There is no clear evidence that these babies are more at risk from abnormalities than those born through natural conception. Indeed, it seems that certain types of abnormality, such as chromosome problems, are less common with IVF. However, IVF babies tend to have more problems at birth, and stillbirths may be slightly more common. This may not be due to IVF, it is probably because women who conceive through IVF are more likely to be at high-risk in pregnancy.
IVF treatment can be very stressful. However, often, infertile couples feel that by undergoing IVF they are doing something positive to resolve their problem. For so many it is undoubtedly better to have gone through IVF and failed, than not to have attempted it all.
If more than one embryo is transferred to the uterus there is a risk of a multiple pregnancy. Sadly multiples are more likely to have birth defects – around one in every 24 babies born as multiples will be stillborn and one in 13 will be seriously handicapped. Since the advent of IVF, the incidence of multiple births in the UK has more than doubled. Most triplets and nearly all quadruplets have been conceived following assisted reproductive treatments; about half are as a result of IVF. Triplets virtually never go to term; if they survive pregnancy at all, most are born six to eight weeks prematurely.
In the UK, the HFEA (Human Fertility and Embryology Authority) regulations limit the number of embryos that can be transferred simultaneously to one where possible (exceptions are made for older women or those who have already failed IVF). One problem is that, not unreasonably, many infertile women after years of childlessness are only too ready to accept the risk of multiple birth, particularly with the rising costs of IVF treatment. While twins may not present too many problems, triplets are difficult to deal with and quadruplets can be disastrous.
Humans are not built to carry more than one child at a time, and twins or other multiples increases every known risk of childbirth. First, a mother’s health can suffer: obstetric haemorrhage, breech presentation, gestational diabetes, stillbirth and Caesarean section are particularly common. Most of these babies are very premature and will require intensive nursing, sometimes for several weeks, in incubators. Multiple births remain a major source of concern in IVF treatment. And until we have better methods for assessing the viability of embryos this going to remain a problem. However, a policy of single embryo transfer together with cheaper freezing of spare embryos will play a vital part in controlling the likelihood of multiple pregnancy.
Whilst the risk of an abnormal baby after IVF is low (apart from the issues related to multiple birth), it is much less clear whether IVF contributes a long-term risk. For example, IVF babies tend to be smaller than average. Babies with a birth weight of less than 2 kg (5 ½ lb) are more likely to develop high blood pressure, heart disease, stroke and possibility osteoporosis at a slightly younger age than is usual, perhaps 50–60 years old. This is probably because of their bodies need to work harder to adapt to the environment after birth. There is increasing evidence that the environment in the womb and at the time of conception and immediately afterwards may have an effect on how a person’s genes function as he or she ages. This field – known as epigenetics – is still in its infancy, but there are certain environmental influences that may occur during IVF that could be important.
This may not be a disease risk, but IVF is still a relatively new technology and it will be many years before we can be sure whether there is any long-term risk for some IVF children after they become adults. Embryo biopsy and intracytoplasmic sperm injection (ICSI) may also carry epigenetic risks. Some mice have been shown to have changes in their brain in adulthood following interventions in their embryonic life. This may be why it has been suggested that autism is slightly more common in children produced by ICSI. There have also been reports of changes in imprinted genes in humans after prolonging embryo culture to the blastocyst stage. Nevertheless, more children than expected have been born with a rare condition associated with an increased risk of childhood cancer, Beckwith–Wiedemann Syndrome (BWS), and certain congenital abnormalities including above average birth weight, hernias and a large tongue.
It may seem surprising that IVF can result in an ectopic pregnancy as people think that IVF should avoid this risk. If the tubes are damaged or partly blocked, the risk is undoubtedly greater, possibly around two or three percent, and the incidence in women with damaged fallopian tubes after IVF is just as high as it is after tubal surgery. This is because after an embryo is transferred it may leave the uterus spontaneously and move into a fallopian tube, where it may implant. The risk of ectopic pregnancy still exists even if the fallopian tubes have been totally removed, or blocked at the junction with the uterus because there is a small section of the tube in the wall of the uterus that cannot be removed or blocked off.
The use of drugs such as FSH to stimulate the ovaries can cause the growth of too many follicles causing ovarian hyperstimulation (OHS), or ovarian hyperstimulation syndrome (OHSS). This unwanted side effect may occur because too much of the drug has been given, but it can happen because the ovaries are unusually sensitive.
OHS is common and usually relatively mild, merely causing some swelling of the ovaries. There may be abdominal discomfort, women feel ‘bloated’, and occasionally there is pain low down in the pelvis. Mild OHS makes some women feel unwell and usually lasts for two or three days. This occurs in as many as eight percent of IVF cycles.
Moderate OHS is less common and associated with more pronounced abdominal discomfort and, sometimes, general pelvic pain. The abdomen may be noticeably swollen and women will feel tired and frequently breathless. In more severe cases there may be general fluid retention, including ankle swelling. Moderate OHS may necessitate a short stay in hospital – usually just for rest and observation.
Severe OHSS is rare, but it is serious. Women will experience all of the above symptoms, but they will be more pronounced. The breathlessness may be quite unpleasant and if too much fluid accumulates in the chest cavity or the abdomen is me need to be drained it surgically. While the fluid is retained in the wrong places, the woman may require an intravenous drip to provide extra fluid into the bloodstream, because the loss of fluid into the tissues concentrates the blood. Hospital admission for at least a week, sometimes two, is essential because left untreated severe OHSS can be life-threatening.
The good news is that hyperstimulation always tends to be worse in pregnant women. It is also true that if it develops after embryo transfer and the woman is pregnant, the pregnancy is more likely to stick. But if hyperstimulation is anticipated, many fertility units delay the embryo transfer as a precaution and freeze the embryos. Once a new menstrual cycle has commenced, the effect of all the drugs will have dissipated and embryo transfer will be safe.
Nearly all moderate or severe cases of hyperstimulation are preventable with adequate monitoring of ovarian development, though mild hyperstimulation is difficult to prevent. There are conditions that predispose a woman to OHSS, for example, polycystic ovary syndrome. Other women just respond very briskly to super-ovulatory drugs and the reason for this is unclear. Women prone to hyperstimulation, should be given lower doses of FSH and be monitored carefully during treatment.
One of the complications associated with all of the drugs given during an IVF treatment cycle is that they can make the menstrual cycle irregular for a short time after treatment has finished. It is common for the first natural period to come unexpectedly; it may be early or late, and may last for longer than normal. It is also common for the period to be heavier than usual. Rarely, menstrual irregularity may last for three or four months. If a woman experiences problems for longer than this, she should see a gynaecologist for a check-up as the symptoms may not result from the IVF cycle, but some other medical cause.
In recent years, there has been considerable concern that fertility drugs – the pills and injections used to induce ovulation – may cause cancer of the ovary. This anxiety has been fanned by mostly well-meaning, but sometimes irresponsible reports that doctors are not being honest about the risks. In order to understand these risks, real or presumed, it is necessary to have some background.
In some women, there is undoubtedly a genetic factor. Ovarian cancer is about twice as common in women who have not had children. According to most studies, it is more common in women who have delayed child-bearing. Women who give birth before the age of 25 are less likely to get ovarian cancer and with each five-year delay, the chance of developing it increases by about ten per cent. Different studies show different associations with miscarriage; some report the risk is higher after a miscarriage, but others suggest it may be lower.
Women who have an early menopause (before the age of 45) are at lower risk than those who go through the menopause after they are 50. Women who use the pill for longer than five years seem to reduce their risk of ovarian cancer by around 50 per cent. It is unclear whether women on hormone replacement therapy (HRT) are at greater risk. Infertile women are about twice as likely to develop ovarian cancer. Interestingly, this effect is also seen in women married to infertile men.
There is no clear evidence of an increased risk of ovarian cancer in women having IVF treatment or fertility injections, compared with women who are infertile. There is some doubt about an increased risk in women who are given these drugs but who do not become pregnant. Unexplained infertility in some women may occasionally be due to some ovarian abnormality – which could possibly include some very early form of ovarian pre-cancer.
Cancer of the uterus is more common in women who have not had children and cancer of the cervix is less common. However, fertility drugs cause neither of these cancers. Nor is there the slightest evidence that there is an increased risk of cancer of the breast following IVF.
Some women undergoing IVF are worried that the drugs used to stimulate the ovaries may cause a premature menopause. Their concern is that, because so many eggs are being produced in one cycle, the ovaries will run out of eggs earlier. There is no serious evidence to support this theory.
Despite countless breakthroughs in medical science, we still do not understand why some pregnancies will end in tragedy. For most of us, having a child of our own is the most fulfilling experience of our lives. All of us can imagine the desperation and sadness of parents who lose a baby, and the life-shattering impact that a disabled or seriously ill child has on a family.
Professor Robert Winston’s Genesis Research Trust raises money for the largest UK-based collection of scientists and clinicians who are researching the causes and cures for conditions that affect the health of women and babies.
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