surgically. Fertility-sparing salpingostomy may be performed during surgical treatment. Medical (pharmacological) treatment consists in the application of methotrexate with a success rate of 75–96%, depending on the initial level of the free beta subunit of human chorionic gonadotropin (b-hCG). This is a safe treatment with minimal side effects. There is no standardization of the blood b-hCG level limits or of the size of the ectopic pregnancy mass for choosing expectant, surgical or medical treatment. A considerable increase in the rate of Cesarean sections over the last decades has led to an increase in the occurrence of the implantation of the gestational sac in the hysterotomy scar. There are several options to address this dia­gnosis, but none is clearly preferred. This issue is also discussed in the article. Conclusion: The goal of ectopic pregnancy treatment is to choose a safe and effective therapy with a low incidence of side effects and maintaining the maximum fertility of women. Properly set indication criteria are most important when choosing the right option.


Safety – ectopic pregnancy – efficacy – cesarean scar pregnancy – cervical pregnancy – medical treatment


1. Hsu JY, Chen L, Gumer AR et al. Disparities in the management of ectopic pregnancy. Am J Obstet Gynecol 2017; 217 (1): 49.e1–49.e10. doi: 10.1016/j.ajog.2017.03.001.

2. Tay JI, Moore J, Walker JJ. Ectopic pregnancy. BMJ 2000; 320 (7239): 916–919. doi: 10.1136/ bmj.320.7239.916.

3. Derbak A. Mimoděložní těhotenství v ultra­zvukovém obraze. Kazuistiky. Retrospektivní analýza. Ceska Gynekol 2016; 81 (1): 63–70.

4. Kubešová B, Líbalová P, Simonová V et al. Re­trospektivní analýza efektivity, dia­gnostiky ektopické gravidity transvaginálním ultrazvu­kovým vyšetřením. Ceska Gynekol 2013; 78 (4): 338–341.

5. Fischerova D, Paškova A, Břeťak M. Těhotenství neznámé lokalizace. In: Calda, P, Břešták M, Fischerova D (eds). Ultrazvuková dia­gnostika v těhotenství a gynekologii. 2. vyd. Praha: Aprofema 2010: 428–434.

6. Zdeňková A, Fanta M, Calda P. Metotrexát v léčbě ektopické gravidity. Actual Gyn 2015; 7: 27–32.

7. Cordeiro DE, Alves JA, Araujo Júnior E et al. Ectopic pregnancies: a retrospective cohort analysis in a tertiary reference center in the Northeast Region of Brazil. Ceska Gynekol 2018; 83 (6): 434–439.

8. Elson CJ, Salim R, Potdar N et al. Dia­gnosis and management of ectopic pregnancy. On behalf of the Royal College of Obstetricians and Gynaecologists. BJOG 2016; 123: e15–e55.

9. Mavrelos D, Nicks H, Jamil A et al. Efficacy and safety of a clinical protocol for expectant management of selected women dia­gnosed with a tubal ectopic pregnancy. Ultrasound Obstet Gynecol 2013; 42 (1): 102–107. doi: 10.1002/uog. 12401.

10. van Mello NM, Mol F, Verhoeve HR et al. Methotrexate or expectant management in women with an ectopic pregnancy or pregnancy of unknown location and low serum hCG concentrations? A randomized comparison. Hum Reprod 2013; 28 (1): 60–67. doi: 10.1093/humrep/des373.

11. Shalev E, Peleg D, Tsabari A et al. Spontaneous resolution of ectopic tubal pregnancy: natural history. Fertil Steril 1995; 63 (1): 15–19. doi: 10.1016/s0015-0282 (16) 57289-6.

12. Zaremba R, Mára M, Razak I et al. Hyste­roskopicky asistovaná laparoskopická salpingostomie při řešení tubární gravidity. Ceska Gynekol 2018; 83 (1): 50–52.

13. Bruhat MA, Pouly JL. Endoscopic treatment of ectopic pregnancies. Curr Opin Obstet Gynecol 1993; 5 (2): 260–266.

14. Cheng X, Tian X, Yan Z et al. Comparison of the fertility outcome of salpingotomy and salpingectomy in women with tubal pregnancy: a systematic review and meta-analysis. PLoS One 2016; 11 (3): e0152343. doi: 10.1371/journal.pone.0152343.

15. Luo Y, Shi Y, Liu D et al. The effect of salpingectomy on the ovarian reserve and ovarian response in ectopic pregnancy: a systematic review and meta-analysis. Medicine (Baltimore) 2019; 98 (47): e17901. doi: 10.1097/MD.000000 0000017901.

16. Wang X, Huang L, Yu Y et al. Risk factors and clinical characteristics of recurrent ectopic pregnancy: a case-control study. J Obstet Gynaecol Res 2020; 46 (7): 1098–1103. doi: 10.1111/jog.14253.

17. Cecchino GN, Araujo Júnior E, Elito Júnior J. Methotrexate for ectopic pregnancy: when and how. Arch Gynecol Obstet 2014; 290 (3): 417–423. doi: 10.1007/s00404-014-3266-9.

18. Tanaka T, Hayashi H, Kutsuzawa T et al. Treatment of interstitial ectopic pregnancy with methotrexate: report of a successful case. Fertil Steril 1982; 37 (6): 851–852. doi: 10.1016/s0015- 0282 (16) 46349-1.

19. 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 (4): 778–784. doi: 10.1016/s0029- 7844 (02) 03158-7.

20. Rotas MA, Haberman S, Levgur M. Cesarean scar ectopic pregnancies: etiology, dia­g­nosis and management. Obstet Gynecol 2006; 107 (6): 1373–1381. doi: 10.1097/01.AOG.0000 218690.24494.ce.

21. 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 (2): 101–104. doi: 10.1016/j.ijgo.2011.09.023.

22. 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 (5 Pt 1): 1052–1057. doi: 10.1097/01.AOG.0000158860.26939.2d.

23. 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 (7): 889–895. doi: 10.3109/00016349.2010.486825.

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 (4): 1203–1207. doi: 10.1016/j.fertnstert.2008.07.1775.

25. 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): 481–484. doi: 10.1016/j.fertnstert.2006.10. 007.

26. Soliman KB, Saleh NM, Omran AA. Safety and efficacy of systemic methotrexate in the treatment of unruptured tubal pregnancy. Saudi Med J 2016; 27 (7): 1005–1010.

27. Vela G, Tulandi T. Cervical pregnancy: the importance of early dia­gnosis and treatment. J Minim Invasive Gynecol 2007; 14 (4): 481–484. doi: 10.1016/j.jmig.2006.11.012.

28. Zahálková L, Kacerovský M. Ektopická gravidita v jizvě po císařském řezu. Ceska Gynekol 2016; 81 (6): 414–419.

29. Karásek V. Gravidita v jizvě po císařském řezu – kazuistika. Ceska Gynekol 2015; 80 (5): 382–385.

30. Kučera E, Křepelka P, Krofta L et al. Ektopická gravidita v jizvě po císařském řezu. Ceska Gynekol 2007; 72 (3): 207–213.

31. Timor-Tritsch IE, Monteagudo A. Unforeseen consequences of the increasing rate of cesarean deliveries: early placenta accreta and cesarean scar pregnancy. A review. Am J Obstet Gynecol 2012; 207 (1): 14–29. doi: 10.1016/j.ajog.2012.03.007.

32. Timor-Tritsch IE, Monteagudo A, Cali G et al. Cesarean scar pregnancy and early placenta accreta share common histology. Ultrasound Obstet Gynecol 2014; 43 (4): 383–395. doi: 10.1002/uog.13282.

33. Timor-Tritsch IE, Monteagudo A, Bennett TA et al. A new minimally invasive treatment for cesarean scar pregnancy and cervical pregnancy. Am J Obstet Gynecol 2016; 215 (3): 351.e1–351.e8. doi: 10.1016/j.ajog.2016.03.010.

34. Maheux-Lacroix S, Li F, Bujold E et al. Cesarean scar pregnancies: a systematic review of treatment options. J Minim Invasive Gynecol 2017; 24 (6): 915–925. doi: 10.1016/ j.jmig.2017.05.019.

35. Hung TH, Shau WY, Hsieh TT et al. Prognostic factors for an unsatisfactory primary methotrexate treatment of cervical pregnancy: a quantitative review. Hum Reprod 1998; 13 (9): 2636–2642. doi: 10.1093/humrep/13.9.2636.

36. Shao MJ, Hu MX, Xu XJ et al. Management of cesarean scar pregnancies using an intrauterine or abdominal approach based on the myometrial thickness between the gestational mass and the bladder wall. Gynecol Obstet Invest 2013; 76 (3): 151–157. doi: 10.1159/000351875.

37. Sun YY, Xi XW, Yan Q et al. Management of type II unruptured cesarean scar pregnancy: comparison of gestational mass excision and uterine artery embolization combined with methotrexate. Taiwan J Obstet Gynecol 2015; 54 (5): 489–492. doi: 10.1016/j.tjog.2015.08. 002.

38. Chan CC, Ng EH, Li CF et al. Impaired ovarian blood flow and reduced antral follicle count following laparoscopic salpingectomy for ectopic pregnancy. Hum Reprod 2003; 18 (10): 2175–2180. doi: 10.1093/humrep/deg411.

39. Gelbaya TA, Nardo LG, Fitzgerald CT et al. Ovarian response to gonadotropins after laparoscopic salpingectomy or the division of fallopian tubes for hydrosalpinges. Fertil Steril 2006; 85 (5): 1464–1468. doi: 10.1016/j.fertnstert.2005.10.036.

40. Lass A, Ellenbogen A, Croucher C et al. Effect of salpingectomy on ovarian response to superovulation in an in vitro fertilization-embryo transfer program. Fertil Steril 1998; 70 (6): 1035–1038. doi: 0.1016/s0015-0282 (98) 00357-4.

41. Dar P, Sachs GS, Strassburger D et al. Ovarian function before and after salpingectomy in artificial reproductive technology patients. Hum Reprod 2000; 15 (1): 142–144. doi: 10.1093/ humrep/15.1.142.

42. Racková J, Driák D, Neumannová H et al. Použití metotrexátu u ektopické gravidity a tehotenství neznámé lokalizace. Ceska Gynekol 2016; 81 (2): 141–146.

43. Mašková H. Donošená vysoká kornuální gravidita. Prakt Gyn 2011; 15 (3–4): 202–203.

44. Long Y, Zhu H, Hu Y et al. Interventions for non-tubal ectopic pregnancy. Cochrane Database Syst Rev 2020; 7 (7): CD011174. doi: 10.1002/14651858.CD011174.pub2.

Paediatric gynaecology Gynaecology and obstetrics Reproduction medicine
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.


Don‘t have an account?  Create new account