Infertility Treatments

The first step for many couples is a course of drugs to help stimulate and regularise ovulation. Clomiphene citrate (brand names are Clomid and Serophene) is a synthetic drug taken in tablet form, usually once a day between Days 2 and 6 of the woman’s cycle, with the aim of stimulating her ovaries into ovulation. The lowest dose given is 50mg. Your doctor may increase this (occasionally up to 200mg) if lower doses don’t work within a couple of months. It is recommended that most women do not stay on the treatment for longer than six months. If it hasn’t worked by then, the chances are low that it will, and there are health risks implicated in longer treatment.

For many women, a course of clomiphene seems like a miracle cure as it ‘kick-starts’ the ovaries into regular ovulation and intercourse at the most fertile time of the cycle is more likely to result in a pregnancy. However, the treatment does not work for all women and there are some side effects:

• Some women find the drug makes them irritable or restless and gives them headaches, breast tenderness, mild abdominal discomfort or hot flushes
• A few get more severe side effects such as nausea and vomiting or vision difficulties, in which case they will need to stop the treatment immediately

Because it stimulates the ovaries, a woman may produce more than one egg in each cycle, which can result in a pregnancy of twins (or, rarely, more). While a multiple pregnancy occurs for only about one in 15 women who conceive while taking clomiphene, it is something to consider before beginning treatment.

One of the most common reasons for a woman being unable to conceive is blocked fallopian tubes, in which case she will be offered surgery to unblock them. The main advantage of surgery is that, if it works, a couple will be able to go on and have one or more ‘spontaneous’ conceptions, without the need for any further invasive treatments. However, the chances of success decrease depending on how great the blockage or the damage is, and unfortunately a few women who undergo surgery find that their tubes become blocked again.

Some women are now being offered a relatively new surgical treatment which is a form of salingostomy. A catheter is passed through the cervix and into the uterus; dye is then injected into the fallopian tubes to show the source of any blockage. Once the point of the blockage can be seen, a thin wire is then passed down the tube to unblock it. The woman can be awake for this procedure so it carries fewer risks than surgery which requires a general anaesthetic.

Surgery may also be recommended if a woman has endometriosis. It may be possible to remove some of the cells with a laser during a laparoscopy, or through more extensive surgery. Surgery may also be advised if the woman has adhesions or fibroids within her uterus, or to open a narrow or scarred cervix and improve fertility. It is sometimes also carried out to treat polycystic ovaries.

Men may be recommended surgery if the ducts through which the sperm travels have become blocked, or to remove a varicocele (swollen vein) if this may be interfering with sperm production or movement. This procedure can be carried out under local anaesthetic.

Artificial insemination (AI) is a relatively straightforward method of assisted conception. A fine plastic tube is placed in the woman’s vagina through which the man’s semen is introduced into the cervix. With intrauterine insemination (IUI), semen is introduced directly into the woman’s uterus to help the sperm get closer to the site of fertilisation. To use these techniques, the woman must be ovulating, and her fallopian tubes must be clear. These insemination techniques can help when:

• The man’s sperm is being killed off by vaginal secretions, as the semen is placed beyond this barrier
• The couple is unable to have sexual intercourse, either because of injury or disability
• There are difficulties with intercourse such as premature ejaculation

Insemination takes place during the most fertile part of the woman’s cycle, sometimes on two or three days in a row. Some clinics do AI/IUI alone, in other cases insemination is carried out in conjunction with ovulation stimulation, and this seems to produce better results (success rates can reach 30 per cent).

After both procedures the woman will need to rest for a short time afterwards, and can then go home.

Because successful AI/IUI depends on the ability of sperm to fertilise an egg, the man will need to produce enough normal sperm in reasonable numbers. If this is not the case, donor sperm can be used.

In vitro fertilisation (IVF) can be of benefit to many couples. In IVF, eggs are gathered from the woman’s ovaries and mixed with the man’s sperm outside the body, usually in a glass dish in a laboratory. ‘In vitro’ comes from the Latin and literally means ‘in glass’, a reference to the glass container where fertilisation takes place. (While this is usually a dish, the term ‘test-tube’ babies has become widely used.) The fertilised eggs are then cultivated to embryo stage and transferred to the woman’s uterus.

Couples may be offered IVF if:

• The woman has damaged or blocked fallopian tubes
• The man has a low sperm count or his sperm don’t move forward well and so may never reach the egg without assistance
• Infertility is caused by immunological factors
• Infertility is ‘unexplained’

While the procedure described above sounds simple, in reality IVF is a complex and emotionally demanding process. It can take between six weeks and two months on average for a single treatment cycle and most couples find it both physically and mentally stressful.

The first stage involves stimulating the woman’s ovaries so that several eggs mature. Normally, a woman produces one egg in each menstrual cycle, but because the chances of getting pregnant through IVF are much higher if more than one embryo is replaced, the aim is to cultivate several eggs.

To achieve this, a woman will need to take drugs to suppress her own hormones. This phase lasts about 21 days. The drugs have the effect of putting the body into a temporary menopause, along with all the side effects that might be expected, such as hot flushes and mood swings.

Once the woman’s own hormones have been suppressed, she can begin taking the drugs that will stimulate egg production. She may need to have injections daily for around 12 days, but this will vary according to the way her body is responding. The response of the ovaries will be carefully monitored using ultrasound scanning to show the size and number of developing follicles.

Monitoring is essential because sometimes a woman’s ovaries respond very strongly to these drugs and begin to swell. This may result in ovarian hyperstimulation syndrome, which can cause a range of symptoms from mild abdominal pain to severe pain, vomiting, nausea and dehydration.

Sometimes (in around 18 per cent of cases) a treatment cycle has to be abandoned at this stage, either because of hyperstimulation or because not enough follicles are produced or they grow very poorly.

If all goes well, however, the next stage of the procedure is egg collection. This takes place when the ultrasound scan shows a sufficient number of large follicles. The woman is given an injection late at night to give the eggs their last ‘push’ towards maturity. Ovulation normally occurs 37-40 hours after this injection, so egg collection is scheduled to take place just before ovulation occurs.

The eggs are usually collected using a fine, hollow needle guided by ultrasound. Around the same time, the man needs to produce his semen sample. The semen is assessed and if it’s of sufficient quality, it is ‘washed’ to separate the best quality sperm in preparation for fertilisation. As soon as they’re extracted, the eggs are put into a nutrient medium with the sperm and then cultured in an incubator. The next day, they’ll be observed through a microscope to see if fertilisation has occurred. If it has, 24 hours later cell division will have started and the embryo might now have two or four cells.

The embryos will be checked by an embryologist to make sure that they’re developing normally and, if all is well, embryo transfer can take place. The embryos, together with a tiny amount of nutrient fluid, are put into a catheter and placed into the woman’s uterus through her cervix. No more than three embryos can be transferred, by law, to reduce the risk of a multiple pregnancy. If there are ‘spare’ embryos of good quality these can be frozen and stored for use in a future treatment cycle.

Transfer is usually quick; some women find it painless, others more uncomfortable - rather like having a cervical smear test. Afterwards, the woman will be advised to rest for a short time and then go home and ‘carry on as normal’.

It will be about two weeks before a pregnancy test can be done, and this waiting is one of the most difficult and stressful times of the whole procedure. During this time, the woman will be prescribed progesterone, either in the form of pessaries or injections, which is needed to provide hormonal support to any potential pregnancy.

If the pregnancy test is positive, an ultrasound scan a couple of weeks later will confirm this. It also allows clinic staff to check that the pregnancy has implanted well in the uterus and to count the number of gestational sacs. If all is developing normally, the woman will be referred back to her GP and make the transition to antenatal care.

However, one of the most important things to remember about IVF is that, statistically, it is much more likely to fail than it is to be successful. Unfortunately, the impression given by some TV programmes and magazine articles is that most couples will emerge from the process of IVF with their longed-for baby, but in reality a success rate of around 15 per cent is the national average.

This ‘failure’ can be a crushing blow for couples, who then have to decide whether to embark upon another treatment cycle with the hope that they will be successful next time. In such situations, the counselling offered by the clinic and the support from groups such as Issue and Child can be invaluable.

A relatively new technique called intracytoplasmic sperm injection (ICSI) allows a single sperm to be injected directly into the centre of the egg. An alternative is sub-zonal insemination (SUZI), where a single sperm is placed just beneath the zona pellucida (the protein shell which surrounds the egg).

ICSI and SUZI can be of great benefit to couples where the man has:

• A low sperm count
• Low numbers of motile sperm
• Poor forward progression of sperm
• A high proportion of sperm with abnormalities
• A sperm blockage, as sperm can be obtained directly from the testicles with a fine needle under anaesthetic

In addition, couples who have had IVF cycles where no fertilisation has occurred, or where there were very low rates of fertilisation, may find ICSI can overcome this problem.

The use of micromanipulation techniques is increasing, as are success rates. However, because these techniques are new, assessment of the risks involved is at an early stage.

There is some concern that because ICSI involves piercing the egg, this may cause a higher incidence of congenital abnormalities. However, studies vary but most show the risk from IVF/ICSI is no greater than when using conventional IVF alone.

Because so few babies (relatively speaking) have been born as a result of IVF/ICSI, much more research will be needed before significant figures are available. However, reflecting these concerns, most clinics will advise couples who conceive through ICSI to have regular ultrasound scans in the early weeks of pregnancy, and many suggest that couples consider an amniocentesis at around 15 weeks.

Gift stands for gamete intra-fallopian transfer. A gamete is the technical term for the basic contribution from each partner to form a new baby: a sperm or an egg. GIFT is similar to IVF in that the woman’s ovaries are stimulated and the eggs are collected in just the same way. The main difference is that fertilisation occurs inside rather than outside the body. Once egg collection has taken place, up to three eggs are mixed with the man’s sperm and the eggs and sperm are then immediately placed in the woman’s fallopian tube in the same operation.

GIFT is done either via a laparoscopy under general anaesthetic, or by using a catheter passed through the cervix, for which a local anaesthetic and sedation can be used. Once the transfer is complete, the cycle then proceeds as for IVF.

GIFT is often used when:

• The couple has unexplained infertility
• There are problems with the cervical mucus
• The woman has mild endometriosis.

However, it is not recommended for women who have already had an ectopic pregnancy (and perhaps lost one fallopian tube) because of the risk of another.

The success rates for GIFT are higher than those for IVF (in some clinics it can be as high as 30 per cent). This may be partly because any resulting embryos develop in the natural surroundings of the fallopian tube, just as they would in a naturally occurring pregnancy.

However, one disadvantage is that if it doesn’t work, it is more difficult to ascertain the reason why not: it is impossible even to tell if fertilisation took place. Some couples are therefore recommended IVF as a first option in order to establish the ability of the sperm to fertilise the eggs. If fertilisation does occur in vitro, GIFT may be appropriate if future treatment is needed.

One advantage of GIFT is that it does not require a license from the Human Fertilisation and Embryology Authority (HFEA) (unless donor eggs or sperm are used) so couples may find more centres offering this treatment in their local area. Also, as embryo culture is not required, it can be a less expensive option than IVF.

A zygote is a newly fertilised egg, before cell division has started to take place. With ZIFT, fertilisation occurs in the laboratory just as it does in IVF. The difference is that the newly fertilised eggs are transferred much sooner than they would be with IVF. Up to three pre-embryos can be transferred at one time to the woman’s fallopian tube. The reasoning behind this procedure is that the natural environment of the body is a better place to encourage an embryo to develop than a laboratory dish.

ZIFT is not without disadvantages, however, the main one being that the woman has to undergo two invasive procedures - egg collection and then zygote transfer - in quick succession. Also, the opportunity to select the best three embryos to transfer is lost, as when the zygotes are transferred it is impossible to tell which of the fertilised eggs are developing most promisingly.

If, for whatever reason, a man does not produce any sperm, or enough of good quality, or a woman does not produce any eggs, then assisted conception using donor gametes (eggs or sperm) offers the couple a chance of conceiving. Using donated eggs may also be advised for women in their forties who have a very small chance of success conceiving with IVF using their own eggs. (However, be aware that there is a national shortage of egg donors; all of the clinics offering this treatment across the country have couples on their waiting lists.)

Except where donation is intentionally between people known to each other, all donations in the UK are regulated by the Human Fertilisation and Embryology Authority (HFEA) and all donations are anonymous. If someone donates sperm or eggs to a couple for fertility treatment, neither the couple nor any resulting child will ever know who the donor is. The donor will be the ‘genetic’ parent of any child, but the couple themselves will be the ‘legal’ parents. Donors have no legal relationship with or any continuing responsibility to any children born from their donation.

Clinics record details of a donor’s physical appearance - such as hair, skin or eye colour, as well as height, build and blood group - and then usually try to match these physical characteristics with those of the male or female partner whose sperm or eggs are to be replaced.

If a couple decide to have DI, or IVF using donor eggs, there will be moral, philosophical and possibly religious aspects which they will need to consider, think through and accept. This is one reason why the HFEA insists that all couples contemplating the use of donor eggs or sperm are offered counselling. It is important, if either partner has doubts about what is involved, that couples take time to explore these issues before beginning treatment.

Insemination using donor semen (DI) is a tried-and-tested method of treatment; in the UK, there are approximately 1,500 such births each year. The way DI is carried out varies; some clinics recommend the use of drugs to ensure that the woman is ovulating, others prefer to rely on the natural cycle and the use of ovulation predictor kits. The number of inseminations carried out in each cycle can also vary, as can the method used - the sperm can be put into the vagina, the cervix or the uterus.

Egg donation is more complex. Women donating eggs need to go through the process of ovarian stimulation and egg collection. At the same time, the recipient’s body must itself be hormonally prepared for pregnancy. The process has to be timed and co-ordinated so that on the day when the eggs are collected from the donor, the man provides the semen so that the eggs can be mixed with the sperm and fertilisation can take place.

As with IVF, the embryos will then be placed in the recipient’s uterus using a fine catheter. She will need to take progesterone supplements until a pregnancy test can be done (about fourteen days later) and, if she is pregnant, these will continue for several more weeks.

Even if everything goes well physically and hormonally, a treatment cycle involving donated eggs or sperm involves complex emotions. For parents with children conceived by DI or through egg donation, a major issue is whether or not to tell the child about their origins, or other family members, or friends. This is something couples need to think through carefully before beginning treatment.