Effect of pentoxifylline in reducing oxidative stress-induced embryotoxicity

  • Xiaoyan Zhang
  • Rakesh K. Sharma
  • Ashok Agarwal
  • Tommaso Falcone
Animal Experimentation


Purpose: To 1) evaluate the embryotoxic effects of hydrogen peroxide on mouse embryo development and 2) examine if pentoxifylline can reverse hydrogen peroxide induced embryotoxicity.

Methods: Prospective in vitro study examining the effects of varying concentrations of hydrogen peroxide and pentoxifylline on the blastocyst development rate alone as well as in combination.

Results: A dose-dependent decrease in % BDR was seen with increasing concentrations of H2O2. High concentrations of hydrogen peroxide (> 60 μM) were embryotoxic. Pentoxifylline (500 μM) was able to reduce the embryotoxic effect of hydrogen peroxide. Percent blastocyst development rate increased from 44% in hydrogen peroxide alone to 85% in hydrogen peroxide and pentoxifylline coincubation.

Conclusions: Pentoxifylline may be beneficial in reducing hydrogen peroxide induced embryo damage and improve IVF outcome. Patients with endometriosis-associated infertility may benefit from the use of pentoxifylline without significantly affecting embryo development.


Embryotoxicity hydrogen peroxide pentoxifylline 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Sharma RK, Agarwal A: Role of reactive oxygen species in gynecologic diseases. Reprod Med Biol 2004;3:177–199CrossRefGoogle Scholar
  2. 2.
    Guerin P, El Mouatassim S, Menezo Y: Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings. Hum Reprod Update 2001;7:175–189CrossRefPubMedGoogle Scholar
  3. 3.
    Bedaiwy MA, Falcone T, Sharma RK, et al.: Prediction of endometriosis with serum and peritoneal fluid markers: A prospective controlled trial. Hum Reprod 2002;17:426–431PubMedGoogle Scholar
  4. 4.
    Attaran M, Pasqualotto E, Falcone T, et al.: The effect of follicular fluid reactive oxygen species on the outcome of in vitro fertilization. Int J Fertil Womens Med 2000;45:314–320PubMedGoogle Scholar
  5. 5.
    Pasqualotto EB, Agarwal A, Sharma RK, et al.: Effect of oxidative stress in follicular fluid on the outcome of assisted reproductive procedures. Fertil Steril 2004;81:973–976CrossRefPubMedGoogle Scholar
  6. 6.
    Bedaiwy MA, Goldberg JM, Falcone T, Singh M, Nelson D, Azab H, Sharma RK: Relationship between oxidative stress and embryotoxicity of hydrosalpingeal fluid. Hum Reprod 2002;17:601–604PubMedGoogle Scholar
  7. 7.
    Szcyzepanska M, Kozlik J, Skrzypczak J, Mikolsajczyk M: Oxidative stress may be a piece in the endometriosis puzzle. Fertil Steril 2003;79:1288–1293Google Scholar
  8. 8.
    Bedaiwy MA, Falcone T, Mohamed MS, et al.: Differential growth of human embryos in vitro: Role of reactive oxygen species. Fertil Steril 2004;82:593–600CrossRefPubMedGoogle Scholar
  9. 9.
    Yang HW, Hwang KJ, Kwon HC: Detection of reactive oxygen species (ROS) and apoptosis in human fragmented embryos. Hum Reprod 1998;13:998–1002CrossRefPubMedGoogle Scholar
  10. 10.
    Nasr-Esfahani MH, Aitken RJ, Johnson MH: Hydrogen peroxide levels in mouse oocytes and early cleavage stage embryos developed in vitro or in vivo. Development 1990;109:501–507PubMedGoogle Scholar
  11. 11.
    Ward A, Stephen PC: Pentoxifylline. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic efficacy. Drugs 1987;34:50–97Google Scholar
  12. 12.
    Steinleitner A, Lambert H, Roy S: Immunomodulation with pentoxifylline abrogates macrophage-mediated infertility in an in vivo model: A paradigm for a novel approach to the treatment of endometriosis-associated subfertility. Fertil Steril 1991;55:26–31PubMedGoogle Scholar
  13. 13.
    Steinleitner A, Lambert H, Suarez M: Immunomodulation in the treatment of endometriosis-associated subfertility: Use of pentoxifylline to reverse the inhibition of fertilization by surgically induced endometriosis in a rodent model. Fertil Steril 1991;55:975–979Google Scholar
  14. 14.
    Juan B, Montserrat C, Francisco F: Pentoxifylline versus placebo in the treatment of infertility associated with minimal or mild endometriosis: A pilot randomized clinical trial. Hum Reprod 1997;12:1046–1050Google Scholar
  15. 15.
    Shanti A, Santanam N, Morales AJ, Parthasarathy S, Murphy AA: Autoantibodies to markers of oxidative stress are elevated in women with endometriosis. Fertil Steril 1999;71:1115–1118CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Xiaoyan Zhang
    • 1
  • Rakesh K. Sharma
    • 1
    • 2
  • Ashok Agarwal
    • 1
  • Tommaso Falcone
    • 1
  1. 1.Center for Advanced Research in Human Reproduction, Infertility and Sexual Function, Department of Obstetrics-Gynecology and Glickman Urological InstituteCleveland Clinic FoundationCleveland
  2. 2.Desk A19.1Cleveland Clinic FoundationClevelandUSA

Personalised recommendations