Prognostic value of determination of matrix metalloproteinase-1 and tissue inhibitor of matrix metalloproteinase-1 in follicular fluid in patients in vitro fertilization programs

Aim. To determine the prognostic significance of matrix metalloproteinase-1 (MMP-1) and tissue metalloproteinase-1 inhibitor (TIMP-1) in the follicular fluid (FF) in patients with infertility to improve the effectiveness of in vitro fertilization (IVF) programs.

Materials and methods. A study of MMP-1 and TIMP-1 in the FF was conducted in 38 patients with infertility in IVF programs. According to the genesis of infertility, the patients were divided into 2 groups. The 1st (control) group included 20 patients with tubal-peritoneal infertility (code N97.1 according to the International Classification of Diseases of the 10th revision – ICD-10). The 2nd group (the main one) included 18 patients with tubal-endocrine infertility (ICD-10: N97.1, N97.0, N97.8). The choice of the ovulation stimulation protocol was made taking into account the anamnesis, previously applied protocols, control over the outcome and final result of IVF programs was developed: a protocol with gonadotropin-releasing hormone agonists was used in 20 patients, and a protocol with gonadotropin-releasing hormone antagonists was used in 18 patients. The effectiveness of IVF programs was 26.3%, the frequency of live births was 26.3%. During the puncture of the follicles, FF was taken and the levels of MMP-1 and TIMP-1 were determined in it by the method of quantitative solid-phase enzyme immunoassay of the sandwich type on an automatic flatbed photometer MultiskanFC (2012). The obtained information was subjected to statistical analysis using the Statistica 10.0 application program.

Results. The level of MMP-1 and TIMP-1 in the FF is an individual indicator and is associated with clinical and anamnestic characteristics. The average level of MMP-1 is 4.9 ng/ml. With negative IVF outcomes, it was 6.1±1.3 ng/ml, with positive outcomes – 1.4±0.1 ng/ml. The content of MMP-1 in women with tubal-peritoneal infertility genesis of 7.9±1.7 ng/ml indicates a residual inflammatory process in the follicle. The average level of TIMP-1 was 2462.2±64.3 ng/ml. The indicator increases: with age (2535.0±125.7 ng/ml), duration of infertility (2611.5±126.7 ng/ml), due to surgical interventions on the reproductive organs (2800±122.7 ng/ml) and in patients with tubal-endocrine genesis of infertility (2550±126.7 ng/ml), which indicates fibrosclerotic changes in the follicles and ovarian tissue.

Conclusion. The level of MMP-1 in the range of 1.3–1.4 ng/ml should be considered a criterion for the successful onset of pregnancy in IVF programs. The criterion of subclinical damage to the collagen matrix in the FF is the level of MMP-1 6.1 ng/ml or higher; it can be considered as an unfavorable prognostic factor for the outcome of IVF. The level of TIMP-1 in the range of 2400–2450 ng/ml should be considered a criterion for the successful onset of pregnancy in IVF programs. The probability of a negative outcome of IVF is in the range of 1500–2300 ng/ml (inability to level the effects of MMP-1 with these indicators), while the level of 2696 ng/ml and higher in tubal-endocrine genesis of infertility reflects a high degree of fibrosclerotic changes in ovarian tissue and can be considered as an unfavorable prognostic factor of IVF outcome.