Embryonic development after follicle culture is influenced by follicle-stimulating hormone isoelectric point range

We evaluated the effects of follicular exposure in vitro to either of two mutually exclusive isoforms of FSH (least acidic and acid) on the subsequent capacity of oocytes for embryonic development. The effects of dose and follicle culture duration were examined. At the threshold dose (that required to produce antra) and at one subthreshold dose, the major difference between the two isoform fractions was the timing and effectiveness of acquisition of two-cell embryonic developmental capacity. With the least-acidic fraction, the highest rate of two-cell development (approximately 80%) occurred after 3 days of follicle culture only at the threshold dose (2.5 ng/ml). With the acid fraction, the highest two-cell rate (approximately 60%) occurred after 5 days of culture but at equivalent rates over a range of doses between 10 ng/ml and 100 ng/ml (threshold dose was 50 ng/ml). At threshold dose or below, the capacity for two-cell embryo production appeared not to be influenced by antral status for either isoform. At above threshold doses, the least-acidic fraction induced an increasing proportion of antral follicles with increasing dose, but this increase was associated with a progressive decrease in embryo production. This relationship was more extreme after longer culture and was due to degeneration of the cumulus-oocyte complex associated with apparently increased differentiation of the mural granulosa cells. The acid fraction was by comparison less bioactive and insensitive to overdosing. The broader isoform mix of the unfractionated FSH provided a measure of protection against overdosing characteristic of the acid fraction while retaining the capacity of the least-acidic fraction to induce antral formation at a low dose.