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

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.

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.

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.

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. Similar content being viewed by others

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We thank Ms. Anne Vaucher for her support in performing the immunoassays. Author information Authors and Affiliations Corresponding author Ethics declarations The study was approved by the local ethical committee and informed written consent was obtained from all patients. Funding This work was financed by grant-in-aid for scientific research from the National Natural Science Foundation for the Youth of China (No. 81601240) and was supported by an unrestricted grant from the IBSA Institut Biochimique SA, Lugano, Switzerland. Conflict of interest The study was supported by an unrestricted research grant from the IBSA Institut Biochimique SA. The authors are clinically involved in the low-dose monofollicular stimulation and IVF therapies, using gonadotropins from all gonadotropin distributors on the Swiss market, including the IBSA Institut Biochimique SA. Rights and permissions About this article Cite this article Wu, G., Bersinger, N.A., Mueller, M.D. et al. Intrafollicular inflammatory cytokines but not steroid hormone concentrations are increased in naturally matured follicles of women with proven endometriosis. J Assist Reprod Genet 34, 357–364 (2017). https://doi.org/10.1007/s10815-016-0865-3 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s10815-016-0865-3