P-158 Quantitative metabolomic profiling of follicular fluid identifies oocyte quality related biomarkers from infertile patients
Authors: Fiscus J , Daverio Z , Battaglia A  G , Drevet Mulard E , Damblon C , Fraison E , Salle B , Panthu B , Labrune E 
Published: July 2024

Abstract

Study question
Is whether there is a metabolomic signature in the follicular fluid depending on oocyte quality and whether infertility may impact on this quality?

Summary answer
46 metabolites were quantified via nuclear magnetic resonance spectroscopy in the follicular fluid, and each metabolite that was a biomarker of oocyte quality was pathology-specific.

What is known already
Literature confirmed that metabolomics had been valuable for exploring follicular fluid and the search for nutritive and non-nutritive biomarkers. There are currently no data in the literature concerning the homeostasis of this follicular fluid, and two options are possible: this fluid is a continuum of blood plasma, or it has its own homeostasis. Studies have highlighted follicular fluid qualitative and quantitative alterations in the metabolome due to one specific infertility pathology footprint and correlated in some instances to outcome measures of in vitro fertilization success but samples are pooled and there are no information concerning quality and competence oocyte assessment.

Study design, size, duration
61 infertile patients who underwent in vitro fertilization (IVF) treatment with intracytoplasmic sperm injection (ICSI) from Femme Mère Enfant hospital (Bron, France) between 6th april 2022 and 12th may 2022 were included.

Participants/materials, setting, methods
61 follicular fluids were collected individually and used for metabolomic profiling by nuclear magnetic resonance spectroscopy. A total of 46 metabolites were quantified. Metabolite concentrations in follicular fluid were compared with serum concentrations.Oocyte was considered mature if it has its first polar body and competent if it was able to develop into a blastocyst after culturing. In vitro fertilized oocytes were cultured and monitored with time-lapses incubation technology until day 5 or 6.

Main results and the role of chance
For 23 metabolites out of 46, follicular fluid exhibited lower concentrations than serum. Glucose and glutamine, which are among the most abundant metabolites, decreased by 54% (not significant) and 47% (P &lt; 0.05) respectively. 7 metabolites exhibited higher concentrations in the follicular fluid than in the serum. An 85%-increase in lactate and a more-than-tenfold increase in pyruvate were noted (P &lt; 0.05). The reverse ratios of lower substrates such as glucose and glutamine and higher waste products like lactate and pyruvate imply that the follicular fluid functions as a homeostatic compartment, being more influenced by exchange within follicular cells than by serum equilibration. The detected metabolic signatures of oocyte maturity and competence were all specific to the patient infertility-related pathology. The follicular fluid concentrations of aspartate, glucose, methionine and methylmalonate were significantly correlated to oocyte maturity in the control group (P &lt; 0.05). For patients having endometriosis, asparagine concentration was significantly decreased by oocyte maturity (P &lt; 0.05). For patients with diminished ovarian reserve, acetone concentration was significantly decreased by oocyte maturity (P &lt; 0.05). The concentration of aspartate, that correlated with oocyte maturity, was also slightly decreased by oocyte competence, and for the patients with endometriosis the concentration of threonine was decreased by 30% by oocyte competence (P &lt; 0.05).

Limitations, reasons for caution
Although 46 metabolites were well quantified, each metabolite that was a biomarker of oocyte maturity or competence was pathology specific. One major reason would be the high metabolite concentration variation observed between the different infertilities. This study indicates that the diagnosis of patients according to their infertility must be prior.

Wider implications of the findings
This study underlines the potential of follicular fluid metabolomics as a diagnostic avenue for oocyte-related becoming in order to enhance the selection of oocytes and improve outcomes in assisted reproductive and preservation fertility techniques.

Trial registration number
not applicable