Intracytoplasmic sperm injection (ICSI)

Twenty years have passed since the birth of the first IVF baby in the UK in 1978. Infertile couples had to suffer great pain in the past, but the situation is greatly improved with the advancement of technology in female infertility treatment and IVF in the past two decades. The topic of the presentation today is intracytoplasmic sperm injection (ICSI). The development of ICSI has become a solution to male infertility and some specific female infertility.

In fact, a complete family unit is composed of a couple and a child/children. Divorce or a bad situation might happen without a child. The process of fertilization is ovulation, insemination in the fallopian tube, and implantation in the uterus. In brief, there are four prerequisites for conception:
 

1. The wife has a good sign of ovulation.
2. The husband has sperm of good quality.
3. An unobstructed environment for the union of egg and sperm.
4. A good fertilized egg and a good environment for implantation.
    

At present, risk factors associated with infertility are almost equally divided in the two genders. Totally, 40-60% of them are female factors, 40% are male factors, and 10-20% are infertility of unknown factors. Female factors are related to ovary, uterus and fallopian tubes, Hormone drugs stimulate ovulation can almost completely solve the problems originated from ovary and ovulation, fallopian tube factors can be solved by in vitro fertilization (IVF).

How does IVF work?
First of all, ovulation under the stimulation by hormones, retrieval of the eggs from vagina, put together the eggs and sperms in the laboratory for fertilization in the best circumstances, if there is the formation of fertilized egg, transfer the fertilized egg via a specialized tube into the uterus for pregnancy. Male factors mainly come from theabnormal sperm production, weak sperm activity, problems with the delivery of sperm, etc.Examples of problems with sperm delivery are sexual dysfunction, impotence, abnormal ejaculation, etc. Intrauterine insemination (IUI) can be use to help the couples in these circumstances, more sophisticated treatments are required for decreased sperm account, urethral stricture and retrograde ejaculation.

Clinically, lots of infertility cases are caused by oligozoospermia, i.e., sperm count below the standard. Possible reasons for oligozoospermia include history of epidemic parotitis, epididymitis or cryptorchidism, temporary oligozoospermia may be caused by fever, alcohol, chemotherapy, infection, varicocele, unilateral testicular obstruction. IVF is required for severe oligozoospermia.

According to the criteria of World Health Organization (WHO) manual, normal sperm content in a sample of semen should be equal to or above 20 million per milliliter. Oligozoospermia may be classified into various types on the quantity of sperm count: mild, below 10 million sperm; moderate, below 5 million; and severe, below 1 million sperm per milliliter of semen. IUI is recommended for sperm count below 10 million, IVF is the second choice when IUI fails. And if sperm count below 5 million or 1 million, the most suitable treatment is IVF using ICSI, since a low concentration of sperm can mean that the oocyte does not fertilized under natural circumstances.

Before ICSI, we will first check for the existence of anti-sperm autoantibodies in the semen. If it is the case, the treatments include antibiotics, corticosteroids or correction of genital tract obstruction.IVF is required to overcome infertility due to server antisperm antibodies. The most severe male infertility is azoospermia. Causes of azoospermia can be divided into two categories. The first is caused by pre-testicular factors, i.e, pituitary gland or hypothalamus. The second is originated from testicle per se, for example, chromosomal abnormalities such as XXY, previous history of epidemic parotitis, epididymitis, radiotherapy, chemotherapy, or obstructive azoospermia, mainly caused by congenital defects in vas deferens. Previous treatment of male infertility caused by azoopsermia involves donor sperm from the sperm bank for insemination (artificial insemination with donor sperm, AID), successful fertility comparable to normal pregnancy rate can be reached in most of the cases. There are particular receptors on the surface of sperm and egg, sperm can penetrate the egg only when the structure of the receptors are the same.

Current managements of male infertility are IVF (test tube baby), special treatment of sperm or ICSI. The sperms of some patients appeared normal in all test, but cannot get the egg fertilized, and these couples have been unable to conceive after multiple IUI trials. Through IVF treatment, it is found that the husband’s sperm could not penetrate the wife’s egg to fertilize it. There are currently two solutions, one is to use the sperms from sperm bank, and the other is ICSI. The development of gamete micromanipulation originated from partial zone dissection (PZD) in 1989, which involves the creation of an opening in the zona pellucida to break the major barrier for sperm penetration. In 1991, subzonal insertion of sperm (SUZI) was developed to bypass the zona pellucida completely and insert the spermatozoon into the perivitelline space between zona pellucida and oocyte. Finally is the development of ICSI in 1992.

ICSI is recommended for the patients receiving two consecutive IVF treatments but the fertilization rates were less than 10% to 20%, or for those receiving surgical sperm harvesting from either testicle or epididymis but ended up with sperms of poor quality, or for those with sperm count less than 50,000, or sperms with unacceptable motility and/or morphology. Other groups of patients recommended for ICSI are those with high level of anti-sperm antibodies, unsatisfactory sperms harvested at the day of egg retrieval, only two or three eggs were retrieved, eggs with particularly thick zona pellucida, and for women older than 40 years old. The embryo quality derived is comparable to that from IVF.

The fertilization rate of ICSI is approximately 70% to 80%, and the conception rate can reach more than 30%, much better than the 8% pregnancy rate of injection of sperm into zona pellucida. For the sperm retrieval surgeries, microsurgical epididymal sperm aspiration (MESA) is carried out with ultrasound guidance, if no sperm recovered, sperm biopsy, i.e., testicular sperm extraction (TESE)is performed by inserting a needle through the testicular skin and aspirating fluid and tissues which containing sperms, or by surgical retrieval of sperm directly from the head, body or tail of epididymis after opening the skin. Testicular biopsy is carried out if still no sperm was recovered. Statistically, the fertilization rate for TESA and MESA are 59% and 49%, and pregnancy rate are 55% and 48%, respectively, so no matter the sperms are recovered from testicle or epididymis, the pregnancy rate in each cycle reaches 50%.However, the fertilization and conception rate are only 39% and 10%, respectively, if a poor ability of patient’s testis in sperm production was encountered. If the patient is obstructive azoospermia, sperm can be retrieved form testis or epididymis without any problem and a good conception rate will be achieved.

According to WHO, the quality of male sperm has decreased rapidly in the past 50 years, and maybe everyone needs ICSI in the near future. The latest advance is fertilization with single immature sperm. ICSI is indeed a great progress in reproductive medicine in the past five years.Albeit originally developed for severe male infertility, ICSI has also solved the problems from the female partner or from both sides of the couples.