Paracrine effects during group culture of bovine embryos as a model for human embryo culture

  • Van Der Elst, Josiane, (Administrative Promotor)
  • Van Soom, Ann (Coördinator)

Project Details

Description

Setting of the project The occurrence of multiple pregnancies has become the most severe complication associated with in vitro fertilization in humans. The transfer of a single embryo (single embryo transfer, SET) is therefore the golden standard to avoid multiple pregnancies. This has been stimulated by the Royal Decree of June 4th 2003 which links the reimbursement of laboratory expenses to complying with the regulations for embryo transfer, which have been described very detailed for SET. For patients younger than 36, only one embryo can be transferred in the first and second IVF-cycle, and afterwards maximum of only two. Since the implementation of this RD the number of multiple pregnancies has decreased in Belgium from about 30 % to 10 % [4,13]. The percentage of single pregnancies can be considered as a quality label for human fertility centres. In the CRG UZ Brussels the steep decrease of multiple pregnancy rates was also observed, and multiple pregnancy rates went even below 10% [10]. The ultimate challenge is to render this criterion of quality permanent by reducing the present rates of multiple pregnancies to a percentage approaching zero. Within this particular context it is very important to be able to choose that one special embryo which is best suited for embryo transfer. In humans, mature oocytes are being collected, fertilized by means of in vitro fertilisation (IVF) or intracytoplasmatic sperm-injection (ICSI) and subsequently being cultured individually. Embryo selection is now based on morphological parameters. The data of the embryos are transferred to the Fertility Database (CRG, UZ Brussels), in order to use these parameters in correlation with pregnancy outcome. As an additional criterion of selection, human embryos are now being cultured to day 5 (blastocyst) and then transferred via SET [5]. It has been shown repeatedly in cattle embryos that suboptimal culture conditions may lead to deviant gene expression in these embryos, hence it is of the utmost importance to ensure that prolonged incubation of human embryos takes place under optimal circumstances. Since results of group culture are significantly better for embryonic development of bovine embryos, such a group culture is an interesting alternative for the current individual culture of human embryos. Because of the fact that we are working in a clinical setting, with patient material, it is not appropriate to implement such an important change in the current human IVF-system, since the cocultivation of good and poor quality embryos may affect the good embryos in a negative way. At present no large scale clinical studies are available which compare group culture against individual culture in humans. The bovine embryo is an appropriate model for the human embryo when it comes to accurately define the possible autocrine and paracrine effects which can exert an effect during group culture of embryos. The bovine embryo is preferable to the murine embryo, because the high level of inbreeding is rendering the mouse embryo relatively resistent against unfavourable culture conditons. The bovine embryo, on the other hand, is extremely sensitive to suboptimal culture conditons, and eventual negative influences on the embryos can be quantified rather easily by means of the cell number, the apoptotic-index and the differentiation-index of the embryos [9,11,12]. Also changes in embryonic gene expression can easily be detected via suppressive subtractive hybridisation (SSH) [2]. In addition cattle are just like humans mono-ovulatory and the embryonic development is happening according to a similar time frame. Moreover, in cattle embryos are always being transferred via SET, whereas transfer experiments in mice are always biased by the presence of several embryos in the uterus. Aims Development and clinical evaluation of a safe and reliable group culture system for human embryos, based on a model developed in the bovine embryo. Specific aims: 1. The bovine as a model for embryonic development in humans - Effect of group culture of good/poor embryos on embryo quality (invasive) - Analysis of culture media in groups of good and poor embryos in bovine - Preclinical testing of several group systems in bovine (endpoint in vitro blastocyst rate) - Identification of autocrine/paracrine effects in the group culture system in cattle. 2. Implementation of the results in the human model - Randomised lab study of group systems vs individual system (endpoint in vitro blastocyst rate) - Randomised clinical model of best group system vs individual system (endpoint clinical pregnancy)
AcronymFWOAL511
StatusFinished
Effective start/end date1/01/0931/12/12

Flemish discipline codes

  • Basic sciences
  • Biological sciences

Keywords

  • reproductive genetics
  • andrology
  • clinical genetics
  • embryology
  • assisted reproductive technology