Assisted Fertilisation in IVF (ICSI)
Assisted fertilisation gives couples with severe male infertility the chance of pregnancy. Over 95% of couples will have at least one oocyte fertilised and the chance of pregnancy, per embryo, is at least as high as with conventional IVF for other types of infertility. The chance of abnormality may be higher in pregnancies arising from assisted fertilisation, probably due to genetic defects in sperm. IVF with assisted fertilisation carries all the risks, side effects and issues of IVF itself.
About 30% of infertility is caused by poor quality sperm. ‘Poor quality’ can mean the number of sperm is reduced, the proportion of sperm moving (motile) is reduced, the patterns of movement are abnormal, or the average shape of the sperm is abnormal. Sometimes sperm have defects in their function that are not reflected in their number, the way they move, or the way they look.
In conventional IVF, sperm and oocytes are mixed in vitro (usually in a Petri dish), a sperm fertilises the egg to form an embryo, and one embryo is placed into the woman’s uterus at a time, in the hope that it may implant.
Although IVF was developed as a treatment for overcoming tubal disease, it can also be used to treat male infertility. However, there are limits to the use of conventional IVF for male infertility – many men have sperm that are unable to fertilise eggs, or the fertilisation rates would be very low. Also, some men have no sperm in their ejaculate but produce sperm that can be retrieved from the testis and used to fertilise oocytes.
What is Assisted Fertilisation?
Assisted Fertilisation is used to describe techniques which help a sperm fertilise an oocyte by bypassing some of the steps that normally occur. In New Zealand, over 50% of in vitro fertilisation cycles involve Assisted Fertilisation.
Normally, fertilisation involves a complex sequence of events. Of the various techniques tried, the one that has been universally adopted is Intra-cytoplasmic sperm injection (ICSI). This uses sophisticated equipment to inject a single sperm into the middle of each mature oocyte. After this injection, the egg and sperm must both form a nucleus in order for normal fertilisation to be achieved.
Men with azoospermia
(no sperm in the ejaculate)
Sperm are produced in the seminiferous tubules and pass into the testis and on into the epididymis. If a man has a blockage to the outflow tract – from infection, vasectomy or even congenital absence of the vas, this will give rise to ‘obstructive azoospermia’. Sperm production continues but the sperm are absorbed as they move down the epididymis. Other men have sperm production in the testis but the number produced is too few for them to appear in the ejaculate. This is called ‘non obstructive azoospermia’. Occasionally in these men, there may be a few sperm in the ejaculate one month but none the next.
It is important to be able to differentiate between the two types of azoospermia since with obstructive azoospermia it is always possible to retrieve sperm from the testis for ICSI whereas with non-obstructive azoospermia, retrieval of sperm for ICSI is only possible in around 50% of men. The differentiation can usually be made on physical examination and a blood test. Occasionally a testicular biopsy will be necessary to be sure.
Therefore, in men with non-obstructive azoospermia, a biopsy is really only helpful to those people who want to be certain it is possible to retrieve sperm from the testis. Since a testicular biopsy is not without risk, (see below), whether or not to have a testicular biopsy before proceeding to IVF, needs careful discussion.
Sperm for ICSI can be obtained directly from the testis in a variety of ways, each with its own acronym.
- MESA (Micro-epididymal sperm aspiration) refers to an operation under general anaesthetic, in which the surgeon collects fluid from the epididymis with the help of an operating microscope. The operation is expensive, so this technique is usually only done if the man is having a vasectomy reversal (or a similar operation) at the same time. The sperm from MESA is frozen for later use. The advantage of MESA is that a couple knows that there is definitely sperm before starting their ICSI cycle.
- PESA (Percutaneous epididymal sperm aspiration) refers to passing a fine needle ‘blindly’ through the skin into the epididymis. Local anaesthetic is usually sufficient. PESA usually gives enough sperm for ICSI treatment and often enough to freeze. It may be done before egg collection and recovered sperm frozen before use, or occasionally on the same day as the egg collection and ICSI procedure.
- TESA (Testicular sperm aspiration) or TESE (Testicular sperm extraction) can be used if there are no sperm on PESA, and for men whose testes make very few sperm. For TESA, a fine needle is used to take tissue from the testes, while in TESE a larger sample of tissue is taken through a cut in the skin. Both techniques are usually done under local anaesthesia. It is preferable to carry out the procedure well before planning a cycle of IVF and freeze any sperm recovered. This approach will ensure sperm are available to fertilise the eggs collected. Occasionally, if very few sperm are frozen and many eggs are collected, it may be necessary to repeat the TESA/TESE procedure on the day of egg collection.
Miscarriage and abnormality
Miscarriage rates for couples with male infertility, pregnant after conventional IVF, may be slightly higher than for IVF pregnancies from other types of infertility, although the difference is slight. The rate of major foetal or neonatal abnormalities is slightly higher in IVF and ICSI pregnancies compared to those from natural conception. It is still unclear whether ICSI causes a further increase – if it does it may be due to the cause of infertility rather than the ICSI technique.
There may be a small extra risk of abnormalities in the number of sex chromosomes in children conceived by ICSI, which usually can only be detected by CVS or amniocentesis. Some of these abnormalities (in the number of X and Y chromosomes) seem to have little or no effect; others can be associated with infertility and/or some degree of mental retardation. They can be detected by CVS or amniocentesis between 11–16 weeks of pregnancy.
At present assisted fertilisation seems to work equally well for all types of severe male infertility; ICSI can be used when there are very few sperm (even fewer than one million/ml), very low motility (1–20%) and very poor morphology (1–4% normal). There have even been ongoing pregnancies when no sperm were moving and when no sperm were considered normal in shape. This is possible because the process of packaging the genetic material in the head of the sperm and the process of forming the shape of the sperm (head, tail, etc) are quite separate. The genetic quality of sperm is true to the adage that ‘you cannot tell a book from its cover’.
At the moment one cannot use the appearance of the sperm to estimate the chance of congenital abnormality or miscarriage. However, fertilisation and hence pregnancy rates are much lower when non-moving sperm are used. Genetic causes of male infertility are thought to involve the Y (or male) chromosome. Up to 15% of men with zero or very low sperm counts have small pieces of the Y chromosome missing. The loss of this genetic information (called a deletion) leads to poor sperm production. There is no known reason for the loss of this genetic material. As expected, boys conceived of fathers who have a Y deletion inherit the Y deletion, and will themselves be infertile when they grow up.
A blood test to determine whether there are deletions on the Y chromosome is available in New Zealand.