IVF

Ever since Steptoe and Edwards announced the birth of the first 'test-tube' baby in 1978, many thousands of babies have been born to couples as a result of IVF treatments who would otherwise have remained childless.

The main indications for IVF are when the woman's fallopian tubes are blocked or damaged, or when there are dense adhesions or endometriosis involving the ovaries. IVF may also be the treatment of choice when the sperm count is very low, and in certain cases of otherwise 'unexplained' infertility. It must be remembered that IVF is not the be-all and end-all of all treatment. But if the fallopian tubes are severely distorted and blocked, IVF may be the only option open to you that gives at least an opportunity for a pregnancy to occur.

"In-vitro" means "in glass" and is the laboratory term used for a biological process that occurs outside the body. It was the media who popularised the term "test-tube" pregnancy. In fact, test tubes are not used in the actual IVF process, flat plastic dishes being used instead.

When you are first seen in the clinic, you will each be given ?Welfare of Child? questionnaires to complete and sign. Under the Human Fertilisation & Embryology Act (1990) and Code of Practice of the HFEA, all assisted conception units have a major obligation in law to take account of the welfare of any child who may be born as a result of licensed treatment, as well as the affect this may have on any other existing children. The welfare of the child is of paramount importance. For this reason, very occasionally clinics will refuse treatment if it is thought that the needs of the child have not been taken into account.

Preliminary tests are carried out on both partners. The female partner requires having Rubella antibody screening and a full hormone profile taken in the first few days of the menstrual cycle. A "dummy run" sperm preparation is carried out to ensure that sperm can be adequately prepared for IVF. Both partners are screened for Hepatitis B, Hepatitis C and HIV. If after preliminary investigations you are found to be suitable for IVF, very detailed explanation about the procedure will be given to both of you. When the treatment cycle is being planned you are given oral and written information and implication counselling relating to IVF. This will include discussion on: the effects of the drugs, the operative risks while obtaining the eggs, abandoning a treatment cycle, coping with failed treatment, the problems linked to successful treatment especially a multiple pregnancy, the risks of ovarian hyperstimulation syndrome (see Ovarian Hyperstimulation Syndrome information), miscarriage and ectopic pregnancy and the problems relating to cryopreservation (freezing) of any 'spare' embryos. A treatment consent form will be explained and both of you will be asked to sign this before treatment begins. The special HFEA consent forms relating to embryo storage will also be explained and will need to be signed before egg retrieval. To better understand the principles behind treatment, it will help if you understand how normal egg production works in each cycle:

The menstrual cycle is controlled by the hypothalamus in the brain and the pituitary gland that lies just beneath it. At the beginning of every normal menstrual cycle, the hypothalamus signals to the pituitary to release a hormone called Follicle Stimulating Hormone (FSH). FSH stimulates a group of about 20 egg follicles to start growing. During the next two weeks, as these follicles grow, they produce an increasing quantity of a hormone called oestrogen. The oestrogen enters the bloodstream and feeds back to the hypothalamus where it is recognised by special receptors. This "feedback" leads to a reduction in FSH output. As a result, there is only enough FSH to allow the biggest 'leading follicle' in the group of 20 growing follicles to continue to develop to maturity. The others shrink. This explains why most human pregnancies are only a single baby.

In IVF more of the group of 20 follicles are stimulated to continue to grow so as to obtain a bigger "harvest" of eggs. To achieve this goal it is necessary to first remove the normal control your pituitary gland has over your ovaries, or block the action

There are two ways of achieving this.

The standard method is to ?down regulate? the pituitary gland by stimulating it to use up all its stores of FSH. A synthetic form of the hormone message from the brain to the pituitary is self-administered either by injection or via a nasal spray. Once there is evidence that the pituitary gland is suppressed, (and while still continuing the suppression treatment), your ovaries are stimulated with daily injections of FSH alone or in combination with another hormone called luteinising hormone (LH).

An alternative method is to block the release of your own FSH while stimulating your ovaries to grow eggs. This method has the advantage of far fewer injections and a much shorter treatment cycle but depending upon the drugs used may have the disadvantage of increased cost.

Therefore, unlike a natural cycle, the FSH levels are not allowed to fall, which means that hopefully more of the original group of 20 follicles continue to grow and mature. The progress in the growth of the follicles is monitored by ultrasound scans and by blood tests, which measure the rising level of oestrogen hormone. Once the ultrasound scan shows that there are a sufficient number of mature follicles, you are given a hormone injection of human chorionic gonadotrophin (hCG ) which primes the eggs before they are collected.

The whole process of egg stimulation, egg retrieval and subsequent embryo transfer is carried out on an out-patient basis.

Thirty-four to thirty-seven hours after the hCG injection, the eggs must be removed from the ovaries before ovulation can occur. This is a remarkably pain-free procedure. This is often carried out under what is termed "sedation anaesthesia". This means that you will essentially feel nothing and may actually remember nothing of the retrieval process.

The eggs are removed through the vagina using ultrasound to guide the direction of the fine needle that is used for this procedure.

On the day of egg retrieval your partner produces a sperm sample at the centre. The embryologist prepares this so that the most vigorous sperm are isolated.

The eggs usually require a few hours of incubation before they are mixed with prepared sperm, as they have been removed a little prematurely and need time to mature. Each egg is then incubated with up to 100,000 sperm. Fertilisation usually occurs in the next 12-16 hours.

Two, three or five days after the egg collection you will be asked to return to the ACU to have one or two of the most promising embryos gently transferred into the uterus through the cervix. This is a painless procedure and does not require any anaesthetic. You will be required to remain horizontal for a short time after the embryo transfer and can then return home.

Under current regulations, the maximum number of embryos that may be transferred is two. In exceptional circumstances three embryos may be transferred to a woman over the age of 40 years. To many infertile couples the prospect of twins or even triplets is fantastic,? a complete family in one go! But the reality can be very different.

If two embryos are replaced there is a significant reduction in the multiple birth rate of triplets and quads. This is true for all age groups although the live birth rate diminishes with age.

There is no doubt that it is safer to be born as a single baby than as a twin. The complications of a multiple pregnancy are significantly increased. There is a greater risk of miscarriage, raised blood pressure and diabetes. IVF twins and triplets are usually delivered by Caesarean section. The major antenatal complication in a multiple pregnancy is premature labour. Gross prematurity can sadly result in learning and development difficulties and even conditions such as cerebral palsy. The stillbirth and neonatal death rate (deaths in the first 28 days after birth) for a triplet pregnancy with one or more of the babies dying is six times higher than for a pregnancy with a single baby. There are then the potential problems of looking after two or three babies at home.

As a result of the problems that are linked to a multiple pregnancy, it is now felt that in those patients who are most likely to become pregnant, the number of embryos to be transferred should be limited to one. While this is the situation in a number of European countries, these countries are able to offer several free attempts at IVF. This is not yet the case in the UK where it is up to the primary care trusts (PCTs) to decide upon the number of NHS treatment cycles that will be funded. Indeed there are some PCTs that will not fund any NHS IVF cycles. There is therefore understandable concern among patients, that to reduce the number of embryos to be transferred down to one will overall reduce the success rate of IVF in the UK. This is something that will be discussed with you. You can be reassured that the single embryo transfer policy will only apply to you if you fulfil the very careful selection process that your clinic will have set up (see Elective Single Embryo Transfer information).

Future improvements in the outcome of IVF treatments depend upon increasing the successful implantation of transferred embryos. One way of achieving this is to transfer embryos at a more advanced stage of development, closer to the natural time that they would enter the uterus. In nature the embryo takes five days to pass along the fallopian tube to enter the uterus as an advanced 100 ? 120 cell embryo known as a blastocyst. In the majority of IVF cycles, embryos are being transferred two or three days after egg retrieval. This means that they are usually at a very early 4 ? 8 cell stage of development and are being introduced into a uterus when the endometrium lining may not yet be sufficiently developed to allow implantation to occur. The problem has been that until recently there has not been a reliable method of keeping embryos in the laboratory for longer periods of time, owing to the difficulty in providing them with the necessary nutrients. New culture media are now available which allow embryos to be developed in the laboratory to a more advanced stage and be transferred on the fifth or sixth day after egg retrieval as blastocysts. However, to complicate matters further, there is no guarantee that simply using new culture media will mean that embryos will progress to become blastocysts. It is quite common for embryos to arrest at the four cell stage and not progress any further. Those that do reach the blastocyst stage are more likely to "hatch out" and implant naturally.

It must also be borne in mind that there is a higher incidence of both identical and non-identical twins with the transfer of blastocysts. This probably reflects the greater potential that these embryos have to implant successfully. Therefore in the majority of cases, only a single blastocyst is transferred.

You must not feel disappointed if your embryo transfer takes place two or three days after egg retrieval. In the majority of cases it is far better to select an earlier time for transfer of your embryos than to take the risk having blastocysts or nothing! The decision as to the timing of embryo transfer is an embryological one and depends upon the egg yield and the quality of the resulting embryos, but you will be involved in the decision making process.

The whole question of the storage of any remaining embryos will have been fully discussed with you before the IVF cycle is even begun. Most clinics have the facility of embryo freezing and this will be offered to you to store suitable 'spare' embryos for your own possible future use. There is no point in storing embryos of dubious quality as this will raise false hopes that they will survive future thawing and be suitable for transfer (see Cryopreservation (freezing) of Embryos and Frozen Embryo Transfer (FET)).

During the next two weeks you will be using progesterone vaginal pessaries or cream to support the lining endometrium of the uterus to encourage implantation of the embryo. If you have not had a period 16 days after the egg retrieval, you will be asked to return for a urine test and blood test that will hopefully detect the pregnancy hormone Beta-hCG.

There is some evidence that the use of low-dose aspirin improves the success of IVF. As long as you are able to tolerate aspirin it may be suggested to you to take this either from the commencement of the FSH injections or after embryo transfer has been carried out. The aspirin is continued until the result of the pregnancy test is known.

Your chances of achieving a successful and happy outcome to your treatment depend upon many factors, the most significant of these being the woman?s age.

In 2006, the percentage of IVFcycles started that resulted in a live birth where the patients? own fresh eggs were used was:

31% for women under 35 (29.6%)
26.4% for women aged 35-37 (23.6%)
18.6% for women aged 38-39 (18.2%)
11.1% for women aged 40-42 (10%)
4.6 % for women aged 43-44 (3.2%)
4.0% for women aged 44+ (0.8%)

The figure for 2005 is shown in brackets for comparison.

(Figures by courtesy of the HFEA)

This is only a very brief summary of what is involved in an IVF treatment cycle. Very detailed information is provided for couples at the planning stage of their IVF treatment. You can perhaps understand and appreciate that emotionally it can be a very tense experience for both of you, especially the waiting time after embryo transfer. For this reason you will be offered support counselling with your counsellor both before and after embarking upon a treatment cycle.

March 2009