What is Intracytoplasmic Sperm Injection?
Intracytoplasmic sperm injection (ICSI) is a modification of the IVF procedure. While IVF involves the mixing of sperm with eggs under laboratory conditions, ICSI is a more sophisticated technique in that it involves the injection of one sperm into the egg. ICSI is carried out using a specialised piece of equipment known as a ‘micromanipulator’ by embryologists who hold a licence to perform this technique.



There are two main groups of patients who may be helped by ICSI. They are: -

1. Those couples where the male partner has a low sperm count, reduced sperm motility, an increase in the number of sperm with an abnormal appearance, or where there are antisperm antibodies, that cause sperm to stick together.
   
   
2. Those couples who have had failed IVF treatment.
   

ICSI can also be used with surgical sperm recovery techniques such as PESA or TESA.

What does ICSI involve?
ICSI follows normal IVF procedures up to the point of egg collection and sperm preparation. In ICSI, first the eggs are carefully separated from the surrounding cumulus cells to check their suitability for injection. Eggs must then be injected at the correct stage of maturity and therefore it is usually not possible to inject all the eggs collected. The embryologist will let you know how many eggs are suitable for injection. Those eggs that are unsuitable for injection may then be mixed with the sperm as in normal IVF procedures, but these eggs rarely fertilise.

The ICSI injection process involves holding a single egg by gentle suction at one end of a microscopic tube and then picking up and injecting a single sperm into the centre of this egg using an even finer glass pipette. The eggs are then left overnight in the incubator for fertilisation to hopefully proceed. The next day the embryologist assesses the eggs for fertilisation.

Two days after the egg collection and ICSI, the fertilised eggs (embryos) are assessed again for signs of continued division and the best are selected for transfer into the womb. To allow monitoring of this technique, all the embryos replaced must be from either injected eggs (ICSI) or straightforward IVF, the two cannot be mixed. Embryos not used can be frozen for later use providing they are suitable (your embryologist will advise you at the time of transfer).

Unfortunately, although ICSI can greatly improve chances of fertilisation it cannot be guaranteed. Although most patients will have embryos suitable for transfer some couples may be unlucky and all the eggs may fail to fertilise.

Risk Associated with ICSI Treatment and Genetic Screening
It is easy to understand why a blockage, surgery to the testicles, or powerful drugs (such as those used to treat cancer) would affect sperm quality. However, in some men, the cause of their reduced sperm quality may be genetic due to an abnormality within their chromosomes (chromosomes are the structures within all cells in your body which contain your unique genetic make up). As ICSI bypasses the normal processes for fertilisation, it is possible that genetic defects present in the male may be transmitted to the children. It is now possible to test for some of these genetic abnormalities. This is usually a simple blood test to look at the number and structure of your chromosomes and this test is known as a karyotype test. The results of this genetic testing may provide an insight into the cause of your infertility as well as the risks of transmitting any defect to a child.

Increased incidence of cystic fibrosis (CF) mutation in azoospermic men
About 5 - 10% of azoospermic men (no sperm in ejaculate) who may be suitable for ICSI have congenital bilateral absence of the vas deferens (CBAVD). The vas deferens is the tube that carries sperm from the testes to the penis. CBAVD is often associated with cystic fibrosis (CF). Genetic testing for the genes that cause cystic fibrosis is advisable for azoospermic men with CBAVD and their partners but is not compulsory. We also offer genetic testing to azoospermic men besides those with CBAVD. Genetic counselling is strongly recommended for CBAVD azoospermic men and their partners. The decision to proceed with ICSI in such cases rests with the patients and the clinician, but should you choose not to have genetic testing, this will not be used as grounds to refuse treatment.

Male sub-fertility relating to Y chromosome deletions
Men have an X and a Y sex chromosome; women have two X sex chromosomes. Some sub-fertile men may lack certain genes on their Y chromosome (called Y chromosome deletions). This abnormality may pass the same type of sub-fertility on to their sons. It is important that couples thinking of ICSI treatment are aware of this possibility.

Sex chromosome abnormalities
Where ICSI is used in the treatment of men with azoospermia (no sperm in ejaculate), or severe oligospermia (a very low number of sperm in the ejaculate), there is a risk of an increased frequency of sex chromosome disorders. Sex chromosome disorders (where individuals have an extra sex chromosomes) such as 47XXX, 47XXY and 47XYY occur in about 1 in 700 births for each of the aforementioned abnormalities in children. It is important that couples thinking of ICSI treatment are aware of this possibility.

Birth defects
Follow up studies on birth defects in children born following ICSI treatment carried out at the Brussels Free University (where the ICSI technique was pioneered) indicated that the prevalence of birth defects in live born infants was “within the expected range” when compared against published data. However, it has been recognised that the system used to classify birth defects in the ICSI babies was not the same as that used in the comparison group. As such, the incidence of birth defects in ICSI babies could be understated in the Belgian study. Re-classification of the Brussels data and re-analysis indicates those children born as a result of ICSI are twice as likely to have a major birth defect and 50% more likely to have a minor birth defect. It is generally appreciated that further studies are needed in order to gain more insight into any possible effects. To date, ICSI has been considered to be a technique that offers considerable benefits to patients without increased risks of birth defects. More studies are required, but at present couples should be aware of the possible increase in the risk of birth defects in children conceived after ICSI.

Developmental delays
Recent research papers concerning the follow up of a relatively small number of ICSI children give an indication of possible developmental delay in some children. This has not been confirmed by ongoing follow up studies in the UK.

Other Problems
Other sex abnormaities have been reported as a result of ICSI treatment. There are also reports that the miscarriage rate may be increased in relation to the degree of sperm abnormality.