Could ovarian stimulation cause an increase in chromosome copy number abnormalities?
Ovarian stimulation undertaken by women of advanced maternal age receiving fertility treatment may be disrupting the normal pattern of meiosis -- a critical process of chromosome duplication followed by two specialized cell divisions in the production of oocytes and sperm - and leading to abnormalities of chromosome copy numbers that result in IVF failure, pregnancy loss or, more rarely, the birth of affected children with conditions such as Down's syndrome, which is caused by the inheritance of three copies of chromosome 21.
Researchers involved in ESHRE's polar body screening study (launched in 2009) will tell the annual conference of the European Society of Human Reproduction and Embryology today (Monday) that results from the study are leading to a new understanding about how such abnormalities are developing, and they believe that the ovarian stimulation a woman receives might be playing a part. Understanding the mechanisms involved could help older women who are trying to have a healthy baby with their own oocytes.
Professor Alan Handyside, Director of The London Bridge Fertility, Gynaecology and Genetics Centre, London, UK, and colleagues from eight countries undertook a proof of principle study of a novel method of screening polar bodies, small cells that are the by-product of oocyte development, using the new technology of microarray comparative genomic hybridisation (array CGH) in order to find whether this was a reliable method of analysing the chromosomal status of an oocyte. This is because many more chromosome copy number abnormalities arise in the oocyte than in sperm.
"In doing so, we obtained a lot of data at the individual chromosome and chromatid level," says Professor Joep Geraedts, co-ordinator of the ESHRE Task Force on preimplantation genetic screening (PGS). (A chromatid is one of the two identical copies of DNA making up a duplicated chromosome). "So we decided to analyse these data separately to see whether they could provide us with information that could be useful in determining better treatment strategies for the future."
"In this unique study, we were able to use the new technology of array CGH to examine the copy number of all 23 pairs of chromosomes, in all three products of female meiosis in over 100 oocytes with abnormal numbers of chromosomes," says Professor Handyside. "What happens in female meiosis is that the 23 pairs of chromosomes duplicate and each pair of duplicated chromosomes comes together and the four single chromosomes, or 'chromatids', become 'glued' together along the whole length of each chromosome. This actually occurs before the woman is born and is the stage at which DNA is swapped between the grandparents' chromosomes.
"Sometimes, decades later, just before ovulation, the glue 'dissolves' first between the two duplicated chromosomes and finally after fertilisation between the two individual chromosomes. This enables pairs of chromosomes to segregate in the first meiotic division producing the first polar body. In the second meiotic division the second polar body is produced, resulting in a single set of chromosomes in the fertilised oocyte or 'zygote', which, when combined with the single set in the fertilising sperm, restores the 23 pairs," he says.
The researchers believe that ovarian stimulation may be disturbing this process in older women because the chromosomes are becoming unglued prematurely, particularly the smaller ones like chromosome 21. Ovarian stimulation uses hormonal medication to stimulate the ovaries to release a large number of oocytes than normal, in order to provide enough good quality oocytes for fertilisation in vitro.
Following natural conception in older mothers, Down's pregnancies are predominantly caused by errors in the first female meiotic division. "Our evidence demonstrates that, following IVF, there are multiple chromosome errors in both meiotic divisions, suggesting more extensive premature separation of single chromosomes resulting in more random segregation, which in turn results in multiple chromosome copy number changes in individual oocytes," says Professor Handyside.
"We need to look further into the incidence and pattern of meiotic errors following different stimulation regimes including mild stimulation and natural cycle IVF, where one oocyte per cycle is removed, fertilised and transferred back to the woman. The results of such research should enable us to identify better clinical strategies to reduce the incidence of chromosome errors in older women undergoing IVF."
"We also believe that our research will help identify women who want to have their own offspring but have practically no chance of doing so that we can advise them to use donor oocytes," says Professor Geraedts. "This in itself is already a big step forward that will aid couples hoping for a healthy pregnancy and birth to be able to achieve one."
Provided by European Society of Human Reproduction and Embryology
- Could ovarian stimulation cause an increase in oocyte chromosome abnormalities? Jul 04, 2011 | not rated yet | 0
- Scientists probe mechanism of asymmetry in meiotic cell division Oct 07, 2008 | not rated yet | 0
- First babies born from genetic screening study Oct 15, 2010 | not rated yet | 0
- A unique arrangement for egg cell division Aug 09, 2007 | not rated yet | 0
- Researchers identify first sex chromosome gene involved in meiosis and male infertility Mar 14, 2008 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Classical and Quantum Mechanics via Lie algebras
Apr 15, 2011 I'd like to open a discussion thread for version 2 of the draft of my book ''Classical and Quantum Mechanics via Lie algebras'', available online at http://lanl.arxiv.org/abs/0810.1019 , and for the...
- More from Physics Forums - Independent Research
More news stories
Early use of tracheostomy for mechanically ventilated patients not associated with improved survival
For critically ill patients receiving mechanical ventilation, early tracheostomy (within the first 4 days after admission) was not associated with an improvement in the risk of death within 30 days compared to patients who ...
Other 5 hours ago | not rated yet | 0
The decision to limit life support in patients in the intensive care unit (ICU) appears to be significantly influenced by physician practices and/or the culture of the hospital, suggests new findings from researchers at the ...
Other 7 hours ago | not rated yet | 0
Knee replacement surgery is a very common procedure. However, it does not always resolve function or pain in all the recipients of new knees. A study by Robert Barrack, MD and his colleagues from the Washington University ...
Other 9 hours ago | not rated yet | 0
Doctors are trained to think "common disease" when they meet patients in their practices, and as they rarely or never meet a rare disease, it often takes many years to reach the right diagnosis. A new search tool called FindZebra ...
Other 9 hours ago | not rated yet | 0
Delayed transfer to the intensive care unit (ICU) in hospitalized patients significantly increases the risk of dying in the hospital, according to a new study from researchers in Chicago.
Other 11 hours ago | not rated yet | 0
(Medical Xpress)—Native peoples in regions where cameras are uncommon sometimes react with caution when their picture is taken. The fear that something must have been stolen from them to create the photo ...
10 hours ago | 4 / 5 (4) | 0 |
(Medical Xpress)—Despite spending billions of dollars on research and development, drug companies have been unable to come up with effective treatments for dementia and Alzheimer's Disease (AD). Now, A. ...
7 hours ago | 4.8 / 5 (6) | 0 |
An experimental sleeping pill from US drug company Merck is effective at helping people fall and stay asleep, according to reviewers at the US Food and Drug Administration, which could soon approve the new drug.
3 hours ago | 5 / 5 (1) | 0
Activating an enzyme known to play a role in the anti-aging benefits of calorie restriction delays the loss of brain cells and preserves cognitive function in mice, according to a study published in the May ...
4 hours ago | 5 / 5 (3) | 0 |
A drug commonly used to treat depression and anxiety may improve a stress-related heart condition in people with stable coronary heart disease, according to researchers at Duke Medicine.
5 hours ago | not rated yet | 0 |
Australian scientists have charted the path of insulin action in cells in precise detail like never before. This provides a comprehensive blueprint for understanding what goes wrong in diabetes.
9 hours ago | 4.8 / 5 (4) | 0 |