Fertility drugs, which are now handed out like candy, can treble your cancer risks, yet may not work as well as a simple supplement programme.
Infertility is so sharply on the increase in the West that it nowaffects one in six couples at some point in their reproductive lives. These days, the childless are led to believe that modern chemistry can easily do something about it, and increasing number of couples are seeking infertility treatment or some form of “assisted conception”.
The number of visits to US doctors for infertility services rose from 600,000 in 1968 to about 1.6 million in 1984 and the number of prescriptions for clomiphene dispensed by US pharmacies nearly doubled from 1973 to 1991. In 1988, approximately two million women said that they had taken fertility drugs. (N Engl J Med, Sept 22, 1994).
But there is strong evidence to suggest that many of them particularly women are being exposed to drugs may be doing absolutely no good and a great deal of harm.
Ovarian cancer and breast cancer are the latest risks to be associated with fertility drugs. These are in addition to a further catalogue of side effects and adverse outcomes already documented in WDDTY (vol 1 no 8), including Ovarian Hyperstimulation Syndrome (OHSS) a serious condition in which there is a build-up of fluid in the abdomen, thorax and sometimes the sac surrounding the heart; and thrombosis in the veins or arteries, which could lead to a heart attack, stroke or loss of a limb. Other risks associated with the drugs include ectopic and multiple pregnancy and multiple births. The latter two are common occurrences which carry further risks such as miscarriage, stillbirth, fetal abnormalities, premature and low birthweight babies.
These babies are much more susceptible to developmental problems, illness and death.
According to the Office of Population and Census Surveys, the rate of multiple births in England and Wales has increased since 1980, when it was 0.98 per cent, compared with 1.25 per cent in 1992. The Human Fertilization and Embryology Authority believe this is due to the use of superovulatory drugs in fertility treatment.
In about half of all infertility cases, there is a contributing male factor. Yet fertility drugs to induce ovulation are often given to women when the cause of infertility is not known, and regardless of whether or not they have ovulation problems.
Ovulation is induced to increase the chances of success in assisted conception therapy, which includes in vitro fertilization (IVF), when an egg is surgically removed from an ovary, fertilized outside the body and then placed in the uterus; gamete intra-fallopian transfer (GIFT), when the eggs are placed with sperm in the fallopian tubes; and zygote intra-fallopian transfer (ZIFT), when the eggs are removed from the ovaries, fertilized outside and placed in the tubes.
In the US, at least 12.5 million courses of fertility drugs have been prescribed since they were launched in the 1960s. In January 1993, the US Food and Drug Administration asked drug manufacturers to add the risk of ovarian cancer to the possible adverse reactions listed on fertility drug labels such as clomiphene citrate (Clomid) and menotrophins. The decision was prompted by an evaluation of the results of 12 studies (analyzed by The American Collaborative Ovarian Cancer Group based at Stanford University, California, and published in the American Journal of Epidemiology) on risk factors for ovarian cancer. These found that the risk of invasive ovarian cancer amongst infertile women who had taken fertility drugs was almost three times that of fertile women, and that infertile women who had not taken fertility drugs were not at increased risk (The Lancet, Jan 23, 1993).
The link between fertility drugs and ovarian cancer is in keeping with the two main theories regarding the possible causes of ovarian cancer. The first is that the surface of the ovaries are damaged each time a woman ovulates, and that this may eventually trigger the cancer. Therefore, by increasing ovulation, fertility drugs are increasing a woman’s risk of developing cancer. The American study also revealed that women who ovulate less often through having a number of pregnancies and breastfeeding their children, for example are at less risk of ovarian cancer.
The second theory is that exposure to high levels of pituitary gonadotropins (which clomiphene stimulates the release of) increases the risk of ovarian cancer.
Ovarian cancer is the fifth most common cancer in women, and because it is not usually discovered until it is in an advanced state, most women die from it. It is also most common in women over 50, and three times more common in women who have never had children. So we may only just be starting to see ovarian cancers caused by fertility drugs taken by women in the Sixties. As more and more women receive treatment for infertility, we may therefore see an increasing number of cases of ovarian cancer over the ensuing decades.
One study found that women taking clomiphene ran an increased risk of ovarian tumours, whether or not they had ovarian abnormalities. They discovered 11 invasive or borderline malignant ovarian tumours, compared with an expected 4.4. Nine of the women had taken clomiphene. Their results also indicated that the risk of a tumour is dependent on the length of time a woman takes the drug. Those who had taken clomiphene for less than 12 menstrual cycles were at no increased risk, whereas those who had used it for 12 or more cycles were at considerably increased risk, according to the researchers.
However, the study found no increase in the risk of ovarian tumours associated with the use of human chorionic gonadotropin, which stimulates the ovaries to produce estrogen and progesterone, although it may also induce ovulation. The study concluded that although its findings suggested that prolonged use of clomiphene increased the risk of ovarian tumours, larger studies were needed to test the hypothesis. (N Engl J Med, Sept 22, 1994)
The French are currently conducting a large-scale epidemiological study to determine the risk of ovarian cancer in women who have been treated with ovulation-inducing drugs. There are about 3200 deaths from ovarian cancer every year in France and about 4000 new cases. Prescriptions for human menopausal gonadotropin (menotrophin) rose from 500,000 ampoules in 1985 to about three million in 1992 (The Lancet, Oct 22, 1994).
A number of women undergoing IVF treatment have also developed breast cancer, although a direct link has not been established. A 1994 study of 950 women who had had IVF treatment found that 16 went on to develop breast cancer before they were 48, which ties in with the theory that the more menstrual cycles a woman has, the greater her risk of breast cancer. Dr Simon Fishel, scientific director of Nurture, an infertility clinic at Nottingham University, says that one stimulated IVF cycle may, in terms of egg production, be the equivalent of one to two years’ worth of natural ovulation and some women may have as many as 20 IVF attempts (The Independent, Sept 24, 1993). IVF may also be responsible for early menopause, postulate some doctors, since it uses up so many eggs at one go.
One 36-year-old woman from Quebec with a family history of breast cancer developed the disease while having IVF treatment. Dr Laura Arbour, from the McGill University in Quebec, Canada has questioned whether the hormonal stimulation of IVF treatment might quicken the progression of cancer in those who are hereditarily disposed (The Lancet, Aug 27, 1994).
According to medical science, the cause of men’s infertility usually remains unknown (N Engl J Med, Feb 2, 1995), although proponents of natural fertility methods such as Foresight, The Association of Preconceptual Care, would disagree.
The various forms of medical therapy that have been tried fall into two broad categories: those whose use is irrational and clearly not effective, and those that are unproved (N Engl J Med, Feb 2, 1995). Likewise, there appears to be little evidence regarding the risks involved.
Japanese research into the adverse effects of the drug interferon on the formation and development of sperm in rats found that some rats showed an increase in sperm count when treated with interferon. The researchers then administered interferon to three men with a history of a very low sperm count and one with no sperm. The cause of infertility in all four was unknown. All three of the men with very low sperm counts showed significant improvement in sperm count and motility after two months’ therapy, and two impregnated their wives. The fourth man produced some sperm, but count and motility were very low. The Japanese researchers were ecstatic, believing their “promising” results would “pave the way” for a new infertility treatment (The Lancet, Aug 27, 1994).
But other research has suggested that interferon might have a harmful effect on testicular function, as impotence has been reported as a side effect. And what the researchers don’t mention are the possible adverse reactions associated with interferon, which is used to treat certain cancers, chronic viral infections such as hepatitis B and C, and multiple sclerosis. Severe fever is common, and there may be lethargy, headaches, dizziness, depression, digestive disturbances and, rarely, hair loss. The blood-producing capacity of the bone marrow may be reduced, and some patients experience high or low blood pressure and heartbeat irregularities. Regular blood counts are essential during treatment, particularly to check on levels of white blood cells that contribute to the immune system.
Of course, for those desperate to have a child, the proven and possible risks associated with infertility treatment might seem worth it. However, the risk factors should be weighed up against the chances of success which are often cruelly inflated at individual clinics or by infertility specialists seeking to boost their reputations. It is estimated that only about 10 per cent of couples conceive on their first IVF attempt. In the UK, according to Human Fertilization and Embryology Authority figures, only 12.7 per cent of IVF treatments resulted in a live birth in 1992. This figure had fallen from 13.9 per cent in 1991, which the authority attributes to the fact that the average age of women seeking treatment has increased.
In contrast, Foresight, the Association for the Promotion of Preconception Care based in Surrey, England, boasts an 80 per cent success rate through its rigorous health and nutrition programme (see box, opposite). A study of 418 couples who had followed the Foresight programme was conducted at Surrey University. It found that of those who’d previously been infertile, 81 per cent delivered live babies, as did 81 per cent of those who’d had previous miscarriages and 73 per cent who’d had previous stillbirths. In the study group, no babies were born earlier than 36 weeks and none weighed less than 5lb 3oz. There were no miscarriages, perinatal deaths, malformations or babies requiring admission to special care. Of the 418 couples, 75 per cent had had either previous infertility or miscarriage (WDDTY, September 1994).
Even for those who don’t conceive as a direct result of being on the programme, Foresight believes that they stand a better chance of success with IVF, GIFT and ZIFT by having first had their health and nutritional status enhanced (J of Nutritional Med, 1990; 1:251-58.)
A study conducted by Dr Stephen Davies, medical director of Biolab in London, noted that magnesium deficiency is associated with female infertility, increased miscarriage rate and increased incidence of premature and low birthweight babies, although the reasons why are not fully understood.
Davies and his team gave magnesium supplements to six magnesium-deficient women with unexplained infertility, whose magnesium levels normalized after four months of treatment. All six conceived within the following eight months and produced normal, healthy babies. Others with unexplained infertility whose magnesium levels did not normalize after four months’ treatment did so after a further two months of magnesium plus selenium supplementation. These women also conceived within the following eight months, going on to produce normal, healthy babies (Magnesium Research, 1994; 7 (1): 49-57).