Maconochie, N., P. Doyle & C. Carson. 2004. Infertility among male UK veterans of the 1990-1 Gulf war: reproductive cohort study.BMJ, DOI: 10.1136/bmj.38163.620972.AE.

In the largest retrospective cohort study of infertility of Gulf War veterans, Maconochie et al. report a small increased risk of infertility and a longer time to conception among male veterans of the war when compared to soldiers who did not serve in the Gulf.

What did they do?

Maconochie et al. mailed questionnaires to UK armed forces personnel who had been deployed to the Gulf region during the 1990-1 war and to a matched comparison group of non-deployed military personnel. They included in the analyses men who had, or had attempted to have, a child after the war and before 1997. Men were excluded if they had tried unsuccessfully for less than a year to have a child, or, if a doctor had never been consulted or, was consulted after 1997.

Participants were defined as having fertility problems if they had tried unsuccessfully for a pregnancy for longer than a year and had seen a physician about infertility since the Gulf war and before 1997. 10,465 Gulf war veterans were included in the study and 732 (7%) of them reported fertility problems. 7376 non-veterans were included, 370 (5%) of whom reported fertility problems. Infertility was divided into two types:

  • Type I: never achieving a recognized pregnancy, and
  • Type II: conception but no live birth.

When available, Maconochie et al. examined physician records to confirm infertility reports and to identify male infertility factors. For a small number of participants, semen analysis results were available and obtained. Diagnoses were coded according to sperm count, sperm motility and abnormal morphology. Participants who had fathered children successfully were asked whether the pregnancy has been planned and how long it had taken to conceive.

What did they find?

Maconochie et al. discovered subtle but significant increases in risks of infertility among Gulf war veterans.

Overall, their data revealed no difference between Gulf veterans and non-Gulf veterans in time trying unsuccessfully for a child. Other measurements, however, indicated differences.

Gulf vets were more likely to have reported fertility problems, to have had no conceptions, and to have had no live births, than veterans who did not serve in the Gulf War.

Table to right adapted
from Maconochie et al.

 

The odds ratios for these outcomes reflect 38% to 50% increases in the likelihood of fertility problems. The lower limit of each of the 95% confidence intervals confidence intervals for these odds-ratios is above one, indicating that the increase is unlikely to be a result of chance.

When they examined the risk of diagnosis of specific male infertility factors they found only weak association with Gulf war deployment.

  Malformed sperm were more likely among Gulf veterans than non-Gulf veterans in cases of Type II infertility.

Maconochie et al. also examined the risk of infertility in association with self-reported Gulf war exposures including vaccination against anthrax of plague, pyridostigmine bromide tablets (popop: a nerve-gas antidote), depleted uranium and pesticides. A high proportion of veterans did not know or could not recall their exposure. Overall, no significant associations were identified. There was a slight suggestion of a link between vaccination exposure and male infertility factor diagnosis, but numbers were small and confidence intervals included 1.0. Odds ratio for male infertility factor with positive vaccine exposure = 2.95 (CI = 0.4-22.0) for type I infertility; OR = 2.68 (CI = 0.64-11.21) for type II.

Among those study participants who did not have fertility problems, pregnancies fathered by Gulf veterans were more often unplanned. Among planned pregnancies, those fathered by veterans took longer to conceive. OR=1.18 (CI=1.04-1.34).

 

What does it mean?

Maconochie et al. found evidence that there is a greater prevalence of fertility problems among military personnel who were deployed during the Gulf war in the early 1990’s. Many soldiers during this war were exposed to one or more toxic agents including anthrax and plague vaccines, depleted uranium, pesticides and anti-nerve gas chemicals. This result would be consistent with testicular damage found in animals exposed to mixtures of some of these compounds. There are many other examples in the recent scientific literature describing animal studies in which exposures to environmental toxicants cause in reproductive abnormalities.

Maconochie et al. acknowledge that their data do not conclusively prove a fertility impact on Gulf war veterans. At least three methodological obstacles undermined the strength of their study: dependence upon retrospective questionnaires, poor recall of actual exposures, and low response rates. Retrospective questionnaires and poor recall can bias toward false negatives, because depending upon memory will introduce an additional level of inaccuracy into exposure estimates. Without a reliable exposure estimate, the soldiers included as Gulf vets will likely include many men who were in the Gulf war, but were not exposed. The ideal comparison would have been exposed veterans vs. unexposed, but this proved unattainable. Thus the fact that they found any statistically significant result is intriguing, and probably indicative of a real effect.