Two UK scientists have made a major advance in assisted reproductive techniques which has allowed them for the first time to check the copy number of all the chromosomes in virtually every cell of a test-tube embryo. Their innovative work could ultimately lead to an improvement in IVF success rates.
The research is the work of Dr Dagan Wells and Professor Joy Delhanty at University College London Medical School and is published in the current issue of the UK journal Molecular Human Reproduction*. The findings are also being presented today (Monday 23 October) by Dr Wells at the American Society for Reproductive Medicine's annual conference in San Diego, California, where the work has been awarded the conference prize.
Compared with most animals, humans have naturally low fecundity - only a 25% chance of achieving a viable pregnancy per menstrual cycle even though fertilisation may occur in as many as 60% of cycles. Much of the difference between conception rate and birth rate is due to a very high incidence of very early pregnancy failure (usually occurring before a woman is even aware she is pregnant) or miscarriage. In couples undergoing IVF treatment the conception rate is also low (20 to 30% per cycle with 2 or 3 embryos transferred) and only around two-thirds of those who have a positive pregnancy test achieve a live birth.
There is evidence that chromosomal abnormalities play a major role in early failure and miscarriage. Being able to detect which embryos are chromosomally 'normal' will eventually allow doctors to transfer only those embryos with the best chance of forming viable pregnancies. Avoiding the transfer of embryos with chromosome abnormalities, which are likely to be incapable of producing a successful pregnancy, could boost IVF success rates per embryo transferred.
Full chromosomal analysis has not been possible in diagnostic cases up to now as existing technology has limited analysis to a small number of chromosomes per cell. In most studies only 5 of the 24 different types of chromosome have been tested.
But Dr Wells and Prof. Delhanty have developed a novel technique which combines whole genome amplification (WGA) and comparative genomic hybridization (CGH) making it possible to assess the copy number of every single chromosome in the majority of cells of a preimplantation embryo. Because this technique can be applied to minute tissue samples (e.g. single cells) it is also likely to find application in several other fields including cancer research, forensics and the analysis of ancient DNA samples.
The researchers used their new technique to examine 12 embryos donated by patients undergoing IVF. The embryos were cultured in vitro for 3 days, by which time most are composed of 6-8 cells. A total of 64 individual cells were separated and analysed.
As well as confirming the success of the technique the results provided another landmark finding - that the number of human embryos that are completely 'normal' is actually very low. Only three of the embryos studied had the correct number of chromosomes in every cell. Nine contained at least one abnormal cell and three of those contained no normal cells at all. This finding lends considerable weight to evidence from other studies that most human embryos contain a proportion of abnormal cells. However, it was contrary to predictions from some researchers that all human embryos probably contain a proportion of abnormal cells.
"Having a small number of abnormal cells does not automatically mean an embryo will fail to implant or that there will be a miscarriage: however, the evidence suggests that the chances of such an embryo forming a successful pregnancy are considerably less than those of a chromosomally normal embryo," said Dr Wells. "We hope that the new technique will help embryologists to decide which embryos are the most likely to implant and develop normally. By preferentially transferring these embryos considerably higher success rates for couples undergoing IVF may ultimately be achieved."
Prof. Delhanty said: "We are currently working on the next step - reducing the length of the procedure so that it can be applied not only in routine IVF but also in preimplantation genetic diagnosis (PGD) where accuracy is even more important because it involves couples already at high risk of passing on serious inherited conditions."
The technique could be available in many specialist IVF clinics within a few years for high-risk patients.
* Comprehensive chromosomal analysis of human preimplantation embryos using whole genome amplification and single cell comparative genomic hybridization. Molecular Human Reproduction. Vol 6. No 11. pp 1055-1062.
Notes
1. Full embargoed text of the paper can be found on website
http://www3.oup.co.uk/eshre/press-release/oct_mhr.pdf
2. Molecular Human Reproduction is a journal of the European Society of Human Reproduction and
Embryology. Please acknowledge Molecular Human Reproduction as a source.
3. Printed text available on request from Dr Helen Beard, Managing Editor.Tel: 44-954-212404 or email: gb54@dial.pipex.com
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