Why Has Metabolomics So Far Not Managed to Efficiently Contribute to the Improvement of Assisted Reproduction Outcomes? The Answer through a Review of the Best Available Current Evidence

Charalampos Siristatidis, Konstantinos Dafopoulos, Michail Papapanou, Sofoklis Stavros, Abraham Pouliakis, Anna Eleftheriades, Tatiana Sidiropoulou, Nikolaos Vlahos, Charalampos Siristatidis, Konstantinos Dafopoulos, Michail Papapanou, Sofoklis Stavros, Abraham Pouliakis, Anna Eleftheriades, Tatiana Sidiropoulou, Nikolaos Vlahos

Abstract

Metabolomics emerged to give clinicians the necessary information on the competence, in terms of physiology and function, of gametes, embryos, and the endometrium towards a targeted infertility treatment, namely, assisted reproduction techniques (ART). Our minireview aims to investigate the current status of the use of metabolomics in assisted reproduction, the potential flaws in its use, and to propose specific solutions towards the improvement of ART outcomes through the use of the intervention. We used published reports assessing the role of metabolomic investigation of the endometrium, oocytes, and embryos in improving clinical outcomes in women undergoing ART. We initially found that there is no evidence to support that fertility outcomes can be improved through metabolomics profiling. In contrast, it may be helpful for understanding and appraising the nutritional environment of oocytes and embryos. The causes include the different infertility populations, the difference between animals and humans, technical limitations, and the great heterogeneity in the variables employed. Suggested steps include the standardization of variables of the method itself, the universal creation of a panel where all biomarkers are stored concerning specific infertile populations with different phenotypes or etiologies, specific bioinformatics contribution, significant computing power for data processing, and importantly, properly conducted trials.

Keywords: assisted reproductive techniques; biomarkers; diagnosis; follicular fluid; in vitro fertilization; metabolomics.

Conflict of interest statement

M.P. reports a grant from the World Health Organization outside the submitted work. The rest of the authors have nothing to disclose.

Figures

Figure 1
Figure 1
A summary of how a large database of metabolomics biomarkers measured in different IVF populations could potentially elucidate role of metabolomics in IVF and improve IVF outcomes. Abbreviations: IVF, in vitro fertilization, RCTs, randomized controlled trials.

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