1 Background... 2 2 Male Factor Infertility... 2 3 ICSI... 3 4 Surgical sperm aspiration... 4 5 What is the chance of success?... 6 6 What are the risks?... 7 M Rajkhowa, October 2004 Authorised by V Kay QM A McConnell Page 1 of 9
1 Background INTRACYTOPLASMIC SPERM INJECTION (ICSI) All pregnancies begin with the joining together of a single sperm and egg, this process is known as fertilisation. The single cell that results will usually go on to develop into an embryo and hopefully later a baby. This would normally take place in the woman s fallopian tubes, which allows eggs to pass from the ovaries into the womb. With in vitro fertilisation (IVF), fertilisation is allowed to happen by mixing each egg with a number of prepared sperm in a test tube (hence the name test tube baby treatment ). Whilst this has obviously been a major advance in the treatment of infertility it can almost be considered as simply changing the site for fertilisation and all other major steps remain the same. Unfortunately, for a number of couples, their infertility can be due to a problem with fertilisation itself. Usually this is due to either: 1. A low number of sperm about 100,000 are required normally to have a reasonable chance of fertilising each egg. 2. A fault in the way the sperm works either the sperm do not move properly or have difficulty in binding to the egg. 2 Male Factor Infertility Such cases are referred to as male factor infertility and can often be predicted from a sperm analysis (count and motility) alone, before any attempt is made at infertility treatments or where there is known to be a blockage in the male reproductive organs. M Rajkhowa, October 2004 Authorised by V Kay QM A McConnell Page 2 of 9
Occasionally couples will be found to have a problem with fertilisation at their first attempt at IVF, this is after all the only chance we get to observe the sperm and egg together. The problem may lie with either the sperm, even though the sperm analysis was normal, the egg or both. If the number of eggs that fertilise (the fertilisation rate) is very few or none at all (failed fertilisation) then further attempts at IVF are also likely to fail. If a problem with sperm numbers, function or fertilisation is expected then usually the recommended treatment is a special form of IVF called Intracytoplasmic Sperm Injection (ICSI). 3 ICSI Intracytoplasmic sperm injection (ICSI for short) is a technique which involves the injection of a single sperm into an egg and so bypasses all the normal steps in fertilisation. Developed in Brussels, the first successful pregnancy was recorded in 1992, fourteen years after the first IVF baby was born. This technique was introduced into this Unit in October 1995, following the granting of a treatment licence by the Human Fertilisation and Embryology Authority. Because ICSI is in fact a specialised version of IVF for most couples there is no apparent difference from that of conventional IVF (please refer to the IVF information sheet). The drugs, ultrasound scans and egg recovery are identical and the men are asked to produce a sample by masturbation. However the handling of the eggs and sperm (the gametes) by the embryologists in the laboratory is very different. Special treatment of the egg is needed before it can be injected, for example the M Rajkhowa, October 2004 Authorised by V Kay QM A McConnell Page 3 of 9
cells surrounding it must be removed, and the sperm prepared so that individual sperm can be recovered for injecting into each egg. Sperm injection 4 Surgical sperm aspiration For a number of couples the man will not have any sperm in his sample (or ejaculate). This can be due to a blockage either after surgery (usually after vasectomy or a failed attempt to reverse a vasectomy) or infection or simply something that the man was born with (a congenital problem). Sperm can be obtained in some of these cases by one of two types of operations, either; 1. Taking a few drops of fluid from the tubes that carry sperm away from the testicle (epididymis) using a small needle. This operation (percutaneous epididymal sperm aspiration or PESA) is carried out under general or local M Rajkhowa, October 2004 Authorised by V Kay QM A McConnell Page 4 of 9
anaesthetic and depending on the reason for the blockage usually has a very high chance of recovering sperm. 2. For those that have no obvious blockage and very little sperm production in the testicle, or when an attempt at PESA has failed, then a small piece of the testicle can be removed and in half or more of these cases sperm can be recovered. This operation is either carried out with a needle or small incision and usually requires a deep sedation or general anaesthetic (testicular extraction of sperm by aspiration/excision or TESA/ Testicular biopsy). These are both quite simple procedures and only TESA/ Testicular biopsy is likely to require stitches afterwards. That is not to say that they are completely free of risk or complications; there will usually be a degree of bruising and very occasionally a wound infection. TESA/ Testicular biopsy can interfere with the blood supply to the testicle, and for example reduce its ability to produce hormones, which though uncommon is more likely after a repeat procedure. For this reason we prefer to keep the number of these operations to a minimum. It must be stressed that these procedures are not needed for all couples and you will be informed during your first assessment whether these operations are required. For those couples that do require surgical recovery of sperm there is a small chance that we are unable to recover sperm, particularly when TESA is used. Occasionally a diagnostic procedure maybe carried out prior to treatment. However in all cases there is no guarantee that sperm will be recovered on the day of egg recovery. Therefore a few couples will find out on the day that eggs are available, that ICSI cannot be carried out as no sperms were recovered. The options then are to either destroy the M Rajkhowa, October 2004 Authorised by V Kay QM A McConnell Page 5 of 9
eggs, freeze them or use donor sperm to fertilise them (Donor Insemination DI). In the past, DI treatment with donor sperm would have been the only option for such couples and in fact a number may have considered this or even had DI cycles carried out (especially if this was before ICSI became widely available). You will be informed before your treatment whether you are at risk of this happening and it is obviously important that you have considered the option of using donor sperm. 5 What is the chance of success? When compared with IVF, the number of embryos created as a result of ICSI is usually lower, and therefore fewer embryos are available for transfer and freezing. There are a number of factors contributing to this; Not all eggs are sufficiently mature to be injected. The injection process can damage some eggs, usually because of abnormalities of the egg, resulting in technical difficulties in achieving the injection of the sperm into the egg. The egg survival rate following the injection procedure is about 94%. Not all eggs fertilise even though a sperm has been injected into the egg. This may be caused by the failure of the egg and sperm to react together. The average, normal, fertilisation rate of injected eggs is approximately 60%. In addition there are a number of eggs which fertilise abnormally (currently 6% of injected eggs) and these embryos cannot be returned to the womb. Over the last three years, the chance of success (or live birth rate for each treatment started) has been about 28%. Individual couples may have a higher or lower chance of success depending on the reason for their infertility, that is the indication M Rajkhowa, October 2004 Authorised by V Kay QM A McConnell Page 6 of 9
for carrying out treatment. The chance of success may be higher for obstructive male factor, for example after failed vasectomy reversal. It can be lower in other cases, particularly for cases of failed fertilisation following IVF. In addition, the age of the woman plays an important role in the quality of the eggs, resulting in older women doing less well. The doctor that you see will be able to give you an estimate of your own chance of success taking all these factors into account. We normally recommend that the best one or two embryos are transferred. Three may be transferred in exceptional circumstances only in women aged 40 or over. The reason for restricting the number of embryos transferred is to avoid the risk of multiple pregnancy. Twins, but more particularly pregnancies with triplets or more, carry significant risks (there is still a chance that a triplet pregnancy will occur, even when only two embryos are transferred). There is an increased risk of miscarriage and premature labour. Largely because of prematurity the babies are also at increased risk of long term health problems or handicap. Around one quarter of ongoing pregnancies are twins and less than 1% are triplets. 6 What are the risks? The risks to the woman are no different from those of IVF (please refer to the IVF information sheet). For those men requiring surgical sperm recovery the risks are small and already outlined above. M Rajkhowa, October 2004 Authorised by V Kay QM A McConnell Page 7 of 9
For patients that are offered ICSI this will be the only real chance that they will have of establishing a pregnancy using their own gametes. A few patients will still have a chance of conceiving on their own without any form of treatment but even for them the chance will be very small. When faced with such a choice it is not surprising that so many patients decide to go ahead with treatment. It is however a relatively new technique and a major step away from all treatments that have been used before where the actual fertilisation process is often encouraged but not bypassed as with ICSI. As with all new techniques we have to be concerned about any possible effects for the children that result from this treatment. There are two main areas of concern; 1. Some of the couples requiring ICSI, or rather the male partners, may be at increased risk of passing on problems to their children. The most obvious example is for men with a very low sperm count without obvious explanation where there is a reasonable chance that some of the instructions carried within every cell (the genes) that control the production of sperm may be missing or defective. Because of how these genes are organised then any male children may have the same type of fertility problem as their father. 2. In men where there are no sperms in the ejaculate, it is possible that this may be due to congenital absence of the vas (a tube which carries the sperm away form the testes). This may be associated with the presence of one copy of an altered gene, which causes cystic fibrosis, without having any symptoms related to Cystic Fibrosis itself. (Two copies of this gene are required to actually cause Cystic Fibrosis). We do carry out a blood test on men with absent sperm in the ejaculate (where they have not previously undergone a vasectomy operation), M Rajkhowa, October 2004 Authorised by V Kay QM A McConnell Page 8 of 9
for this gene (Cystic Fibrosis gene mutation), to see if there is any risk of passing this gene to an offspring. 3. There are links with other problems but these apply only to a clearly identified minority and are best discussed on an individual basis. 2 The possibility that the ICSI process itself may in some way harm the baby that results. Until recently, the evidence from follow up studies on children born following ICSI was very reassuring. No child, however it is conceived, can be guaranteed to be free of problems. About 1 in 30 of all children will be born with a minor or major problem that can affect their quality of life in some way. This can vary from simple skin blemishes through to major heart problems, etc and original studies suggested that none of these problems were significantly increased in ICSI children. However, this data is now being challenged and it is possible that these problems may be increased by a further 1-2%. The intention is not in any way to frighten people off having this treatment but simply point out that the treatment may not be entirely risk free for the child. Because no two couples are the same these points will be discussed in detail with you by the doctor that sees you in the Unit. Counselling will also be available from our independent counsellor and any aspect of the above can also be discussed with the senior embryologist responsible. You may also wish to read the HFEA s own leaflet on ICSI from the website www.hfea.gov.uk M Rajkhowa, October 2004 Authorised by V Kay QM A McConnell Page 9 of 9