Family doctor

What is IVF (in vitro fertilisation)?

Approximately 20 percent of infertile couples have damaged fallopian tubes. Sometimes the tube can be repaired surgically, but the pregnancy rates following surgery are low. Attempts at transplanting tubes and making artificial tubes have not been successful.

IVF and ET (in vitro fertilisation and embryo transfer) were developed as a technique to bypass damaged tubes by doing the things normally done within the tube (egg collection, fertilisation and early embryo development) in the laboratory. IVF can also be used for several types of infertility in which normal egg collection, fertilisation or embryo transfer to the uterus are somehow impaired. Examples include endometriosis, male infertility, immunological infertility, and infertility due to defects in cervical function. IVF has also been found to be useful for couples in which the cause of infertility cannot be diagnosed.

A procedure related to IVF, called GIFT (gamete intra fallopian transfer) can be used instead of IVF if the tube is undamaged and if sperm quality is adequate. Often IVF should be used in the first treatment cycle, since only IVF can confirm that fertilisation actually occurs.

The IVF procedure:

The IVF procedure has four steps:

• Treatment with hormones to stimulate more than one egg to mature
• The collection of the eggs
• Fertilisation of the eggs by the sperm
• Replacement of the embryos into the uterus

(Very occasionally no ovarian stimulation is used).

Stimulation

Only mature eggs are capable of being fertilised and of developing into babies. Drugs are given to stimulate the maturation of the eggs, which develop in the ovary inside fluid filled cysts called follicles. The progress of maturation is assessed by the size of the follicles, and by the amount of hormone produced by the follicle, which is measured in blood.

When the follicles are the right size, the final maturation process is initiated by injection of a hormone called human chorionic gonadotrophin (hCG) or sometimes by a rise in the levels of the woman's own hormone called luteinising hormone (LH). The next step, egg pick-up, should be performed 33 to 38 hours after the human chorionic gonadotrophin (hCG) injection, or the detection of the luteinising hormone (LH) rise. Attempts to collect eggs much before 36 hours will result in a poor yield; much after 38 hours the follicles will have burst, and the eggs will be lost in the abdominal cavity.

Egg collection

Egg collection is performed by guiding a needle into the follicle and drawing off the contents of the follicle into a test tube. The eggs are placed in a test tube in special culture fluid and held at body temperature in an incubator.

Egg collection is performed under ultrasound guidance using sedation. With ultrasound, the needle is directed via the vagina into the follicles. The vaginal route is preferable to the abdominal route because egg recovery rates are higher and because it is less painful.

Fertilisation

Eggs are usually inseminated 4 - 6 hours after collection. Semen is obtained by masturbation, and the sperm are isolated. A controlled number of sperm are added to each egg. The eggs are carefully inspected 14 - 18 hours after addition of the sperm, to check for signs of fertilisation.

Embryo replacement into the uterus

Two days after the egg pick-up, the embryos are drawn up into a fine catheter which is then gently inserted via the cervix into the uterus. No anaesthesia is required. Only three embryos at most are replaced to control the risk of a multiple pregnancy.

Embryo freezing

If more than three eggs are collected and sperm are added to all eggs it is possible that there will be more than three embryos available for replacement. In this case, embryos that continue to develop normally can be frozen, and stored for later use.

Pregnancy

The chance of becoming pregnant from any one cycle of IVF treatment depends on the number of embryos replaced and the age of the woman. At Fertility Associates over the last three years, 21% of the egg collections and 23% of the embryo transfers have resulted in the birth of children. In the last six months pregnancy rates/embryo transfer have improved further so that women under 38 should now reasonably expect about a 30% chance of having a live born infant.

When two or three embryos are placed, about 20 percent of pregnancies involve twins. Sometimes treatment is stopped before egg collection because follicles do not develop correctly or because the hormone levels can not be confidently interpreted. In cycles proceeding to egg collection, occasionally no eggs are obtained, or the eggs that are obtained do not fertilise.

In comparison, couples without infertility have about a 20 percent chance of pregnancy each month, so IVF is about as efficient as nature. About 25-30 percent of IVF pregnancies miscarry, usually early on. This figure appears to be higher than in non-IVF cycles, mainly because IVF pregnancies are detected very early and a lot of pregnancies which miscarry early in fertile woman go undetected.

Failure to become pregnant does not mean you have a reduced chance of becoming pregnant the next cycle, usually you have the same chance again.

The GIFT procedure

GIFT is an acronym for Gamete Intra-Fallopian Tube Transfer. The procedure was first successfully practised by a group in Texas in 1984. Since then it has been used quite widely, for several different types of infertility. The procedure is similar to in vitro fertilisation (IVF) in that the woman receives drugs to stimulate the maturation of several eggs, and follicular maturation is monitored in the same way. Eggs are retrieved under the guidance of ultrasound, but the technique then differs in that the eggs and spermatozoa are transferred directly into the fallopian tubes rather than cultured in the laboratory.

Up to three eggs are placed into the fallopian tubes. The pregnancy rate increases as the number of eggs transferred increases. Pregnancy rates are similar to, or slightly higher than, those of IVF (with the increasing pregnancy rate for IVF and because of the success of other treatments for unexplained infertility, GIFT is now a much less commonly used treatment).

As for IVF, the chance of multiple pregnancy increases with the number of eggs replaced. If more than three eggs are collected, it is possible to add sperm to the excess eggs which enables fertilisation to be checked. Embryos so produced can be frozen for later use.

Side effects and risks

Most women will experience some mild abdominal discomfort, mood swings and sore ovaries for a day or two after egg collection when on an IVF/GIFT cycle.

Drugs

Individual people respond differently to the drugs used to stimulate the ovaries to produce more than one follicle. Some women, who are particularly sensitive to the drugs used to stimulate the ovary, may develop 'the hyperstimulation syndrome'. This syndrome is characterised by swollen ovaries, secretion of fluid into the abdomen (called 'ascites') and abdominal pain. This condition usually settles with rest, but occasionally medical intervention is necessary. This may include admission to hospital for bed rest and observation, draining of fluid from the abdomen, and assessment of fluid output. The condition in its severe form may increase the risks of formation of a blood clot (called a 'thrombo embolic episode') usually in the limbs but occasionally in the brain, which can cause a stroke.

More common risks are presented as a percentage, less common risks as the number of times something occurs in 100,000 people or operations. The chance of any type of severe hyperstimulation syndrome occurring has been calculated at 1,000 per 100,000, ie: 1%, and the chance of a blood clot occurring is around 2 to 6 per 100,000 cycles. There are many ways of identifying those more at risk of severe hyperstimulation syndrome and the management can be changed to almost abolish the risk. Before women start on ovarian stimulation, they complete a questionnaire to help identify any risk factors, such as high blood pressure or migraine.

Cancer

There have media reports suggesting that breast and ovarian cancers may be caused by the drugs used to stimulate ovulation. The breast is very sensitive to oestrogen and so there is a theoretical risk that the high oestrogen levels in an IVF cycle might cause or accelerate breast cancer. Proving any link may be difficult because so many women develop breast cancer. (The lifetime risk of breast cancer is 10 percent). There is currently no evidence of a causal link between IVF treatment and breast cancer.

It is now well established that the risk of ovarian cancer is altered by a number of factors relevant to fertility and reproductive health. Pregnancy, breast feeding and the use of oral contraceptives have a well-documented effect of reducing the risk of ovarian cancer. It is therefore not surprising that the risk of ovarian cancer is higher in infertile women.

Recently, the possibility has been raised of an association between the risk of ovarian cancer and treatment with fertility medications.

Since the initial report in 1992, there have been several large-scale studies. These have shown that it is infertility, and not its treatment, which is associated with an increased risk of ovarian cancer. Having a pregnancy reduces the risk.

Procedure

Although a surgical procedure, transvaginal egg recovery is remarkably free of risks. Puncture of a large vessel in the abdomen, leading to internal bleeding, has been reported in about 0.06% of cycles. Pelvic infection can follow the procedure as well and may occur in up to 0.5 % of cycles. The chances of infection can be reduced by giving antibiotics at egg collection if a damaged fallopian tube is punctured or symptoms develop.

General anaesthetic

GIFT requires a general anaesthetic and so carries the risk of general anaesthesia.

Multiple pregnancy/abnormality

The major risk from IVF/GIFT treatment is multiple pregnancy and this can be reduced by replacing only two embryos in women who are more likely to conceive. The risk of congenital abnormality seems to be the same as in the general population, although the type of abnormality may be different. We encourage you to take 0.8mgs of folic acid daily prior to a cycle since this has been well shown to reduce the risk of congenital malformations, especially neural tube defects like spina bifida.

Laparoscopy/hysteroscopy

Serious complications of laparoscopy are rare, the major risk being damage to the bowel or major blood vessels, which would require emergency surgery to repair. The chance that emergency surgery will be required is about 1 per 1000 procedures. There are other risks associated with laparoscopy but they are all uncommon. Bleeding from the abdominal wall incisions would be the most common.

Laparoscopy is a low risk surgical procedure but all procedures have some associated risks. The risk of death from this or a similar operation is about 1-5/100,000 procedures.

Other risks in life

All risks are relative. For instance, the overall chance of dying from IVF is somewhere around 1 to 2 per 100,000 egg collections. The chance of dying from medical and obstetric complications in pregnancy in New Zealand is 26 per 100,000 pregnancies and the chance of dying in a car accident is about 24 per 100,000 people per year.

Optimising the chance of success

There are very few things you can do to improve the chance of pregnancy before or during treatment, and your doctor will discuss these with you. However, there is good evidence that if a woman smokes cigarettes during an IVF cycle her chances of conception are halved. This is due to the cigarettes having a direct effect on the ovaries, reducing the number and quality of eggs produced. Miscarriages are also more frequent in women who smoke. No consistent effect has been demonstrated if the male partner smokes. We would like to strongly encourage women to give up smoking prior to starting any fertility treatment so as to maximise your chances of success.

Conclusions

IVF and GIFT are complicated procedures, that are time consuming, intense, and fraught with disappointments. The treatment raises ethical problems for some, and any long-term physical or psychological implications for the child are unknown. Couples contemplating this type of therapy are strongly encouraged to read, discuss and think about the technique before they embark on treatment.

Counselling

A confidential counselling service is available at Fertility Associates. A counsellor can help you to explore the practical, legal, ethical and emotional issues involved.

Counselling gives you the opportunity to consider whether you wish to proceed with a particular treatment and whether you are ready to begin the procedure.

Self help resources

There are infertility societies in the main centres and support groups in some other areas, which offer information, support and counselling for people experiencing infertility.

Auckland Infertility Society, PO Box 68428, Auckland

Wellington Infertility Society, PO Box 31279, Wellington

Christchurch Infertility Society, PO Box 29188, Christchurch

Otago/Southland Infertility Society, PO Box 6286, Dunedin North