Skip to main content
    • Aa
    • Aa
  • Access
  • Cited by 4
  • Cited by
    This article has been cited by the following publications. This list is generated based on data provided by CrossRef.

    Miranda, Moysés S. Nascimento, Hamilton S. Costa, Mayra P. R. Costa, Nathália N. Brito, Karynne N. L. Lopes, Cinthia T. A. Santos, Simone S. D. Cordeiro, Marcela S. and Ohashi, Otávio M. 2016. Increasing of blastocyst rate and gene expression in co-culture of bovine embryos with adult adipose tissue-derived mesenchymal stem cells. Journal of Assisted Reproduction and Genetics,

    Swain, Jason E. Carrell, Doug Cobo, Ana Meseguer, Marcos Rubio, Carmen and Smith, Gary D. 2016. Optimizing the culture environment and embryo manipulation to help maintain embryo developmental potential. Fertility and Sterility, Vol. 105, Issue. 3, p. 571.

    Assou, Said Pourret, Emilie Péquignot, Marie Rigau, Valérie Kalatzis, Vasiliki Aït-Ahmed, Ounissa and Hamamah, Samir 2015. Cultured Cells from the Human Oocyte Cumulus Niche Are Efficient Feeders to Propagate Pluripotent Stem Cells. Stem Cells and Development, Vol. 24, Issue. 19, p. 2317.

    Coughlan, C. Ledger, W. Wang, Q. Liu, Fenghua Demirol, Aygul Gurgan, Timur Cutting, R. Ong, K. Sallam, H. and Li, T.C. 2014. Recurrent implantation failure: definition and management. Reproductive BioMedicine Online, Vol. 28, Issue. 1, p. 14.


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

  • M. Benkhalifa (a1) (a2), A. Demirol (a3), T. Sari (a3), E. Balashova (a4), M. Tsouroupaki (a5), Y. Giakoumakis (a5) and T. Gurgan (a3)
  • DOI:
  • Published online: 07 April 2011

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.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Autologous embryo–cumulus cells co-culture and blastocyst transfer in repeated implantation failures: a collaborative prospective randomized study
      Your Kindle email address
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      Autologous embryo–cumulus cells co-culture and blastocyst transfer in repeated implantation failures: a collaborative prospective randomized study
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      Autologous embryo–cumulus cells co-culture and blastocyst transfer in repeated implantation failures: a collaborative prospective randomized study
      Available formats
Corresponding author
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:
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

E.D. Adamson (1993). Activities of growth factors in preimplantation embryos. J. Cell. Biochem. 53, 280–7.

A.M. Bamberger , I. Erdmann , S. Jenatschke , C. Bamberger & H.M. Schulte (1997). Regulation of the human leukemia inhibitory factor (LIF) promoter in HEC-1B endometrial adenocarcinoma cells. Mol. Hum. Reprod. 3, 789–93.

D.K. Barnette & B.D. Bavisier (1992). Hypotaurine requirement for in vitro development of golden hamster one-cell embryos into morulae and blastocysts, and production of term offspring from in-vitro fertilized ova. Biol. Reprod. 47, 297304.

M. Benkhalifia , D. Montjean , P. Cohen-Bacrie & Y. Ménézo (2010). Imprinting: RNA expression for homocysteine recycling in the human oocyte. Fertil Steril. 93, 1585–90.

A. Bongso , S. Ng , C. Fong & S. Ratnam (1991). Cocultures: a new lead in embryo quality improvement for assisted reproduction. Fertil. Steril. 56, 179–91.

D. Carrel , C. Peterson , K. Jones , H. Katasaka , L. Udoff , C. Cornwell , C. Thorp , P. Kuneck , L. Erickson & B. Campbell (1999). A simplified coculture system using homologous, attached cumulus tissue results in improved human embryo morphology and pregnancy rates during in vitro fertilization. J. Assist. Reprod. Genet. 16, 344–9.

S. Cecconi , A. Mauro , G. Cappachietti , P. Berardenelli , N. Bernabo , A. Di Vencenzo , M. Mattioli & B. Barboni (2008). Meiotic maturation of incompetent prepubertal sheep oocytes is induced by paracrine factor(s) released by gonadotropin stimulated oocyte cumulus cells complexes and involves mitogen activated protein kinase activation. Endocrinology 149, 100–7.

S. Croteau , Y. Menezo & M. Benkhalifa (1995). Transforming growth factors expression in fertilized and parthenogenetic pre-implantation mouse embryos: RNA detection with fluorescent in situ hybridization. Dev. Growth Differ. 37, 433–40.

T. Ebner , M. Moser , M. Sommergrube , O. Shebl & G. Tews (2006). Incomplete denudation of oocytes prior to ICSI enhances embryo quality and blastocyst development. Hum. Reprod. 21, 2972–7.

V. Eyheremendy , F. Raffo , M. Papayannis , G. Barnes , C. Granados & J. Blaquier (2010). Beneficial effect of autologous endometrial cell coculture in patients with repeated implantation failure. Fertil. Steril. 93, 769–73.

R.C. Fry , P.A. Batt , R.J. Fairclough & R. Parr (1992).Human leukemia inhibitory factor improves the viability of cultured ovine embryos. Biol. Reprod. 46, 470–4.

Y. Fukui , T. Saito , A. Miyamoto , H. Yamashina & Y. Okamoto (1994). Effect of leukemia inhibitory factor on in vitro development of bovine morulae. Theriogenology 42, 1133–9.

D.K. Gardner & M. Lane (1997). Culture and selection of viable blastocysts: a feasible proposition for human IVF. Hum. Reprod. Update 3, 367–82.

N. Godard , B. Pukazhenthi , D. Wildt & P. Comizzoli (2009). Paracrine factors from cumulus-enclosed oocytes ensure the successful maturation and fertilization in vitro denuded oocytes in the cat model. Fertil. Steril. 91, 2051–60.

I. Goovaerts , J. Leroy , A. Van Soon , J. De Clerq , S. Andries & P. Bols (2009). Effect of cumulus cell coculture and oxygen tension on the in vitro developmental competence of bovine zygotes cultured singly. Theriogenology 71, 729–38.

Y. Ho , A.S. Doherty & R.M. Schultz (1994). Mouse preimplantation embryo development in vitro: effect of sodium concentration in culture media on RNA synthesis and accumulation and gene expression. Mol. Reprod. Dev. 38, 131–41.

S. Ikeda , K. Saeki , H. Imai & M. Yamada (2006). Abilities of cumulus and granulosa cells to enhance the developmental cumulus of bovine oocytes during in vitro maturation period are promoted by midkine; a possible implication of its apoptosis suppressing effect. Reproduction 132, 549–57.

J. Johnson , H. Higdon & W. Boone (2008). Effect of cumulus cell coculture using standard culture media on the maturation and fertilization potential of immature human oocyte. Fertil. Steril. 90, 1674–9.

T. Jung (1989). Protein synthesis and degradation in non-cultured and in vitro cultured rabbit blastocysts. J. Reprod. Fertil. 86, 507512.

N. Kattal , J. Cohen & L. Barmat (2008). Role of coculture in human in vitro fertilization. Fertil. Steril. 90, 1069–75.

S.W. Kauna & D.W. Matt (1995). Coculture cells that express leukemia inhibitory factor enhance mouse blastocyst development in vitro. J. Assist. Reprod. Genet. 12, 153–6.

R.C. Larson , G.G. Ignotz & W.B. Currie (1992). Transforming growth factor β and basic fibroblast growth factor synergistically promote early bovine embryo development during the fourth cell cycle. Mol. Reprod. Dev. 33, 432–5.

H. Leese (1995). Metabolic control during preimplantation mammalian development. Hum. Reprod. Update 1, 6372.

E. Levitas , E. Lunenfeld , I. Har-Vardi , S. Albotiano , Y. Sonnin , R. Hackman-Ram & G. Potashnik (2004). Blastocyst stage embryo transfer in patient who failed to conceive in three or more day 2–3 embryo transfer cycles: a prospective randomised study. Fertil. Steril. 81, 567–71.

Y. Lin , J. Hwang , K. Seow , L. Huang , H. Chen & C. Tzeng (2009). Effects of growth factors and granulosa cell co-culture on in-vitro maturation of oocytes. Reprod. Biomed. Online 19, 165–70.

Y. Ménézo , J.F. Guérin & J.C. Czyba (1990). Improvement of human early embryo development in vitro by co-culture on monolayers of Vero cells. Biol. Reprod. 42, 301–6.

A. Mercader , J. Garcia Valesco , E. Escudero , J. Remohi , A. Pellicie & C. Simon (2003). Clinical experiences and perinatal outcome of blastocyst transfer after coculture of human embryos with human endometrial epithelial cells: a 5 years follow up study. Fertil. Steril. 80, 1162–8.

F. Moulavi , H. Hosseini , S. Ashtiani , A. Shahverdi & M. Nasr-Esfahani (2006). Can Vero cell coculture improve in vitro maturation of bovine oocytes? Reprod. Biomed. Online 13, 404–11.

S. Munné , CM. Howles & D. Wells (2009). The role of preimplantation genetic diagnosing embryo aneuploidy. Curr. Opin. Obstet. Gynecol. 21, 442–9.

F. Omar & M. Vlad (2008). In vitro development of mouse pronuclear embryos to blastocysts in sequential media with and without coculture of autologous cumulus cells. J. Reprod. Dev. 54, 385–90.

E. Papanikolaou , M. Camus , E. Kolibianakis , L. Van Landuyt , A. Van Steirtegheim & P. Devroey (2006). In vitro fertilization with single blastocyst stage versus single cleavage stage embryos. N. Engl. J. Med. 354, 1139–46.

E. Papanikolaou , E. Kolibianakis , H. Tournaye , C. Venetis , H. Fatemi , B. Tarlatsi & P. Devroey (2008). Live birth rates after transfer of equal number of blastocysts or cleavage-stage embryo in IVF. A systematic review and meta-analysis.Hum. Reprod. 23, 91–9.

F. Parikh , S. Nadkarni , N. Naik , D. Naik & S. Uttamchandani (2006). Cumulus coculture and cumulus aided embryo transfer increase pregnancy rates in patients undergoing in vitro fertilization. Fertil. Steril. 86, 839–47.

P. Quinn & R. Margualit (1996). Beneficial effect of coculture with cumulus cells on blastocyst formation in prospective trial with supernumerary human embryos. J. Assist. Reprod. Genet. 13, 912.

A. Veiga , M. Torello , Y. Menezo , A. Busquets , O. Sarrias , B. Coreleu & P. Barri (1999). Use of coculture of human embryos on vero cells to improve clinical implantation rate. Hum. Reprod. 14, 112–20.

M. Vlad , D. Walker & R.C. Kennedy (1986). Nuclei number in human embryos co-cultured with human ampullary cells. Hum. Reprod. 11, 1678–86.

A.J. Watson , E. Hogan , A. Hahnel , K. Wiemer & G. Schultz (1992). Expression of growth factor ligand and receptor genes in the preimplantation bovine embryo. Mol. Reprod. Dev. 31, 8795.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

  • ISSN: 0967-1994
  • EISSN: 1469-8730
  • URL: /core/journals/zygote
Please enter your name
Please enter a valid email address
Who would you like to send this to? *