Assessment of VEGF and TNF-alpha levels in patients with an unexpectedly poor and suboptimal response during the treatment of infertility using ART methods

Abstract

Introduction: The problem of infertility treatment currently has medical, socio-demographic and economic significance. Progress in the field of reproductive technologies has improved the situation, but the issue has not yet been completely resolved. Infertility is diagnosed in 8-12% of couples of reproductive age; in Russia this figure exceeds 15%, and, according to WHO, it is a critical level. It is known that immunological factors can disrupt the reproductive process at the stages of folliculogenesis, ovulation, and implantation. These include vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α) and others. The aim of this study: to assess the levels of VEGF and TNF-α in women with different outcomes of hormonal stimulation of the ovaries during the treatment of infertility using ART methods.

Materials and methods: Based on voluntary informed consent, a simple open comparative randomized study was conducted with the participation of 71 women in the Volgograd region undergoing infertility treatment using ART methods. Inclusion criteria were the age up to 42 years inclusive and the anti-Mullerian hormone level over 1.2 ng/mL. Before ovulation stimulation with gonadotropins, data on ovarian reserve parameters were collected. Based on the results of stimulation, women were divided into 3 groups: Group 1 – with high and normal ovarian response – 10 or more oocytes were obtained (control group); Group 2 – with suboptimal ovarian response – 5-9 oocytes received; Group 3 – with a poor response – 4 or less oocytes were received. After venipuncture, which was performed in preparation for standard anesthesia, VEGF and TNF-α were quantitatively determined in the blood plasma using an enzyme-linked immunosorbent assay.

Results: The study results showed a statistically significant difference in VEGF levels in follicular fluid and serum between the groups of women with high/normal, suboptimal and poor ovarian response to gonadotropin stimulation. A higher level of this marker was observed in the serum of patients with high/normal and poor response – 48.15±4.23 and 41.29±8.26 pg/mL, respectively, while in women with a suboptimal response a lower VEGF level was determined –29.19±3.41 pg/mL. The levels of VEGF in the follicular fluid of women included in the high/normal, suboptimal and poor response groups were 35.95±3.20; 27.42±2.53 and 41.22±3.23 pg/mL, respectively (Table 1). As for TNF-α, its serum level in women with a high and normal response was lower than in the patients with a suboptimal response. In the follicular fluid of patients of group 3, there was a higher level of TNF-α, compared to groups 1 and 2, where the indicator was almost the same. However, the difference was not statistically significant.

Conclusions: Thus, VEGF is directly involved in the mechanisms of regulation of oocyte maturation and can be not only a marker of poor ovarian response, but also a predictor of unsatisfactory results of ovarian stimulation in the treatment of infertility using ART methods. TNF-alpha in follicular fluid does not have a statistically significant effect on follicle development in the treatment of infertility using assisted reproductive technologies.

Graphical Abstract