IN VITRO FERTILISATION (IVF)

IVF is probably the most well known of the "Assisted Reproductive Technologies". It is otherwise known as "test tube baby", and has helped infertile couples conceive and bear children for over two decades. These days, fertilization actually occurs in a dish, and not a test tube. It was originally developed to help couples overcome tubal factor infertility, but has become useful in treating other factors, such as immunological problems, unexplained infertility and male factor infertility.

IVF is basically a four step process.

• First, you take medications to make multiple follicles begin to develop on your ovaries. This step is referred to as ovarian stimulation, or superovulation.
• Step two involves monitoring follicular growth by ultrasound, to determine egg growth and uterine lining development. When it is determined that the follicles and the uterine lining are appropriately mature, a trigger shot of Human Chorionic Gonadotropin is then administered.
• 36 hours after the trigger shot, the third step begins with retrieval of the eggs by ultrasound-guided-needle aspiration, this process is best done under light anaesthesia. A sperm specimen is then washed and prepared for insemination. The washed sperm is then placed in a dish with the eggs, and they are placed in an incubator for 18 hours. After 18 hours, the embryos are observed for normal fertilization, under a microscope, where the pronucleus of egg and sperm can be seen. The embryos are then incubated for further development into multi-cell embryos.
• The fourth and final step involves transferring the embryos into the uterine cavity via a catheter inserted through the cervix. The number returned varies with the desires of the patient, under the guidelines of age categories; under 40 years old, up to two embryos; 40 years and older, up to a maximum of three embryos. Additional embryos may be frozen and stored for future use.

ICSI is used when the male partners' sperm is suboptimal, when previous standard IVF treatment has been associated with a low fertilisation rate and occasionally used if only a few eggs are available. With ICSI a single motile sperm is isolated from the male partner' sperm and the tail of the sperm is cut to immobilise the sperm. The sperm is aspirated into a very fine glass needle (about one tenth of the diameter of a human hair at its tip). The sperm is then injected directly into the centre of the egg and the needle withdrawn. A very small percentage of eggs can be damaged by the injection procedure but this is more than offset by the increased fertilisation rate.

Are there any risks to the IVF/ICSI procedure?

Couples undergoing what is a relatively new procedure are naturally concerned to know about all of the risks involved. Certain risks are common to in-vitro fertilisation and ICSI; namely, the chance of developing ovarian hyperstimulation syndrome and the chance of multiple pregnancy. However, while there have been nearly two million babies born following standard in-vitro fertilisation treatment, the number of babies born following ICSI is probably a few hundred thousand. From assessment of these babies following ICSI, the following represents the current state of our knowledge about the possibility of abnormalities. It is an unfortunate fact that 3 in every 100 babies born naturally, i.e. not as a result of fertility treatment, are born with a major malformation. The largest studies performed to date of 3,000 pregnancies following ICSI treatment has shown that the overall percentage of ICSI babies born with an abnormality is no greater than that arising in the normal population.

Over the past few years it has been realised that approximately 10% to 15% of men who have no sperm or very low numbers of sperm have a specific defect in one of their genes that is responsible for producing sperm (this is called the DAZ gene). It is quite possible that this gene defect will be passed on to a male child, which could result in the child also, in the future, being infertile.

1. Ovarian Hyperstimulation Syndrome
   This is probably the most serious side effect of in-vitro fertilisation treatment. It is related to the drug stimulation that you receive rather than the in-vitro fertilisation itself and the syndrome can occur in women receiving these drugs for other reasons. As the ovaries are stimulated more than would normally be the case in a natural cycle, they always are larger than normal and contain fluid filled structures (follicles), which contain the eggs. This occurs in all women having IVF treatment and is not a cause for concern. In approximately one woman in a hundred, the more serious form of ovarian hyperstimulation syndrome develops. Here, the ovaries become greatly enlarged and contain large cysts. These cysts produce copious quantities of fluid, which is released into the tummy cavity. The fluid is rich in minerals and protein. The symptoms of severe ovarian hyperstimulation syndrome include abdominal pain, a marked degree of abdominal swelling, shortness of breath, nausea and possibly vomiting, and a reduction in urine output. In the presence of severe symptoms, hospitalisation may be necessary. This enables the fluid minerals and protein to be replaced and corrective measures put in place to prevent further complications. Due to the seriousness of the problem, prevention is better than cure. Although it is not possible to be certain about which patients will develop ovarian hyperstimulation syndrome, those with the ovarian hormone abnormality called polycystic ovaries are known to be more at risk. This will be assessed at the time of your preliminary consultation prior to starting IVF treatment. Patients who respond to the drug treatment by producing very many eggs, particularly if they are experiencing lower abdominal pain before the time of the egg collection are also at increased risk. In these circumstances, the treatment cycle may be cancelled before the late night pregnyl injection or, if the egg collection is performed, all of the embryos may be frozen and none transferred immediately. This should reduce the chance of the serious form of hyperstimulation syndrome from developing.
2. Multiple Pregnancy
   The Ministry of Health Singapore has recently advised all IVF clinics that no more than 3 embryos can be transferred in an IVF cycle except in exceptional cases eg: patients over the age of 40 years having treatment with their own eggs. Many infertile couples are quite pleased at the idea of having twins although most couples would prefer not to conceive a triplet pregnancy. It is still possible to conceive a triplet pregnancy even if just 2 embryos are replaced and this happens if one of the embryos divides into identical twins. Fortunately this is very uncommon. In couples who conceive naturally, the chance of a twin pregnancy is approximately one in every eighty pregnancies. With IVF treatment, the chance of a twin pregnancy is one in every three to four pregnancies. Apart from the social and professional problems of multiple pregnancies, particularly triplets, the medical problems related to the carriage of two or three babies can be very significant. These include an increased risk to the mother of pregnancy related complications such as high blood pressure, diabetes and haemorrhage. Problems for the babies include the risk of delivery of very premature babies who may not survive or who may survive with important handicaps including brain damage. The ideal outcome of IVF is to have a single healthy baby.
3. Infection/Haemorrhage
   At egg collection a fine needle is passed through the vagina into the ovary to remove the eggs. There is a small risk at that time of causing bleeding from the ovary or introducing inflection into your pelvis. Great care is taken during the egg collection to minimise these risks and antibiotics are given. In practice, while a little bit of spotting of blood from the vagina is likely after the egg collection, significant bleeding is extremely rare. The chance of infection is less than one in one hundred.