What is ICSI?

ICSI is an acronym for in tracytoplasmic sperm injection - which is a long, fancy way of saying "inject sperm into the middle of the egg". ICSI is a very effective method to get fertilization of eggs in the IVF lab after they have been retrieved from the female partner. IVF with ICSI involves the use of specialized micromanipulation tools and equipment and inverted microscopes that enable embryologists to select and then pick up individual sperms in a tiny specially designed hollow ICSI needle. Then the needle is carefully advanced through the outer shell of the egg and egg membrane and the sperm is then injected into the inner part (cytoplasm) of the egg.  This will usually result in normal fertilization in approximately 70-85% of eggs injected with viable sperm. First, the woman must be stimulated with medications and have an egg retrieval procedure so that we can obtain several eggs in order to attempt in vitro fertilization and ICSI.

Who should be treated with intracytoplasmic sperm injection?

There is no "standard of care" in this field of medicine regarding which cases should have the ICSI procedure and which should not. Some clinics use it only for severe male factor infertility, and some use it on every case. The large majority of IVF clinics are somewhere in the middle of these 2 extremes. Our thinking has changed over time - we are now doing more ICSI (as a percentage of total cases) than in the past. Certainly, as we learn more about ways that we can help couples conceive, our thinking in this area will continue to evolve. Having said that, we are currently recommending in vitro fertilization (IVF) with ICSI for:

1. All couples with severe male factor infertility that do not want donor sperm insemination 

2. All couples with infertility with:

Sperm concentrations of less than 15-20 million per milliliter

OR

Sperm motility less than 35%

OR

Very poor sperm morphology (subjective - specific cutoff value is not appropriate)

3. All couples having IVF who have had a previous cycle with no fertilization - or a low rate of fertilization (low percentage of mature eggs that are normally fertilized).

4. All couples having IVF who have a very low yield of eggs at the egg retrieval - our current cutoff is 5-6 (or less) eggs. In this scenario, ICSI is being used to try to get a higher percentage of eggs fertilized than with conventional insemination of the eggs (just mixing eggs and sperm together).

How is ICSI performed?

1. The mature egg is held with a specialized holding pipette.

2. A very delicate, sharp and hollow needle is used to immobilize and pick up a single sperm.

3. This needle is then carefully inserted through the zona (shell of egg) and in to the cytoplasm of the egg.

4. The sperm is injected in to the cytoplasm and the needle carefully removed.

5. The eggs are checked the next morning for evidence of normal fertilization.

Fertilization and pregnancy success rates with ICSI

Fertilization rates for ICSI: Most IVF programs see that about 70-85% of eggs injected using ICSI become fertilized. We call this the fertilization rate, which is different from the pregnancy rate.

Pregnancy success rates for in vitro fertilization procedures with ICSI have been shown in some studies to be higher than for IVF without ICSI. This is because in many of the cases needing ICSI the female is relatively young and fertile (good egg quantity and quality) as compared to some of the women having IVF for reasons other than male factor infertility. Another way to say this is - average egg quantity and quality is usually better in ICSI cases (male factor cases) because it is less likely that there is a problem with the eggs - as compared to cases with unexplained infertility in which there is more probability of a somewhat reduced egg quantity and quality (on the average, since some women in this group have egg related issues).

ICSI success rates vary according to the specifics of the individual case, the ICSI technique used, the skill of the individual performing the procedure, the overall quality of the laboratory, the quality of the eggs, and the embryo transfer skills of the infertility specialist physician performing the procedure.

Sometimes IVF with ICSI is done for "egg factor" cases - low ovarian reserve situations. This is when there is either a low number of eggs, or lower "quality" eggs (or often both). In such cases, ICSI fertilization and pregnancy success rates are somewhat lower (as a group) since the main determinant of IVF success is the quality of the transferred embryos - and the quality of the eggs is the most crucial factor determining the quality and viability of the resulting embryo.

In some cases, assisted hatching might be done on the embryos prior to transfer, in order to maximize chances for pregnancy.

The Procedure

The ICSI Procedure

During the ICSI procedure, the head of a single sperm is injected into the egg, eliminating the need of the sperm to penetrate the egg for fertilization.

Step 1: Ovulation Stimulation and Egg Retrieval

A full ICSI cycle includes a number of steps. First, the woman may be prescribed fertility drugs to help stimulate ovulation, control the egg ripening, and make it possible to collect multiple eggs. When it has been determined through ultrasound that the eggs are ready, they are retrieved in a minor surgical procedure in which a hollow needle is used to remove the eggs from the ovaries.

Step 2: Sperm Retrieval

For men with low sperm count or motility, sperm is obtained through normal ejaculation. For those with other fertility problems, surgical procedures such as microepididymal sperm aspiration (MESA), percutaneous epididymal sperm aspiration (PESA), or testicular sperm extraction (TESE) may be necessary to retrieve the sperm.

Step 3: Fertilization

Once the sperm and eggs have been retrieved, a single sperm is picked up with a very small needle which is inserted through the zona pellucida (the shell of the egg) and into its center (cytoplasm). The fertilization will be confirmed within about one to six days.

Step 4: Embryo Transfer

The resulting embryo or embryos are placed in the woman's uterus in a procedure called embryo transfer. Multiple embryos, typically between two and four, may be placed in the uterus to increase the probability of pregnancy.

Are ICSI babies more likely to have birth defects?

Despite widespread use and acceptance, ICSI is still a relatively new procedure. Currently there are no reports of increased birth defects or congenital abnormalities in babies born through ICSI. Children born as the result of ICSI are very young and have not yet reached an age to reproduce.

 ICSI bypasses the natural selection process at the egg surface that may prevent "undesirable" sperm from fertilizing the egg. This may permit the transfer of certain male infertility conditions that have a genetic basis. Where a genetic basis to male infertility is suspected or known, the couple can consult with a genetic counselor before choosing to use ICSI.

A cycle of ICSI and IVF costs $10,000 or more, depending on where you live and what extra options are involved, and it may take more than one cycle to achieve a pregnancy. ICSI costs about $1200 to $1500 as a stand alone procedure.

ICSI Risks

Most studies show that there is no increase in birth defects and other problems with babies born from an ART pregnancy than babies born by natural methods. Regardless, concern still exists about the quality of the sperm used in the ICSI procedure.

In natural conception, only the hardiest sperm are able to fertilize an egg, thereby weeding out lower-quality sperm. During the ICSI treatment, sperm is chosen and injected into the egg, allowing for the possibility that weaker sperm will be used. If severe male infertility is a factor, the concern is that the causes of the infertility may be passed on to children, along with other chromosomal abnormalities and genetic problems that are associated with infertility.

 To determine the risk of passing these genetic problems to children, some specialists suggest that a couple undergo genetic screening before ART procedures such as ICSI.

What’s So Great About It?

Previous to ICSI, the only options to couples where the male partner had a low sperm count, a complete absence of sperm in his semen, a damaged or even absent vas deferens, an irreversible vasectomy or a host of other problems was to adopt, use a sperm donor or deal with the possibility of never having children. Understandably, many couples did not care for these limited options.

Using micromanipulation technology, ICSI allows fertility specialists to fertilize an egg using just one sperm. While it is preferred to use sperm from a semen sample, specialists can retrieve sperm from the testicles if it is necessary. Once sperm has been collected, the specialist will draw a single sperm into a needle and inject it directly into an egg that has been collected from the female partner through the usual retrieval methods. This process bypasses the conventional IVF methods of fertilization, thereby ensuring that fertilization has taken place. The fertilized eggs are then left to culture for a few days before being transferred back to the woman’s uterus. ICSI is always used alongside IVF.

Who is Suited to ICSI?

Couples that are infertile due to any of the following reasons may want to consider using ISCI with their IVF treatment.

  • Low sperm count

  • Poor sperm motility

  • Abnormally high amount of morphologically atypical sperm

  • Experienced fertilization failure for unknown reasons in a previous IVF cycle

  • Lack of any sperm in ejaculate due to CAVD, failed vasectomy reversal, failure to produce sperm, or an obstruction in the epididymus due to past inflammation

  • Retrograde ejaculation

  • Immunological factors

Additionally, men who have been diagnosed with testicular cancer may choose to freeze a semen sample before undergoing treatment as this can later be used in ICSI.

Success with ICSI

While the fertilization rates with ICSI remains pretty high at between 60% and 70% depending on the quality of sperm used, pregnancy rates remain about the same as they do with IVF. Approximately 20% to 25% of couples undergoing ICSI and IVF will have a live birth. However, one concern among many experts is how healthy this procedure is for the resulting children.

Because ICSI is used mainly in men with extremely poor sperm quality, the fact that it allows an egg to be fertilized with any sperm, rather than the strongest, has caused concern that congenital defects may be passed on at a greater rate. Additionally, it is a relatively new procedure and the long term effects in children conceived through ICSI have yet to be properly analyzed. However, so far no studies have shown that children conceived with ICSI do have any increase in congenital defects. If there is a known risk of genetic diseases or disorders in your family, though, you may want to consider using PGD.

Moreover, because ICSI is used alongside IVF, couples undergoing this treatment do have an increased risk of ectopic pregnancy as well as multiple births.