The developmental potential of the human oocyte is related to the dissolved oxygen content of follicular fluid: association with vascular endothelial growth factor levels and perifollicular blood flow characteristics

Abstract

Regardless of whether fertilization occurs in vivo or in vitro, a large proportion of human embryos do not develop progressively through the pre-implantation stages or arrest development after implantation. This study examined the association between the chromosomal/spindle normality of the mature human oocyte and the dissolved oxygen content, vascular endothelial growth factor concentration (VEGF) and perifollicular blood flow characteristics of the corresponding ovarian follicles. Findings from >1000 samples of follicular fluid show that developmentally significant differences in dissolved oxygen content occur in follicular fluids aspirated from follicles of equivalent size and ultrasonographic appearance. Oocytes from severely hypoxic follicles were associated with high frequencies of abnormalities in the organization of the chromosomes on the metaphase spindle that could lead to segregation disorders and catastrophic mosaicisms in the early embryo. Oocytes with cytoplasmic defects and cleavage stage embryos with multinucleated blastomeres are derived predominantly from severely hypoxic follicles. VEGF measurements of follicular fluid and colour pulsed Doppler ultrasonographic analysis of follicle-specific blood flow characteristics indicated a potentially important role for this factor both in perifollicular angiogenesis and in the regulation of intrafollicular oxygen levels. The results are discussed with respect to how severe intrafollicular hypoxia may influence the normality of chromosomal organization and segregation in the oocyte, and whether detailed pulsed Doppler analysis of individual pre-ovulatory follicles may provide an indirect indication of the 'health' of the follicle and possibly the developmental competence of the corresponding oocyte.