Since the early nineties, Intracytoplasmic Sperm Injection (ICSI) has been a tremendous tool in the treatment of severe male factor infertility. With ICSI, normal fertilization can be achieved by injecting a single sperm through micromanipulation right into the mature egg.

Fertilization of the egg by the sperm is critical to generate an embryo. Under normal circumstances, successful fertilization depends on the sperm's ability to bind to and penetrate the egg; with ICSI some of the steps occurring during natural fertilization are bypassed since the sperm is placed directly into the egg.

Until the early 1990's couples in which the male produced only a very few sperm or those in which the sperm was of sub-optimal quality had little or no hope that conventional In Vitro Fertilization could help them since achieving fertilization of the egg was very difficult.

With ICSI, couples in which the man has very low numbers of sperm, or poorly functioning sperm are able to generate embryos and establish pregnancies. ICSI can also be successful in men who have sperm only in the testicle, such as those with history of a vasectomy, congenital absence of the vas deferens (CAVD), or non-obstructive azoospermia.

In some cases where abnormal oocytes are recovered which may not allow sperm to penetrate the zona pellucida ICSI may also be of benefit. Over the years as IVF laboratories developed experience with this technique, it's use was gradually broadened and it is currently also used in patients who have had suboptimal fertilization rates with conventional IVF and in patients with high rates of abnormal fertilization in previous cycles.

ICSI is performed a few hours after oocyte retrieval when the oocytes are at the proper stage of maturation for fertilization. A comprehensive evaluation of the male partner before the IVF cycle allows us to identify in advance those cases in which ICSI is of benefit. In some isolated cases of very severe male factor infertility usually in combination with other female factors, even with ICSI sub-optimal, or absent fertilization can be seen. Once the sperm enters the oocyte, it must communicate with the oocyte to initiate the process of fertilization and embryo formation; in some men the possibility exists that the sperm are unable to perform this function and fertilization does not occur even after ICSI.

On the day of oocyte retrieval, a sperm sample is collected and processed to produce a clean preparation of viable sperm. Prior to the ICSI procedure the granulosa cells that surround the oocyte are removed in the IVF laboratory and the mature oocytes are then selected for ICSI. Under most circumstances, 60-85% of oocytes are considered mature. Shortly after oocyte retrieval, the embryologist selects a single sperm from the preparation using a microscopic pipette. The pipette has a needle like tip that is used to pierce the egg's membrane. A small amount of egg cytoplasm is aspirated into the micropipette allowing the sperm to mix with the cytoplasmic material. The cytoplasm, now containing the sperm, is replaced into the oocyte. The procedure requires the use of micromanipulators which allow for fine control of microscopic movement of the micropipettes. Immediately after ICSI is performed, each oocyte is returned to the incubator for about 18-20 hours. The next day, the embryologist inspects the oocytes and determines which have fertilized successfully.

The normally fertilized egg also known as "zygote", is identified by the appearance of two round structures called "pronuclei" in it's cytoplasm in addition to two polar bodies on it's periphery. Zygotes are cultured in the IVF Lab for 2-7 days during which cell division takes place allowing them to become embryos.

ICSI is generally indicated in couples where sperm are deficient in number or function. Sometimes, a man is unable to produce a semen specimen on the day of retrieval. If you cannot be certain that you will be able to provide a semen sample, we ask that you notify us well in advance of the retrieval day. We will arrange for you to cryopreserve (freeze) a sample before your IVF cycle. Alternatively, you can choose to use donor sperm as a back-up or we can aspirate sperm directly from the testicle using a technique known as testicular sperm extraction (TESA). Sometimes, an adequate number of sperm cannot be obtained either from the ejaculate or the testicular aspiration on the day of the oocyte retrieval. If you have very rare sperm then we suggest that you select a sperm donor in advance of the cycle as a backup.

The success with ICSI depends largely on the ability and skill of the embryologist performing the procedure; 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. As part of our ongoing quality control procedures we strive to maintain very low egg damage rates post ICSI.

ICSI does not guarantee fertilization of an oocyte. However, the probability of fertilization of any oocyte with ICSI is 10-15% greater than for oocytes inseminated conventionally with normal sperm. In addition, the probability of no fertilization with ICSI is significantly reduced, whereas with conventional insemination in as many as 10% of treatment cycles fertilization may not occur due to unknown factors. The average fertilization rate of oocytes with conventional IVF and ICSI is about 60-80%.

In men who have abnormal sperm or low sperm production due to a genetic defect such as a deletion of genetic material from the Y chromosome performing ICSI 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 ml.

We cannot guarantee that any babies born from IVF with ICSI will be normal. A pregnancy conceived naturally carries about a 4% 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 have reported 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.

TESTICULAR SPERM ASPIRATION (TESA) AND ICSI

This outpatient procedure allows us to easily and quickly obtain adequate numbers of sperm for ICSI in many men who have no sperm in their semen because of vasectomy or other causes of blocked ducts, in men who cannot ejaculate (including men with spinal cord injury), or in some men who do not have any duct obstruction (non-obstructive azoospermia).

Men who lack sperm in their ejaculate frequently have at least some sperm in their testicles, where sperm are made. Testicular sperm can fertilize eggs if they are injected directly into eggs with ICSI. While an ejaculate normally contains 100 to 300 million sperm, aspiration of as few as 100 to 200 sperm in a small biopsy is enough to achieve pregnancy when it is combined with ICSI. Before TESA was available men with no sperm in their ejaculate had to undergo surgery to remove sperm either from their testes or from the tubes connected to the testes (vas deferens or epididymis). The operation required a hospital stay and lengthy recuperation. A testicular sperm aspiration is rapid procedure performed under local anesthesia that can be performed right at our Center, it does not require hospitalization, and recovery is virtually immediate.

The technique has been very useful for men who have had vasectomies and later decide that they want to have children frequently because they have remarried. The reversal of a vasectomy by having bypass surgery is possible, but the operation is frequently not successful, especially for men with longstanding vasectomies; additionally, sperm quality after vasectomy reversal is often reduced and ICSI is required even if sperm appear in the ejaculate. For many men, sperm aspiration eliminates the need for vasectomy reversal surgery.

A testicular sperm aspiration can also help infertile men who lack sperm in their semen because the route out of the testes has been blocked by prior infection or congenital lack of development, as well as men who have had their prostates removed and can no longer ejaculate but do make sperm.

Men who cannot ejaculate due to spinal cord injuries or neurological conditions like multiple sclerosis can also become fathers through the new technique. There is also a large group of infertile men who simply produce no sperm and other men who have only dead sperm in their semen although their ducts and ejaculatory process are normal, however, such men may have some living testicular sperm that can be obtained through TESA. Men with non-obstructive azoospermia, that is, men with no sperm in the ejaculate and no obstruction in the ducts leading from the testicle to the outside often need surgery to find the sperm. We work with the urologists who specialize in male infertility to have them perform testicular biopsy often with the aid of microsurgery to identify tissue that contains a few sperm. A significant number of men in this category do not have any sperm and must resort to using donor sperm or adoption. A testicular biopsy also allows the pathologist to aid in the diagnosis.

Testicular sperm must be used in conjunction with ICSI because they cannot enter fertilize eggs on their own. We schedule your TESA the same day as the egg retrieval for IVF. After egg retrieval and sperm aspiration, our embryologists inject each egg with a single sperm. We transfer embryos back to the uterus three to five days following fertilization; with cryopreservation (freezing) of additional embryos as requested. In some men the TESA procedure yields enough sperm for freezing for subsequent ICSI attempts. Please let us know in advance if you want any extra sperm frozen and stored. There are fees associated with the cost for cryopreservation and storage of the sperm. Because so few sperm are actually frozen and many of those will die during the freeze-thaw process, you may not have any viable sperm when the sample is thawed and a repeat TESA may still be necessary.