Skip to main content

Advertisement

Log in

Controlled Ovarian Hyperstimulation—An Inflammatory State

  • Hypothesis
  • Published:
The Journal of the Society for Gynecologic Investigation: JSGI Aims and scope Submit manuscript

Abstract

Objective

Controlled ovarian hyperstimulation (COH) is apparently a key factor in the success of in vitro fertilization-embryo transfer. One of the major complications of COH is severe ovarian hyperstimulation syndrome (OHSS), which may be attributable to a massive increase in systemic inflammatory cytokines or to neutrophil activation. The aim of the present review was to investigate the role of COH in the induction of an inflammatory response.

Methods

Major studies that have reported on the association between COH and inflammation were identified through MEDLINE searches and the published literature.

Results

Several inflammatory mediators, namely, C-reactive protein and leukocyte and endothelial selectins, showed a significant increase after human chorionic gonadotropin (hCG) administration in vivo, reflecting an inflammatory state, and neutrophil and endothelial activation, respectively. On the other hand, hCG showed a direct depressive effect on mononuclear cells in vitro. Because the development of OHSS almost always follows hCG administration, the negative effect of hCG on peripheral mononuclear cells indicates that it probably causes OHSS by an indirect mechanism.

Conclusion

We suspect that hCG stimulates the ovaries to produce and secrete a still unknown intermediate factor, which in turn activates inflammatory processes that may lead to an increase in capillary permeability.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Orvieto R, Voliovitch I, Fishman P, Ben-Rafael Z. Interleukin-2 and ovarian hyperstimulation syndrome—A pilot study. Hum Reprod 1995;10:24–7.

    Article  CAS  Google Scholar 

  2. Orvieto R, Ben-Rafael Z. Ovarian hyperstimulation syndrome: A new insight into an old enigma. J Soc Gynecol Invest 1998;5:110–3.

    Article  CAS  Google Scholar 

  3. Delvigne A, Rezenberg S. Systematic review of data concerning etipathology of ovarian hyperstimulation syndrome. Int J Fertil Womens Med 2002;47:211–6.

    PubMed  Google Scholar 

  4. Carey PD, Wakefield CH, Gulillou PJ. Neutrophil activation, vascular leak toxicity, and cytolysis during interleukin-2 infusion in human cancer. Surgery 1997;122:918–26.

    Article  CAS  Google Scholar 

  5. Athreya BH, Pletcher J, Zulian F, Weiner DB, Williams WV. Subset-specific effects of sex hormones and pituitary gonadotropins on human lymphocyte proliferation in vitro. Clin Immunol Immunopathol 1993;66:201–11.

    Article  CAS  Google Scholar 

  6. Brunelli R, Frasca D, Perrone G, et al. Hormone replacement therapy affects various immune cell subsets and natural cytotoxicity. Gynecol Obstet Invest 1996;41:128–31.

    Article  CAS  Google Scholar 

  7. Kincade PW, Medina KL, Smithson G. Sex hormones as negative regulators of lymphopoiesis. Immunol Rev 1994;137:119–34.

    Article  CAS  Google Scholar 

  8. Ho HN, Wu MY, Chen HF, et al. In vivo CD3+CD25+ lymphocyte subpopulation is downregulated without increased serum-soluble interleukin-2 receptor (sIL-2R) by gonadotropin releasing hormone agonist (GnRH-a). Am J Reprod Immunol 1995;33:134–9.

    Article  CAS  Google Scholar 

  9. Giuliani A, Schoell W, Auner J, Urdl W. Controlled ovarian hyperstimulation in assisted reproduction: effect on the immune system. Fertil Steril 1998;70:831–5.

    Article  CAS  Google Scholar 

  10. Hock DL, Huhn RD, Kemmann E. Leukocytosis in response to exogenous gonadotrophin stimulation. Hum Reprod 1997;12:2143–6.

    Article  CAS  Google Scholar 

  11. Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 2002;347:1557–65.

    Article  CAS  Google Scholar 

  12. Kluft C, Leuven JA, Helmerhorst FM, Krans HM. Pro-inflammatory effects of oestrogens during use of oral contraceptives and hormone replacement treatment. Vasc Pharmacol 2002;39:149–54.

    Article  CAS  Google Scholar 

  13. Orvieto R, Chen R, Ashkenazi J, Ben-Haroush A, Bar J, Fisch B. C-reactive protein levels in patients undergoing controlled ovarian hyperstimulation for in vitro fertilization cycle. Hum Reprod 2004;19:357–9.

    Article  CAS  Google Scholar 

  14. Almagor M, Hazav A, Yaffe H. The levels of C-reactive protein in women treated by IVF. Hum Reprod 2004;19:104–6.

    Article  Google Scholar 

  15. Sacks GP, Seyani L, Lavery S, Trew G. Maternal C-reactive protein levels are raised at 4 weeks’ gestation. Hum Reprod 2004;19:1025–30.

    Article  CAS  Google Scholar 

  16. Post MS, van der Mooren MJ, Stehouwer CD, et al. Effects of transdermal and oral oestrogen replacement therapy on C-reactive protein levels in postmenopausal women: A randomised, placebo-controlled trial. Thromb Haemost 2002;88:605–10.

    Article  CAS  Google Scholar 

  17. Thomas L. Labor und diagnose. 4th ed. Marburg: Die Medizinische Verlagsgesellschaft, 1992:781.

    Google Scholar 

  18. Butcher EC. Leukocyte endothelial cell migration: three (or more) steps to specificity and diversity. Cell 1991;67:1033–6.

    Article  CAS  Google Scholar 

  19. Springer TA. Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm. Cell 1994;76:301–14.

    Article  CAS  Google Scholar 

  20. Cronstein BN, Weissmann G. The adhesion molecules of inflammation. Arthritis Rheum 1993;36:147–57.

    Article  CAS  Google Scholar 

  21. Lawrence MB, Springer TA. Leukocytes roll on a selectin at physiologic flow rates: Distinction from and prerequisite for adhesion through integrins. Cell 1991;65:859–73.

    Article  CAS  Google Scholar 

  22. Kishimoto TK, Jutila MA, Butcher EC. Identification of a human peripheral lymph node homing receptor: A rapidly down-regulated adhesion molecule. Proc Natl Acad Sci U S A 1990;87:2244–8.

    Article  CAS  Google Scholar 

  23. Jutila MA, Rott L, Berg EL, Butcher EC. Function and regulation of the neutrophil MEL-14 antigen in vivo: Comparison with LFA-1 and Mac-1. J Immunol 1989;143:3318–24.

    CAS  PubMed  Google Scholar 

  24. Gearing JH, Newman W. Circulating adhesion molecules in disease. Immunol Today 1993;14:506–12.

    Article  CAS  Google Scholar 

  25. Marik AB, Lo AS. Vascular endothelial molecules and tissue inflammation. Pharmacol Rev 1996;48:213–29.

    Google Scholar 

  26. Orvieto R, Ben Rafael Z, Schwartz A, et al. Soluble L-selectin levels during controlled ovarian hyperstimulation. Gynecol Endocrinol 2001;15:29–33.

    Article  CAS  Google Scholar 

  27. Orvieto R, Schwartz A, Bar Hava I, et al. Controlled ovarian hyperstimulation—A state of endothelial activation. Am J Reprod Immunol 2000;44:257–60.

    Article  CAS  Google Scholar 

  28. Orvieto R, Ben-Rafael Z, Abir R, Bar Hava I, Fisch B, Molad Y. Controlled ovarian hyperstimulation- a state of neutrophil activation. Am J Reprod Immunol 1999;42:288–91.

    Article  CAS  Google Scholar 

  29. Orvieto R, Leites T, Abir R, et al. Interleukin-2 production in whole blood cell cultures of women undergoing controlled ovarian hyperstimulation for assisted reproductive technology cycles. Am J Reprod Immunol 2003;50:220–3.

    Article  Google Scholar 

  30. Komorowski J, Gradowski G, Stepien H: Effects of hCG and β-hCG on IL-2 and sIL-2R secretion from human peripheral blood mononuclear cells: A dose-response study in vitro. Immunol Lett 1997;59:29–33.

    Article  CAS  Google Scholar 

  31. Orvieto R. Prediction of OHSS—Challenging the estradiol mitos. Hum Reprod 2003;18:665–7.

    Article  CAS  Google Scholar 

  32. Orvieto R, Achiron A, Margalit R, Ben-Rafael Z. The role of intravenous immunoglobulin in the prevention of severe ovarian hyperstimulation syndrome. J Assist Reprod Genet 1998;15:46–9.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Raoul Orvieto MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Orvieto, R. Controlled Ovarian Hyperstimulation—An Inflammatory State. Reprod. Sci. 11, 424–426 (2004). https://doi.org/10.1016/j.jsgi.2004.05.001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1016/j.jsgi.2004.05.001

Key words

Navigation