Treatments and investigations



Until the technique of micro-assisted fertilisation became readily available, the alternatives for couples where the male partner had a very poor or even zero sperm count were quite stark. The choices were:- to give up, try IVF (if some sperm were available) as a "test of fertilisation", bypass the problem by means of donor insemination or consider the option of adoption.

When faced with the fact that the sperm count is extremely low, couples often say "But it only takes one sperm to fertilise an egg". That of course is quite true, but natural fertilisation is a numbers game when it comes to sperm. If in normal fertility several hundred million sperm are deposited by intercourse at the cervix at ovulation, only a few hundred sperm actually reach the egg. The vast majority trickle out of the vagina, are destroyed by vaginal acidity, are lost in glands in the cervix, go down the wrong tube (towards the ovary that is not ovulating), go down the right tube but miss the egg altogether. If the sperm count is very low, it is quite likely that no sperm will survive to reach the egg.

In standard IVF programmes, up to 100,000 specially prepared sperm are added to each egg and incubated. If the original sperm sample is very low in numbers and/or poor in quality, the final sperm preparation is likely to be poor. In such situations, even though the sperm have been placed in direct contact with the egg, fertilisation may very well not occur. For this reason, in the past after considerable counselling and planning, it was quite common practice for clinics to split the patient’s eggs between the partner’s sperm and those of a matched donor. If the partner’s sperm brought about fertilisation, then those were the embryos that would be transferred. However, if the partner’s sperm failed to fertilise the eggs, there was the back-up of the donor sperm fertilised eggs.

What is ICSI?

The development of micro-assisted fertilisation by means Intra-Cytoplasmic Sperm Injection or ICSI is the most major advance in achieving successful pregnancy, as long as some live sperm (even in very very low numbers) can be obtained.

ICSI is an extension of the normal IVF programme. Up to the point of egg retrieval, the management of the treatment cycle is identical to standard IVF. But instead of incubating each egg with prepared sperm, ICSI is performed instead. The resulting embryos are transferred as in standard IVF.

In ICSI, a prepared egg is held while a single sperm is injected into it thereby placing the genetic material within the sperm inside the egg. This does not mean the egg is fertilised, but at least there is now a chance for that complex process to commence. This is a major over-simplification. If you consider that an egg cannot be seen with the naked eye, that a sperm is minute in comparison and has to be caught and immobilised and then injected into the egg using a glass needle far finer than a human hair, you begin to get some idea of the complexity and skill of the process. It is also very time consuming.

Having the necessary tools to carry out ICSI is of course essential, but far more vital is to have a skilled ICSI trained operator. Embryologists need to undergo specialised training in the technique and must satisfy the high standard of competence required by the Human Fertilisation & Embryology Authority before being granted a licence as ICSI practitioners.

Who is suitable for ICSI?

ICSI may be suitable for the following groups of patients:

  • failed fertilisation at IVF.
  • very poor sperm preparations which would be unsuitable for IVF:
    • - very low sperm numbers
    • - very poor motility
    • - very high abnormality rate
  • when the sperm count is zero and donor (sperm) insemination is not wanted

Essentially, as long as a man is producing some normal sperm, ICSI is possible. Even if the sperm count is zero, it may be possible to perform a surgical procedure to obtain sperm, as long as the testicles are normal and not poorly developed or seriously damaged. This would initially be assessed by examination and subsequent hormone blood tests.

The sperm count may be zero because there is a known obstruction (e.g. vasectomy) beyond the normal testicles, where sperm are still being produced but are prevented by the obstruction from being a normal part of an ejaculated semen sample. Another form of obstruction is when each vas is congenitally absent (i.e., has never developed).

The sperm count may also be zero because of a failure by the testicles to produce sperm adequately. In this seemingly hopeless situation, unless the testicles have been damaged and atrophied (shrunken due to a damaged blood supply), it may still be possible to obtain sperm from some of these men, even if preliminary hormone blood tests have suggested a diagnosis of testicular failure. There may be little "pockets" of sperm production scattered in areas that have largely failed to produce sperm. Additional preliminary tests are necessary. A blood test is performed to measure hormone levels to check if the absence of sperm is due to testicular failure. Referral to a urological surgeon for testicular biopsy may be necessary to determine whether the cells in the testicle are manufacturing any sperm. It would also be possible to carry out surgical retrieval of sperm (see below) as a “dummy run” to see if sperm can be retrieved. Such sperm could then be stored for your future use. However, freezing of low numbers of sperm is no guarantee of their survival or suitability for ICSI.

If no sperm were seen at testicular biopsy or at the “dummy run”, there would be no point in considering ICSI. Occasionally the biopsy reveals that there is an absence of the sperm making cells (known as the germinal epithelium) and only the cells that support and nourish immature sperm are present. These cells are called Sertoli cells and this condition is referred to as the "Sertoli Cell-only syndrome". Donor insemination itself (see donor insemination information) may then become an option to consider. IVF with donor sperm would not be necessary unless there was an indication for IVF in the woman’s own history.

Before being able to offer ICSI, the normal screening tests for IVF are performed. In addition the male partner (unless his zero sperm count is due to vasectomy) has his chromosome make-up (Karyotype) checked as it is known that chromosome abnormalities are commoner in male infertility. However even a normal karyotype does not exclude the possibility of a future problem arising. Should a chromosome abnormality be detected at karyotyping, genetic counselling is readily available.

When the sperm count is very low or zero, screening for cystic fibrosis is performed as well. One in 20 of us carry the gene for cystic fibrosis and this can be linked to poor sperm production or to a congenital absence of each vas leading to a zero sperm count. If the male partner is found to be a carrier of the cystic fibrosis gene, screening would then be carried out on the female partner to ensure that she is not a carrier too. Genetic counselling would be given as well.

Surgical retrieval of sperm

The majority of men will at least wince at the thought of anything sharp being introduced into the most sensitive portion of their anatomy! Local anaesthetic or sedation anaesthesia is used to carry out the surgical retrieval of sperm.

Sperm can be obtained by applying suction pressure to a special needle that is introduced into either the epididymis at the beginning of the vas or into the testicle itself.

PESA (Percutaneous Epididymal Sperm Aspiration) is the method used to obtain sperm from the epididymis and TESA (Testicular Sperm Aspiration) and TESE (Testicular Sperm Extraction) are similar techniques to obtain sperm from the testicle itself. (For TESE a small incision has to be made in the scrotum in order to obtain an adequate testicular biopsy. TESE is only used when sperm cannot be retrieved using PESA and TESA).

For those men whose sperm counts have always been zero, it is probable that no sperm will be retrieved. If the zero sperm count is due to vasectomy it would be surprising and disappointing if no sperm were retrieved.

If the surgical retrieval procedure is being performed immediately before egg retrieval and no sperm have been obtained for ICSI, there are a number of alternative options. These will include using donor sperm for IVF, abandon the cycle if that can be done safely, discard the eggs that are subsequently retrieved, or (if available at your centre) to consider egg freezing and storage.

In readiness for this situation, before surgical retrieval of sperm is attempted, the option of using donor sperm for standard IVF may have been discussed in depth and planned for. This means that if no sperm can be retrieved, there is no sudden panic. You are both completely prepared and ready to use pre-selected donor sperm for IVF should this situation arise. You will have already gone through the same full counselling as for donor insemination.

If only a few live normal sperm are obtained, ICSI is still possible, making the statement about only requiring one sperm literally true.

When PESA is carried out for vasectomy patients, sperm can often be obtained in surprisingly large numbers. This is not always the case in TESA and particularly in TESE, as sperm need to be searched for in the testicular tissue that has been obtained.

The freezing of surgically retrieved sperm does not necessarily guarantee sperm availability for ICSI when performed at a later date. Sperm numbers may be very low and the freezing and eventual thawing out process always destroys some of the sperm.

When sperm are surgically retrieved, it is important to understand that:

  • there is no certainty that any suitable sperm can be retrieved;
  • there is no guarantee that if sperm / testicular tissue is frozen, sperm will survive the freezing and subsequent thawing out process;
  • there is no guarantee that fertilisation of eggs will occur when ICSI is carried out using retrieved sperm;
  • there is no guarantee that if eggs fertilise using retrieved sperm, that embryos will develop which will be suitable for transfer.

The advantage of performing both the sperm and egg retrievals on the same day is that fresh sperm are then available for ICSI as opposed to frozen stored sperm.

As both partners are involved in a surgical procedure involving anaesthesia or sedation on the same day, advice will be given on transport arrangements, as for reasons of safety and car insurance cover, neither partner will be able to drive for 24 hours.

For the week following surgical sperm retrieval, the man is strongly advised to wear very good scrotal support underwear day and night. It is also essential to remain horizontal for the next 2 days. This is in order to reduce the chances of very significant swelling and bruising.

What are the chances of successful fertilisation after ICSI?

It is important to realise that not all eggs will be suitable for ICSI. For ICSI to succeed the eggs must be mature. Whether or not an egg is mature can only be detected after the outer coating of cells has been stripped away. Immature eggs will not fertilise by ICSI. (If sperm numbers are adequate, immature eggs may occasionally become fertilised if incubated with sperm as in standard IVF, although this is generally unsuccessful).

Up to 15% of the eggs will be damaged during the ICSI process and will not fertilise. About 60% of the eggs that are treated with ICSI, will fertilise. As in standard IVF, it is not always possible to find out why fertilisation has not occurred. It is possible that an apparently normal egg has a defect that cannot yet be recognised. As in IVF, some of the resulting embryos may be considered unsuitable for transfer.

The situation may very occasionally arise where some of the retrieved eggs are treated with ICSI and others are treated by standard IVF. If eggs in the IVF group have apparently failed to fertilise, they cannot then be used for ICSI. The transferred embryos must either be from standard IVF or ICSI unless the circumstances are exceptional.

In 2005, the percentage of ICSI cycles started that resulted in a live birth where the patients’ own fresh eggs were used was:

  • 31.4% (2160/6872) for women aged under 35
  • 25.7% (886/3442) for women aged between 35–37
  • 18.8% (364/1938) for women aged 38–39
  • 10.3% (162/1574) for women aged 40–42
  • 2.1% (7/328) for women aged 43–44
  • 0% (0/102) for women aged over 44

Figures given in brackets are (ICSI cycles resulting in a live birth / ICSI cycles started). The data does not include IVF cycles.

Figures by courtesy of the HFEA

Risks of ICSI

ICSI was only developed in the early 1990's. While several thousand ICSI babies have been born world-wide, it may be too soon to know if there could be any long term problems. It was initially feared that ICSI would be giving an advantage to a sperm that would not normally be capable of fertilising an egg and causing a pregnancy. There may be an increased risk of miscarriage but the fear that significant abnormalities would result from ICSI has not been borne out. It must be remembered that after natural conception, 1 in 30 babies is born with a congenital abnormality. That abnormality may be very mild and unnoticeable, or can often be surgically correctable. Very occasionally it can be serious or even lethal.

The results of ICSI have been very reassuring and are kept under constant review. To date there has not been any significant increase in congenital abnormalities among children born as a result of ICSI when compared to those children born after natural conception. During 1999 a national follow-up study of children conceived using ICSI was established.

It is known that chromosome abnormalities are commoner in male infertility. There is therefore a greater chance that a subtle abnormality due to a micro-deletion in the male Y chromosome could be passed on to a male child and lead to the child’s own future infertility. This would be an inherited abnormality and not one caused by ICSI.

You will appreciate that there is a considerable amount of counselling involved before you will embark upon an ICSI programme. You will be made very aware of the limitations and the risks of the procedure.

March 2009