Intra-Cytoplasmic Sperm Injection (ICSI)

1 Intra-Cytoplasmic Sperm Injection (ICSI)

Intra-Cytoplasmic Sperm Injection (ICSI) is a relatively new technique when compared with standard IVF but has been in use for around 15 years. It is based on In Vitro Fertilisation (IVF) principles. The key difference between the 2 methods is how fertilisation takes place. Whereas in IVF, collected eggs and selected sperm are mixed together in a dish and fertilisation occurs naturally, in ICSI, a single sperm is forced into the egg, for fertilisation to occur.

When can ICSI be Used?

Intra-Cytoplasmic Sperm Injection (ICSI) can be a very useful tool in treating male infertility although it can also be used for various causes of female infertility too. Examples of when ICSI may be useful include;

Low sperm counts in men (oligozoospermia),

Sperm cells appear abnormal or are abnormally shaped (poor morphology),

Sperm do not move or swim normally (poor motility),

Sperm cannot pass through the cervix due to problems with the cervical mucus or production of anti-sperm antibodies by the female which attack and kill sperm,

Sperm are incapable of penetrating the egg for fertilisation to take place,

Sperm cannot pass into the urethra during ejaculation. There may be many reasons for this including vasectomy, failed vasectomy reversal, retrograde ejaculation and others,

For men with impotence, erectile dysfunction and other sexual problems,

Failure of previously tried IVF or other assisted conception methods.

What are the Chances of Success?

These are similar to the success rates in IVF - around 30% in couples chosen correctly. As with other methods, your actual success rate depends on a number of factors which include;

maternal age: as women get older, the quality of their eggs decreases and the chances of conception also decline,
the cause of subfertility: the more complex and more numerous the reasons for the failure to conceive naturally, the lower the success rates with IVF,
the number of embryos implanted: the right balance must be found between implanting a few healthy embryos to ensure reduction of complications during pregnancy versus insertion of a larger number of embryos to ensure that some will survive even if others perish,
the expertise of the clinic: there are differences between success rates at different clinics depending on their experience and degree of expertise in this field.

What is the Difference Between ICSI and IVF?

Essentially, both procedures are identical for the majority of steps including investigation, stimulation of ovaries, tracking the follicle, egg collection, sperm collection, transfer of the embryo and confirmation of pregnancy. It is at the key stage of fertilisation that the difference becomes obvious.

In IVF, fertilisation occurs naturally as selected sperm are mixed with eggs in a glass dish and left for up to 20 hours. Fertilisation is therefore a natural process, albeit in an unnatural environment. However, in ICSI, a selected single sperm is injected directly into the centre of the egg. Fertilisation in this instance can occur where sperm were previously unable to penetrate the egg on their own for various reasons.

Because the various causes of male related infertility can include genetic disorders, experts usually advise men to undergo genetic testing. If the presence of a genetic disorder is confirmed, it may be passed onto the baby conceived using assisted conception methods. In contrast, those with genetic disorders who are trying to conceive naturally often fail to conceive because of the presence of this genetic disorder and therefore no inheritance of this disorder takes place. The advent of assisted conception methods therefore increases the likelihood of genetic diseases being passed onto your offspring. It is therefore vital for the treating clinic to offer adequate and appropriate counselling before any decision is taken by the couple on both genetic testing and subsequent ICSI.

Before sperm can be used in this way, they are tested for the presence of infections such as Hepatitis B and C and HIV.

How is ICSI Carried Out?

ICSI is usually carried out in an induced cycle, i.e. ovulation is artificially induced using hormone drugs. Please read "Drugs Used in Infertility" for further details regarding this subject. Using induced cycles, a number of eggs may be harvested from the ovaries at the same time.

To understand the complexities of ICSI, it is best to divide the whole process into stages similar to IVF as follows;

1. Investigation

Before anything else can be done, the clinic needs to assess both the male and female in the couple to ascertain the reason for the lack of conception. This is done in the ways described in the previous pages and may take several days or weeks to complete depending on where the various investigations are carried out.

2. Ovarian Stimulation.

Various drugs are used to take control of the menstrual cycle. Other hormonal drugs are then used to stimulate the ovaries into starting the egg maturation process. Several eggs will start to develop simultaneously.

3. Developmental Checks

Blood tests and vaginal ultrasound scans are carried out regularly to assess the development of the eggs. From here on, timing is crucial as an injection of another hormone is given approximately 36 hours before egg collection. This injection forms the final phase of egg maturation, at the end of which, eggs will be ready for harvesting.

4. Egg Collection

This is done immediately after Step 3. If done too early or too late, the chances of successful conception are greatly reduced. Collecting eggs can be done in 2 ways;

Ultrasound guidance: this can be done with a local or general anaesthetic and takes around 30-60 minutes. A vaginal ultrasound scan is used to guide a needle through the vagina and into each ovary in turn. The needle is guided to each egg sac and the eggs are sucked into the needle and retrieved. Generally, this is the favoured approach these days.

By laparoscopy: this is done using a general anaesthetic. A thin telescope like instrument containing a light and camera is inserted through a tiny incision, into the abdomen to view the pelvic organs. A needle is then inserted to the egg sacs to suck out the eggs. This procedure is used less often these days.

5. Sperm Collection

This can be done in 2 ways;

Using your own sperm: a sample is produced by masturbation very close to the time of egg collection. This is done either close to or at the clinic. This is vital as the laboratory requires immediate access to the sperm. Sperm may also be collected using various surgical sperm extraction procedures. They can be extracted directly from the epididymis using methods such as Percutaneous Epididymal Sperm Aspiration (PESA) or Microsurgical Sperm Aspiration (MESA), or from the testicles using Testicular Sperm Extraction (TESA).

Using a sperm donor: if this option is chosen, then sperm will already be available to the clinic. Many samples may be kept by the clinic and a suitable sample is selected. The discussion about donor sperm and which sample to use is usually had at the outset of treatment. Clinics may try to match certain characteristics of the sperm donor to the male partner in the couple. Traits such as hair colour, eye colour, height and build can be matched. These sample are kept frozen for 6 months and tested for various sexually transmitted infections such as Hepatitis B and HIV before being deemed suitable for use.

Once a semen sample is obtained, sperm are separated from the plasma (consisting of seminal fluid), washed to remove chemicals and infections and spun using a centrifuge at high speed so that the "best" sperm can be selected.

6. Fertilisation

This is the key difference in ICSI. A single sperm is used to fertilise a single egg by injecting the sperm directly into the egg. The sperm thus bypasses all obstructions and dangers from the male directly into the egg.

7. Preparing the Womb

2 days after egg collection, women are given a dose of progesterone by pessary, gel or injection. This starts the process of preparing the womb (uterus) to receive the embryo by thickening the womb lining (endometrium).

8. Transferring the Embryos to the Womb

Between 2-5 days after fertilisation has taken place, 1-3 of the best and most healthy embryos are selected for transfer. This is done by inserting a catheter into the vagina, through the cervix and into the inside of the uterus. The appropriate number of embryos are then injected through the catheter and into the womb. Implantation occurs naturally. Following embryo transfer, women are often advised to stay lying down for several hours.

The decision as to the number of embryos to insert is a complex one. If not enough are inserted, the chance that none will survive is greater. But if many are inserted, the chance of a multiple pregnancy with all of it's complications is greater.

9. Dealing with the Remaining Embryos

Once the correct number of embryos are inserted into the womb, a decision is made on the remainder. The choices include;

discarding the embryos if no further attempts at IVF are to be made,
freezing the embryos for use in another IVF cycle. In these cases, steps 1-6 are eliminated as embryos are already present,
the embryos are donated to another couple.

10. Confirming Pregnancy

A pregnancy test can be performed 2 weeks after embryo transfer, either at home by using a urine pregnancy test or at the clinic by either a urine pregnancy or blood test. If pregnancy is confirmed, the usual antenatal care will be initiated in most cases. In some, there will be extra input and closer monitoring of the pregnancy if it is deemed to be at higher risk. Higher risk cases include;

women aged 40 years of over,
multiple pregnancy,
a history of previous complications of pregnancy including recurring miscarriage, stillbirths or developmental anomalies,
a history of maternal complications such as pre-eclampsia.

What are the Risks of ICSI?

1. Disability

It has been suggested that injecting sperm directly into the egg may damage the sperm causing disability to the child. It has also been suggested that the risks of genetic disorders are also greater. However, this is not proven as ICSI is a relatively new procedure. Research into the effects and long term risks of ICSI continue.

2. Future Infertility

It has also been suggested that males born by ICSI methods may themselves have future infertility problems inherited from their fathers. Since the oldest males born by ICSI are still young teenagers, this remains unproven at this time.

3. Miscarriage

The risk of miscarriage may be greater in ICSI pregnancies as these pregnancies are conceived with sperm that would otherwise be incapable of conception. Once again, research is ongoing to prove or disprove this theory.

4. Side Effects from the Use of Fertility Drugs

Side effects can include: abdominal pain and discomfort, flushing, breast pain, mood swings and headaches as well as many other symptoms. Although most of these symptoms are mild, some may by troublesome and require treatment such as pain killers.

5. Pain

Some procedures can by uncomfortable, especial egg collection, after the anaesthetic wears off. This again requires pain killers sometimes.

6. Infection

This is rare these days as meticulous preparation of sperm takes place before fertilisation. All instruments used are sterilised in the usual way and invasive procedures are done in sterile operating theatres.

7. Ovarian Hyper-Stimulation Syndrome (OHSS)

This is a well recognised potential side effect of trying to artificially stimulate the ovaries to produce eggs for ovulation. It occurs with the use of some of infertility drugs. OHSS can be dangerous and usually requires hospital assessment and monitoring in severe cases.

Fertility drugs over react and excessively stimulate the ovaries. Multiple cysts develop on the ovaries and fluid builds up in the abdomen. In more severe cases, the ovaries swell and fluid fills the abdomen and chest cavities. There then develops a risk of blood clots and kidney damage.

Symptoms include;

abdominal swelling or distention
nausea and vomiting
abdominal pain
breathlessness
feeling faint

Women who are taking infertility drugs and who experience these symptoms should contact their clinic immediately. Treatment for infertility will usually be stopped. In severe cases, you may require urgent admission to hospital.

8. Ectopic Pregnancy

An ectopic pregnancy is where the embryo attaches to the wall of a fallopian tube rather then the wall of the womb. This unfortunately leads to a non-viable pregnancy as the fallopian tubes are not able to sustain the growing embryo beyond 8-10 weeks. If left untreated, the tube will rupture, causing bleeding inside the pelvis. This is a potentially fatal situation for the mother. The embryo must therefore be surgically removed. It is sometimes possible to save part or all of the fallopian tube though generally, the tube is also removed.

Symptoms of an ectopic pregnancy include; vaginal bleeding, lower abdominal pain, shock and death. The chances of ectopic pregnancies seem to be higher in women undergoing IVF, possibly as a result of their tubes already being damaged, thus necessitating the need for IVF in the first place.

9. Multiple Pregnancy

The chances of having multiple pregnancies is considerably higher with ICSI than with natural conception. The more embryos are transferred, the greater the risk. Also, the greater the number of embryos that succeed in implantation, the greater the complication rate for the pregnancy as a whole. Problems include;

an increased risk of miscarriage,
an increased risk of low birth weight,
an increased risk of stillbirths.

10. Emotional Problems

This can be a long standing issue contributing to the lack of natural conception or it may be as a result of going through the sometimes difficult and psychologically traumatic process of assisted conception. Either way, most well run and successful clinics will offer counselling for couples before and throughout the ICSI process. Couples should feel free to discuss their fears and concerns. They should also be encouraged to be open with themselves and discuss how they feel with their partners. Having access for both males and females in a couple to counselling is vital for the process of assisted conception to be successful.