Intrafollicular interleukin-8, interleukin-12, and adrenomedullin are the promising prognostic markers of oocyte and embryo quality in women with endometriosis

Abstract

Purpose The study aimed to investigate key intrafollicular prognostic factors among various cytokines and angiogenic molecules for prediction of mature oocytes and good-quality embryos in women with endometriosis undergoing in vitro fertilization (IVF). Methods Paired follicular fluid and serum samples were collected from 200 women with advanced stage endometriosis and 140 normal ovulating women during oocyte retrieval. The concentrations of cytokines (pro-inflammatory: IL-1β, TNF-α, IL-2, IL-8, IL-12, IFN-γ; anti-inflammatory: IL-4, IL-6, IL-10) and angiogenic molecules (vascular endothelial growth factor (VEGF), adrenomedullin, angiogenin) were determined in follicular fluid and serum using ELISA. Expression of these molecules was subjected to multivariate analysis for the identification of major predictive markers of oocyte and embryo quality. Receiver operating characteristic (ROC) curve was applied to determine the best cutoff point for the discrimination between mature and immature oocytes in these women. Results Significant increases in levels of cytokines and angiogenic molecules were observed in women with endometriosis compared to controls (P < 0.001). From the validated partial least squares-discriminant analysis (PLS-DA) model, IL-8, IL-12, and adrenomedullin were identified as the most important factors contributing to endometriosis and were negatively associated with oocyte maturity and embryo quality. Conclusion The levels of IL-8, IL-12, and adrenomedullin may be good indicators of embryo and oocyte quality in endometriosis patients undergoing IVF. Further studies are necessary to ascertain the potential of these markers for oocyte and embryo developmental competence which may help improve the chances of a successful IVF in endometriosis patients.

Is the oocyte quality affected by endometriosis? A review of the literature

“…More recently, two prospective case-control studies found similar results and confirmed significantly lower number of mature oocytes and lower fertilization rates in patients with endometriosis compared to patients with other causes of infertility [24, 74]. In both studies, unfortunately, no information regarding previous surgical treatments received is provided.…”

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

“…Therefore, no conclusions can be made yet about possible correlations between T and B cells in FF, endometriosis and the effect on folliculogenesis, oocyte maturation and infertility. Singh et al (2016) reported an increase in the levels of pro-inflammatory (IL1B, TNFa, IL2, IL8, IL12) and anti-inflammatory (IL4, IL6 and IL10) cytokines in FF of patients with endometriosis (grade III/IV) undergoing IVF as compared with patients with tubal factor infertility (Box 2). The percentage of mature oocyte and goodquality embryos was significantly lower in endometriosis as compared with controls.…”

Etiopathogenesis of endometriosis-associated infertility (a review)

“…У фолликулов имеется метаболически активное микроокружение, в состав которого входят стероидные гормоны, факторы роста, цитокины, свободные радикалы и антиоксиданты наряду с другими элементами, продуцирующимися гранулезными клетками, эндотелиальными клетками и лейкоцитами. В большей степени снижение качества ооцитов коррелирует с повышением содержания IL-8, IL-12, ADM, при этом экспрессия остальных провоспалительных цитокинов также существенно повышена [38]. Один из маркеров окислительного стресса, обнаруженных в перифолликулярной жидкости -миелопероксидаза, может служить потенциальным таргетом при попытках улучшения качества ооцита в программах ВРТ.…”