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Blastocyst stage transfer: pitfalls and benefits. The benefits of extended culture.

It is common practice in most human assisted reproduction programmes around the world to carry out embryo transfers on day 2 of culture and, very occasionally, on day 3. However, the need for change has been raised (Tsirigotis, 1998). Embryos are almost always transferred to the patient’s uterus at the early cleavage stage even though, in vivo, the embryo does not normally enter the uterus until the morula stage (Croxatto et al., 1972), which is closer to day 4 of culture. In rodents and domestic ruminants, premature exposure of early cleavage stage embryos to the uterine environment results in the embryos failing to develop further and a poor pregnancy outcome (Moore and Shelton, 1964; Holst and Braden, 1972). However, in both ruminants (Hasler et al., 1987) and mice (Bronson and McLaren, 1970), deferring uterine transfer to the blastocyst stage results in very high pregnancy rates. In the human, premature exposure of early cleavage stage embryos to the uterine environment does not appear to severely compromise embryo development, as pregnancy rates of 20–40% are now routinely reported. However, these pregnancy rates are usually attained following transfer of multiple embryos and the resulting implantation rates are low (10–20%). This indicates that 80% of the early cleavage stage embryos selected for transfer following assisted reproductive techniques (ART), either have no further developmental competence, or at least no developmental competence in the uterine environment. Alternatively, the uterine endometrium may remain unreceptive to transferred embryos, limiting both pregnancy and implantation rates (Rogerset al., 1986). Early cleavage stage embryos are usually selected for transfer on the basis of morphological criteria, e.g. number of blastomeres, symmetry of blastomeres, granularity and degree of extracellular fragmentation. In several studies, these features have been shown to be weakly correlated with pregnancy rates (Puissantet al., 1987; Steeret al., 1992; Roseboomet al., 1995). However, by day 2 in culture, embryo development is governed primarily by presynthesized maternal transcripts and stored messages rather than the true embryonic genome (Braude et al., 1988). Deferring embryo transfer to day 3 (or beyond) of culture