An estimated 48 to 72 million couples worldwide suffer from infertility, around half of which lack an explanation for their failure in conceiving. Among the reasons leading to female subfertility are primary and secondary ovulatory dysfunction, such as ovarian insufficiency or polycystic ovary syndrome (PCOS).
Assisted reproductive technologies (ART), including in vitro-fertilization (IVF) and intracytoplasmic sperm injection (ICSI), offer promise but it is essential to understand which factors may optimise the outcome of these as live birth rate (LBR) is still observed in only 36% to 50% of attempts.
The follicular fluid (FF) surrounding the oocyte (immature egg which develops to maturity within a follicle) creates a special microenvironment for oocyte maturation and development. Alterations in the microenvironment of oocytes in the FF have been suggested to influence oocyte quality from maturation to fertilisation, early embryo development, and subsequent pregnancy course.
Experimental and clinical studies indicate that growth and fertility are strongly affected by trace element (TE) supply. In particular copper (Cu), selenium (Se), and zinc (Zn) have emerged as the most essential micronutrients for both female and male fertility.
Yet knowedge of the molecular details of Se supply to follicles is limited, and the interaction of the essential micronutrients with oocyte maturation is poorly understood, especially in relation to PCOS. Improved knowledge and a better database may support attempts to improve the selection of the optimal oocyte for fertilisation.
In order to close some of the research gap, the current study determined Cu, Se, and Zn along with additional informative protein biomarkers of Se status in FF of women with or without a diagnosis of PCOS undergoing ART and compared the results to corresponding serum concentrations to identify potential interactions.
Serum and FF samples from women undergoing ART at the Kinderwunsch Institut Schenk GmbH in Dobl, Austria, were collected, stored, and retrieved from the Biobank Graz of the Medical University of Graz, Austria.
Concentrations of TE were measured by total reflection X-ray fluorescence. Extracellular glutathione peroxidase 3 (GPX3) and selenoprotein P (SELENOP) were determined as additional Se biomarkers. Corresponding serum and follicular fluid (FF) samples were available from women with (n = 20) and without (n = 20) PCOS diagnosis undergoing hormone treatment within the ART procedure, respectively, and FF samples were classified into five groups based on morphological assessment.
Serum showed higher TE concentrations than FF, and TE levels correlated positively between both matrices. Individual FF from the same women showed surprisingly high variability in TE concentration, and follicles without oocytes displayed the lowest TE concentrations. Both Se biomarkers GPX3 and SELENOP were present in FF and correlated positively to Se concentrations.
Some notable relationships were observed between morphokinetic parameters, TE concentrations, and GPX3 activity. A slightly depressed serum Zn concentration was observed in PCOS.
The researchers conclude that these results indicate a direct relationship between TE in serum and FF, positive correlations between the three Se biomarkers in FF, and high variability between the FF from the same woman with the lowest TE concentrations in the follicles with the poorest quality.
The report concludes: "There is a direct relationship between TE in serum and FF and that, in particular, the three biomarkers of Se status correlate positively in FF, highlighting their similar suitability for follicle-specific Se status assessment.
"The mechanisms connecting TE in serum and FF are poorly understood, in particular in view of the high variability between different FF obtained from the same woman at the same time. As the FF with the poorest quality showed a trend to the lowest TE concentrations, we conclude that TE deficiencies should be avoided during ART and oocyte development.
"It is likely that FF does not control their TE status by simple filtration of serum but rather by highly regulated and feedback-controlled mechanisms likely involving endocrine effects on uptake and maintenance of TE and the TE-dependent proteins and enzymes to ensure an optimal microenvironment for oocyte development."
Schmalbrock, L.J.; Weiss, G.; Rijntjes, E.; Reinschissler, N.; Sun, Q.; Schenk, M.; Schomburg, L.
"Pronounced Trace Element Variation in Follicular Fluids of Subfertile Women Undergoing Assisted Reproduction"