High density lipoprotein (HDL) particle size and composition predicts embryo fragmentation

Abstract

OBJECTIVE: HDL particles are the predominant lipoprotein in human follicular fluid (FF) and only small HDLs cross the blood follicle barrier. We previously showed that FF-HDL cholesterol and its component protein, ApoAI, negatively predict embryo fragmentation (EF). We hypothesized that: (1) FF-HDL particle size and composition are different from plasma HDL particles; and (2) FF-HDL particle composition is an important determinant of embryo quality. DESIGN: Cross-sectional study MATERIALS AND METHODS: Characterization of homologous human plasma and FF lipoprotein particle sizes using NMR spectrometry and HDL2/HDL3 subclass fractionated biochemical analysis was performed in 9 IVF patients. Prospective clinical correlations were made between FF HDL lipid compositions (by HPLC) and EF in 38 study patients in whom individual mature follicles were aspirated and embryos tracked. RESULTS: We confirmed that EF is inversely correlated with levels of FF HDL cholesterol (p<0.003). Compared to serum, FF contains a significantly higher proportion of small relative to large HDL particles with a conspicuous lack of medium-sized HDL particles. The HDL phospholipid to cholesterol molar ratio (PL/C ratio) is positively correlated with a higher proportion of small HDL particles as measured by NMR (n=9, r=0.77, p<0.01) and HDL2/HDL3 subclass composition. The PL/C ratio is further positively correlated with embryo fragmentation during IVF (n=38, r=0.67, p<0.01). CONCLUSIONS: This is the first study to demonstrate the existence of different HDL particle size distributions in FF compared to blood by NMR. We further show a correlation between parameters of HDL particle lipid composition and size with embryo fragmentation. Future work will focus on molecular characterization of FF HDL components. This work suggests the possibity that remodeling of FF HDL is important to oocyte and embryo development which requires further investigation.