For whom ICSI is advised?

Intra-cytoplasmic sperm injection (ICSI) is a relatively new but well-established procedure first performed in 1992. The procedure was developed to help male factor infertility. The procedure involves injecting a single sperm into the cytoplasm of each egg using a fine glass needle. The first ICSI baby was reported in 1992. The ICSI has largely replaced the two previously developed procedures, PZD (partial zona dissection) and SUZI (subzonal insemination) because it achieves much higher fertilization rates.
The injection of immature sperm (spermatid) into the egg is not allowed in the UK because in immature sperm the nuclear maturation processes may not be complete.

There are selected groups of patients to whom intracytoplasmic sperm injection (ICSI) is recommended.
• Couples who have failed to achieve fertilization or had very poor fertilization following standard IVF treatment.
• Men with abnormal sperm parameters (e.g. low count, poor motility, high percentage of abnormal forms and high levels of antisperm antibodies in the semen) to allow a reasonable chance of success with standard IVF.
• Azoospermic (complete absence of sperm in the ejaculate) men who have their sperm surgically retrieved. This could be due to failed vasectomy reversals or congenital absence of both vas deferenses and non-obstructive azoospermia.
• When frozen sperm is limited in number and quality.
ICSI is generally unsuccessful when used to treat fertilization failure that is primarily due to poor egg quality.

The early stages of ICSI are the same as for standard IVF. The woman takes fertility drugs to stimulate her ovaries with the aim to grow several mature follicles. The eggs are usually collected by vaginal ultrasound scan into a specially prepared culture medium. Once the eggs are collected, they are examined under the microscope to assess their quality. The eggs are then placed in the incubator for a period of time usually between 3-6 hours. Thereafter the eggs are removed from the incubator and the cells that surround the egg are stripped off to assess the maturity of the egg, because ICSI can only be performed on mature eggs. Immature eggs can be kept in the culture medium and injected the following day if they show signs of maturation.
Sperm collection from ejaculate or aspirate from the epididymis (PESA) or testis (TESA or TESE) is prepared using special cultured medium. Sperm preparation may also be obtained from frozen semen sample or testicular tissues.
Once the eggs have been selected, a chosen sperm is rendered immotile, then sucked into the tip of a very fine glass needle and injected directly into the egg. The egg is held in place by gentle suction on the opposite side using a holding pipette. This is a very delicate procedure and involves using a micromanipulator. This process is repeated for each egg. The elastic nature of the egg membrane means that the tiny hole made by the needle closes very quickly. About 5% of the injected eggs may be damage by the procedure.
The eggs are examined the next morning for signs of fertilization. The developing embryos are allowed to grow and cleave (divide) for a further 24-48 hours. Not all fertilized eggs will divide and some embryos may arrest (stop growing) at an early stage of development. Up to three embryos are transferred into the uterus in the United Kingdom. Any excess embryos of suitable quality are then frozen for later transfer.

Treatment outcome. ICSI has now been in use for over 11 years and there are over 26,000 babies already born as a result of ICSI worldwide. Fertilization rates are in the region of 60-70% of the injected eggs and cleavage rates of about 80% are expected after ICSI. The risk of complete failure of fertilization is less than 5%. The overall live birth rate per embryo transfer is about 23.1% (HFEA 2000) and 28.7% (SART 2002). This represents an increases of 1-2% compared with last years results. There is wide variability in results between centres. The success rates of ICSI treatment are dependent on the skill and experience of the practitioners. Other factors, which also affect ICSI success rates, include the woman’s age, duration of infertility and the number of embryos transferred.
ICSI does not increase the incidence of multiple pregnancy as compared to standard IVF.

Is ICSI safe? In addition to the risks associated with the standard IVF treatment, there is some concern about the safety of the ICSI procedure. This is mainly because of the risk of injecting an abnormal sperm since ICSI bypasses the natural stages of sperm maturation and selection. It is also possible that ICSI may result in fertilization of an abnormal egg (during natural or standard IVF a natural selection process is in action and it is less likely for an abnormal egg to be fertilized successfully).

Research has so far shown that there is an association between male infertility and the following disorders:

• Defects in the Y chromosome “Y chromosome micro-deletion” (the male chromosome) occurs in about 5% of males tested.
• Abnormalities in the number or structure of chromosomes e.g. Klienfelter syndrome (10 times higher than normal population) and translocation.
• Cystic fibrosis.
• Androgen receptor gene defects. Since the gene is on the X chromosome the daughters of men who become fathers by ICSI will eventually carry such defects and the sons of these women would have a fifty percent chance of being affected.
There are over 26,000 babies already born as a result of ICSI treatment worldwide. In general, the available data are broadly reassuring for the short-term health of ICSI babies but no information as yet available on long-term health.
It has been suggested that the rate of major birth defects may be as twice as high as in the background population (7.4% vs.3.8%). There may also be a slightly increased risk of mildly delayed mental development. There is a slight increased of sex chromosome abnormalities such as Turner’s syndrome and Klinefelters syndrome (1.2% vs. 0.5% in the general population). There is no apparent reason to suspect that ICSI technique is itself harmful (not a procedure related). It is possible that the genetic disorders, which have led to the sperm problem in the father’s sperm, may be passed on to the offspring.
There is anecdotal reports that ICSI may increase the incidence of syndromes associated with aberrant genetic imprinting, such conditions include Prader-Willi and Angelman syndromes.
Before a couple considers treatment with ICSI, they should be offered counseling and screening for the above disorders with the exception of vasectomy cases. When a genetic abnormality is identified the couple should undergo genetic counseling before proceeding with treatment and should be made fully aware of the risk of transmission of the abnormality to the offspring.
It is clear that careful follow up of the children born after ICSI is important and patients who conceive by ICSI should carefully consider antenatal screening tests such as chorionic villus sampling or amniocentesis.