intracytoplasmic sperm injection (icsi)Male infertility is very common and male factor problems contribute to approximately one-third of infertile couples. Male infertility makes up an increasing proportion of ART cycles and currently accounts for 40% of our program at Monash IVF.
In male factor couples, sperm problems include a low sperm count, reduced sperm motility, abnormally shaped sperm or combinations of these defects. Standard IVF depends upon the availability of adequate numbers of motile sperm, which are capable of recognising and binding to eggs, resulting in fertilisation. Finally, some men have antibodies against their sperm, which can prevent their motility or ability to bind to eggs.
In a significant number of male factor couples, conventional techniques like IVF may not be possible due to a low number of motile sperm in the ejaculate. In other couples, IVF may no longer be a useful option because previous poor fertilisation rates imply a problem with sperm function. For this group, sperm microinjection provides the best means of achieving pregnancy.
Professor Alan Trounson's group developed sperm microinjection at Monash IVF in the late 1980s. The original technique involved the injection of a few motile sperm into the space between the outer coating of the egg (zona pellucida) and the egg. This "subzonal" microinjection procedure (SUZI) has resulted in many pregnancies for severe male factor patients worldwide. The SUZI technique has been superseded by intracytoplasmic sperm injection (ICSI), which is not only more effective, but is also more useful in male factor couples previously regarded as untreatable.
The ICSI technique involves the injection of a sperm through both the zona pellucida and the wall of the egg directly into the centre of the egg. The technique was developed by Professor Van Steirteghem's group in Belgium and made possible by the production of extremely fine glass needles. The procedure requires a great deal of technical skill in the picking up of individual sperm and its injection into the egg without damaging it. All procedures are performed under a microscope using a sophisticated micromanipulation system. Following injection, the eggs are cultured and assessed for fertilisation in a similar way to conventional IVF. Embryos are transferred into the uterus two to three days later or frozen for later use. Embryo transfer is usually a simple procedure in which the embryos are placed in a fine tube called a catheter, which is guided through the neck of the womb (cervix) into the main part of the womb.
What are the risks of ICSI?
ICSI is a relatively new treatment, the first children having been born in 1992. Although information to date suggests that it is safe, couples considering ICSI should be made aware of several issues including the possibility of unknown risks.
Transmission of genetic defects
There are a variety of chromosomal and genetic causes of male infertility, which may be transmitted to future generations by ICSI or by natural reproduction where this is possible.
Some otherwise healthy men are thought to have a genetic cause for their poor sperm quality. The Y (male) chromosome is a particularly important site of genetic changes causing infertility. As boys inherit their Y chromosome from their father, they may have similar fertility problems later in life. Screening tests for some of these conditions are available.
Are congenital abnormalities associated with the ICSI procedure?
It is theoretically possible ICSI may cause specific problems through injury to the sperm or egg or injection of damaged or defective sperm.
The Australian National Perinatal Statistics Unit (NPSU) (supported by the Fertility Society of Australia), and other overseas agencies collect data on the outcome of infertility treatments. Results to date do not indicate increased rates of abnormal pregnancy, miscarriage or birth defects (congenital malformations) in ICSI children. The only exception may be an approximately three-fold increase in sex chromosome disorders such as Klinefelter's Syndrome in which boys have defective testicular development.
Long-term health of ICSI children
There is less known about the long-term outcome of children conceived by ICSI, given that the oldest children are now only 10 years old. There have been two studies of mental development in ICSI, standard IVF and naturally conceived children. One performed at age 1 year showed an increase in the incidence of mild developmental delay. The other larger study of children up to age 2 years did not show any such differences. The research methods used in both studies may not predict later intellectual impairment. Further work is in progress to assess the development and health of children born after infertility treatments including ICSI.
Conclusion
ICSI is a useful treatment for severe male infertility. It has increased choices for couples with severe male infertility that in the past may have used donor insemination. So far examination of results does not suggest that ICSI increases pregnancy loss or birth defects, however it is still too early to be absolutely certain. The transmission of chromosomal and genetic diseases, particularly genetic causes of infertility to male offspring, is a distinct possibility. Current information is insufficient to establish that there are long-term developmental problems in children born from ICSI. More research is needed.
Indications for ICSI
There is evidence from several centres now that fertilisation and pregnancy rates are markedly improved with ICSI in severe male factor infertility (sperm counts less than 1 million/ml) and in patients with a previous history of failed IVF. In addition, men previously considered untreatable seem to have similar success, including those with very abnormally-shaped sperm or those where sperm must be obtained from the testicle at surgery.
Success rates
The success rates for all IVF treatments vary between patients, however ICSI produces similar live birth rates to standard IVF treatments. Slight differences in ICSI fertilisation and pregnancy rates with different causes of infertility have been observed.
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