Patients with three or fewer embryos attain the highest delivery by culturing embryos to the blastocyst stage (blast) and assuring embryonic-endometrial synchrony rather than day 3 (d3) transfer


      Enhanced delivery rates are attained with blast transfer. Much of this improvement has been attributed to enhanced selection although other mechanisms are possible. In those cases with limited embryos (≤3), the opportunity for enhanced selection is reduced. So what is optimal management? Can extended culture be of value or are outcomes equivalent due to the lack of selection or even reduced based on exposure to extended culture? This study addresses those questions.



      Materials and Methods

      5539 IVF patients aged <43 years with ≤3 embryos on D3 were studied. Cycles were divided into those with D3 transfer (1999-2009) versus those placed into extended culture (2010-12). Patients using extended culture whose blastocysts were not expanded by late day 5 were cryopreserved and transferred the next cycle. Outcomes included sustained implantation rate, delivery rate per transfer and an intent-to-treat analysis (no transfer was considered a failed cycle).


      5001 patients underwent D3 transfer and 538 were placed into extended culture. The D3 group was slightly younger (37.7 vs 37.2; P=0.002) and had more embryos transferred (2.2 vs 1.2; P<0.0001). All D3 patients had a transfer while 454 of 538 (84.4%) using extended culture had a transfer. Sustained implantation rates were higher with blast vs D3 (40.9% vs 21.3%; P <0.0001). Delivery rates per transfer were also higher with blast vs D3 (44.5% vs 33.4%; P<0.0001). Most significantly, the intent-to-treat analysis shows a higher delivery rate when utilizing extended culture (202/454 - 37.5% vs 1670/5001 - 33.4%; P=0.05).


      Extended culture improves outcomes - even in women ≤3 embryos available on day 3 of culture. This benefit does not result from enhanced selection based on the limited number of embryos available for transfer. Possible mechanisms include transferring blastocysts into a more physiologic milieu and/or enhanced embryonic endometrial synchrony attained by observing the timing of blastulation.