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Infertility and assisted reproduction

MagazineDecember 2010 (Vol. 21 Issue 9)Infertility and assisted reproduction

Babies born as a result of invitro fertilization (IVF) are up to two times more likely to have birth defects than those born naturally, says an alarming study from France

Babies born as a result of invitro fertilization (IVF) are up to two times more likely to have birth defects than those born naturally, says an alarming study from France.

The study-the largest of its kind so far-looked at more than 15,000 children conceived through assisted reproductive technology (ART), which includes IVF and ICSI (intracyto-plasmic sperm injection). Led by Dr G'eraldine Viot, a clinical geneticist at a hospital in Paris, it found a major congenital malformation in 4.24 per cent of children vs the 2-3 per cent reported in the general population.

This higher rate of birth defects was due in part to an excess of heart disease and malformations involving the urinary tract and reproductive organs. Also, among the minor mal-formations, there was a fivefold higher rate of angiomas, benign tumours made up of small blood vessels lying on or near the surface of the skin (Proceedings of the Annual Conference of the European Society of Human Genetics, 12-15 June 2010, Gothenburg, Sweden; Abstract no. 313).
Although more research is needed, this is not the first time that infertility treatments have been linked to birth defects. Previous studies have reported a rate of major malformations as high as 11 per cent. Yet, according to Dr Viot, couples considering ART are often kept in the dark concerning the associated risks. She's now calling on fertility clinics to routinely warn prospective parents of the dangers, regardless of whether or not such data are specifically asked for.

A report last year by the US Centers for Disease Control and Prevention (CDC) came to the same conclusion. After analyzing data from the National Birth Defects Prevention Study, babies conceived through ART were found to be two to four times more likely to have birth defects compared with babies born naturally. Of pregnancies resulting in a single birth, ART was associated with twice the risk of heart defects and more than twice the risk of a cleft lip, with or without a cleft palate, and more than four times the risk of gastrointestinal defects.

Whether these malformations are caused by ART or by infertility itself is not clear. In any case, it's believed that it is important to inform couples considering ART of all the potential risks and benefits (Hum Reprod, 2009; 24: 360-6).

Other ART-ful risks

Sadly, it's not only birth defects that are linked to ART. A study presented at this year's International Meeting for Autism Research in Philadelphia revealed that children born through IVF are more likely to be diagnosed with autistic spectrum disorder (ASD).

The findings, based on 564 children visiting an autism centre in Israel, showed that 10.2 per cent of children with ASD were conceived using IVF, a significantly higher rate than the 3.5 per cent seen in the general Israeli population (Proceedings of the 9th Annual International Meeting for Autism Research, 20-22 May 2010, Philadelphia, PA; Abstract no. 103.004).

Although it's too early to draw any definitive conclusions, Dr Ditza Zachor, lead author of the study, suggests that 'imprinting' might explain their findings. This refers to a biochemical process that takes place during cell division and determines the genes to be selected or 'expressed' in the embryo. Epigenetic studies-of changes in gene expression that occur without changing the DNA sequence-suggest that malformations may be caused by imprinting abnormalities introduced into the embryo while it's in the test-tube, says Dr Zachor. One such disorder linked to IVF is the Angelman syndrome, characterized by severe learning difficulties, seizures and jerky movements. Something similar might be going on with autism.

The single biggest risk with ART is for multiple births, which increases the chances of stillbirths, neonatal deaths and disability in the children born. The UK's Human Fertilisation and Embryology Authority (see www. hfea.gov.uk) says that, on average, one in four IVF pregnancies are a multiple pregnancy compared with one in 80 for women who conceive naturally.

Babies are also more likely to be born prematurely and, so, are under-weight at birth (Eur J Obstet Gynecol Reprod Biol, 2009; 146: 138-48). This can lead to a number of health problems such as visual impairment and cerebral palsy. Indeed, children born through IVF are about twice as likely to have cerebral palsy (Arch Pediatr Adolesc Med, 2009; 163: 72-83).

There are also risks to the mother, such as ectopic pregnancy and ovarian hyperstimulation syndrome (OHSS), a potentially dangerous overreaction to the drugs used to stimulate egg production. Even more worrying is that ART might increase the risk of cancer (Int J Fertil Womens Med, 2005; 50: 259-66).

What to do instead

While many couples may believe that assisted reproduction is their only option for conception, in fact, there are a number of natural ways to boost fertility and pregnancy.

o Eat well. To raise levels of fertility hormones, follow a varied whole-food diet with high-quality proteins, and plenty of fresh vegetables and fruits, and drink only filtered or glass-bottled water.

o Maintain a healthy weight. Being either too overweight or under-weight can contribute to infertility (Fertil Steril, 1988; 50: 721-6).

o Stop smoking. A British study of more than 17,000 women found that the more cigarettes a woman smokes per day, the less likely she is to conceive (Br Med J (Clin Res Ed), 1985; 290: 1697-700). Smoking has a negative impact on male fertility, too (Acta Med Port, 2009; 22: 753-8).

o Avoid alcohol. Even moderate drinking of alcohol (five or fewer drinks per week) can contribute to infertility in women (BMJ, 1998; 317: 505-10). Also, the risk of endometri-osis, a common cause of infertility, was around 50-per-cent higher in women with any amount of alcohol intake compared with teetotallers (Am J Public Health, 1994; 84: 1429-32).

o Limit caffeine. In 104 healthy women trying for a baby, those who consumed a cup of coffee or more
a day were half as likely to become pregnant, per cycle, as women who drank less than that (Lancet, 1988; 2: 1453-6). Indeed, the more caffeine-from any source (tea, cola drinks, chocolate)-the lower the chances of pregnancy (Reprod Toxicol, 1998; 12: 289-95). Caffeine also appears to enhance the negative effects of alcohol (Fertil Steril, 1998; 70: 632-7).

o Investigate allergies. Food allergies such as coeliac disease may also play a role in infertility (J Reprod Med, 2010; 55: 3-8). One case study was of a woman with primary infertility and coeliac disease. Eight months after being put on a gluten-free diet, she conceived. The researchers concluded that "coeliac disease should be checked in infertile patients of unexplainable aetiology with anaemia, as just changing their diet can solve their fertility problem" (Fertil Steril, 2010 May 25; Epub ahead of print).

o Consider nutritional deficiencies. A study by Dr Stephen Davies, of
the Biolab Medical Unit in London, showed that magnesium deficiency is associated with female infertility, increased miscarriage rates, and increased incidences of premature and low birth-weight babies. Mag-nesium supplements were given to six magnesium-deficient women who had unexplained infertility. After four months of treatment, all six conceived within the following eight months and produced normal healthy babies.

Six other women with unexplain-ed infertility, whose magnesium levels did not normalize after four months of treatment, did so after a further two months of magnesium plus selenium supplementation. These women also conceived within the following eight months, and all gave birth to normal healthy babies (Magnes Res, 1994; 7: 49-57). In men, low levels of zinc have been linked to poor sperm quality and infertility (Nutr Res, 2009; 29: 82-8).

o Get yourself tested for infections. Genital infection is a major cause
of infertility worldwide (Enferm Infecc Microbiol Clin, 2001; 19: 261-6). Chlamydia trachomatis infections are the most common, and their incidence has increased over the past 10 years. When left untreated, Chlamydia infection leads to a large proportion of cases of salpingitis (inflammation of the fallopian tubes), ectopic pregnancy and infertility (Clin Microbiol Infect, 2009; 15: 4-10).

o Manage stress. Infertile couples tend to be more stressed out than fertile couples, which suggests that stress might have adverse effects on reproductive health (Int J Fertil, 1986; 31: 153-9). This also suggests that relaxation techniques, such as meditation and yoga, may well be beneficial (Fertil Steril, 2003; 80 Suppl 4: 46-51).

o Avoid environmental toxins. Infertility may be caused by commonly found contaminants in the environment. Nowadays, we are all bombarded by an ever-increasing array of toxic chemicals-many of which are hormone mimics or disruptors-as we go about our daily lives. The main chemicals of concern for women include:

v perfluorinated chemicals (PFCs), which are used in a variety of consumer goods-from non-stick cookware (Teflon) and carpets to pesticides and personal-care items.
A recent study found that women with high blood levels of two types of PFCs took significantly longer
to become pregnant and were more likely to be infertile (Hum Reprod, 2009; 24: 1200-5).
v bisphenol A (BPA), a plastics chemical known to leach from food and drink containers into the food that we then eat. Blood levels of BPA in women have been linked to recurrent miscarriages, endo-metrial hyperplasia (where the lining of the womb becomes abnormally thick) and polycystic ovary syndrome (PCOS), one of the most common causes of female infertility (Hum Reprod, 2005; 20: 2325-9; Endocr J, 2004; 51: 595-600; Endocr J, 2004; 51: 165-9).
v chlorinated hydrocarbons (or CHCs), a class of persistent environ-mental toxins such as dioxins, polychlorinated biphenyls (PCBs) and organochlorine pesticides. One study found that women with uterine fibroids, endometriosis, miscarriages, persistent infertility and hormonal disturbances had higher than usual concentrations
of CHCs in their blood (Environ Res, 1999; 80: 299-310).
Although it's impossible to avoid all such dangerous chemicals, there are ways to minimize your exposure (see WDDTY vol 20 no 8) and to detoxify your body (see WDDTY vol 20 no 10).

The Foresight programme

There's a distinct lack of research on the effect of preconception advice on the chances of a live birth and other fertility outcomes (Cochrane Database Syst Rev, 2010; 4: CD008189).

However, the British charity Foresight, the Association for the Promotion of Preconceptual Care, has managed to accumulate an impressive success rate. Over 75 per cent of couples who had problems with infertility went on to have babies using the Foresight programme-a method that addresses all of the factors listed above and more. Compare this with the chances of success with IVF-which, at best, is only 28.6 per cent (see www.hfea.gov.uk/ivf-success-rate. html). Among the minority that still needs or wants IVF, Foresight can raise the couple's chances of success with
a 43.5-per-cent pregnancy rate.

To find out more about the Foresight Fertility Programme, visit www.foresight-preconception.org.uk or call 01243 868 001.
One final option to consider is adoption or fostering, as there's no shortage of foreign-born babies and domestic children who are in need of loving homes.

Joanna Evans

Potential treatments for women

o Propolis. In a preliminary study of women with infertility and mild endometriosis, supplementation with bee propolis (500 mg twice a day for nine months) was associated with a pregnancy rate of 60 per cent compared with only 20 per cent in those taking a placebo (Fertil Steril, 2003; 80 suppl 3: 32).
o Vitamin C may be useful for women with luteal phase defect (LPD), a hormonal abnormality that commonly leads to infertility. In infertile women with LPD, 750 mg/day of the vitamin taken for up to six months led to a pregnancy rate of 25 per cent compared with 11 per cent in the untreated control group (Fertil Steril, 2003; 80: 459-61).

o Multivitamins. Taking just a simple multivitamin was found to increase female fertility in one trial. Compared with the placebo group, those taking a multivitamin supplement took 5-per-cent less time to conceive (Int J Vitam Nutr Res, 1996; 66: 55-8).

o l-Arginine (16 g/day) can improve fertilization rates in women with a history of failed IVF attempts (Hum Reprod, 1999; 14: 1690-7). The amino acid can also improve sperm counts and sperm motility in men, as can carnitine, zinc, selenium and vitamin B12 (Altern Med Rev, 2000; 5: 28-38).

o Agnus castus. In one double-blind trial, more infertile women became pregnant after taking a product containing this herb (30 drops twice a day for three months) than did those who took a placebo (Forsch Komplement"armed, 1998; 5: 272-8).

o Acupuncture. In 104 women with unexplained infertility, a 60-per-cent pregnancy rate for seen in those who underwent six months of treatment with a standard therapeutic package of acupuncture plus moxibustion and herbal medicine developed in a hospital in Seoul, Korea (J Altern Complement Med, 2010; 16: 193-8

WDDTY VOL. 21 ISSUE 5


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