In Vitro Fertilization
In vitro fertilisation is a demanding procedure with emotional, physical and financial consequences. Couples are often only considered for IVF, if surgery, drug therapy and IUI have not been successful. Previously, only couples whose fertility problem was the result of blocked fallopian tubes were considered for IVF. However today, its use has extended to include couples affected by endometriosis, severe male infertility and long-term unexplained infertility.
It is important not to underestimate the demands of IVF. However as long as you prepare yourselves properly as a couple and talk about it openly and honestly, the chances are greater that you will come through the treatment well, irrespective of the outcome.
The IVF Process
As several egg cells are required for IVF to maximize the chances of fertilization, the ovaries are stimulated with drug therapy.
When the egg cells are mature they are generally collected vaginally.Fertilization: After the egg cells have been aspirated from the ovaries, they are mixed with the sperm cells in the laboratory. Fertilization takes place at this point.
One or, at the very most, three embryos (fertilized eggs) are replaced into the uterus generally two days after the aspiration.
The outcome 2 weeks later you will find out whether treatment has succeeded.
Preparation
- The preliminary examinations that have to take place will also be discussed with you. These might include, for example, an extra blood test (for infectious diseases or hormone assessment), or another semen analysis.
- Additional heredity tests (chromosomal studies) on a blood sample from the man in the case of ICSI treatment. You will also be given further information on daily practice in your clinic; it is essential that you know whom to contact, and when, if you have questions or problems.
- IVF treatment not only takes up a lot of time, but also demands considerable flexibility.
- The course and duration of the stimulation is not easy to predict, as a result of which follow-up checks and even the day of the puncture to collect the eggs can only be scheduled shortly in advance. It is important that you bear this in mind during the month of your treatment.
Treatment Plan:
- 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.
Checkups:
Puncture:
- 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.
Fertilisation:
- 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.
Fertilisation:
- 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.
Embryo Transfer:
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”.
Frozen Embryos (Cryopreservation):
- After thawing, the frozen embryos can be transferred in a normal menstrual cycle or in what is called a “cryo-cycle”, in which the woman takes hormone tablets to prepare the uterus for possible implantation. However, you must bear in mind that, once the embryos have been thawed and if the quality is insufficient, they may no longer be suitable for implantation.
- The chances of success with transferring frozen embryos is lower than with replacing “fresh” embryos, but it is still an extra chance with less stress for the woman.How you and your partner feel about the freezing and storing of embryos is a very personal matter.
- The ethical aspects are sometimes a source of discussion and it is important that you both reach an agreement about whether you would like to use this opportunity before you start an IVF/ICSI treatment. Prior to commencement of the treatment, the centre will require a written instruction from you and your partner in which the conditions for storage are all set
Suitable candidates for IVF are:
If both fallopian tubes are completely blocked, IVF is directly indicated. If the function of the fallopian tubes is reduced, IVF is only considered after other treatments.
Endometriosis
- Depending on the severity, drug or surgical treatment will be the indicated treatment in the first instance.
- IVF is considered if a pregnancy has not occurred after treatment.
- For mild forms of endometriosis, the guidelines for unexplained subfertility are applied.
ICSI is also considered in severe cases of subfertility. In less severe forms, IVF is considered after a number of IUI cycles.
Premature ovarian failure
No cause found after full investigation, at least 3 years of marriage, and having completed alternative approaches to fertility management for at least 1 year. However, this will not apply to female above 35 years old.
- Other conditions acceptable to the local obstetric/gynaecologic community.
- IVF shall only be carried out on a married woman and only with the consent of her husband, whether or not her husband’s semen is used.
- The most important reason for considering a couple for IVF at an earlier stage is the age of the woman: the chances of a pregnancy over the age of 35 rapidly reduce, and with them the chances of success after IVF.
- The doctor treating you will assess when and if IVF is an option for you. A strict selection is justified given that IVF is an invasive and intensive treatment with associated risks.
When does IVF not make sense?
Age
Weight
Being seriously overweight not only has an effect on fertility, but also on general health and therefore on a possible pregnancy. In addition, ovaries for IVF have to be accessible for puncture. Sometimes this is scarcely possible in heavier women. Therefore, weight loss is a necessity in some cases before a possible treatment.
Sperm Quality
Pregnancy
The IVF clinic concerned will carefully map out your situation, after which it will decide whether you can be considered for IVF.
Risks
Because the IVF process involves various stages, patients can experience different side effects at different times.
- 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.
- 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.
- 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.
- 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.
- 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.
Success Rates
How great are the chances of success?
Because there are new chances with every cycle, half the couples on average return home with one child or more after three attempts.IVF results can be displayed in various ways. The following definitions have been used:
Started cycle:
Follicle puncture:
Embryo Transfer:
Pregnancy:
On-going pregnancy:
interval in which there is a 95% certainty.
The number of continuing pregnancies per cycle started has been chosen as the method of recording and comparing the IVF figures. This percentage tells us something about the care delivered by a centre – but is far from the whole story.
- Firstly, this percentage is dependent on all sorts of other factors, such as the age of the woman, the length of time she has wanted a child and the number of previous treatments.
- These factors may vary from centre to centre. For example, if a centre primarily treats older women, that centre’s chances of a pregnancy will be lower.
- Secondly, this percentage may vary from year to year for unpredictable causes. It therefore makes sense to look at the results over several years.
- Finally, other factors such as patient satisfaction, the percentage of complications and the percentage of multiple births are also important to the quality of care.
- If several embryos are transferred, for example, not only do the chances of a pregnancy increase, but so also do the chances of multiple births with all the associated risks.