Intrafollicular inflammatory cytokines but not steroid hormone concentrations are increased in naturally matured follicles of women with proven endometriosis

Abstract

Purpose The aim of this study was to assess whether the intrafollicular cytokine profile in naturally developed follicles is different in women with endometriosis, possibly explaining the lower reproductive outcome in endometriosis patients. Methods A matched case-control study was conducted at a university-based infertility and endometriosis centre. The study population included 17 patients with laparoscopically and histologically confirmed endometriosis (rAFS stages II-IV), each undergoing one natural cycle IVF (NC-IVF) treatment cycle between 2013 and 2015, and 17 age-matched NC-IVF women without diagnosed endometriosis (control group). Follicular fluid and serum was collected at the time of follicle aspiration. The concentrations of inflammatory cytokines (IL-1β, IL-6, IL-8, IL-15, IL-18, TNF-α) and hormones (testosterone, estradiol, AMH) were determined in follicular fluid and serum by single or multiplexed immunoassay and compared between both groups. Results In the follicular fluid, IL-1β and IL-6 showed significantly (P < 0.001 and 0.01, respectively) higher median concentrations in the endometriosis group than in the control group and a tendency towards endometriosis severity (rAFS stage) dependence. The levels of the interleukins detectable in follicular fluid were significantly higher than those in the serum (P < 0.01). Follicular estradiol concentration was lower in severe endometriosis patients than in the control group (P = 0.036). Follicular fluid IL-1β and IL-6 levels were not correlated with estradiol in the same compartment in neither patient group. Conclusions In women with moderate and severe endometrioses, some intrafollicular inflammatory cytokines are upregulated and not correlated with intrafollicular hormone concentrations. This might be due to the inflammatory microenvironment in endometriosis women, affecting follicular function and thereby possibly contributing to the reproductive dysfunction in endometriosis.

Is there an immune modulating role for follicular fluid in endometriosis? A narrative review

“…The results of the study by Pellicer et al were confirmed in the study of Wu et al (2017) in natural cycle IVF in women with moderate-to-severe endometriosis. On the other hand, Opøien et al (2013) found no difference in cytokine levels (IL1B, IL6, IL8, IL10, IL12 and TNFa) in the leading follicle adjacent to endometriomas.…”

“…Possibly, the higher levels of FF cytokines are produced by the granulosa cells or the FF immune cells which might be more activated in endometriosis. However, the activity of these FF immune cells is yet to be analyzed in endometriosis patients (Wu et al 2017).…”

Endometriosis Lowers the Cumulative Live Birth Rates in IVF by Decreasing the Number of Embryos but Not Their Quality

“…Indeed, follicular fluid is an active microenvironment which has a critical role in oocyte growth and maturation. Differences in the concentration of inflammatory cytokines [31][32][33] and oxidative stress markers [34,35] in follicular fluid have been reported between women with and without endometriosis. Endometriosis could also affect the metabolic processes, thereby altering the microenvironment of the follicle and the oocyte development.…”

Endometriosis and oocytes (a review)

“…В нескольких исследованиях показано, что эндометриоз яичников и других участков тазовой области может отрицательно влиять на стероидогенез гранулезных клеток (ГК) яичников, уменьшая экспрессию ароматазы P450, являющейся ключевым ферментом синтеза эстрогенов, согласно теории двух клеток, и выработку 17β-эстрадиола (E 2 ) [10,23]. Эстрадиол, в свою очередь, имеет решающее значение для развития фолликулов и образования компетентного ооцита, способного достичь стадии МII и оплодотвориться [7].…”