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The problem

Is it very unnatural?

Genetic issues

Other indications

Pregnancy without sperm

Cost of therapy to get pregnant


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Intracytoplasmic Sperm Injection or ICSI

ICSI is a variation for obtaining egg fertilization with IVF which involves injection of individual sperm into individual eggs. It is a microsurgical technique involving eggs and sperm which has revolutionized the treatment of male factor infertility.

The problem

From a sperm viewpoint, getting pregnant is a probabilistic event. 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 since 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-cytoplasmic sperm injection or ICSI was developed primarily to handle this situation. With ICSI, a single sperm is selected and transferred 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 of the egg which protects it from being fertilized by too many sperm or by abnormal sperm. Few sperm 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.

Is it very unnatural?

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 "unnaturalness" 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. Current understanding of the fertilization process suggests that there are 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 as normal appearing a sperm as possible is selected 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. In routine IVF, in contrast to ICSI and natural fertilization, the egg is surrounded by a 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.

Genetic issues

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 abnormal it es almost always occur in men with very low sperm counts (usually less than 5 million sperm/ml) and some of these abnormalities can be tested for (See karyotype abnormalities 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.

Other indications

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 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.

Pregnancy with no sperm

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.

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 usually not 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.

Cost effectiveness of ICSI

ICSI is a powerful technique and if male factor is the only problem that a could has than it immediately completely compensates for it.  The traditional approach with male factor infertility is to do IUI with or without pregnancy accelerator drugs and then if that fails after a certain number of tries, then move to IVF with ICSI.  One of the reasons for this approach is because of the high cost of IVF.  However, with the availability of lower cost types of IVF which use ICSI such as IVM and Mini-stim IVF™(available in this practice at about half the cost of traditional IVF), this reasoning may no longer apply.  What is most cost efficient for a couple will in part depend on what insurance coverage they have for different procedures.  However, because of the lower pregnancy rates with IUI compared to ICSI, for the self-pay patient with isolated male factor, ICSI may be the more cost effective approach to achieving pregnancy.