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 t o the blastocyst stage. We have developed a co-culture system with autologo us 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 implanta tion failure, and which factors may contribute to the failure of human embr yos 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 fai lure, and 80 cycles in 57 women having oocyte donation with 3.0 +/- 0.2 pre vious implantation failure. Tn 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 ra tes). 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 t he 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 a nd 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 da y 2 transfer, results (10.7 and 35%) were similar to those with co-culture. A second question addressed was whether chromosomal abnormalities may cont ribute 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 de monstrates that co-culture of human embryos with EEC and blastocyst transfe r is safe, effective, and may be a new approach to improve implantation in patients with implantation failure undergoing oocyte donation, but not in I VF patients. The system shows that abnormal embryos can also grow to the bl astocyst stage, although to a lower rate. Prospective randomized studies ar e needed to confirm the preliminary conclusion that coculture is an accepta ble system to select good quality embryos, and the endometrium is a limitin g factor in implantation that needs to be carefully managed.