Advances in Therapy

, Volume 23, Issue 5, pp 772–777 | Cite as

Examination of the rescue effects of folic acid on derangement of the tubo-ovarian ultrastructural architecture caused by methotrexate

  • Merih Bayram
  • Candan Ozogul
  • Z. Sevim Ercan
  • Ergin Dilekoz
  • Canan Soyer
  • Orhan Bayram


The purpose of this examination was to observe the effects of folic acid (FA) on methotrexate (MTX)-induced derangements in the fallopian tubes. Investigators in this study sought to explore whether MTX-induced dysfunction in the fallopian tubes would be lessened by the addition of FA to MTX treatment. For this study, 18 albino Wistar rats were randomly divided into 6 groups, each of which comprised 3 rats; 0.1 mg/kg FA, 1 mg/kg MTX + 0.1 mg/kg FA, 5 mg/kg MTX + 0.1 mg/kg FA, 1 mg/kg MTX, and 5 mg/kg MTX were given to groups 2, 3, 4, 5, and 6, respectively; group 1 was the control group. After MTX injection, fallopian tube samples from all groups were prepared for examination under electron microscopy. The findings observed in groups 1 and 2 were similar. The level of cellular destruction was greater with the higher doses of MTX without FA; in particular, loss of cilia in the epithelium was prominent in groups 5 and 6. However, there was less cellular destruction observed in groups 3 and 4 than in groups 5 and 6. As a result, the addition of FA should not be overlooked, even when a single-dose MTX regimen is chosen for the treatment of patients with unruptured ectopic pregnancy


methotrexate folic acid electron microscopy ultrastructure of fallopian tube 


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  1. 1.
    Chabner BA, Allegra CJ, Curt GA, Calabresi P. Antineoplastic agents. In: Hardman JG, Limbird LE, eds.Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 9th edition. McGraw Hill Corp. 1996:1243-1247.Google Scholar
  2. 2.
    Bagshawe KD, Wilde CE. Infusion therapy for pelvic trophoblastic tumors.J Obstet Gynaecol Br Commonw. 1964; 71: 565–570.PubMedGoogle Scholar
  3. 3.
    Grim J, Chladek J, Martinkova J. Pharmacokinetics and pharmacodynamics of methotrexate in non-neoplastic diseases.Clin Pharmacokinet. 2003; 42: 139–151.PubMedCrossRefGoogle Scholar
  4. 4.
    Moreno JC, Velez A, Medina I, et al. Psoriasis, vasculitis and methotrexate.J Eur Acad Dermatol Venereol. 2003; 17: 466–468.PubMedCrossRefGoogle Scholar
  5. 5.
    Ory SJ, Villanueva AL, Sand PK, Tamura RK. Conservative treatment of ectopic pregnancy with methotrexate.Am J Obstet Gynecol. 1986; 154: 1299–1306.PubMedGoogle Scholar
  6. 6.
    Borgatta L, Burnhill MS, Tyson J, Leonhardt KK, Hausknecht RU, Haskell S. Early medical abortion with methotrexate and misoprostol.Obstet Gynecol. 2001; 97: 11–16.PubMedCrossRefGoogle Scholar
  7. 7.
    Stoval TG, Ling FW, Gray LA, Carson SA, Buster JE. Methotrexate treatment of unruptured ectopic pregnancy: a report of 100 cases.Obstet Gynecol. 1991; 77: 749–753.Google Scholar
  8. 8.
    Ankum WM, Mol BWJ, Van Der Veen F, Bossuyt PMM. Risk factors for ectopic pregnancy: a meta-analysis.Fertil Steril. 1996; 65: 1093–1096.PubMedGoogle Scholar
  9. 9.
    Stovall TG, Ling FW, Buster JE. Reproductive performance after methotrexate treatment of ectopic pregnancy.Am J Obstet Gynecol. 1990; 162: 1620–1624.PubMedGoogle Scholar
  10. 10.
    El-Lamie IK, Shehata NA, Kamel HA. Intramuscular methotrexate for tubal pregnancy.J Reprod Med. 2002; 47: 144–150.PubMedGoogle Scholar
  11. 11.
    Mol BWJ, Hajenius PJ, Engelsbel S, et al. Treatment of tubal pregnancy in The Netherlands: an economic comparison of systemic methotrexate administration and laparoscopic salpingostomy.Am J Obstet Gynecol. 1999; 181: 945–951.PubMedCrossRefGoogle Scholar
  12. 12.
    Leeton J, Davison G. Nonsurgical management of unruptured tubal pregnancy with intra-amniotic methotrexate: preliminary report of two cases.Fertil Steril. 1988; 50: 167–169.PubMedGoogle Scholar
  13. 13.
    Hopwood D, Nyfors A. Liver ultrastructure in psoriatics related to methotrexate therapy. 2. Findings in bile ducts from 11 methotrexate treated psoriatics and 2 controls.Acta Pathol Microbiol Scand. 1977; 85: 801–811.Google Scholar
  14. 14.
    Harb JM, Werlin SL, Camitta BM, Oechler H, Kamin BA, Blank EL. Hepatic ultrastructure in leukemic children treated with methotrexate and 6-mercaptopurine.Am J Pediatr Hematol Oncol. 1983; 5: 323–331.PubMedCrossRefGoogle Scholar
  15. 15.
    Jeynes BJ, Altmann GG. Light and scanning electron microscopic observations of the effects of sublethal doses of methotrexate on the rat small intestine.Anat Rec. 1978; 191: 1–17.PubMedCrossRefGoogle Scholar

Copyright information

© Health Communications Inc 2006

Authors and Affiliations

  • Merih Bayram
    • 1
  • Candan Ozogul
    • 2
  • Z. Sevim Ercan
    • 3
  • Ergin Dilekoz
    • 4
  • Canan Soyer
    • 5
  • Orhan Bayram
    • 6
  1. 1.Department of Obstetrics and GynecologyBilkent-AnkaraTurkey
  2. 2.Department of Histology and EmbryologyFaculty of Medicine Gazi UniversityAnkaraTurkey
  3. 3.Department of PharmacologyFaculty of Medicine Gazi UniversityAnkaraTurkey
  4. 4.Department of PharmacologyFaculty of Medicine Gazi UniversityAnkaraTurkey
  5. 5.Department of Obstetrics and GynecologyKecioren HospitalAnkaraTurkey
  6. 6.Department of General SurgeryGazi UniversityAnkaraTurkey

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