ICSI for Male Factor Infertility

by Benjamin C. Wong, MD, FRCSC, FACOG

Fall 2008

The injection of sperm directly into an egg under the microscopy is a procedure that started in the early 1990s to help patients with severe male factor infertility achieve a pregnancy. The procedure is usually referred to as ICSI, which stands for intracytoplasmic sperm injection. Here, the cytoplasm refers to the substance inside the human egg that surrounds the nucleus and it is surrounded by the cell membrane and the ‘shell’ (zona pellucida) of the egg. The procedure is done under a special microscope and involves drawing up a sperm into a fine glass needle, inserting the needle through the shell and the cell membrane of the egg into its cytoplasm and leaving the sperm in the egg while withdrawing the needle. In the hands of a skilled embryologist, the chance of the egg being damaged by ICSI is very low and the fertilization rate is usually around 70-80% on average.

In order for ICSI to be performed, the couple does need to undergo ovarian stimulation as for in-vitro fertilization (IVF). The female partner will need to inject herself with fertility drugs to stimulate her ovaries to produce mature eggs. Based on ultrasound appearance of her ovaries and the estrogen level, the physician will determine the appropriate timing for removal of eggs from her ovaries. The eggs obtained that are fully mature can then be used for ICSI. The fertilized eggs will then be observed in the next few days for development into embryos. An appropriate number of embryos are then selected for replacement into the uterus based on the patients age and embryo quality.

Before the advent of ICSI, couples with severe male factor infertility had very poor fertilization of the eggs with conventional in-vitro fertilization. The latter refers to the placement of sperm and eggs in dishes and allowing the sperm and the eggs to fuse together on their own. Without good fertilization of the eggs, the pregnancy rate following IVF treatment remains poor. Before ICSI, couple with severe male factor infertility usually had to resort to donor sperm treatment or adoption.

There are several factors that physicians will use to determine whether to recommend ICSI in additional to IVF for couples. First of all, poor fertilizationwith standard IVF tends to occur when the male partner has very low sperm counts, poor motility or significant structural abnormalities and the more severe the abnormalities, the less likely that the sperm will be able to fertilize the eggs without ICSI. Men with the absence of sperm in their semen may still undergo ICSI to achieve a pregnancy if sperm can be successfully extracted from higher up the reproductive tract such as the epididymis or tests by surgery. An example would be men who have undergone vasectomy.

The presence of high concentration of anti-sperm antibodies is another indicator for the need for ICSI. Sperm is considered to be foreign objects in our body and normally there is a barrier in the testes that blocks the exposure of the sperm to our immune system to prevent the triggering of an immune response towards our own sperm, leading to the production of anti-sperm antibodies. This barrier can be breached due to trauma or surgeries (e.g. vasectomy and subsequent vasectomy reversal) to the male genital region. If the antibodies coat the sperm head, they will prevent the sperm from attaching to the surface of the eggs, a step that is crucial to achieve fertilization. A third reason to suggest the need of ICSI is when there has been previous failed fertilization by conventional IVF. In this case, the assumption is that failed fertilization occurs because the sperm is unable to get into the eggs and ICSI will circumvent this problem.

The use of ICSI in the treatment of couples with unexplained infertility is more controversial. A couple is said to have unexplained infertility if all basic fertility testing shows normal results. A small percentage of these couples fail to achieve a pregnancy due to inability of sperm fertilizing the eggs and they will have poor fertilization without the performance of ICSI. There is, however, no reliable ways to identify these couples before they undergo IVF treatment. Because of this, most physicians will discuss the option of ICSI with couples having unexplained infertility and give them the chance to decide whether to do it or not.

Last but not least, a small percentage of couples who have a high chance of conceiving a child with a genetic disorder will choose to undergo IVF in order to allow genetic testing to be done on the embryos before they are returned to female partners’ uteri. This process is called pre-implantation genetic diagnosis (PGD). Couples undergoing PGD also need to be ICSI done to avoid false results from the genetic testing.

Some men with no or very few sperm in their semen have chromosomal abnormalities, abnormal cystic fibrosis genes or abnormalities on their Y chromosome. Therefore, for couples undergoing ICSI treatment for severe male factor infertility, genetic testing is recommended prior to treatment. If the testing shows abnormalities, there may be a concern of passing these on to future offspring’s. In this case, the couple will usually be referred to see a physician specialized in genetics for further counseling.

The performance of ICSI does have potential risks. Current data shows that there is an increased chance of children born with an abnormal number of sex chromosomes. Normal men have one X and one Y chromosome. Normal women have two X chromosomes. Since the X and Y chromosomes determine the gender of the human, they are collectively known as the sex chromosomes. Children born after ICSI do have a slightly increased risk of sex chromosome abnormalities. The most common sex chromosome abnormalities following ICSI is a condition called Klinefelter’s syndrome (XXY). This infant is born as a male but due to the presence of an extra X chromosome, he will be infertile as an adult. The IQ score of people with Klinefelter’s syndrome is slightly lower than that of the general population. In general, Klinefelter’s syndrome is not considered to be a serious genetic condition. It is, however, a risk that any couple undergoing ICSI treatment should be aware of and feel comfortable with.

Overall, ICSI is an effective treatment for several specific infertility situations. Not all infertility couples benefit from ICSI though. Infertile couples who suspect that ICSI treatment may apply to their situation should consult their physician for assessment. The performance of ICSI since 1992 has helped many infertile couple to achieve pregnancies.

About the author

Benjamin C. Wong, MD, FRCSC, FACOG is a Clinical Assistant Professor of Obstetrics & Gynaecology at the University of Calgary. He is a reproductive endocrinologist at the Regional Fertility Program and the Foothills Medical Centre in Calgary.