Effect of pentoxifylline in reducing oxidative stress-induced embryotoxicity

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

Abstract

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.

Keywords

Embryotoxicity hydrogen peroxide pentoxifylline 

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References

  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

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