Serum dioxin concentrations and time to pregnancy.
BACKGROUND
Pollution may play a role in population trends of declining semen quality and regional differences in time to pregnancy (TTP) in industrialized societies. Dioxins including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have been suspected. In 1976, an explosion near Seveso, Italy resulted in the highest TCDD exposure known in residential populations. Twenty years later, we conducted a retrospective cohort study, the Seveso Women's Health Study.


METHODS
Of 981 participants, 472 women attempted pregnancy after the explosion, and 278 delivered a livebirth not associated with contraceptive failure. Individual serum TCDD levels were measured from samples collected soon after the explosion and extrapolated to the conception attempt. We examined the relation of TCDD levels to time to pregnancy (parameterized as the monthly probability of conception within the first 12 months of trying) and to infertility (defined as conception after at least 12 months of trying). We modeled fecundability with discrete-time Cox proportional hazards regression, and we modeled fertility with logistic regression. We tested the sensitivity of the conclusions to differing definitions of eligibility and outcome.


RESULTS
Median TCDD level was 50 parts per trillion, median time to pregnancy was 2 months, and 17% reported taking 12 or more months to conceive. For every 10-fold increase in serum TCDD, we observed a 25% increase in time to pregnancy (adjusted-fecundability odds ratio = 0.75 [95% confidence interval (CI) = 0.60-0.95]) and about a doubling in odds of infertility (adjusted odds ratio = 1.9 [95% CI = 1.1-3.2]). Results were similar for extrapolated TCDD and sensitivity analyses.


CONCLUSIONS
We found dose-related increases in TTP and infertility associated with individual serum TCDD levels in the women from Seveso, Italy. These findings may have implications for fertility in industrialized areas.
Eskenazi
Brenda
B
School of Public Health, University of California at Berkeley, Berkeley, CA 94720-7380, USA. eskenazi@berkeley.edu
Warner
Marcella
M
Marks
Amy R
AR
Samuels
Steven
S
Needham
Larry
L
Brambilla
Paolo
P
Mocarelli
Paolo
P
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D005306:Fertilization / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007247:Infertility, Female / Q000139:chemically induced / Q000453:epidemiology; D007558:Italy / Q000453:epidemiology; D016015:Logistic Models; D016017:Odds Ratio; D000072317:Polychlorinated Dibenzodioxins / Q000009:adverse effects / Q000097:blood*; D011247:Pregnancy; D016016:Proportional Hazards Models; D055906:Seveso Accidental Release / Q000706:statistics & numerical data; D013997:Time Factors; D055815:Young Adult
D000072317:Polychlorinated Dibenzodioxins