NMR metabolic profiling of follicular fluid for investigating the different causes of female infertility: a pilot study

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NMR metabolic profiling of follicular fluid revealed distinct metabolite differences between women with endometriosis or PCOS and controls, suggesting diagnostic biomarker potential for these conditions.

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This pilot study used 1H NMR spectroscopy to analyze follicular fluid metabolite profiles from 53 women undergoing IVF, grouped by infertility pathology (tubal disease, unexplained infertility, endometriosis, or PCOS). The authors found significant metabolic differences between control women and those with endometriosis and PCOS, while metabolite profiles could not significantly discriminate control participants from women with tubal disease or unexplained infertility. A key limitation was the small pilot design and the resulting inability to separate some groups. This paper is centrally about endometriosis — it specifically compares follicular fluid NMR metabolic profiles in IVF patients with endometriosis versus controls and reports significant metabolite differences.

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Abstract

INTRODUCTION: Several metabolomics studies have correlated follicular fluid (FF) metabolite composition with oocyte competence to fertilization, embryo development and pregnancy but there is a scarcity of research examining the metabolic effects of various gynaecological diseases. OBJECTIVES: In this study we aimed to analyze and correlate the metabolic profile of FF from women who were following in vitro fertilization (IVF) treatments with their different infertility pathologies. METHODS: We selected 53 women undergoing IVF who were affected by: tubal diseases, unexplained infertility, endometriosis, polycystic ovary syndrome (PCOS). FF of the study participants was collected at the time of oocytes retrieval. Metabolomic analysis of FF was performed by nuclear magnetic resonance (NMR) spectroscopy. RESULTS: FF presents some significant differences in various infertility pathologies. Although it was not possible to discriminate between FF of control participants and women with tubal diseases and unexplained infertility, comparison of FF metabolic profile from control women with patients with endometriosis and PCOS revealed significant differences in some metabolites that can be correlated to the causes of infertility. CONCLUSION: NMR-based metabolic profiling may be successfully applied to find diagnostic biomarkers for PCOS and endometriosis and it might be also used to predict oocyte developmental potential and subsequent outcome.
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Abstract

Introduction Several metabolomics studies have correlated follicular fluid (FF) metabolite composition with oocyte competence to fertilization, embryo development and pregnancy but there is a scarcity of research examining the metabolic effects of various gynaecological diseases.

Objectives

In this study we aimed to analyze and correlate the metabolic profile of FF from women who were following in vitro fertilization (IVF) treatments with their different infertility pathologies.

Methods

We selected 53 women undergoing IVF who were affected by: tubal diseases, unexplained infertility, endometriosis, polycystic ovary syndrome (PCOS). FF of the study participants was collected at the time of oocytes retrieval. Metabolomic analysis of FF was performed by nuclear magnetic resonance (NMR) spectroscopy.

Results

FF presents some significant differences in various infertility pathologies. Although it was not possible to discriminate between FF of control participants and women with tubal diseases and unexplained infertility, comparison of FF metabolic profile from control women with patients with endometriosis and PCOS revealed significant differences in some metabolites that can be correlated to the causes of infertility.

Conclusion

NMR-based metabolic profiling may be successfully applied to find diagnostic biomarkers for PCOS and endometriosis and it might be also used to predict oocyte developmental potential and subsequent outcome. Similar content being viewed by others

References

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Free Radical Biology and Medicine, 86, 295–307. https://doi.org/10.1016/j.freeradbiomed.2015.05.013. Zullo, F., Spagnolo, E., Saccone, G., Acunzo, M., Xodo, S., Ceccaroni, M., et al. (2017). Endometriosis and obstetrics complications: A systematic review and meta-analysis. Fertility and Sterility, 108(4), 667–672. https://doi.org/10.1016/j.fertnstert.2017.07.019. Funding The authors received no financial support for this study. Author information Authors and Affiliations Contributions SS, AI, and AO designed the study. AI selected the participants and executed oocyte retrieval. DP executed oocyte retrieval. AF identified oocytes in follicular fluid and executed their fertilization. PC selected the follicular fluids to be used for metabolomic analyses. CM performed the analysis of NMR data and multivariate analysis. LV run the NMR experiments. FC performed statistical analysis. AO, AI, and CM were responsible for conducting the study and writing the manuscript which was critically discussed, edited and approved by all co-authors. Corresponding author Ethics declarations Conflict of interest The authors declare no conflicts of interest. Research involving human rights All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional, national research committee and with the 1964 Helsinki Declaration and its later amendments. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Electronic supplementary material Below is the link to the electronic supplementary material. Rights and permissions About this article Cite this article Castiglione Morelli, M.A., Iuliano, A., Schettini, S.C.A. et al. NMR metabolic profiling of follicular fluid for investigating the different causes of female infertility: a pilot study. Metabolomics 15, 19 (2019). https://doi.org/10.1007/s11306-019-1481-x Received: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s11306-019-1481-x

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endometriosisinfertility

MeSH descriptors

Follicular Fluid Follicular Fluid Infertility, Female Adult Endometriosis Endometriosis Female Fertilization in Vitro Fertilization in Vitro Follicular Fluid Humans Infertility, Female Magnetic Resonance Imaging Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Magnetic Resonance Spectroscopy Metabolome Metabolome Metabolomics Metabolomics

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