Intra-Cytoplasmic Sperm Injection (ICSI)

Intracytoplasmic sperm injection (ICSI) was introduced into clinical treatment for certain types of infertility in 1992.

ICSI is a type of IVF treatment that involves the injection of a single sperm straight into each egg. The fertilised egg (embryo) can then be transferred into the womb of the woman as in a normal IVF cycle. ICSI is a relatively new technique, but has already helped many couples.

What does it involve?
ICSI is similar to conventional IVF in that gametes (eggs and sperm) are collected from each partner. To achieve fertilisation, a single sperm is taken up in a fine glass needle and is injected directly into an egg. The eggs are incubated and examined the following day for fertilization. Usually two embryos are transferred back to the uterus after two to three days fertilization.

Not all eggs collected will be of a high enough quality or mature enough to be suitable for injection. Also, some eggs may not survive the injection process.

When is ICSI used?
In conventional IVF the eggs and the sperm are mixed together in a dish and the sperm fertilise the eggs naturally. ICSI bypasses the natural processes involved in a sperm penetrating an egg, and is therefore used when there are problems that make it impossible to achieve fertilisation naturally or by conventional IVF. Circumstances in which ICSI may be appropriate include:

• When the sperm count is very low
• When the sperm cannot move properly or are in other ways abnormal
• When sperm has been retrieved directly from the epididymis (PESA) or the testicles (TESA/TESE), from the urine, or by electroejaculation
• When there are high levels of antibodies in the semen
• When there have been previous fertilisation failures

What are the risks of ICSI treatment?
ICSI is an invasive technique and may also use sperm that would not otherwise be able to fertilise an egg. For these reasons, concerns about the potential risks to children born as a result of ICSI have been raised, and several follow-up studies have been published. ICSI is still a relatively new technique, and all children conceived using ICSI are still very young. Consequently, these follow-up studies involve relatively small numbers of children and do not include effects that may only be seen in older children or in the next generation. Clearly, more studies are needed, but the use of ICSI has been potentially linked with certain genetic and developmental defects as explained below:

1. Possible inheritance of genetic and chromosomal abnormalities:
   
   • Inheritance of cystic fibrosis gene mutations
     Some men who have no sperm in their semen are found to have congenital bilateral absence of the vas deferens (CBAVD). In this condition, the tubes that carry sperm from the testes to the penis are missing. Two thirds of men with CBAVD are also carriers of certain cystic fibrosis mutations. Men with CBAVD and their partners may therefore wish to undergo genetic testing before proceeding with ICSI. Your clinic should be able to give you more information and counselling about the implications of genetic testing.
   • Sex chromosome defects and the inheritance of sub-fertility
     A small proportion of sub-fertile men have parts of the Y chromosome missing. Certain genes on the Y chromosome have been shown to be involved in the production of sperm, and deletion of these genes may be responsible for some men having few or no sperm in their semen. Consequently, using sperm with such deletions to create an embryo may result in the same type of sub-fertility being passed from father to son.
     Abnormal numbers or structures of chromosomes, particularly the sex chromosomes (X and Y), may be associated with infertility in both men and women, and babies born from ICSI treatment may have a slightly increased risk of inheriting these abnormalities. Studies have found that up to 3.3% of fathers of ICSI babies have abnormal chromosomes. It is estimated that up to 2.4% of the wider population have a chromosomal abnormality.
2. Novel chromosomal abnormalities:
   The complexity of the process of egg and sperm production means that even if an individual possesses a normal number of chromosomes, their gametes could potentially have an abnormal number. It is not possible to detect beforehand which eggs or sperm have chromosomal abnormalities, and gametes that might not have been able to participate in natural fertilisation could therefore be used in ICSI. Babies born after ICSI have been reported to have new chromosomal abnormalities in up to 3% of cases. The rate in the general population is around 0.6%.
3. Possible developmental and birth defects:
   
   • Birth defects
     There is not yet any clear evidence whether ICSI results in higher rates of birth defects. The number of babies reported to have major birth defects, such as cleft palate, is between 1 and 5% in both the general population and in babies born following ICSI. Studies suggest that minor abnormalities occur in up to 20% of ICSI babies, compared to up to 15% of the population. More studies are needed in order to gain further insight into these possible effects.
   • Developmental delays
     One recent study that followed up a relatively small number of children has given an indication of possible delays in mental development at one year in some children born following ICSI. Other studies have not shown this link and further research is needed in this area.
4. Possible risks during pregnancy
   
   • Miscarriage
     With ICSI, it is possible that abnormal sperm and eggs which would not normally be able to produce a viable embryo , could be used, increasing the chance of an abnormal embryo being formed. Many abnormal embryos will not implant into the womb and grow, but some might, leading to a possible higher risk of miscarriage. It has been reported that the risk of miscarriage increases in proportion to the severity of male infertility.

Glossary
Gametes - male sperm and female eggs

Epididymis - coiled tubing outside the testicles which store sperm

PESA - Percutaneous Epididymal Sperm Aspiration, which involves sperm being retrieved directly from the epididymis using a needle

TESA - Testicular Sperm Aspiration, which involves sperm being retrieved directly from the testes using a needle

TESE - Testicular Sperm Extraction, which involves sperm being retrieved from a biopsy of testicular tissue.

electroejaculation - the use of electrical stimulation to aid production of a semen sample in impotent or paralysed men.

Azoospermia - Complete absence of sperm in the ejaculate

Oligozoospermia - Low numbers of sperm in the ejaculate.

This information was provided by the HFEA