Extended vs short culture in patients with small number of embryos

EMBCOL PRACTICE COMMITTEE OPINION 

The development of culture systems supporting embryo development in vitro until the blastocyst stage is one of the most important achievements in IVF since its inception. The extended culture allows the selection of embryos with the highest chance of implantation. This has led to the improvement in pregnancy rates and a reduction in multiple pregnancies.

However, it is not certain whether the in vitro culture environment is equivalent to in vivo (1, 2) and one of the concerns with extended culture is that some otherwise viable embryos may arrest due to imperfection of the in vitro system. If that were the case, the extended culture may deprive a couple the chance of achieving pregnancy when only a few embryos are created in vitro.

The extended embryo culture procedure was initially recommended based on several prospective randomized trials (3,4,5) for patients with high number of embryos available for transfer. However, recently some IVF programs are switching almost exclusively to extended embryo culture for all patients, irrespective of female's age or number of embryos available.

It is important to note that in clinical trials where all patients were randomized between short or extended culture, the majority of patients had more embryos than would be transferred at any single time and improved embryo selection translated into improved chance of pregnancy. Therefore such trials cannot serve as a basis of recommendation for patients with only a few embryos, where embryo selection is not an issue.

In order to recommend extended embryo culture for patients with a few embryos, the trial should include only patients with a few embryos. Furthermore, to be valid, the comparison has to be made on the basis of deliveries per retrieval and not per embryo transfer.

EMBCOL practice committee has reviewed available literature and has not found any peer-reviewed evidence that would fulfill the above criteria.

It is, therefore, EMBCOL opinion that at present there is no evidence that extended culture can be recommended to patients with only a few embryos.  

Recognizing the importance of the issue, and to encourage a relevant clinical trial, EMBCOL will award US$1000 prize to the first researcher(s) who provides conclusive results clarifying this question. In addition to the prize, EMBCOL will promote the results of this research globally using EMBCOL PR Network.

The trial should fulfill the following criteria:

1. Patients with 6 or less embryos have to be randomized between day 3 or day 5 transfer.

2. At least 50% of patients have to be recruited in a US based clinic

3. Egg donor cases may not be included

4. US-based clinics must obtain IRB approval for the study

References:

1. Ménézo Y, Lichtblau I, Elder K. New insights into human pre-implantation metabolism in vivo and in vitro. J Assist Reprod Genet. 2013 Mar;30(3):293-303. doi: 10.1007/s10815-013-9953-9. Epub 2013 Feb 21. Review. PubMed PMID: 23430228; PubMed Central PMCID: PMC3607680.
2. DeScisciolo C, Wright DL, Mayer JF, Gibbons W, Muasher SJ, Lanzendorf SE. Human embryos derived from in vitro and in vivo matured oocytes: analysis for chromosomal abnormalities and nuclear morphology. J Assist Reprod Genet. 2000 May;17(5):284-92. PubMed PMID: 10976416; PubMed Central PMCID: PMC345520
3. Emiliani S, Delbaere A, Vannin AS, Biramane J, Verdoodt M, Englert Y, Devreker F. Similar delivery rates in a selected group of patients, for day 2 and day 5 embryos both cultured in sequential medium: a randomized study. Hum Reprod. 2003  Oct;18(10):2145-50. PubMed PMID: 14507836
4. Papanikolaou EG, D'haeseleer E, Verheyen G, Van de Velde H, Camus M, Van Steirteghem A, Devroey P, Tournaye H. Live birth rate is significantly higher after blastocyst transfer than after cleavage-stage embryo transfer when at least four embryos are available on day 3 of embryo culture. A randomized prospective study. Hum Reprod. 2005 Nov;20(11):3198-203. Epub 2005 Jul 29. PubMed PMID: 16055454.
5. Kolibianakis EM, Devroey P. Blastocyst culture: facts and fiction. Reprod Biomed Online. 2002 Nov-Dec;5(3):285-93. Review. PubMed PMID: 12470528.

Please contact EMBCOL for more information.