A new study of obesity and the probability of pregnancy has shown that a woman's chances of a spontaneous pregnancy steadily decrease the fatter she is.
In the first prospective cohort study to examine the relationship between body mass index (BMI) and pregnancy chances in women who have no obvious reasons for infertility but who have spent a year or more trying unsuccessfully to conceive, the study found that for every BMI unit above 29 kg/m2, the probability of pregnancy was reduced by four per cent compared to women with a BMI between 21-29 kg/m2. Very obese women (BMI 35-40) had a probability of pregnancy that was between 26 and 43 per cent lower than women with a BMI between 21-29.
Dr Jan Willem van der Steeg, the lead author of the study , which is published in Europe's leading reproductive medicine journal, Human Reproduction, today (Wednesday 12 December) said: "This reduction in fertility is comparable to the increment of one year in female age. This study tells us that not only obese women with anovulation have lower chances of conception, but also obese women with a regular cycle. Given the increased prevalence of obesity, this is a worrying finding." The incidence of obesity is reckoned to be 12 per cent in women of child-bearing age in Western Europe and 25 per cent in North America.
As women in developed countries are tending to have their babies later in life, a woman aged 30 or over, who is also obese, would have an even greater reduction in her chances of becoming pregnant.
Obesity is known to be a risk factor for anovulation (absence of ovulation) and NICE  guidelines recommending that obese women should be told that they are likely to take longer to conceive are based on studies that looked at BMI and time to pregnancy in women who were pregnant or had delivered a child, and on a study analysing fat distribution and chances of conception in women in a donor insemination programme. However, this new study is the first to show that obesity also affects the chance of spontaneous pregnancy in women who are ovulating normally, but are subfertile , and to analyse BMI as a continuous variable that shows the steady decline in pregnancy rates in women with BMIs over 29.
Dr van der Steeg, a medical researcher and resident in obstetrics and gynaecology at the Academic Medical Center, Amsterdam, The Netherlands, and colleagues investigated the effects of obesity on spontaneous pregnancy in 3,029 subfertile couples between 2002 and 2004 in 24 hospitals in The Netherlands. The women had to be ovulating and have at least one, correctly functioning fallopian tube; the men had to have a normal semen analysis. A fertility history and other details, including height, weight and smoking habits, were taken at the start of the study and the couples were followed until pregnancy or the start of fertility treatment within 12 months. Timing and frequency of sexual intercourse was not documented, but Dr van der Steeg believes that this did not affect the results of the study.
"Most studies on subfertility do not report on frequency of intercourse. We assume that most people suffering from subfertility have no problems with the timing and frequency of intercourse, which is an integral part of the history taking in the basic fertility work-up. Couples with serious sexual problems are usually excluded from studies like this one," he said.
The World Health Organization (WHO) defines overweight as a BMI of between 25-29.9, and obesity as a BMI of 30 or over. In this study 3.7 per cent of women had a BMI below 18.5, 67 per cent had a BMI between 18.5-25, 19 per cent had a BMI between 25-30, 6.7 per cent had a BMI between 30-35, and 3.8 per cent had a BMI of 35 or more. The researchers used the women with a BMI between 21 and 29 as their reference group and found that BMI above 29 was associated with a statistically significant lower probability of spontaneous pregnancy than the reference group.
"In the case of a woman with a BMI of 35, the probability of spontaneous pregnancy was 26 per cent lower, and in the case of a woman with a BMI of 40 it was 43 per cent lower compared to the reference group," said Dr van der Steeg.
The researchers believe that a possible mechanism to explain the relationship between BMI and pregnancy probability is the hormone leptin that regulates appetite and energy expenditure and is secreted by fatty tissues. "It is possible that obese women may have disturbed hormone levels, which decrease the chances of successful fertilisation and implantation," said Dr van der Steeg. "The level of leptin in the body is positively related with the amount of fat in individuals without any mutations in their leptin regulation genes. Leptin levels are increased in obese people, suggesting a relative resistance to leptin. It is unclear whether or not obesity causes a resistance to leptin or vice versa. There is evidence that leptin may influence the process of steroid production by the ovaries."
Dr van der Steeg believes that obesity is a factor in the increasing numbers of couples seeking fertility treatments. "Nowadays, one out of six couples will deal with subfertility once in their life. Adult obesity levels have increased four-fold over the last 25 years, with two-thirds of adults deemed overweight. Professor William Ledger has stated that obesity is a key factor in predictions that the number of couples seeking infertility treatments will double over the next ten years," he said. Prof Ledger is professor of obstetrics and gynaecology at the University of Sheffield, UK, and made this statement in 2005 at the annual conference of the European Society of Human Reproduction and Embryology.
Dr van der Steeg continued: "We think that women should be informed about their lower pregnancy chances due to their overweight. Although this study does not show whether women's chances of conceiving rise if they lose weight, because of the size of the cohort, with comparable women in different weight groups, we hypothesise that losing weight will increase the chance to conceive without treatment. Therefore, we would advise women to lose weight. Although the effect on better fertility is not proven, it is shown that the chance of a serious complication during pregnancy and labour is reduced."
The researchers are developing a new model for predicting pregnancy chances and which includes factors such as BMI. The original prediction model without the BMI is available on the internet (http://www.freya.nl/probability.php) and can be used by couples and their doctors to help them decide whether to go for fertility treatment or not. Dr van der Steeg said the next step would be to perform a trial in which obese subfertile couples are allocated to a weight losing programme or no intervention, with the number of pregnancies without treatment being the primary outcome.
 Obesity affects spontaneous pregnancy chances in subfertile, ovulatory women. Human Reproduction. Doi:10.1093/humrep/dem371
 NICE -- National Institute for Health and Clinical Excellence.
 Subfertility is defined as at least one year of unprotected sexual intercourse without conception, regardless of any previous conceptions.
Materials provided by European Society for Human Reproduction and Embryology. Note: Content may be edited for style and length.
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