The Follicle

It is well accepted that the developmental fate of an embryo is largely dictated by the quality of the oocyte, which in turn reflects the follicular milieu.

Most likely, affected gametes are derived from follicles with reduced blood supply since various reports suggest a close relationship between fol-licular blood flow and developmental competence of the corresponding oocyte or embryo (4,5). If vascularization in ovaries is underdeveloped, some follicles will be confronted with hypoxia which in turn causes a change in energy metabolism by switching from oxidative phosphorylation to gly-colysis. As a consequence, adenosine triphosphate (ATP) production in the affected follicle will decrease dramatically, since glycolysis generates only two molecules of ATP compared with oxidative phosphorylation (38 molecules). In addition, ATP depletion is increased since the vast majority of ATP is used for remodeling the vascular network via angiogenesis which is triggered by chronical underoxygenation (6). Since vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis, it can be expected that it is produced by granulosa and theca cells in response to hypoxia. In fact, a significant correlation between elevated levels of VEGF in follicles and a reduced viability of the corresponding embryo has been described (7).

Since conventional parameters, such as follicle size or fluid volume, are not considered to be adequate predictors of developmental potential of harvested oocytes and arising embryos, pulsed color Doppler ultrasound may be the first-line indirect technique for screening for competent oocytes which might serve as a basis for viable embryos or blastocysts, followed by follicu-lar fluid analysis for oxygen, ATP, and/or VEGF.

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