Gamete Biology

Meiotic Arrest In Vitro by Phosphodiesterase 3-Inhibitor Enhances Maturation Capacity of Human Oocytes and Allows Subsequent Embryonic Development

Abstract
Controlling nuclear maturation during oocyte culture might improve nuclear-cytoplasmic maturation synchrony. We aimed to evaluate the quality of in-vitro matured germinal-vesicle (GV)-stage human oocytes following a pre-maturation culture (PMC) with a meiotic arrester, phosphodiesterase 3-inhibitor (PDE3-I). Follicles (6-12 mm) were retrieved 34-36 h post-hCG administration from informed, consenting patients who had undergone controlled ovarian stimulation. Cumulus-enclosed oocytes (CEO) presenting moderate expansion or full compaction were placed in PMC with the PDE3-I, Org9935, for 24 h or 48 h. Subsequently, oocytes were removed from PMC, denuded of cumulus cells, matured in-vitro, fertilized and resulting embryos cultured. In the presence of PDE3-I ~98% of the oocytes were arrested at GV-stage. Following PDE3-I removal, oocytes acquired a higher maturation rate than oocytes that were immediately in vitro matured denuded of cumulus cells after retrieval (67% versus 46%, P = 0.01). In controls, immature CEO retrieved with moderate expansion reached higher maturation rates than fullycompacted CEO, but in PMC groups high values of maturation were achieved for both morphological classes of CEO. There was no effect of PMC on fertilization. A 24h-PMC period proved most effective in preserving embryonic integrity. Similar proportions of nuclear abnormalities were observed in embryos of all in-vitro groups. In summary, PMC with the specific-PDE3-I had a beneficial effect on human CEO by enhancing maturation, benefiting mainly fully-compacted CEO. This resulted in increased yield of mature oocytes available for insemination, without compromising embryonic development. These results suggest that applying an inhibitor to control the rate of nuclear maturity by regulating intra-oocyte PDE3 activity may allow the synchronization of nuclear and ooplasmic maturation.

Key words: Gamete Biology • Cumulus cells • Cyclic adenosine monophosphate • Oocyte development • Phosphodiesterases

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