Embryonic human chorionic gonadotropin secretion and hatching: poor correlation with cleavage rate and morphological assessment during preimplantation development in vitro.

Of 593 bipronucleate eggs allowed to develop in vitro, 275 (46%) achieved the blastocyst stage and beyond, 124 (21%) initiated hatching, but only 49 (8%) fully hatched. About half of the pre-embryos (48%) which developed to these more advanced stages were incapable of secreting significant amounts (> 200 microIU) of cumulative human chorionic gonadotropin (HCG) up to day 14. HCG production does not appear to begin until the expanded stage and is independent of hatching. Assessing cleavage rate through successive stages and morphological grades up to the 8-cell stage had little bearing on the ability of a pre-embryo to hatch or secrete HCG. Progression through the stages of preimplantation development in vitro does not always appear to be accompanied by the necessary biochemical stages. If only 46% of pre-embryos with two pronuclei are capable of achieving the blastocyst stage, and of these only 52% are capable of secreting HCG, then it follows that only 24% of the original bipronucleate pre-embryos in vitro can be considered anatomically and biochemically competent. However, this is only applicable for pre-embryos not transferred or frozen, and is thus subject to a selection bias. Inability to detect HCG in vitro is not conclusive proof that a pre-embryo is developmentally incompetent. Similarly failure to hatch in vitro may not be taken as definitive evidence that hatching would have failed had fertilization and development been completed in vivo. Nevertheless, if pre-embryonic development in vitro is similar to that in vivo, this may be a contributory factor in the low pregnancy rates following in-vitro fertilization treatment.