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INTRACYTOPLASMIC SPERM INJECTION
ISO 9001:2008 certified
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
Revision: 05
Reviewed by V Kay: June 2014
Due for review: June 2015
Authorised by V Kay
QM A McConnell
D:\769840049.doc PL016
© 2004, ACU Dundee – all rights reserved
Page 1 of 9
INTRACYTOPLASMIC SPERM INJECTION
ISO 9001:2008 certified
INTRACYTOPLASMIC SPERM INJECTION (ICSI)
1
Background
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.
Occasionally couples will be found to have a problem with fertilisation at their first
M Rajkhowa, October 2004
Revision: 05
Reviewed by V Kay: June 2014
Due for review: June 2015
Authorised by V Kay
QM A McConnell
D:\769840049.doc PL016
© 2004, ACU Dundee – all rights reserved
Page 2 of 9
INTRACYTOPLASMIC SPERM INJECTION
ISO 9001:2008 certified
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
Revision: 05
Reviewed by V Kay: June 2014
Due for review: June 2015
Authorised by V Kay
QM A McConnell
D:\769840049.doc PL016
© 2004, ACU Dundee – all rights reserved
Page 3 of 9
INTRACYTOPLASMIC SPERM INJECTION
ISO 9001:2008 certified
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
Revision: 05
Reviewed by V Kay: June 2014
Due for review: June 2015
Authorised by V Kay
QM A McConnell
D:\769840049.doc PL016
© 2004, ACU Dundee – all rights reserved
Page 4 of 9
INTRACYTOPLASMIC SPERM INJECTION
ISO 9001:2008 certified
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
Revision: 05
Reviewed by V Kay: June 2014
Due for review: June 2015
Authorised by V Kay
QM A McConnell
D:\769840049.doc PL016
© 2004, ACU Dundee – all rights reserved
Page 5 of 9
INTRACYTOPLASMIC SPERM INJECTION
ISO 9001:2008 certified
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
for carrying out treatment. The chance of success may be higher for obstructive male
M Rajkhowa, October 2004
Revision: 05
Reviewed by V Kay: June 2014
Due for review: June 2015
Authorised by V Kay
QM A McConnell
D:\769840049.doc PL016
© 2004, ACU Dundee – all rights reserved
Page 6 of 9
INTRACYTOPLASMIC SPERM INJECTION
ISO 9001:2008 certified
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 10% 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
Revision: 05
Reviewed by V Kay: June 2014
Due for review: June 2015
Authorised by V Kay
QM A McConnell
D:\769840049.doc PL016
© 2004, ACU Dundee – all rights reserved
Page 7 of 9
INTRACYTOPLASMIC SPERM INJECTION
ISO 9001:2008 certified
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
Revision: 05
Reviewed by V Kay: June 2014
Due for review: June 2015
Authorised by V Kay
QM A McConnell
D:\769840049.doc PL016
© 2004, ACU Dundee – all rights reserved
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INTRACYTOPLASMIC SPERM INJECTION
ISO 9001:2008 certified
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
Revision: 05
Reviewed by V Kay: June 2014
Due for review: June 2015
Authorised by V Kay
QM A McConnell
D:\769840049.doc PL016
© 2004, ACU Dundee – all rights reserved
Page 9 of 9