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.
Similar content being viewed by others
References
Giudice LC, Kao LC. Endometriosis. Lancet. 2004;364(9447):1789–1799.
Koninckx PR, Kennedy SH, Barlow DH. Endometriotic disease: the role of peritoneal fluid. Hum Reprod Update. 1998;4(5):741–751.
Van Langendonckt A, Casanas-Roux F, Donnez J. Oxidative stress and peritoneal endometriosis. Fertil Steril 2002;77(5):861–870.
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.
Nagase H, Visse R, Murphy G. Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res. 2006;69(3):562–573.
Osteen KG, Yeaman GR, Bruner-Tran KL. Matrix metalloproteinases and endometriosis. Semin Reprod Med. 2003;21(2):155–164.
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.
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.
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.
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.
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.
The Practice Committee of the American Society for reproductive Medicine. Endometriosis and infertility. Fertil Steril. 2006;8(suppl):S156–S160.
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.
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.
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.
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.
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.
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.
Simpson ER, Misso M, Hewitt KN, et al. Estrogen—the good, the bad, and the unexpected. Endocr Rev. 2005;26(3):322–330.
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.
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.
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.
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.
Barnhart K, Dunsmoor-Su R, Coutifaris C. Effect of endometriosis on in vitro fertilization. Fertil Steril. 2002;77(6):1148–1155.
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.
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.
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.
Pellicer A, Navarro J, Bosch E, et al. Endometrial quality in infertile women with endometriosis. Ann N Y Acad Sci. 2001;943:122–130.
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.
Lebovic DI, Mueller MD, Taylor RN. Immunobiology of endometriosis. Fertil Steril. 2001;75(1):1–10.
Author information
Authors and Affiliations
Corresponding author
Rights 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
Published:
Issue Date:
DOI: https://doi.org/10.1177/1933719112459234