PURPOSE: To assess levels of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) in follicular fluids and sera of female patients undergoing in vitro fertilization (IVF) treatment, and discover the role of MMPs in IVF outcome prediction. METHODS: Sera and follicular fluids were obtained from 58 female patients treated for infertility by IVF. Twenty-nine of them became pregnant after the embryo-transfer; another 29 were not successful in IVF and did not conceive. Forty female non-pregnant blood donors and 38 healthy pregnant patients in the first trimester after the physiological conception were examined as control groups. MMP-2 and MMP-9 were quantitively assessed using enzyme-linked immunosorbent assay. RESULTS: IVF females successfully conceiving after the IVF have shown the highest MMP-9 concentrations in sera (833.5 {686.0;958.7} ng/mL) and follicular fluids (9.6 {6.0; 17.0} ng/mL) compared to all other examined cohorts. Different behavior of MMP-2 and MMP-9 during the artificial ovulation was confirmed, because only MMP-9 has shown a vast difference between serum and follicular concentrations. CONCLUSIONS: MMP-9 could be a good predictor of the successful IVF outcome (pregnancy), which was proven for serum as well as follicular MMP-9 levels.

General University Hospital and 1st Faculty of Medicine of Charles University Prague U nemocnice 2 128 00 Prague 2 Czech Republic

Zobrazit více v PubMed

Baka S, Zourla K, Kouskouni E, Makrakis E, Demeridou S, Tzanakaki D, Hassiakos D, Creatsas G. Matrix metalloproteinases 2 and 9 and their tissue inhibitors in the follicular fluid of patients with polycystic ovaries undergoing in vitro fertilisation. In Vivo. 2010;24(3):293–6. PubMed

Baka S, Zourla K, Malamitsi-Puchner A, Makrakis E, Kaparos G, Demeridou S, Moustakarias T, Tzanakaki D, Hassiakos D, Kouskouni E. Intrafollicular levels of matrix metalloproteinases-2 and -9 in patients with polycystic ovaries are not associated with pregnancy rate during IVF cycle. In Vivo. 2009;23(1):89–92. PubMed

Bischof P, Meisser A, Campana A. Control of MMP-9 expression at the maternal-fetal interface. J Reprod Immunol. 2002;55(1–2):3–10. doi: 10.1016/S0165-0378(01)00142-5. PubMed DOI

Curry TE, Jr, Song L, Wheeler SE. Cellular localization of gelatinases and tissue inhibitors of metalloproteinases during follicular growth, ovulation, and early luteal formation in the rat. Biol Reprod. 2001;65(3):855–65. doi: 10.1095/biolreprod65.3.855. PubMed DOI

Curry TE, Jr, Osteen KG. The matrix metalloproteinase system: changes, regulation, and impact throughout the ovarian and uterine reproductive cycle. Endocr Rev. 2003;24(4):428–65. doi: 10.1210/er.2002-0005. PubMed DOI

D’Ascenzo S, Giusti I, Millimaggi D, Marci R, Tatone C, Colonna RC, Moscarini M, Pavan A, 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. doi: 10.1530/eje.0.1510087. PubMed DOI

Dubois B, Arnold B, Opdenakker G. Gelatinase B deficiency impairs reproduction. J Clin Invest. 2000;106(5):627–628. doi: 10.1172/JCI10910. PubMed DOI PMC

Eng J. ROC analysis: web-based calculator for ROC curves. Baltimore: Johns Hopkins University, 2006. Available from: http://www.jrocfit.org.

Fu J, Wang XJ, Wang YW, Sun J, Gemzell-Danielsson K, Sun XX. The influence of early cleavage on embryo developmental potential and IVF/ICSI outcome. J Assist Reprod Genet. 2009;26(8):437–41. doi: 10.1007/s10815-009-9342-6. PubMed DOI PMC

Gomes VA, Vieira CS, Jacob-Ferreira AL, Belo VA, Soares GM, Fernandes JB, Ferriani RA, Tanus-Santos JE. Imbalanced circulating matrix metalloproteinases in polycystic ovary syndrome. Mol Cell Biochem. 2011;353(1–2):251–7. doi: 10.1007/s11010-011-0793-6. PubMed DOI

Gottsch ML, Kirk EA, Murdoch WJ. Role of matrix metalloproteinase 2 in the ovulatory folliculo-luteal transition of ewes. Reproduction. 2002;124:347–352. doi: 10.1530/rep.0.1240347. PubMed DOI

Isaka K, Nishi H, Nakai H, Nakada T, Feng Li Y, Ebihara Y, Takayama M. Matrix metalloproteinase-26 is expressed in human endometrium but not in endometrial carcinoma. Cancer. 2003;97(1):79–89. doi: 10.1002/cncr.11030. PubMed DOI

Jovanović M, Stefanoska I, Radojcić L, Vićovac L. Interleukin-8 (CXCL8) stimulants trophoblast cell migration and invasion by increasing levels of matrix metalloporteinase (MMP)2 and (MMP)9 and integrin alpha5 and beta1. Reproduction. 2010;139(4):789–798. doi: 10.1530/REP-09-0341. PubMed DOI

Koucký M, Germanová A, Kalousová M, Hill M, Cindrová-Davies T, Pařízek A, Svarcová J, Zima T. Low maternal serum matrix metalloproteinases (MMP)-2 concentrations are associated with preterm labor and fetal inflammatory response. J Perinat Med. 2010;38(6):589–596. doi: 10.1515/jpm.2010.092. PubMed DOI

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):946–51. doi: 10.1111/j.1471-0528.2005.00574.x. PubMed DOI

Liu B, Cai LY, Lv HM, Xia L, Zhang YJ, Zhang HX, Guan YM. Raised serum levels of matrix metalloproteinase-9 in women with polycystic ovary syndrome and its association with insulin-like growth factor binding protein-1. Gynecol Endocrinol. 2008;24(5):285–8. doi: 10.1080/09513590802056995. PubMed DOI

Naruse K, Lash GE, Innes BA, Otun HA, Searle RF, Robson SC, Bulmer JN. Localization of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitors for MMPs (TIMPs) in uterine natural killer cells in early human pregnancy. Hum Reprod. 2009;24(3):553–61. doi: 10.1093/humrep/den408. PubMed DOI

Ny T, Wahlberg P, Brändström IJ. Matrix remodeling in the ovary: regulation and functional role of the plasminogen activator and matrix metalloproteinase systems. Mol Cell Endocrinol. 2002;187(1–2):29–38. doi: 10.1016/S0303-7207(01)00711-0. PubMed DOI

Ogiwara K, Takano N, Shinohara M, Murakami M, Takahashi T. Gelatinase A and membrane-type matrix metalloproteinases 1 and 2 are responsible for follicle rupture during ovulation in the medaka. Proc Natl Acad Sci U S A. 2005;102(24):8442–7. doi: 10.1073/pnas.0502423102. PubMed DOI PMC

O’Sullivan MJB, Stamoui A, Thomas ES, Richardson MC. Gonadotropin regulation of production of tissue inhibitor of metalliproteinases and by luteinized human granulated cells a potential mechanism for luteal rescue. Mol Hum Reprod. 1997;3:405–14. doi: 10.1093/molehr/3.5.405. PubMed DOI

Page-McCaw A, Ewald AJ, Werb Z. Matrix metalloproteinases and regulation of tissue remodeling. Nat Rev Mol Cell Biol. 2007;8(3):221–233. doi: 10.1038/nrm2125. PubMed DOI PMC

Riley SC, Gibson AH, Leask R, Mauchline DJW, Pedersen HG, Watson ED. Secretion of matrix metalloproteinases 2 and 9 and tissue inhibitor of metalloproteinases into follicular fluid during follicle development in equine ovaries. Reproduction. 2001;121:553–560. doi: 10.1530/rep.0.1210553. PubMed DOI

Russell L, Salamunsen LA, Findlay LR. Immunization against the N-terminal peptide of the inhibin alphaY3-subunit (Alpha N) disrupts tissue remodeling and the increase in matrix metalloproteinase-2 during ovulation. Endocrinology. 1995;136:3657–3664. doi: 10.1210/en.136.8.3657. PubMed DOI

Seval Y, Cakmak H, Kayisli UA, Arici A. Estrogen-mediated regulation of p38 mitogen-activated protein kinase in human endometrium. J Clin Endocrinol Metab. 2006;91(6):2349–57. doi: 10.1210/jc.2005-2132. PubMed DOI

Sternlicht MD, Werb Z. How matrix metalloproteinases regulate cell behavior. Ann Rev Cell Dev Biol. 2001;17:463–516. doi: 10.1146/annurev.cellbio.17.1.463. PubMed DOI PMC

Tsafriri A, Reich R. Molecular aspects of mammalian ovulation. Exp Clin Endocrinol Diabetes. 1999;107(1):1–11. doi: 10.1055/s-0029-1212066. PubMed DOI