In Vitro Fertilisation (IVF)

In vitro fertilisation (IVF) has been practised since 1978. By 2006, roughly three million children had been born worldwide with the help of IVF. The principle behind this method can be briefly described as follows: after stimulating the ovaries with natural mediators (gonadotropins), the eggs are removed and placed in a test tube with the partner's sperm. The sperm fertilise the eggs and the resulting embryos are returned to the uterus. Ideally they then grow, i.e. pregnancy ensues. Such a pregnancy is natural and just as "normal" as any other pregnancy.

Treatment

Treatment commences with stimulation by natural mediators. If we were to rely on the natural cycle alone, there would normally only be one fertilisable egg. Stimulation therapy with the body's own, natural mediators (gonadotropins) increases the chances of obtaining more eggs. The mediator is normally administered by injection. The procedure is quite straightforward ? you can simply administer the product by injecting it under your skin, or ask your partner to do it. Therapy lasts ten to twelve days and is usually tolerated very well. In very rare cases ovarian hyperstimulation syndrome may occur. This syndrome has three different degrees of severity, whereby grade 3 is the most severe. Temporary accumulation of water in the abdomen or a tight sensation in the breasts are common symptoms. On account of the growth in size of the ovaries, there is a slightly higher risk of torsion of the ovary on its own axis. We try to rule out all the risk factors beforehand and thus keep the gonadotropin dosage as low as possible. Special prophylaxis helps to keep the probability of hyperstimulation syndrome to much lower than one percent.

During stimulation therapy, an ultrasound scan is performed once or twice to check the size of the follicles. In parallel, the blood levels of the hormones relevant to follicle maturation are measured ? in such a way we can decide when is the best time to retrieve the fertilisable eggs. Ovulation is then induced by injecting a specific medication (hCG). Ovulation ensues 36 hours after this injection.

Just before ovulation, the mature eggs are removed through the vagina under ultrasound guidance (this method is called follicular puncture) and placed in a nutrient solution. We always carry out this procedure at our clinic with brief, general anaesthetic.

Now the partner's sperm cells are needed. Many patients feel stressed at the notion of "ejaculation to order", which can have a negative effect on sperm quality. It therefore helps to collect the sperm at home and bring them to the clinic. The seminal fluid is prepared in the laboratory, and the motile sperm are placed in a nutrient solution together with the fertilisable eggs. After about 24 hours in an incubator we can see whether the eggs have been fertilised.

If the eggs have been fertilised as expected, they are returned to the uterine cavity using a thin, flexible tube ? a procedure which is usually painless. At our clinic, we agree with our patients on the transfer of one to a maximum of three fertilised eggs (embryos). This depends on the nature and severity of the given fertility disorder and the woman's age. In younger women we recommend returning a maximum of two embryos. Even in older women we recommend the return of three embryos only in very exceptional cases due to the risk of multiple pregnancy.

Just two weeks later, measurement of the pregnancy hormone hCG will reveal whether treatment has been successful. If the results are not conclusive, the test will be repeated.

Blastocyst transfer

Contrary to popular opinion, blastocyst transfer is not prohibited in Germany. Blastocyst transfer involves the transfer of embryos at a later point, when they are at a more advanced stage of development than usual ? mostly on the fifth or sixth day after collecting the follicles.

In principle, however, blastocyst transfer does not promise a higher rate of pregnancy. It has even been conjectured that leaving the embryos in the nutrient solution for longer may be disadvantageous ? namely if difficulties arise as they continue to grow. By such a time, the embryos ? if transferred earlier ? would already have been safely returned to the uterus. Nevertheless, in certain cases blastocyst transfer may be wise. For this reason we also offer this modern method of fertility medicine.

Risks and prospects of success

The risk of hyperstimulation syndrome has already been discussed above. Egg harvesting can also cause tissue damage. Since we conduct all procedures with ultrasound guidance, such a risk is extremely rare. A further risk is ectopic pregnancy, although the embryos are returned directly to the uterus.

The numbers of miscarriages from in vitro fertilisation amount to roughly 15 percent, which is 5 percent higher than in "normal" pregnancies. The reason is found not in the IVF method, however, but in the fact that women conceiving with the help of IVF tend to be older, on average, and the risk of miscarriage increases with age. Since the practice at our clinic is to return three embryos only in very rare cases, there is no risk of triplets.

Pregnancy rates following IVF are very much dependent on the causes for the infertility and the woman's age. The figures worldwide are given as approximately 25 percent per transfer.

What happens in the laboratory?

An important element of in vitro fertilisation ? i.e. the fertilisation of the egg ? takes part in the laboratory. To make you feel more comfortable, let us tell you about what goes on in there.

To start, you need to know that not every fertilised egg can actually become a viable embryo. This is perfectly normal and also occurs during "natural" reproduction. Nowadays it is possible to identify viable embryos and return them to their mothers, however. In this respect there is no disadvantage in Germany as compared to treatments abroad.

As described in the section on in vitro fertilisation, the mature eggs are removed through the vagina using ultrasound guidance (follicular puncture) and transferred to the laboratory immediately.

There, all the eggs which have been harvested, depending on the number, are divided into culture dishes and placed in an incubator for about 3 hours, where they continue to grow and mature.

While this is happening, the sperm are being prepared. They are cleaned, and then their concentration and motility are analysed. On this basis, only appropriate sperm with high motility and density are selected for use.

The sperm are now combined in the culture dishes with the eggs, i.e. the sperm are added to the eggs. The culture dishes are then returned to the incubator. The sperm enzymes dissolve the cell mass surrounding the eggs and fertilisation can now take place: the sperm penetrate the eggs.

The cells are examined under a microscope after 18 to 20 hours for signs of fertilisation. This procedure is known as pronuclear screening. In the egg, a female pronucleus develops from the genetic material of the egg cell, and a male pronucleus develops from the genetic material of the sperm head. If the egg reveals pronuclei, it can be assumed that there has been a fusion of the pronuclei and thus the egg has been fertilised.

During pronuclear screening the cells are separated into fertilised and unfertilised cells, meaning that the eggs to be selected ultimately for transfer will be taken from those with pronuclei. At this point cells are also selected for cryopreservation. Cryopreservation is the method of freezing eggs for later fertilisation.

After a further 24 hours, the initial stages of embryonic division are monitored and documented. Now, the cells are monitored daily until transfer of the embryos. In agreement with the patient, the embryos are returned to her between the second and fifth day of harvesting the eggs. If the embryos are not returned until the fifth day, this is known as blastocyst transfer.