A little ICSI history

In conventional IVF, successful fertilization depends on the sperm’s ability to bind to and penetrate the eggs. Until the advent of ICSI, couples in which the male produced few or imperfect sperm had little hope that IVF would benefit them. However, in 1992, a Belgian team successfully obtained fertilization by injecting a single sperm into each of the eggs or “ oocytes”.

The success of this procedure has allowed men with rare sperm or with poorly functioning sperm to produce in vitro embryos with their partner’s eggs. Even men who have sperm only in the testicle, such as after vasectomy or congenital absence of the vas deferens, can now use their own sperm to have a child.

In addition, IVF with ICSI is now useful in cases where abnormal oocytes may not allow sperm to penetrate the zona pellucida. ICSI is also a tool for patients with a history of poor (less than 50 percent) normal fertilization rates or abnormally high rates of “polyspermic” fertilization (penetration by more than one sperm) following conventional IVF.

Fertility specialists perform ICSI shortly after oocyte retrieval when the oocytes are at the proper stage of maturation for fertilization. On occasion, fertilization unexpectedly fails in conventional IVF and specialists perform a so-called “rescue ICSI” the day following egg retrieval. This rarely results in normal embryos because the genetic and cytoplasmic material of the oocytes is aged.

Consequently, a proper and thorough evaluation of the male partner before the IVF cycle allows us to identify in advance those cases in which ICSI is advisable.

ICSI can benefit nearly all men with abnormal sperm. But some sperm result in very poor or absent fertilization even after ICSI. Once the sperm enters the oocyte, it must communicate with the oocyte to initiate the process of fertilization and embryo formation (we call this “activation”). Presumably, some men have sperm that are unable to perform this function and fertilization does not occur. Scientists are still working to understand the details of the process of oocyte activation.

The process of ICSI IVF

Just prior to oocyte retrieval, the man provides a sperm sample, and laboratory specialists process it to produce a clean preparation of viable sperm. Prior to the ICSI procedure itself, lab staff use enzymes to remove the granulosa cells surrounding the oocyte at the time of retrieval. The staff then selects mature oocytes for ICSI. Under most circumstances, 65 to 75 percent of oocytes are considered mature.

Shortly after oocyte retrieval, the embryology staff selects a single sperm from the preparation using a microscopic pipette, or long tube. The pipette has a needle like tip that pierces the zona and egg membrane. The specialist performing the procedure aspirates (or gathers) a small amount of egg cytoplasm into the micropipette, allowing the sperm to mix with the cytoplasmic material.

Then the specialist replaces the cytoplasm, now containing the sperm, into the oocyte. The procedure requires the use of a “micromanipulator”, a device that carefully modulates the tiniest movements of the micropipette.

Immediately after micromanipulation, the lab staff returns each oocyte to the incubator for about 18 hours. The next day, the embryologist inspects the oocytes and determines which have fertilized successfully. A fertilized egg ( zygote) is identifiable by the appearance of two pronuclei within the egg (noted as "2PN"). The zygotes further incubate for two to six days, permitting cells to divide and produce embryos. 

ICSI is indicated in couples where sperm are deficient in number or function. Alternative treatments for this condition include:

1. conventional IVF insemination of some or all eggs without micromanipulation
2. the use of donor sperm either by insemination or IVF treatment
3. adoption
4. no treatment and remaining child-free by choice

Optional treatments & choices

At times, a man is unable to produce a semen specimen on the day of retrieval. If a patient cannot be certain that he will be able to provide a semen sample, we ask him to notify us well in advance of the retrieval day. We will arrange for patients to cryopreserve (freeze) a sample before the IVF cycle.

Alternatively, a patient can choose to use donor sperm as a back-up, or a fertility doctor can aspirate sperm directly from the testicle using a technique known as non-surgical sperm aspiration (NSA). Sometimes, though, we cannot obtain an adequate number of sperm either from the ejaculate or from the testicular aspiration on the day of the oocyte retrieval.

If a patient has very rare sperm, we suggest that a couple select a sperm donor in advance of the cycle as a backup (see the Donor Sperm Fact Sheet).

The risks from egg micromanipulation include trauma to the oocyte, leading to non-viability (death of the oocyte), or other unanticipated/unidentified risks. This trauma can occur during the enzymatic removal of the granulosa cells or the ICSI procedure itself. ICSI does not guarantee fertilization of an oocyte.

The probability of fertilization of any oocyte is the same as for oocytes inseminated with normal sperm. The average fertilization rate of oocytes with conventional IVF and ICSI is about 65 to 70 percent.

Some men have abnormal sperm or low sperm production because they have a genetic defect such as a small deletion of genetic material from the Y chromosome. Performing ICSI for men with one of these genetic abnormalities may result in male offspring with the same fertility disorder. Men most likely to have these genetic disorders are those with sperm concentrations below 5 million per cubic centimeter. In this circumstance, we recommend genetic counseling before treatment with IVF/ICSI.

Risks & complications for IVF with ICSI

Performing ICSI for men with one of these genetic abnormalities may result in male offspring with the same fertility disorder. Men most likely to have these genetic disorders are those with sperm concentrations below 5 million per cubic centimeter. In this circumstance, we recommend genetic counseling before treatment with IVF/ICSI.

Of course, doctors cannot guarantee that any babies born from IVF with ICSI will be normal. A pregnancy conceived naturally carries about a 4-percent risk that it will have a birth defect.

Assisted reproduction, including cycles with ICSI, may increase the risk of birth defects according to some studies while many others found no increased risk of birth defects. A recent study of the long-term development of babies born after ICSI found no increase in defects up to 10 years after the procedure.

ICSI and Pregnancy Rates

Patients have been concerned that Intracytoplasmic Sperm Injection (ICSI) might have an impact on pregnancy rates. This graph shows the process of injecting the sperm into the egg does not have an adverse impact on subsequent outcomes.