Research Article

Autologous embryo–cumulus cells co-culture and blastocyst transfer in repeated implantation failures: a collaborative prospective randomized study

M. Benkhalifaa1a3 c1, A. Demirola4, T. Saria4, E. Balashovaa5, M. Tsouroupakia6, Y. Giakoumakisa6 and T. Gurgana4

a1 ATL R&D Reproductive Biology & Genetics Laboratory, 4 Rue Louis Lormand, 78320 La Verriere, France.

a2 ATL R&D, Reproductive Biology & Genetics Laboratory, 78320 France.

a3 Eylau/UNILABS Laboratories, Paris, France.

a4 Women's Health Clinic, IVF & Genetics, Ankara, Turkey.

a5 IVF Dept. National Institute of Surgery and Rehabilitation, Moscow, Russia.

a6 Mediterranean Fertility Centre & Genetics Services, Chania, Greece.


In repeated implantation failure, the co-culture of human embryos with somatic cells has been reported to promote the improvement of embryos quality, implantation and pregnancy rate. It was reported that feeder cells can be more beneficial to the oocyte and embryo by detoxifying the culture medium and supporting embryo development via different pathways. In this study, 432 patients, each with a minimum of three repeated implantation failures, were accepted for a prospective randomized study with or without autologous cumulus cell embryo co-culture and transfer at day 3 or day 5–6. We also investigated the expression of leukaemia inhibitor factor (LIF) and platelet activating factor receptor (PAF-R) on day 3 confluent cumulus cells. The statistic analysis of the data showed significant difference of implantation and clinical pregnancy rates between classical culture and day 3 compared with co-culture and day 5–6 transfer. The molecular analysis showed that cumulus cells express the LIF and the PAF-R genes and confirmed the possible positive role of growth factors and cytokines in early embryo development. Embryo co-culture systems with autologous cells can be beneficial in routine in vitro fertilization for embryo selection and implantation improvement. More molecular investigations need to be done to improve elucidation of the complex dialogue between the embryo and feeder cells prior to implantation and to understand the involved biological function and molecular process during embryo development.

(Received September 02 2010)

(Accepted November 29 2010)

(Online publication April 07 2011)


c1 All correspondence to: Moncef Benkhalifa. ATL R&D Reproductive Biology & Genetics Laboratory, 4 Rue Louis Lormand, 78320 La Verriere, France. Tel: +33 1 30480178. Fax: +33 1 30571934. e-mail: ATL78@aol.com