Coculture of human embryos with autologous human endometrial epithelial cells in patients with implantation failure

We have developed a coculture system with autologous human endometrial epit helial cells (AEEC) that retained many features of human endometrial epithe lium. Implantation failure (IF; >3 previous cycles failed with 3-4 good qua lity embryos transferred) is a distressing condition in which 2-day embryo transfer repetition is the routine option. The objective of this study was to investigate the basics and to evaluate prospectively the clinical value of embryo coculture on AEEC and blastocyst transfer with their own oocytes [in vitro fertilization (IVF) patients] or with donated oocytes (oocyte don ation patients) compared to a routine day 2 embryo transfer for patients wi th IF. Scanning electron microscopy and mouse embryo assays demonstrate tha t EEC from fertile and IF patients were morphologically and functionally si milar; similar findings were observed in EEC obtained from fresh or frozen endometria. Clinically, 168 IVF cycles were performed in 127 patients with 3.8 +/- 0.2 previously failed cycles, and 80 cycles were performed in 57 pa tients undergoing oocyte donation with 3.0 +/- 0.2 previously failed cycles . Twenty IVF patients and 15 ovum donation patients with 3 previously faile d cycles in whom a 8-day embryo transfer was performed were used as control s. In 88% of ovum donation cycles, at least 2 blastocysts were available fo r transfer, with 60.1% blastocyst formation; 2.2 +/- 0.1 blastocysts were t ransferred/cycle, and 36 pregnancies (determined by fetal cardiac activity) were obtained (32.7% implantation and 54.5% pregnancy rates). In 168 IVF c ycles, 8.1 +/- 0.2 embryos/cycle started coculture, resulting in 49.2% blas tocyst formation; 2.3 +/- 0.2 blastocysts were transferred/cycle, and 29 cl inical pregnancies were obtained (11.8% implantation and 20.2% pregnancy ra tes). Fifteen cycles were canceled (9%). In oocyte donation patients with I F undergoing 2-day embryo transfer, implantation and pregnancy rates were s ignificantly lower (4.5% and 13.3%; P < 0.01) than with coculture; however, in IVF patients with IF, results with day 2 transfer (10.7% and 35%) were similar to those with coculture. The present study demonstrates that cocult ure of human embryos with AEEC and blastocyst transfer is safe, ethical, an d Effective and constitutes a new approach to improve implantation in patie nts with IF undergoing ovum donation, but not in IVF patients.