ICSI

Information for patients

ICSI stands for Intra Cytoplasmic Sperm Injection. The technique was developed in 1992. ICSI is a modification of the IVF procedure whereby each egg is injected with a single sperm to fertilise it. The embryo can then be replaced into the uterus in the hope that a pregnancy may result.

ICSI treatment is suitable for couples with severe male factor infertility where conventional IVF is inappropriate, has failed, or has produced very poor fertilisation previously. The decision to opt for ICSI rather than IVF may be clear-cut but in some cases it is not possible to predict which treatment will give the best outcome.

Circumstances where ICSI might be used include:

• Where the sperm count is very low (oligozoospermia).
• Sperm are abnormally shaped (poor morphology)and/or poor swimmers (poor motility)
• Sperm cannot penetrate their partner's eggs for some reason
• Tubes carrying sperm from the testicles to the penis(vas deferens) are damaged or missing
• Immune system reacts to the sperm they produce (anti-sperm antibodies)
• If the male partner has had a vasectomy which cannot be reversed.
• If sperm has been frozen prior to any procedure or treatment
• If there is an erectile problem i.e. spinal damage.
• When there has been previous poor IVF fertilisation

Because ICSI is a fairly new treatment, it is not yet known whether there is any risk that injecting the sperm into an egg could damage it, with possible long-term consequences for the child. It has been suggested that ICSI is associated with certain genetic and developmental defects in a very small number of children born using this treatment. However, it is also possible that problems that have been linked with ICSI may have been caused by the underlying infertility - rather than by the technique itself.

Another issue to consider is the possibility that if your child conceived as a result of ICSI is a boy, he may inherit his father's infertility. At this stage it is too early to know if this is the case, as the oldest boys born from ICSI have not yet reproduced.

If there is no sperm in the ejaculate but we know that the sperm is still producing sperm then is often possible to retrieve sperm suitable for use in the ICSI process. This is known as 'percutaneous epididymal sperm aspiration' or PESA if from the epididymis. Sperm can also be retrieved from the testicles, a process known as 'testicular sperm extraction' or TESE. For more information about PESA and TESE and what they involve, and whether these may be options for you, please speak to your doctor.

To increase the chances of success of ICSI the ovaries are stimulated with drugs to produce multiple egg development. This may result in an excess of eggs and embryos. Replacing more than one may result in a multiple birth. There are increased pregnancy risks from multiple pregnancy. For this reason only the best one or two embryos are transferred into the uterus.

The ideal would be to replace the embryos one by one in different cycles. We do understand that patients may not have this view and that there is also a cost implication. In rare instances in women over 40 transfer of 3 embryos is allowed which is the legal maximum.

Further information about the ICSI procedure itself is contained in the HFEA ICSI leaflet. It may be possible to freeze spare embryos for later use if they are of sufficient quality (see the HFEA leaflet Freezing and storing embryos.

The first ICSI baby was born in 1992. At that time ICSI was only used for severely low sperm counts. Recent evidence has confirmed that in the first few males born, some now have lower than normal sperm counts. It is probably a gene passed on from the father and may have been the cause of the fathers low count. Their reproductive potential is as yet unknown.

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Preparation for treatment

All couples have at least one or two preliminary consultation to discuss what treatment is best in their circumstances. A semen analysis will be needed before treatment and ideally before the first consultation, so that the results can be discussed.

The services of an independent counsellor are available and there is no charge for the first consultation. This is available through the Winterbourne Hospital. IVF and ICSI treatment is a time-consuming and stressful process, as well as being expensive, and many people benefit from the opportunity to discuss matters with a non-medical person who is familiar with what is involved.

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HIV and Hepatitis testing

It is our policy to screen all couples for HIV, Hepatitis B and C and Chlamydia. These are required by the HFEA prior to licensed treatment. The HIV test is looking for antibodies to the HIV virus which causes AIDS. It is extremely unlikely that any of our patients will have positive test results. Should this occur then the options will be discussed with the patient. The implications of these tests will be discussed fully before they are done. These tests are required before embryos may be stored in our storage tanks. This is to maximise the safety of embryo storage for all patients. Couples who do not wish to have these tests will need to discuss the alternative arrangements, which can be made.

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The treatment cycle

When you are ready to start treatment you should let us know the first day of your period and we will arrange for you to have an ultrasound scan on approximately day 21 of the cycle prior to the treatment cycle. This scan will ensure that no cysts are present on your ovaries and that you are ready to start treatment.

Next the ovaries are stimulated to produce eggs. A variety of drugs can be used for this process and regimes may differ according to each woman's requirements. The Dorset Fertility Services most commonly use the regimes below:-

1. BUSERELIN This drug is called a GnRH agonist. It is given, usually as an injection daily or a nasal spray, one puff in each nostril three times a day. You will be advised to commence Buserelin EITHER on day 21 of the cycle before the treatment cycle OR day 1 of the treatment cycle. Buserelin is continued until the Pregnyl injection is given (see number 3 below). Buserelin has the effect of 'switching off' the woman's ovaries so that we can control precisely the development of the eggs. You should therefore only respond to the stimulant drugs and not your own hormones. It prevents premature natural ovulation occurring before the egg collection. After 10-14 days you will often have a bleed. An alternative similar drug, a GnRH antagonist (see below) can also be used. This starts after your stimulation drug and is used in some circumstances.

2. GONAL F, MENOPUR or MERIONEL (Follicle Stimulating Hormone injections). Depending on the individual, one of these drugs will be given, by subcutaneous injection to stimulate multiple egg growth. These are hormone preparations, similar to the natural hormones that act on the ovary in a spontaneous cycle but much more powerful.

   We will teach you to self-administer these drugs. They are easy to administer and similar to diabetic injections

   These drugs are started once the Buserelin has done its initial work. The starting date will be given on your schedule. You will be asked to attend the hospital for an ultrasound scan to check the ovaries and womb, and, if this is satisfactory, the course of daily Follicle Stimulating Hormone injections will start, usually for about 10-14 days. It is very important to confirm with Centre staff before starting the injections. During this time scans and blood tests will be performed to check that the ovaries are responding and, if necessary, the dose of the injections may be adjusted.

3. CETROTIDE This drug is called a GnRH antagonist. It acts in a similar way to Buserelin but is taken during stimulation only. It blocks the LH surge that would otherwise make you ovulate. You need to take this daily from day 6 of your cycle at the same time as the stimulant drug. The antagonist cycle requires a scan on day 1 or 2 of the menstrual cycle before starting the stimulant drugs on day 2-3. Although you can use other hormone drugs to manipulate the menstrual cycle it is less easy to plan treatment in advance. It is useful in patients who are at increased risk of hyperstimulation.

4. Once the scans show that the ovaries have responded adequately you will need to give yourself an injection of PREGNYL or OVITRELLE. This injection has the effect of stimulating a final maturation phase in the egg and would eventually allow egg release (ovulation) approximately 40 to 48 hours later. The egg collection is timed for 35-6 hours when the eggs have matured but not been released. The timing of the injection is very important and needs to be given in the late evening. The Centre staff will confirm the time of injection and you will get written instructions. You will give this injection yourself.

   BUSERELIN OR CETROTIDE SHOULD NOT BE STOPPED UNTIL THE DAY OF THIS INJECTION.

5. Egg Collection is carried out 35-36 hours after the Pregnyl/Ovitrelle Injection. This is after the final maturation phase of the egg but well before they would naturally be released. This is carried out using ultrasound guidance and a general anaesthetic or sedation is necessary, but you can normally go home later the same day. The vaginal ultrasound probe is similar to the one you have already been monitored with. Egg collection is very safe. Although there are risks of perforation of blood vessel and bowel these are extremely rare. You may experience bleeding from the puncture point in the vagina. This should be less than a period and will quickly reduce to a brown loss. This bleeding will not affect the outcome.

6. Your partner will be asked to produce a semen sample on the same day. His appointment may be before or after the egg collection. He should abstain from ejaculation for 2 days beforehand. The ICSI procedure will be carried out later on the day of egg collection. ICSI can only be performed by a practitioner whose expertise has been examined by the HFEA. After 24 hours it is usually possible to see if fertilisation has occurred. It is important to realise that not all the eggs will be suitable for injection, some eggs may not survive the injection procedure, and some may not show the signs of normal fertilisation. Very occasionally, none of the eggs will be fertilised. This is very rare with ICSI as ICSI is designed to resolve sperm problems. This would suggest that a previously unidentified egg problem has been identified. The embryologist will telephone you on the day after egg collection to tell you the egg news.

7. Embryo transfer is scheduled for two, three or 5 days after the egg collection. It is our policy to replace the best one or two embryos. Transfer of three embryos may only be considered for women over 40. It is important to discuss this number before your treatment starts to have an 'ideal plan'. The procedure is usually very simple, involving the passage of a fine tube through the cervix, high up into the uterine cavity, where the embryos are released in a small volume of fluid. An anaesthetic is rarely needed for this process. We ask you to come with a full bladder: this can make the procedure easier by 'tipping' the uterus in the right direction. The time required at the hospital is usually about 1 hour. Usually the catheter is guided into the middle of the womb under ultrasound control.

8. Luteal Support . After the egg collection the womb lining w, which has been stimulated by oestrogen needs progesterone to change it from proliferative endometrium to secretory endometrium. The embryo will only implant in secretory endometrium. To assist implantation luteal support is required. If luteal support is given the pregnancy rate improves. You need luteal support to maximise your chance. This is usually given in the form of progesterone or hCG. In a natural cycle the collapsed follicle starts to produce progesterone. In a stimulated cycle the hormone levels are far from normal and the corpus luteum will tend not to work as there is no stimulation. Stimulation of the corpus luteum by hCG allows it to make progesterone. More commonly however progesterone is given. This is usually in the form of vaginal pessaries (CRINONE and CYCLOGEST), tablets of micronized progesterone (such as uterogestan) or intramuscular progesterone (GESTONE)

9. After the Transfer

   There is nothing that you could do to reduce your chance of pregnancy. There is no advantage in resting and our advice is to return to your normal activity. If you work; then go back to work. The embryo is very small and sticks to the womb wall (endometrium) by surface tension. It does not implant until about 7 days after the egg collection. The mechanism of success or failure is whether implantation occurs. This is almost always dependant on the genetic capability of the embryo. Your womb having received appropriate oestrogen and progesterone stimulation will be ready. It is unusual for implantation failure to be caused by the womb and common for it to be caused by the embryo. Part of this is a natural mechanism preventing most genetically abnormal embryos from developing into an abnormal pregnancy.

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Am I Pregnant?

It is important to have a pregnancy test within three weeks of the embryo transfer, even if you have had a light period. A urine test can be done 13-15 days after egg collection, which will give you the earliest indication of a possible pregnancy. This can be done at home or we can do the test for you. There would be an additional cost for this. A negative urine test, or a very light period, may yet give a positive test within a few days. Within 3 weeks of embryo transfer it should be clear whether an early pregnancy has been established. An ultrasound scan will be performed in the Fertility Centre 2-3 weeks later for further confirmation.

If the blood or urine test is negative or your period comes you will understandably be very disappointed. If you feel it would help to chat to someone, a member of the Fertility Centre team can always be contacted. When you feel ready we can make you an appointment to come for a follow-up consultation to discuss the future.

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Reasons For Cancellation Of An ICSI Treatment Cycle

1. Unfortunately not all women respond to the medication. If after several days of injections little or no follicular development is seen on the scans we may decide to abandon the treatment and arrange another cycle at a later date, perhaps with a higher dose of Follicle Stimulating Hormone injections.
2. If there are an excessive number of follicles developing in the ovary this may lead to the risk of development of Ovarian Hyperstimulation Syndrome. This is rare. It is also possible that we might collect eggs and freeze all the embryos rather than replace any in this circumstance (OHSS: Please ensure that you have read the hand-out on OHSS and that you have the emergency contact numbers.)
3. If there are no sperm available for injection of the eggs it may be necessary to abandon the cycle before egg collection. This possibility, and the alternative arrangements which may need to be considered, will be discussed at your consultation.

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You May Have Some Of These Questions

Q.

What are my chances of having a baby with ICSI?

A.

The chances of having a baby using ICSI are similar to those for IVF, around 35% for women aged less than 35 years. As with most fertility treatment, success depends on many factors, including the women's age and if the cause of infertility has been identified

Q.

When can I return to work?

A.

You may return to work when you feel well enough. Additional rest will not improve the chance of success.

Many people prefer to be at work the following day, others like to rest at home or take a break from work.

Q.

Do I need to rest following embryo transfer?

A.

No

There is no evidence to show that rest increases your chances of pregnancy. You should carry on with your normal routine once you are discharged from hospital.

Q.

Do I need to do anything special after embryo transfer?

A.

No

We know that nothing you do or do not do (including intercourse) following transfer makes any difference to whether or not you get pregnant. All normal activities can be resumed immediately you feel ready and time of work is usually unnecessary.

If you have any queries whatsoever regarding your treatment please do not hesitate to ask any member of the Fertility Team who will be pleased to help you at any time.

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What You Need To Know Before Your Treatment Begins

Before starting treatment, please ensure that you have been given the following information:-

• The limitations and possible outcomes of the proposed treatment.
• The possible side effects and risks of the treatment.
• The technique involved.
• All alternative treatments.
• The costs involved of treatments and alternatives
• The possible disruption to your life.
• The Availability of counselling facilities.
• The Human Fertilisation and Embryology Authority (HFEA) Regulations.
• The need to give informed consent in writing.
• The Fertility Centre's statutory duty to take into account the welfare of any resultant child from treatment and the welfare of any existing children.

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If You Are The Recipient Of Donated Sperm Or Eggs

It is also important to be aware of:

• Who will be the child's parents under the Act.
• The child's potential need to know about his or her origins.
• The child's entitlement to see information from the HFEA about his or her origins on reaching the age of 18, or on contemplating earlier marriage.

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The Partner's Role

Many men feel rather left out as ICSI treatment so obviously revolves around the woman.

You are welcome to attend with your partner at any time and many partners find the scans particularly interesting.

You will need to produce your sperm sample on the day of the operation to collect the eggs and we ask you to abstain from ejaculating for about 2 days before.

Throughout the treatment you and your partner will be a great comfort to each other.

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