INTRA-CYTOPLASMIC SPERM INJECTION (ICSI)

What is ICSI and why is it necessary?

Intra-Cytoplasmic Sperm Injection (ICSI) refers to the technique of injecting a single sperm into the centre (cytoplasm) of the egg. In natural conception a large number of sperm surround the egg and many attach to the outside, but only one sperm penetrates and fertilises each egg. In IVF we mimic nature by adding a large number of sperm to the dish containing the egg. When fertilisation does not occur, it is usually because the sperm cannot attach to or penetrate the egg. This can be because of a fault with either sperm or egg. When abnormal fertilisation occurs, it is usually because more than one sperm has entered the egg.

ICSI overcomes problems of failed or abnormal fertilisation by placing a single sperm directly in the centre of the egg. Any problems with ICSI arise because this one sperm may not be the ‘right’ one, or because the injection procedure damages the egg. ICSI is relatively new and as such should still be regarded as experimental.

Which couples require ICSI?

We currently use ICSI in couples with reduced semen counts or where there is reduced sperm motility, in which the risk of fertilisation failure is increased, and also those who have previously had very low or no fertilisation in an IVF cycle.

The bulleted points below detail the circumstances in which we use ICSI:

• Sperm concentration less than 15 X 10⁶/ml

OR

• Progressive sperm motility (categories a+b) less than 32%

OR

• Normal sperm morphology less than 2%

We also use ICSI in the following situations:

• Reduced fertilisation rate after conventional IVF: <40% normal fertilisation with at least 4 mature eggs collected
• Failed fertilisation after conventional IVF
• Use of Epididymal/Testicular sperm
• Use of frozen stored sperm (this is not mandatory but we do recommend it in certain situations)
• Patients who have had ICSI in previous IVF cycles should continue to have ICSI in future cycles

How is ICSI carried out?

Except for the method of fertilisation, every other aspect of your treatment cycle is identical for ICSI and convention IVF; including hormonal stimulation, egg recovery, producing the sperm sample and embryo replacement.

On the day of ICSI, the embryologist carefully removes the outer (cumulus) cells from each egg, using an enzyme normally produced by sperm. This enables the embryologist to see inside the egg using a high powered microscope and assess if the egg is ‘mature’. All eggs can be inseminated by IVF, but only mature eggs can be used in ICSI. In most treatment cycles, approximately 80% of eggs are mature. The sperm are prepared as normal for IVF. The embryologist then picks out individual live sperm, of normal appearance and injects one into each egg, using a special glass needle (see diagram below).

After ICSI the eggs are returned to the incubator overnight and checked for fertilisation the following morning, as for conventional IVF.

How successful is ICSI

Approximately 6 out of every 10 eggs will fertilise successfully with ICSI, similar to IVF. The reasons ICSI fertilisation is not 100% successful are:

1. Immature eggs cannot be injected
2. Some eggs may be damaged by the injection procedure. This appears to be related to the properties of the inner egg membrane.
3. Even when injected directly into the egg, many sperm are not capable of ‘activating’ and fertilizing the egg.

Following successful fertilisation, embryo development is similar for ICSI and IVF. Following embryo transfer, pregnancy rates are similar for IVF and ICSI. Many clinics report higher success rates for ICSI compared to IVF, but this is only because the women having ICSI are relatively more fertile.

 

What risks are associated with ICSI treatment?

ICSI offers the opportunity of success for couples who could not achieve it otherwise. However, it is still a relatively new technique and was not preceded by long term animal studies, as is usually required for new medical techniques or drugs. It is known that abnormal sperm production, as is the case in men with very low sperm count or absent sperm in the ejaculate, can be associated with genetic defects in the male. As ICSI bypasses the normal processes of sperm ‘selection’ and fertilisation, these genetic defects may be transmitted to the children. It is also possible that the egg may be damaged by the injection procedure. Theoretically, this can result in damage to the resulting embryo if the damaged egg is fertilized normally. Although the great majority of babies born by ICSI appear to be normal, the full implications of treatment will not be known for many years, and you should be aware of the possible risks of this procedure as detailed below. For further information please see our main Assisted Conception Information booklet.

Chromosomal abnormalities

Men with very low sperm counts are more likely to have a rearrangement of their chromosomes – known as a balanced translocation (approximately 3 – 5%). This will be discussed with you in clinic and a blood test can be arranged if this is the case. Many of these rearrangements involve the chromosomes responsible for sex determination (XX for women and XY for men). If there is a rearrangement, this can lead to a chromosome abnormality in any baby conceived. Some men with low sperm counts will have a small deletion of a portion of their Y chromosome i.e. a tiny genetic fragment may be missing. This will not be found in routine chromosome testing.  This deletion may be passed on to a baby boy and may cause him to have a lowered sperm count when he grows up.

 

What happens if your chromosome test shows a rearrangement?

If an abnormality is found, the chance of a pregnancy is less. The abnormality may increase your chance of miscarriage and there may be implications for any child conceived. The child may be unaffected, it may display the same abnormality as its father or it may inherit an abnormality, which will affect the child more than the father. If an abnormality is found in your chromosomes this would be discussed with you in detail by the Consultant and you would be referred to the Regional Genetics service for further counselling.

Birth defects

The evidence on whether or not babies born after IVF or ICSI treatment have a greater risk of birth defects is not yet completely clear, and more studies are needed in order to gain further insight into these possible effects. In 2005, a major European review of children born after ICSI and IVF (followed up until 5 years of age) found that so-called major birth defects involving the heart, lungs, musculoskeletal or gastrointestinal systems, were present in about 2% of naturally conceived offspring, 4% of children conceived by routine IVF, and in 6% of children conceived after ICSI. A substantial proportion of the abnormalities in the ICSI children were problems in the development of the urinary or genital organs, especially in boys. However, all of them were correctable by surgery and they reflected paternal genetic factors than the ICSI procedure itself.

Minor birth defects were present in about 20% of naturally conceived offspring, 31% of children conceived by routine IVF, and in 29% of children conceived after ICSI. Minor anomalies are those which do not in themselves have serious medical, functional or cosmetic consequences for the child. More recent studies reported no difference in the risk for any anomaly or specific anomalies after different types of IVF technologies including ICSI.

Developmental delay

Some research papers on follow up of small numbers of ICSI children suggest possible developmental delay in some children conceived using the ICSI technique. This has not been found in ongoing follow up studies in the UK and Europe.

 

If you have any questions you feel need answering we would be pleased to do this when you next attend clinic.

“ICSI is relatively new and as such should still be regarded as experimental”