Clinical experience employing co-culture of human embryos with autologous human endometrial epithelial cells

Attempts to improve the outcome in IVF and related techniques has drawn our attention to the development of culture systems that can grow embryos up to the blastocyst stage. We have developed a co-culture system with autologous human endometrial epithelial cells (EEC) that retained many features of the endometrium. In this review, we analyse our experience over the last 4 years; in particular, we address the question of whether the system would be safe and useful in cases of IVF and oocyte donation with previous implantation failure, and which factors may contribute to the failure of human embryos to develop in vitro up to the blastocyst stage. In all, 168 IVF cycles were carried out in 127 patients with 3.8+/-0.2 previous implantation failure, and 80 cycles in 57 women having oocyte donation with 3.0+/-0.2 previous implantation failure. In 168 IVF cycles, a 48.9% blastocyst formation rate was recorded; 2.3+/-0.1 blastocysts were transferred per cycle and 30 clinical pregnancies obtained (11.9% implantation and 19.6% pregnancy rates). A total of 20 IVF and 15 oocyte donation patients with three previous implantation failures in whom a day 2 embryo transfer was performed were the controls. In 88% of oocyte donation cycles, a 61.0% blastocyst formation rate was observed; 2.3+/-0.1 blastocysts were transferred per cycle and resulted in 38 clinical pregnancies (32.7% implantation and 54.3% pregnancy rates). In all, 15 cycles were cancelled (9%). In oocyte donation patients with implantation failure undergoing day 2 embryo transfer, implantation and pregnancy rates were significantly lower (4.5 and 13.3%; P < 0.01) than with co-culture; however, in IVF patients with implantation failure with day 2 transfer, results (10.7 and 35%) were similar to those with co-culture. A second question addressed was whether chromosomal abnormalities may contribute to the failure of human embryos to develop in vitro. We observed the performance of human embryos from our preimplantation diagnosis programme, which were biopsied and subsequently cultured in EEC before transfer. Out of 68 chromosomally normal embryos, 37 reached the blastocyst stage (54.4%) compared with 35 out of 104 abnormal embryos (33.6%). The present study demonstrates that co-culture of human embryos with EEC and blastocyst transfer is safe, effective, and may be a new approach to improve implantation in patients with implantation failure undergoing oocyte donation, but not in IVF patients. The system shows that abnormal embryos can also grow to the blastocyst stage, although to a lower rate. Prospective randomized studies are needed to confirm the preliminary conclusion that co-culture is an acceptable system to select good quality embryos, and the endometrium is a limiting factor in implantation that needs to be carefully managed.