Anti-oxidative function of follicular fluid HDL and outcomes of modified natural cycle-IVF

Abstract

High density lipoproteins (HDL) are the main cholesterol carriers in follicular fluid (FF), the natural environment of oocyte development. Additionally, HDL have critical biological functions such as anti-oxidative capacity, which have not been studied in reproduction. Therefore, this study aimed to investigate whether the anti-oxidative function of FF-HDL is associated with fertility outcomes. From 253 women undergoing modified natural cycle (MNC)- IVF at a single academic centre FF and plasma were collected (n = 375 cycles). Anti-oxidative function of FF was mainly attributable to HDL (n = 8; 83%). FF-HDL had a higher anti-oxidative function than plasma HDL (n = 19, P < 0.001) coinciding with increased vitamin E and sphingosine 1 phosphate content (P = 0.028 each). Proteomic analysis indicated no significant differences in major anti-oxidative proteins such as paraoxonase 1, apolipoprotein (apo) A-I or apoA-IV between FF-HDL and matched plasma-HDL (n = 5), while apoC-III, apoE and apoC-II were relatively lower in FF-HDL. Finally, FF-HDL anti-oxidative function was related to a decrease in the odds of the oocyte undergoing normal fertilization, an association that persisted after adjustment for confounders (odds ratio 0.97 (0.93-1), P = 0.041). In conclusion, FF-HDL has considerable anti-oxidative properties that might be relevant for embryo quality.

Figure 1

Flow diagram of sample selection. Of the 620 MNC-IVF cycles that were initially considered for inclusion in the study, 375 cycles were consistent with all of the selection criteria as detailed in methods. MNC, modified natural cycle.

Figure 2

Comparison of the abundance of HDL-associated proteins between HDL from follicular fluid and from matched plasma (n = 6 each). Protein intensity ratio was calculated as the median protein intensity in follicular fluid-HDL samples divided by the median protein intensity in matched plasma-HDL samples. Apolipoprotein D and serum amyloid A1 could not be detected in plasma-HDL from one patient and in follicular fluid-HDL and plasma-HDL from three patients, respectively, hence the n number for these proteins is lower. *P < 0.05 by Wilcoxon Signed Ranks test (protein intensity). Apo – apolipoprotein, SAA – serum amyloid A, PON1 – paraoxonase/arylesterase 1.