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

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Intrafollicular interleukin-8, interleukin-12, and adrenomedullin levels were identified as key factors negatively associated with oocyte maturity and embryo quality in women with endometriosis undergoing IVF.

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This study measured intrafollicular and systemic concentrations of multiple cytokines and angiogenic molecules in paired follicular fluid and serum samples from 200 women with advanced-stage endometriosis and 140 normal ovulating controls undergoing oocyte retrieval for IVF, using ELISA and multivariate (PLS-DA) analyses plus ROC curves. Compared with controls, women with endometriosis had significantly higher levels of several cytokines and angiogenic factors, and IL-8, IL-12, and adrenomedullin emerged as the most important contributors to endometriosis and were negatively associated with oocyte maturity and embryo quality. The main caveat is that the study does not establish biological causality and focuses on prognostic associations in this IVF setting (including advanced-stage disease). This paper is centrally about endometriosis — it identifies IL-8, IL-12, and adrenomedullin as prognostic markers linked to oocyte and embryo quality in women with endometriosis undergoing IVF.

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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.
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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. Similar content being viewed by others

References

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Acknowledgments The first author is grateful to the Government of India, Indian Council of Medical Research for financial support under the ICMR-JRF scheme. The authors are grateful to all the volunteers who participated in this study, as well as to Gunja Bose from IRM, Kolkata for helping in collection of samples. Author information Authors and Affiliations Corresponding author Additional information Capsule Levels of IL-8, IL-12, and adrenomedullin as good indicators of embryo and oocyte quality in women with endometriosis undergoing IVF Rights and permissions About this article Cite this article Singh, A.K., Dutta, M., Chattopadhyay, R. et al. Intrafollicular interleukin-8, interleukin-12, and adrenomedullin are the promising prognostic markers of oocyte and embryo quality in women with endometriosis. J Assist Reprod Genet 33, 1363–1372 (2016). https://doi.org/10.1007/s10815-016-0782-5 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s10815-016-0782-5

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Condition tags

endometriosis

MeSH descriptors

Adrenomedullin Endometriosis Fertilization in Vitro Interleukin-12 Interleukin-8 Adrenomedullin Adult Embryo Transfer Embryo Transfer Endometriosis Endometriosis Female Follicular Fluid Follicular Fluid Humans Infertility, Female Infertility, Female Infertility, Female Interleukin-12 Interleukin-8

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