Our finding of reduced fertility among women with reported exposure to solvents is in accordance with the findings of several previous studies.14,15,16,17,18,19,20,21,22
A few studies, however, have been negative.23,24
The risk is difficult to attribute to specific solvents, because the studied solvents varied.
The evidence for males is less consistent. A few studies have shown a weak association,17,25,26,27
but others have been negative.14,20,23,28,29
Interestingly, a recent Dutch study of in vitro fertilisation (IVF) patients showed decreased implantation rates for women whose partners were exposed to organic solvents.30
In the Agricultural Health Study, we see an association for both male and female solvent exposure, though the male effect is less consistent than the female effect across analyses of separate subsets of the population.
Our study has several strengths: (1) the study population is large and homogenous (licensed pesticide applicators in Iowa and North Carolina, all of whom were farmers); (2) exposure data were reported directly by men and women themselves rather by one of the partners as is sometimes the case in occupational studies, and information on exposures was collected independently of fertility information; (3) our study subjects are independent farmers who function as both management and labour, which increases the quality of information they can provide about farm activities and chemicals used; (4) periods of infertility that did not result in pregnancy were included (this is important because exclusion of unsuccessful attempts may mask a true effect31
); and (5) the design used reduces the potential for time‐trend bias.13
In this study, the distribution of start of attempt times was similar for the fertile and subfertile subjects. This is critical because only information on current (or usual) solvent exposure was available.
Our study has some weaknesses that must be considered. Only categorical data on subfertility were available rather than actual time to pregnancy. This may make it more difficult to detect a true association. Exposure to solvents was based on self‐reported work description, and no biological or environmental measures were available. Timing of exposure in relation to the start of attempt times could not be ascertained precisely. However, this type of exposure misclassification is likely to be non‐differential, because the times of attempts are not expected to be differentially distributed by fertility status. Therefore, our findings may be biased towards unity. Moreover, we observed a strong association for women who had lived on a farm 10 years ago, but a weaker association for women who did not live on a farm 10 years ago. We think that this reflects potential for exposure misclassification. Depending on when these women moved to the farm, their current exposure patterns may not reflect exposure during their pregnancy attempt. To the extent that farm activities remain stable, the exposures at enrolment of women that lived on a farm 10 years ago would be more likely to reflect exposures throughout the four year study window.
Another source of potential exposure misclassification is related to the reproductive status of the wife. As expected, pregnant or breast feeding women at the time of interview were less often exposed to solvents than other women. Furthermore, we found that women who had preschool aged children at the time of data collection also were less likely to report exposure than did childless women or women who had older children. The opposite exposure pattern seemed to be true for men. Since farm tasks must be done regardless of family structure, it is likely that farm couples redistribute these tasks when family situations change. Thus, it is possible that applicators assume responsibility for chores previously done by the wife when she is pregnant or occupied by the care of small children. Because current pregnancy, breast feeding, or having young children reflect higher fertility, on average, it is likely that this type of differential exposure misclassification will bias the findings towards overestimation of the subfertility association for women and underestimation of the subfertility odds ratio for men. Therefore, we also assessed risk using a composite variable for combined parental exposure to solvents. Parental exposure to solvents was significantly related to subfertility and the effect was consistent across subsets of the population. The strongest association was seen in families where both parents were exposed to solvents. This adds to the evidence for adverse effects of solvent exposures on males as well as females.
The overall rate of subfertility was high in the analysis sample. This is expected because unsuccessful attempts to conceive were included (couples currently trying to conceive totalled 14% of the eligible subjects), and half the couples were over 30. In general, infertility rates are highly dependent on the definition of infertility. In a US study,32
the prevalence of a history of infertility ranged from 6.1% (physician diagnosis) to 32.6% (unprotected intercourse for 12 months), the latter figure being similar to that in our study (28%). It was difficult to define fertility status in the case of multiple pregnancies because infertility history was not pregnancy specific. However, the findings were very similar when the analysis was restricted to those couples with the more certain subfertility data.
Data were available on many potential confounders and the findings remained after adjustment. However, the data on confounders were not collected to coincide with the start of the attempt time. This could introduce bias, especially for women, because women often change their habits when in different reproductive situations. Smoking data may show the most misclassification, as women are encouraged to stop smoking when pregnant or raising children. When we restricted the analysis to women who never smoked, however, the association with solvents was virtually unchanged. Therefore, misclassification of potential confounders may not be an important source of bias in the present study.
We have no explanation for the different findings between the states. For the variation by age, however, it is possible that that susceptibility to toxins increases with increasing age for both women and men.
The findings of our study provide further evidence that organic solvents can impair fertility. There is ample evidence that solvent exposure is associated with reduced female fertility, and women trying to conceive should avoid exposure. However, little is known about effects of specific solvents, hazardous exposure levels, and relevant exposure windows. Males may also be adversely affected, though the evidence for female effects is still stronger than for male effects.
- The findings provide further evidence that use of solvents can impair female fertility.
- Males may also be adversely affected.
- Couples on farms often share work; current pregnancy or young children in household can influence who is exposed.
- Women and men trying to achieve conception should minimise solvent exposure.