Skip to main content

Advertisement

Log in

Increased Circulating MMP-2 Levels in Infertile Patients With Moderate and Severe Pelvic Endometriosis

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

The current study compares the levels of matrix metalloproteinase (MMP)-2 and MMP-9 in the follicular fluid (FF) of infertile patients with and without endometriosis submitted to ovarian stimulation for in vitro fertilization and the levels of MMP-2 in the serum of the same patients. We also evaluated whether the severity of endometriosis can influence serum and/or FF concentration of these metalloproteinases. A cross-sectional study was conducted on 30 patients: stage I/II endometriosis (n = 10), stage III/IV endometriosis (n = 10), and control (infertility due to tubal and/or male factor; n = 10). Blood samples for the analysis of MMP-2 levels were obtained during the early follicular phase of the menstrual cycle. The FF samples for the analysis of MMP-2 and MMP-9 were obtained on the day of oocyte retrieval. The concentrations of MMP-2 and MMP-9 were determined by zymography. No intragroup or intergroup difference was observed in MMP-2 or MMP-9 levels in FF. Significantly higher MMP-2 levels were detected in the serum of infertile women with stage III/IV endometriosis compared to women with stage I/II endometriosis. In conclusion, no differences were observed in the follicular levels of MMP-2 and MMP-9 between infertile patients with and without endometriosis. However, the levels of MMP-2 were significantly higher in the serum of infertile women with advanced stages of endometriosis. Taken together, the present results demonstrate that advanced pelvic endometriosis severity is related to higher serum MMP-2 levels but does not influence follicular MMP-2 or MMP-9 levels in periovulatory follicles obtained from stimulated cycles.

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. Giudice LC, Kao LC. Endometriosis. Lancet. 2004;364(9447):1789–1799.

    Google Scholar 

  2. Koninckx PR, Kennedy SH, Barlow DH. Endometriotic disease: the role of peritoneal fluid. Hum Reprod Update. 1998;4(5):741–751.

    Article  CAS  Google Scholar 

  3. Van Langendonckt A, Casanas-Roux F, Donnez J. Oxidative stress and peritoneal endometriosis. Fertil Steril 2002;77(5):861–870.

    Article  Google Scholar 

  4. Gupta S, Goldberg JM, Aziz N, Goldberg E, Krajcir N, Agarwal A. Pathogenic mechanisms in endometriosis-associated infertility. Fertil Steril. 2008;90(2):247–257.

    Article  CAS  Google Scholar 

  5. Nagase H, Visse R, Murphy G. Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res. 2006;69(3):562–573.

    Article  CAS  Google Scholar 

  6. Osteen KG, Yeaman GR, Bruner-Tran KL. Matrix metalloproteinases and endometriosis. Semin Reprod Med. 2003;21(2):155–164.

    Article  CAS  Google Scholar 

  7. Di Carlo C, Bonifacio M, Tommaselli GA, Bifulco G, Guerra G, Nappi C. Metalloproteinases, vascular endothelial growth factor, and angiopoietin 1 and 2 in eutopic and ectopic endometrium. Fertil Steril. 2009;91(6):2315–2323.

    Article  Google Scholar 

  8. Bruner KL, Matrisian LM, Rodgers WH, Gorstein F, Osteen KG. Suppression of metalloproteinases inhibits establishment of ectopic lesions by human endometrium in nude mice. J Clin Invest. 1997;99(12):2851–2857.

    Article  CAS  Google Scholar 

  9. Salata IM, Stojanovic N, Cajdler-Luba A, Lewandowski KC, Lewinski A. Gelatinase A (MM-2), gelatinase B (MM-9) and their inhibitors (TIMP 1, TIMP-2) in serum of women with endometriosis: Significant correlation between MMP-2, MMP-9 and their inhibitors without difference in levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in relation to the severity of endometriosis. Gynecol Endocrinol. 2008;24(6):326–330.

    Article  CAS  Google Scholar 

  10. Szamatowicz J, Laudanski P, Tomaszewska I. Matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1: a possible role in the pathogenesis of endometriosis. Hum Reprod. 2002;17(2):284–288.

    Article  CAS  Google Scholar 

  11. Lee DM, Lee TK, Song HB, Kim CH. The expression of matrix metalloproteinase-9 in human follicular fluid is associated with in vitro fertilization pregnancy. BJOG. 2005;112(7):946–951.

    Article  CAS  Google Scholar 

  12. The Practice Committee of the American Society for reproductive Medicine. Endometriosis and infertility. Fertil Steril. 2006;8(suppl):S156–S160.

    Google Scholar 

  13. Demacq C, de Souza AP, Machado AA, Gerlach RF, Tanus-Santos JE. Genetic polymorphism of matrix metalloproteinase (MMP)-9 does not affect plasma MMP-9 activity in healthy subjects. Clin Chem Acta. 2006;365(1–2):183–187.

    Article  CAS  Google Scholar 

  14. Gerlach RF, Demacq C, Jung K, Tanus-Santos JE. Rapid separation of serum does not avoid artificially higher matrix metalloproteinase (MMP)-9 levels in serum versus plasma. Clin Biochem. 2007;40(1–2):119–123.

    Article  CAS  Google Scholar 

  15. Di Carlo C, Bonifacio M, Tommaselli GA, Bifulco G, Guerra G, Nappi C. Metalloproteinases, vascular endothelial growth factor, and angiopoietin 1 and 2 in eutopic and ectopic endometrium. Fertil Steril, 2009;91(6):2315–2323.

    Article  Google Scholar 

  16. Iurlaro M, Loverro G, Vacca A, et al. Angiogenesis extent and expression of matrix metalloproteinase-2 and -9 correlate with upgrading and myometrial invasion in endometrial carcinoma. Eur J Clin Invest. 1999;29(9):793–801.

    Article  CAS  Google Scholar 

  17. Huang HF, Hong LH, Tan Y, Sheng JZ. Matrix metalloproteinase 2 is associated with changes in steroid hormones in the sera and peritoneal fluid of patients with endometriosis. Fertil Steril. 2004;81(5):1235–1239.

    Article  CAS  Google Scholar 

  18. Chung HW, Lee JY, Moon HS, et al. Matrix metalloproteinase-2, membranous type 1 matrix metalloproteinase, and tissue inhibitor of metalloproteinase-2 expression in ectopic and eutopic endometrium. Fertil Steril. 2002;78(4):787–795.

    Article  Google Scholar 

  19. Simpson ER, Misso M, Hewitt KN, et al. Estrogen—the good, the bad, and the unexpected. Endocr Rev. 2005;26(3):322–330.

    Article  CAS  Google Scholar 

  20. D’Ascenzo S, Giusti I, Millimaggi D, et al. Intrafollicular expression of matrix metalloproteinases and their inhibitors in normally ovulating women compared with patients undergoing in vitro fertilization treatment. Eur J Endocrinol. 2004;151(1):87–91.

    Article  Google Scholar 

  21. Shibahara H, Suzuki T, Kikuchi K, Hirano Y, Suzuki M. Serum matrix metalloproteinase and tissue inhibitor of metalloproteinase concentrations in infertile women achieved pregnancy following IVF-ET. Am J Reprod Immunol. 2005,54(4):186–192.

    Article  CAS  Google Scholar 

  22. Campos Petean C, Ferriani RA, dos Reis RM, de Moura MD, Jordão AA Jr, Navarro PA. Lipid peroxidation and vitamin E in serum and follicular fluid of infertile women with peritoneal endometriosis submitted to controlled ovarian hyperstimulation: a pilot study. Fertil Steril. 2008,90(6):2080–2085.

    Article  Google Scholar 

  23. Barcelos ID, Vieira RC, Ferreira EM, Martins WP, Ferriani RA, Navarro PA. Comparative analysis of spindle and chromosome configuration of in vitro-matured oocytes from patients with endometriosis and from control subjects: a pilot study. Fertil Steril. 2009;92(5):1749–1752.

    Article  Google Scholar 

  24. Barnhart K, Dunsmoor-Su R, Coutifaris C. Effect of endometriosis on in vitro fertilization. Fertil Steril. 2002;77(6):1148–1155.

    Article  Google Scholar 

  25. Al-Fadhli R, Kelly SM, Tulandi T, Tanr SL. Effects of different stages of endometriosis on the outcome of in vitro fertilization. J Obstet Gynaecol Can. 2006;28(10):888–891.

    Article  Google Scholar 

  26. Brizek CL, Schlaff S, Pellegrini VA, Frank JB, Worrilow KC. Increased incidence of aberrant morphological phenotypes in human embryogenesis—an association with endometriosis. J Assist Reprod Genet. 1995;12(2):106–112.

    Article  CAS  Google Scholar 

  27. Pellicer A, Oliveira N, Ruiz A, Remohí J, Simón C. Exploring the mechanism(s) of endometriosis-related infertility: an analysis of embryo development and implantation in assisted reproduction. Hum Reprod. 1995;10(suppl 2) 91–97.

    Article  Google Scholar 

  28. Pellicer A, Navarro J, Bosch E, et al. Endometrial quality in infertile women with endometriosis. Ann N Y Acad Sci. 2001;943:122–130.

    Article  CAS  Google Scholar 

  29. Katsoff B, Check JH, Davies E, Wilson C. Evaluation of the effect of endometriosis on oocyte quality and endometrial environment by comparison of donor and recipient outcomes following embryo transfer in a shared oocyte program. Clin Exp Obstet Gynecol. 2006;33(4):201–202.

    CAS  PubMed  Google Scholar 

  30. Lebovic DI, Mueller MD, Taylor RN. Immunobiology of endometriosis. Fertil Steril. 2001;75(1):1–10.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Paula Andrea Navarro MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Malvezzi, H., Aguiar, V.G., Paz, C.C.P.d. et al. Increased Circulating MMP-2 Levels in Infertile Patients With Moderate and Severe Pelvic Endometriosis. Reprod. Sci. 20, 557–562 (2013). https://doi.org/10.1177/1933719112459234

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719112459234

Keywords

Navigation