A research group led by Dagan Wells (Associate Professor and BRC Scientific Leadership Fellow) received the Society of Assisted Reproductive Technologies (SART) prize in 2011 for an abstract submitted to the largest reproductive medicine conference in the USA, the American Society for Reproductive Medicine.
SART is a society associated with the ASRM that works on the regulation and promotion of technologies used in the treatment of infertility. The project involved collaboration with industry (Oxford Gene Technology) and also received funding from the Oxford NIHR Biomedical Research Centre.
The prize was awarded for the development of an innovative new tool for assessing the health of eggs or embryos produced using IVF treatment.
In theory this should significantly improve IVF success rates, especially in cases where only one embryo is transferred, as well as reducing the risks of miscarriage and Down syndrome. The new test primarily looks at the number of chromosomes in each egg or embryo.
Having the wrong number of chromosomes is a frequent problem in human eggs and embryos and is usually incompatible with successful development, causing the embryos to spontaneously stop growing. The new test also looks even deeper in to the biology of the egg or embryo, examining the mitochondria (the powerhouses of the cell) and the telomeres (specialised structures that protect the ends of chromosomes). These additional features may provide yet more information on embryo viability. It is anticipated that the use of these techniques will improve IVF success rates significantly, but we will have to wait for proper clinical trials before we can be certain how great the improvement will be.
A NOVEL TOOL ALLOWS SIMULTANEOUS GENOMIC AND CYTOGENETIC ASSESSMENT OF OOCYTES AND EMBRYOS AND YIELDS UNIQUE DATA OF SCIENTIFIC AND CLINICAL IMPORTANCE
Wells, D; Konstantinidis, M.; Alfarawati, S.; Hurd, D.; Fragouli, E.
Objective: In order to maximise IVF success rates, it is essential that the embryo most likely to produce a healthy birth is identified and prioritised for transfer. Unfortunately, traditional methods of embryo selection provide a relatively poor guide to embryo competence. We sought to develop a new tool that quantifies critical aspects of embryo biology invisible to morphological analysis.
Design: A novel microarray was designed, allowing combined analyses of chromosome abnormalities, telomere length and mitochondrial copy number in oocytes and embryos. Additionally, multiple single nucleotide polymorphisms (SNPs) could be typed.
Materials and Methods: 37 polar bodies, 64 blastomeres and 16 trophectoderm biopsies were assessed in a blinded fashion. Each aneuploidy result was verified using two established methodologies (aCGH and FISH). Telomere length and quantity of mitochondrial DNA (mtDNA) were validated using real-time PCR.
Results: 226/240 aneuploidies were detected (94% accuracy). SNP genotyping confirmed paternity/maternity in all cases. Telomeric and mtDNA quantification results were 100% concordant with real-time PCR. Interestingly, aneuploidy and age were both associated with diminished telomere length in polar bodies and blastomeres (p<0.001), although normalisation was apparent at the blastocyst stage. A decrease in mtDNA was seen in aneuploid blastomeres (p<0.05).
Conclusions: We describe an easy to use tool for the simultaneous analysis of multiple aspects of oocyte/embryo biology. Quantification of mtDNA and telomere length, features likely to be of clinical relevance, may allow chromosomally normal oocytes/embryos to be further differentiated in terms of developmental competence. This study also revealed interactions between aneuploidy, senescence and energy production, with significant implications for future gamete and embryo research. The versatile platform described here adds to a growing repertoire of powerful tools for improved embryo selection.
Funded by NIHR Biomedical Research Centre Programme