New and revolutionary 24 chromosomes aneuploidy screening by array-CGH aims to improve IVF clinical pregnancy and live birth rates


What is CGH? 
CGH or Comparative Genomic Hybridization is a technique developed to look at the total number of chromosomes in a single cell to check for extra or missing chromosomes.
 
Why array CGH? 
Array CGH is a significant advance on conventional CGH as it is a more refined, robust and is much quicker. Results are typically available within 24-48 hours allowing a fresh embryo transfer whereas conventional CGH can take at least 5 days, making it necessary to freeze the embryos and transfer at a later date. 

What is a chromosome? 
A chromosome is a highly complex structure containing genes that make us who we are, and they are found in every cell of our body (except red blood cells). One chromosome may carry over 1000 genes. Chromosomes are in pairs, and in humans there are 23 pairs. 

Why are chromosomes important in fertility? 
Approximately 70% of embryos produced either through natural conception or IVF are lost before birth. The vast majority of embryos are lost within the first three months of pregnancy, most of these even before implantation. A major cause of embryo loss, including miscarriage, is a chromosome anomaly (known as ‘aneuploidy’) where there is either a loss of a chromosome or a gain. Some of these anomalies are compatible with full term delivery, such as three copies of chromosome 21 (known as Down syndrome) or three copies of chromosome 18 (Edward Syndrome). Some are not compatible with full term delivery; and others cause the embryo to arrest its development before implantation.




The rate of aneuploidy in eggs also increases with a woman’s age, with Down syndrome being the most commonly known. This table shows that as age increases, so does the risk of aneuploidy and chromosome-related miscarriage, causing a major reduction in live birth rates. The incidence of Down syndrome rises from 1 in 900 at age 30, through 1 in 230 at age 37 to 1 in 20 at 46. 


The hope for CGH-‘One Embryo-One Baby’ 
Embryologists in routine IVF practice cannot differentiate between chromosomally viable and aneuploid embryos, and hence aneuploid embryos will unwittingly and inevitably be transferred to the womb, thereby compromising IVF outcome. Conversely, it follows that by identifying the aneuploid status of the embryo, embryologists have the chance of eliminating the chromosomally abnormal embryos before transfer. 
It is hoped that this technology should: 

• lead to markedly improved IVF success rates; 
• reduce the incidence of multiple pregnancies (by transferring fewer but ‘competent’ embryos); 
• reduce the incidence of pregnancy wastage (miscarriage); 
• reduce the cost of achieving a viable IVF pregnancy and, 
• reduce overall reproductive health care costs. 

How will array CGH work for me? 
IVF will be planned in the normal way: 

• Phase 1: A protocol of drugs will be prescribed for ensuring the most appropriate ovarian stimulation regimen. You will come to GENOMA for monitoring and at the appropriate time undergo egg collection. At this point you can return home whilst the work continues in the laboratory. The collected eggs will be examined for their maturity. Only mature eggs that have their polar body extruded will be used. Each of these mature eggs will undergo ICSI and then blastomeres from day3 embryos will be removed for PGS analysis.
• Phase 2: Only those embryos whose chromosomes were normal will be transferred or frozen for future use. 

Risks -general 
There are no health risks associated with the programme that are not apparent in conventional IVF. 

Array CGH is a new experimental technology and as such must still be considered to be in a test phase. There is insufficient data to provide any reliable guide to how effective this technique is in embryo selection. We acknowledge that there is therefore a risk of technical, equipment or analysis failure or malfunction which may affect the accuracy of assay results, or prevent the delivery of any results. 

Risks – related to biopsy and analysis procedures 
The procedure for this technique has been used for many years. Accidental risk to the embryos is less than 0.2%. 

Misdiagnosis
It is estimated that the risk of a misdiagnosis [either positive or negative] is less than 1%. However we advise that a prenatal diagnosis (CVS or amniocentesis in early pregnancy) is still performed in the routine way for pregnant women, for further reassurance. 


No normal embryos 
There is approximately a 25% chance that all embryos tested show abnormal results, with none of the embryos therefore being available for transfer. If this occurs you will be offered a detailed review with your consultant to discuss the relevance and options. GENOMA cannot under any circumstances transfer any embryo(s) shown to carry abnormal chromosomes. 

Indeterminate results 
Occasionally it could arise that there are no results from any of the chromosomes from an embryo. In this case we do not know if the embryo is chromosomally normal or abnormal. If this occurs for the only available embryo(s) for transfer, the relevance of this will be discussed between you and your consultant. 

Pregnancies following CGH 
There is no guarantee against miscarriage occurring even after screening all the chromosomes. Some miscarriages occur due to other factors such as immune conditions or undiagnosed genetic problems. If you do become pregnant following screening the pregnancy will still be subject to all risks and problems that can be associated with natural pregnancies including ectopic pregnancies and congenital abnormalities. The procedure itself should not affect any resulting pregnancy. Thousands of children have now been born following biopsy for other reasons. 

How do I consider if this is right for me? 
GENOMA can offer you a detailed clinical consultation where the medical and scientific issues will be discussed, and you will also be offered counselling by a trained independent counsellor. We recognise that the issues are complicated and we urge all patients to feel free to discuss with our specialised team any aspect of the procedure or any concerns. 

Are there any additional tests we will need before we proceed? 
All the normal screening tests required before a normal IVF/ICSI cycle are also needed before an array-CGH cycle and these are document in our separate “IVF/ICSI Cycle” Information document. In addition though, we will need to have information on karyotypes for both partners and we advise that the man considers having his sperm tested for both sperm aneuploidy and Sperm DNA Fragmentation. We advise these additional tests before treatments as abnormalities in these tests can be significant confounding variables for outcome of a treatment cycle and may affect the decision whether to proceed with array-CGH. 

Costs 
The cost of array CGH is additional to the cost of IVF with ICSI. Please see GENOMA fee schedule, available from GENOMA.



We recognise that there is a lot of information contained in this document. However, as this technology is very new it is important that we provide you with comprehensive information to help you make an informed decision. Please read the information carefully and do ask any questions of our consultants or senior clinical staff during your consultation or at any time. 

Glossary
 

Aneuploid (aneuploidy)	An abnormal chromosome profile in a cell
Biopsy	The removal of a portion of cellular material for testing
Blastocyst	The stage 5 – 6 days after fertilisation when the zygote has reached about 30 or more cells
CGH	“Comparative Genomic Hybridization” – a technique used to analyse all the chromosomes of a single cell
Chromosome	Paired structures within each cell containing the genes of the individual
Embryo	The name given to the fertilised egg once it divides into two cells, and continues cell division
Euploid	A normal chromosome profile
Follicles	Sacs in the ovary that contain the eggs
Gamete	The sperm or egg
ICSI	“Intra Cytoplasmic Sperm Injection” – a method to directly inject a single sperm into an egg
Nucleus	The central part of almost all cells, which contains the chromosomes and genetic material
Oocyte	The female gamete; egg
Polar Body	The tiny part of an egg that contains half the egg’s chromosomes but does not take part in the fertilization process
Zygote	The fertilized egg, containing the chromosomes from both the egg and the sperm