Intracytoplasmic Sperm Injection or ICSI
From a sperm viewpoint, getting pregnant is a probabilistic event with sperm being like lottery tickets.
When there are consistently fewer than 30 million motile sperm in the total ejaculate and especially if there are some functional problems with those sperm as noted by their morphology, spontaneous pregnancy or pregnancy after IUI is unlikely to occur dependably in a reasonable period of time. Twenty years ago, we would have recommended routine IVF for this, since fewer sperm are required because the sperm are put directly in a dish with the wife's eggs. However, particularly in the more severe situations (say less than five million sperm in the total ejaculate), frequent failure of adequate fertilization would still occur. Since each egg requires only one sperm for fertilization and since the sperm is primarily a DNA delivery mechanism, scientists and clinicians sought a solution to this disappointing situation.
Intra-Cytopasmic Sperm Injection or ICSI was developed primarily to handle this situation. With ICSI, a single sperm is selected and tranferred into single egg. By bending the sperm's tail in a certain way before injecting it into an egg, the sperm is able to activate the egg so that the normal process of fertilization takes place using the DNA delivered by the sperm head. By injecting the sperm into the egg, the sperm is able to pass through the zona pellucida (See science of infertility) . This is the natural barrier to the egg which protects it from being fertilized by too many sperm or by abnormal sperm. Relatively few sperm in an ejaculate have the ability to attach to the zona pellucida and penetrate it. When one sperm succeeds, a reaction takes place in the zona pellucida which hardens it and makes it impenetrable to any other sperm.
ICSI is a very successful technique for helping men with sperm problems achieve pregnancy. Most men who require ICSI have genetically normal sperm, but have few sperm with the ability to penetrate the zona pellucida. For such men, ICSI overcomes a natural problem which has a low probability of resolving itself. The ageing of the couple and the existence of subfertility factors in the wife make spontaneous success even less likely. Some couples worry about the "un-naturalness" of the ICSI procedure. They should be reassured by the large population studies showing no increase in genetic abnormalities in children from genetically normal men compared to routine IVF. Current understanding of the fertilization process suggests that there may be fewer differences from natural fertilization with ICSI than with routine IVF. With ICSI the tail of the sperm does enter the egg cytoplasm and this does not occur with natural fertilization or with routine IVF. With ICSI, the embryologist selects as normal appearing a sperm as possible for injection into the egg. In routine IVF and especially with natural fertilization there is a natural more random selection process that takes place to "select" the sperm involved in fertilization. However, in routine IVF, in contrast to ICSI and natural fertilization, the egg is surrounded by a very large quantity of sperm and consequently the metabolic products and breakdown products of those sperm. Eggs and embryos are very sensitive to biochemical contaminants and this may make ICSI superior to routine IVF in some patients.
For ICSI, few sperm are required. We have helped a couple get pregnant with ICSI when we could locate only six sperm in the husband's ejaculate. Sperm shape is only weakly related to a sperm containing normal DNA. About 10% of the sperm of all men contain abnormal DNA. Some men with severe sperm problems will have decreased fertilization with ICSI, compared to other patients, but usually there are some sperm that will produce normal appearing embryos. ICSI is powerful enough to enable pregnancy to take place from men with genetic abnormalities that are responsible for the limited sperm production. Those genetic abnormalites almost always occur in men with very low sperm counts (usually less than 5 million sperm/ml) and some of these abnormalies can be tested for (See karyotype abnormalies and Y chromosome microdeletions). Some couple choose to evaluate their men for these abnormalities prior to undertaking IVF and some choose not to do so.
Although ICSI was developed to treat male factor problems, its indications for use have expanded. There clearly are other difficult to diagnose problems that lead to failure of fertilization. These are more common in patients with unexplained infertility. Some women may have abnormal zona pellucidas around their eggs. Their eggs may undergo premature zona hardening. ICSI appears to be able to overcome many failures of fertilization. Unanticipated failure of fertilization occurs in about 5% of IVF cases. Our approach is to perform ICSI on at least some of the eggs in all patients undergoing their first IVF cycle. If possible, we try to obtain information about the ability of the sperm to fertilize eggs since this may explain a couple's infertility, but our primary objective is to fertilize at least some eggs so that we can evaluate a couple's embryos and always have the potential to achieve pregnancy. In subsequent cycles, if fertilization without ICSI was as effective as fertilization with ICSI, we will then solely use traditional IVF.
ICSI also enables us to extend our infertility therapies in other ways. In men with obstructive azoospermia (e.g., vasectomy, absent vas deferens), sperm can be easily harvested surgically from the testicles or the vas deferens in our office. This sperm can then be used with ICSI to achieve pregnancy. The procedure is referred to as TESE.
World-wide data suggests that programs are increasingly using ICSI. This is likely because the use of ICSI appears to give the embryologist more control of the fertilization situation. More control generally means a higher success rate. Some programs believe ICSI is so valuable that they perform ICSI on all patients all of the time. The national data published by SART shows the proportion of cases in which ICSI was used for most programs in the United States. Because of the approach described above, we use ICSI for at least some of the eggs in about 90% of our patients.
Life often poses the question of whether the cup is half empty or half full. Many couples despair after they learn that they have to deal with poor sperm and that there are not usually simple or good procedures to correct the situation. We now have the technology to compensate for almost any sperm problem. These techniques did not exist just a few years ago.