Follicular Fluid: A Powerful Tool for the Understanding and Diagnosis of Polycystic Ovary Syndrome

Abstract

Polycystic ovary syndrome (PCOS) represents one of the leading causes of anovulatory infertility and affects 5% to 20% of women worldwide. Until today, both the subsequent etiology and pathophysiology of PCOS remain unclear, and patients with PCOS that undergo assisted reproductive techniques (ART) might present a poor to exaggerated response, low oocyte quality, ovarian hyperstimulation syndrome, as well as changes in the follicular fluid metabolites pattern. These abnormalities originate a decrease of Metaphase II (MII) oocytes and decreased rates for fertilization, cleavage, implantation, blastocyst conversion, poor egg to follicle ratio, and increased miscarriages. Focus on obtaining high-quality embryos has been taken into more consideration over the years. Nowadays, the use of metabolomic analysis in the quantification of proteins and peptides in biological matrices might predict, with more accuracy, the success in assisted reproductive technology. In this article, we review the use of human follicular fluid as the matrix in metabolomic analysis for diagnostic and ART predictor of success for PCOS patients.

Volatilomics as an Emerging Strategy to Determine Potential Biomarkers of Female Infertility: A Pilot Study

“…Germ cell–somatic cell communication is possible due to follicular fluid (FF), a complex milieu. It includes a range of metabolites and allows for several reactions essential to oocyte development [ 12 , 50 ]. It is composed of metabolites produced in the follicular wall, transudates of plasma, and serum diffusion.…”

“…Additionally, substances derived from regional follicular metabolic processes and ovarian cell biological functions, such as granulosa and theca cells, also contribute to and change FF composition according to the oocyte’s needs. Therefore, the oocyte’s growth and differentiation in vivo are directly linked to this biological matrix [ 50 , 51 , 52 , 53 ]. Further research into conditions such as PCOS, endometriosis, and early ovarian failure will benefit from a thorough knowledge of FF, since it is a non-invasive matrix that provides biological insights into fertility, reflecting the changes in the patient’s microenvironment.…”

“…FF chemical and biomolecular hallmarks have sparked a great deal of attention, becoming a crucial source of knowledge and inspiring much research to find new targets for assessing oocyte development. Therefore, a detailed characterization and consideration of FF may identify potential metabolites that interfere with normal female function and promote infertility [ 50 , 52 , 53 , 54 ].…”

“…Metabolomics, a high-throughput technique, identifies various metabolic components in diverse biological matrixes. Untargeted metabolomics focuses on the dynamic adjustment of small molecules in response to an organismal disturbance, offering significant insights into the pathophysiology of various diseases and helping identify specific biomarkers [ 12 , 50 ]. These molecules are present in biological matrixes such as tissues, cells [ 10 , 50 , 55 , 56 ], blood, urine, plasma, serum, and FF [ 10 , 50 , 51 , 55 , 56 , 57 ] due to their medical and chemical signature, which allows for the quantitative measurement of the dynamic chemical reactions that take place in living systems in response to pathophysiological insults or genetic variations [ 10 , 50 , 55 , 56 ].…”

“…Untargeted metabolomics focuses on the dynamic adjustment of small molecules in response to an organismal disturbance, offering significant insights into the pathophysiology of various diseases and helping identify specific biomarkers [ 12 , 50 ]. These molecules are present in biological matrixes such as tissues, cells [ 10 , 50 , 55 , 56 ], blood, urine, plasma, serum, and FF [ 10 , 50 , 51 , 55 , 56 , 57 ] due to their medical and chemical signature, which allows for the quantitative measurement of the dynamic chemical reactions that take place in living systems in response to pathophysiological insults or genetic variations [ 10 , 50 , 55 , 56 ]. Volatilomics, a metabolomic subgroup that reflects biochemical metabolic activity and environmental influences, offers new insights into the physiological processes of several disorders [ 58 , 59 , 60 , 61 ].…”