In Vitro Fertilization

The information in this section provides greater insight into the world of IVF. In this way, you will arm yourself with knowledge, which you can use to find your way in this difficult, but possibly worthwhile process. Most IVF clinics have extensive information about IVF treatment. Make sure you read this as details of the treatment can vary from clinic to clinic.

Once you have been selected for IVF treatment, it is important to find out as much as you can about the way IVF is performed at your clinic. As soon as it becomes apparent that IVF is appropriate for your situation, you can be placed on the waiting list for treatment.

This waiting list can vary greatly from clinic to clinic. However, it is generally preferable to undergo treatment at the fertility clinic you are already attending due to the relationship that you have built up with the people treating you to date, or, if not available there, locally because of the travelling time associated with the frequent checkups.

There are different types and brands of the drugs that may be prescribed to you. The precise drug therapies you use will depend on your personal situation and the clinic’s general policy. Usually the women’s own hormone production must be suppressed initially. Various methods are available for this.The woman then begins daily injections to stimulate the ovaries to produce a number of egg cells. Ideally the aim is to obtain 10 (5 – 15) egg cells.

• The quantity of drugs (dosage) required for this is estimated in advance. Do not expect from the start, however, to always be able to predict how the ovaries will react.
• If there are too many egg cells, your treatment may have to be cancelled.
• If the reaction is moderate, the dosage can sometimes be increased during the treatment, but a treatment may also be cancelled if there are too few egg cells.
• Although disappointing, you can at least take some solace from the fact that this experience can be used to improve the chance of success for a possible subsequent IVF treatment.

The egg cells are found in fluid-filled follicles in the ovaries. The size of a follicle provides an indication of the maturity of the egg cell. During the treatment, you will have frequent checkups at the outpatients department to track the reaction of the ovaries to drug therapy using vaginal ultrasonography. The size of the follicles and the viscosity (thickness) of the cervical mucus are measured at each check-up to determine the right time for the puncture. Blood may also be taken to measure the hormone levels.

At the point when the egg cells are almost mature, ovulation is artificially induced by means of an injection of human Chorionic Gonadotropin (hCG). It is crucial that this injection is carried out correctly and at exactly the stated time. This injection stimulates the final maturation of the egg cells so that they are released from the follicles. The egg cells are removed from the body by needle biopsy (puncture) 35 hours after the injection.

• Puncturing the follicles is called follicle puncture. The puncture is carried out via the vagina with the aid of vaginal ultrasonography. You are generally given an anaesthetic for this, although practice may vary from clinic to clinic.
• The vaginal ultrasonic probe is fitted with a thin needle holder. A special hollow needle is then inserted into this holder. Both the needle and the follicles are visible using ultrasonography on the monitor.
• The follicles are punctured with the needle one at a time and aspirated (collected). You can follow the procedure yourself on the screen.
• The egg cells and surrounding fluid are drawn into a tube, which is then transferred to the embryo laboratory. The whole procedure generally takes about half an hour. The puncture itself lasts approximately five or ten minutes depending, among other things, on the number and position of the follicles.
• You will only find out whether egg cells have been obtained during the puncture, and if so how many there are, after the embryologist has been able to examine the fluid obtained.
• The number of egg cells may be lower than the number of follicles punctured, either because not all the follicles contain an egg cell or some egg cells are not fully mature.

The pain or discomfort felt during the puncture may vary from patient to patient, but is generally well-tolerated. You may also feel some discomfort after the procedure. It is therefore sensible not to make any other plans for that day. Just as with every other medical intervention, puncture carries a small risk of complications. Haemorrhages and infection are two possible complications, but are relatively rare. In general, the recovery period is short.

In the laboratory, embryologists then examine the fluid removed from the ovary for egg cells. The egg cells are graded according to their maturity, to see whether they are suitable for fertilisation. If fresh sperm is used, the male partner is asked to supply sperm. A semen analysis is then carried out and the sample is washed with a special nutrient solution to isolate the more motile sperm.

• Then comes fertilisation. Exactly which process is used depends on the clinic and the type of infertility involved. In standard IVF, the sperm is placed in a dish along with the egg cells.
• Within 18 hours the embryologist can tell whether fertilisation has occurred.
• Within 24 to 72 hours the embryologist can tell whether the embryos are growing.
• The sperm and the egg cells are placed in growth media; special nutrient solutions to give them the maximum chance to fertilise or to be fertilised.
• In conventional IVF, every dish containing an egg is filled with at least 50,000 sperms. In the laboratory, the embryos are then left, for between 2 – 5 days, to grow and divide into several cells. This is called an embryo culture.

In the laboratory, embryologists then examine the fluid removed from the ovary for egg cells. The egg cells are graded according to their maturity, to see whether they are suitable for fertilisation. If fresh sperm is used, the male partner is asked to supply sperm. A semen analysis is then carried out and the sample is washed with a special nutrient solution to isolate the more motile sperm.

• Then comes fertilisation. Exactly which process is used depends on the clinic and the type of infertility involved. In standard IVF, the sperm is placed in a dish along with the egg cells.
• Within 18 hours the embryologist can tell whether fertilisation has occurred.
• Within 24 to 72 hours the embryologist can tell whether the embryos are growing.
• The sperm and the egg cells are placed in growth media; special nutrient solutions to give them the maximum chance to fertilise or to be fertilised.
• In conventional IVF, every dish containing an egg is filled with at least 50,000 sperms. In the laboratory, the embryos are then left, for between 2 – 5 days, to grow and divide into several cells. This is called an embryo culture.

After the puncture, the woman is often prescribed drugs to prepare the uterus (womb) for embryo transfer. Embryo transfer usually occurs two to three days after fertilisation. There are special criteria against which the quality of an embryo can be assessed.

Embryos can be classified into different quality categories. A good or perfect embryo is an embryo that the embryologist believes has a good chance of implantation. If an embryo is classified as “bad”, the theoretical chances of implantation are indeed smaller, but implantation is not ruled out. If this type of embryo does implant, it can develop into a normal pregnancy and a healthy baby.

• However, embryos can usually only be assessed on external features. In some cases, closer examination of the embryo’s hereditary material can be done prior to the embryo transfer..
• The best embryo, or the three best embryos at most, are placed in the woman’s uterus. The embryos are transferred into the uterus by inserting a thin tube, or catheter, through the cervix. The depth of the uterus is measured in advance to determine the right place for the transfer.
• Transferring several embryos increases the risk of multiple births. A strict transfer policy (see below), is therefore adopted to try and limit the number of twins and multiple births due to the increased chance of complications.
• The maximum safe number depends on the age of the woman, the quality of the embryos and the success rate of the programme concerned. In Singapore, a maximum of three embryos are replaced in the woman’s uterus.

The embryo is sometimes transferred after five to seven days. As a result, the embryo has had more time to develop and is referred to as a blastocyst. During this extra time, embryologists can better identify the best quality embryos for transfer. By transferring fewer but better quality embryos, the chances of success are improved and the risk of a multiple pregnancy is reduced. Not all embryos that begin the fertilisation process grow into a blastocyst. On average, 40 to 50% of the fertilised embryos develop into blastocysts so delaying transfer allows the “survival of the fittest”.

The woman has to be able to carry a pregnancy to term.
The IVF clinic concerned will carefully map out your situation, after which it will decide whether you can be considered for IVF.

The advantage of any medical procedure must be balanced against the possible side effects and risks. The same applies to in-vitro fertilisation (IVF).
Because the IVF process involves various stages, patients can experience different side effects at different times.

1. The drugs used in IVF treatment can cause side effects such as mood swings and headaches. Besides side effects, risks are also associated with the use of these drugs. Because you are going to use drugs that have to stimulate the ovaries to produce several eggs, the ovaries may overreact.
2. This can be assessed by ultrasound checks, as a result of which either too many follicles are seen or the ovaries have increased greatly in size. It is possible that, in the period following the puncture, the ovaries will be even more disturbed and release fluid into the abdominal cavity. This is called overstimulation.
3. Fluid is released into the abdomen, which can lead to complaints of stomach ache, nausea, vomiting, serious weight gain (> 1 kg/day), breathlessness and reduced urine production (ovarian hyperstimulation syndrome, or OHSS). In severe cases, fluid may accumulate in the lungs causing breathing difficulties.
4. If an ultrasound scan shows that the ovaries are overreacting, the treatment is stopped. If the reaction is still acceptable, but there is a risk of overstimulation, you will be given separate instructions. If any of the symptoms described above occur, you must contact your doctor directly.
5. The doctor will perform an ultrasound scan to determine the size of the ovaries and to see if there are cysts (fluid-filled blisters) in them. The doctor will also look to see if there is free fluid in the abdominal cavity and carry out blood tests. Generally you should wait, rest and drink plenty of fluid, although admission to hospital may be required once in a while.

Although the risks of the rupture are slight, occasionally haemorrhage or very rarely infections can occur. Organs in the vicinity of the ovaries, such as the bladder or the intestines, are rarely damaged during the puncture.

Although the work on egg cells, sperm and embryos is done with the greatest care in the laboratory, IVF remains the work of humans – and subject to human error. Fortunately human errors are made very rarely.

• There is a chance of a multiple pregnancy. A strict transfer policy is operated in order to maximise the chance of a pregnancy but minimise the chances of a multiple pregnancy.
• Even if a single embryo is transferred, a (single-egg) twin can result, just as in a natural course of events. If two embryos are replaced, the chances of having twins are 25% and for triplets 1%, which is why the risk of complications as a result of multiple pregnancies (such as miscarriage, premature birth or diabetes) is kept as low as possible.
• While a positive pregnancy test is a promising sign of a successful treatment, pregnancy goes wrong in approximately 25% of cases.
• There is a 20% chance of a miscarriage and a 5% chance of an ectopic pregnancy.
  At the present time, no increased risks have been demonstrated in the incidence of hereditary defects in children conceived through IVF.
• If there is an indication of this, for example, the age of the woman (36 years or older), or hereditary defects in the family, prenatal diagnoses can be carried out.

Finally, the IVF process can be psychologically stressful. Patients are well advised to take steps to reduce stress, such as keeping good health, using relaxation techniques and seeking help and support from family or professionals.