Use of methotrexate in the ectopic pregnancy and pregnancy of unknown location


Authors: J. Racková;  D. Driák ;  H. Neumannová;  K. Hurt;  B. Sehnal;  M. Halaška
Authors‘ workplace: Gynekologicko-porodnická klinika 1. LF UK, Nemocnice Na Bulovce, Praha, přednosta prof. MUDr. M. Halaška, DrSc.
Published in: Ceska Gynekol 2016; 81(2): 140-146

Overview

Objective:
There are only a few gynaecological departments in the Czech Republic that use medical treatment of the ectopic pregnancy (EP) or persistent pregnancy of unknown location (PUL). We have started using this method in 2008 at our clinic. The aim of this study was to assess the success rate of conservative medical treatment with methotrexate (MTX) in the dose of 1 mg/kg intramuscularly in patients with ectopic pregnancy or persistent pregnancy of unknown location and to compare the results of clinical history, clinical finding and laboratory results in a group of successful and a group of unsuccessful treatment.

Type of study:
Retrospective analysis.

Setting:
Charles University in Prague, 1st Medical Faculty and Hospital Bulovka, Department of Obstetrics and Gynaecology, Prague.

Methods:
Patients diagnosed with EP or persistent PUL diagnosed at the outpatient of our clinic in 01/2008 - 08/2014 who were hemodynamically stable and fulfilled the indication for medical treatment were enrolled in the study. Treatment success was decrease of free subunit of β-hCG (β-hCG) < 5 IU/L independent of the number of methotrexate doses administered.

Results:
Two hundred and eleven patients were diagnosed with EP or PUL, sixty-three were eligible for our study and fulfilled the criteria for methotrexate treatment, fifty six women were finally analysed. From this number forty eight (86%) had clinically and laboratory diagnosed EP and eight (14%) were diagnosed with persistent PUL. Forty one patients (73%) had a successfull treatment (Group I) with the β-hCG level decrease <5 IU/L in a mean time of 27 days. When comparing the data of successful and unsuccessful treatment (Group II) we found a difference in the non-significant initial β-hCG level. In Group I there was a median β-hCG 538 IU/L (100–3852 IU/l), whereas in the unsuccessful Group II it was 1100 IU/L (300–3240 IU/l). Group I included more nuliparous women and more women with clinical histories of EP. Group II included more heavy smokers. The mean hematosalpinx diameter for group II, measured by transvaginal ultrasound, was larger. There were also more patients with endometriosis or deep infiltrating endometriosis in Group II, subsequently verified during laparoscopy, compared to Group I. There was no tubal rupture in these patients.

Conclusion:
The results of our study are comparable with foreign literature publications. We consider the pharmacological treatment of ectopic preganancy or persistent pregnancy of unknown location as effective and relatively safe for patients, with similar impact on a woman's fertility as laparoscopic salpingectomy.

Keywords:
ectopic pregnancy, pregnancy of unknown location, pharmacological treatment, methotrexate


Sources

1. Abusheikha, N., Salha, O., Brinsden, P. Extra-uterine pregnancy following assisted conception treatment. Hum Reprod Update, 2000, 6(1), p. 80–92.

2. Adam, MP., Manning, MA., Beck, AE., et al. Methotrexate/misoprostol embryopathy: report of four cases resulting from failed medical abortion. Am J Med Genet A, 2003, 123A(1), p. 72–78.

3. Barnhart, K. Clinical practice. Ectopic pregnancy. N Engl J Med, 2009, 361(4), p. 379–387.

4. Barnhart, K., Hummel, AC., Sammel, MD., et al. Use of „2-dose“ regimen of methotrexate to treat ectopic pregnancy. Fertil Steril, 2007, 87(2), p. 250–256.

5. Barnhart, K., van Mello, NM., Bourne, T., et al. Pregnancy of unknown location: a consensus statement of nomenclature, definitions, and outcome. Fertil Steril, 2011, 95(3), p. 857–866.

6. Bouyer, J. [Epidemiology of ectopic pregnancy: incidence, risk factors and outcomes]. J Gynecol Obstet Biol Reprod (Paris), 2003, 32(7), Suppl, p. S8–S17.

7. Dudley, PS., Heard, MJ., Sangi-haghpeykar, H., et al. Characterizing ectopic pregnancies that rupture despite treat­ment with methotrexate. Fertil Steril, 2004, 82(5), p. 1374–1378.

8. Fernandez, H., Capmas, P., Lucot, JP., et al. Fertility after ectopic pregnancy: the DEMETER randomized trial. Hum Reprod, 2013, 28(5), p. 1247–1253.

9. Gamzu, R., Almog, B., Levin, Y., et al. The ultrasonographic appearance of tubal pregnancy in patients treated with methotrexate. Hum Reprod, 2002, 17(10), p. 2585–2587.

10. Gervaise, A., Masson, L., de Tayrac, R., et al.. Reproductive outcome after methotrexate treatment of tubal pregnancies. Fertil Steril, 2004, 82(2), p. 304–308.

11. Gilani, MM., Fariba, B., Behtash, N., et al. The WHO score predicts treatment outcome in low risk gestational trophoblastic neoplasia patients treated with weekly intramuscular methotrexate. J Cancer Res Ther, 2013, 9(1), p. 38–43.

12. Hjordt Hansen, MV., Dalsgaard, T., Hartwell, D., et al. Reproductive prognosis in endometriosis. A national cohort study. Acta Obstet Gynecol Scand, 2014, 93(5), p. 483–489.

13. Hoover, RN., Hyer, M., Pfeiffer, RM., et al. Adverse health outcomes in women exposed in utero to diethylstilbestrol. N Engl J Med, 2011, 365(14), p. 1304–1314.

14. Chung, K., Sammel, MD., Coutifaris, C., et al. Defining the rise of serum HCG in viable pregnancies achieved through use of IVF. Hum Reprod, 2006, 21(3), p. 823–828.

15. Kelly, H., Harvey, D., Moll, S. A cautionary tale: fatal outcome of methotrexate therapy given for management of ectopic pregnancy. Obstet Gynecol, 2006, 107(2 Pt 2), p. 439–441.

16. Kirk, E., Papageorghiou, AT., Condous, G., et al. The diagnostic effectiveness of an initial transvaginal scan in detecting ectopic pregnancy. Hum Reprod, 2007, 22(11), p. 2824–2828.

17. Lecuru, F., Robin, F., Chasset, S., et al. Direct cost of single dose methotrexate for unruptured ectopic pregnancy. Prospective comparison with laparoscopy. Eur J Obstet Gynecol Reprod Biol, 2000, 88(1), p. 1–6.

18. Lian, F., Wang, Y., Chen, W., et al. Uterine artery embolization combined with local methotrexate and systemic methotrexate for treatment of caesarean scar pregnancy with different ultrasonographic pattern. Cardiovasc Intervent Radiol, 2012, 35(2), p. 286–291.

19. Lloyd, ME., Carr, M., Mcelhatton, P., et al. The effects of methotrexate on pregnancy, fertility and lactation. QJM, 1999, 92(10), p. 551–563.

20. Lund Kårhus, L., Egerup, P., Wessel Skovlund, C., Lidegaard, O. Long-term reproductive outcomes in women whose first pregnancy is ectopic: a national controlled follow-up study. Hum Reprod, 2013, 28(1), p. 241–246.

21. Medical treatment of ectopic pregnancy: a committee opinion. Fertil Steril, 2013, 100(3), p. 638–644.

22. Moore, GD., Eddy, CA., Pauerstein, CJ. Rabbit endosalpinx inhibits implantation in vitro. Fertil Steril, 1992, 57(4), p. 902–907.

23. Murakami, T., Mori, N. Involvement of multiple transporters-mediated transports in mizoribine and methotrexate pharmacokinetics. Pharmaceuticals (Basel), 2012, 5(8), p. 802–836.

24. Murray, Hm, Baakdah, H., Bardell, T., Tulandi, T. Diagnosis and treatment of ectopic pregnancy. CMAJ, 2005, 173(8), p. 905–912.

25. O‘Neill, SM., Agerbo, E., Kenny, LC., et al. Cesarean section and rate of subsequent stillbirth, miscarriage, and ectopic pregnancy: a Danish register-based cohort study. PLoS Med, 2014, 11(7), p. 1001670.

26. Oriol, B., Barrio, A., Pacheco, A., et al. Systemic methotrexate to treat ectopic pregnancy does not affect ovarian reserve. Fertil Steril, 2008, 90(5), p. 1579–1582.

27. Parashi, S., Moukhah, S., Ashrafi, M. Main risk factors for ectopic pregnancy: a case-control study in a sample of Iranian women. Int J Fertil Steril, 2014, 8(2), p. 147–154.

28. 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), p. 851–852.

29. ÚZIS. http://www.uzis.cz/katalog/zdravotnicka-statistika/potraty

30. 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), p. 60–67.

31. Yao, M., Tulandi, T., Kaplow, M., Smith, AP. A comparison of methotrexate versus laparoscopic surgery for the treatment of ectopic pregnancy: a cost analysis. Hum Reprod, 1996, 11(12), p. 2762–2766.

Labels
Paediatric gynaecology Gynaecology and obstetrics Reproduction medicine
Login
Forgotten password

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

Login

Don‘t have an account?  Create new account