Designing prospective cohort studies for assessing reproductive and developmental toxicity during sensitive windows of human reproduction and development – the LIFE Study

Abstract

Summary Buck Louis GM, Schisterman EF, Sweeney AM, Wilcosky TC, Gore-Langton RE, Lynch CD, Boyd Barr D, Schrader SM, Kim S, Chen Z, Sundaram R, on behalf of the LIFE Study. Designing prospective cohort studies for assessing reproductive and developmental toxicity during sensitive windows of human reproduction and development – the LIFE Study. Paediatric and Perinatal Epidemiology 2011; 25: 413–424. The relationship between the environment and human fecundity and fertility remains virtually unstudied from a couple-based perspective in which longitudinal exposure data and biospecimens are captured across sensitive windows. In response, we completed the LIFE Study with methodology that intended to empirically evaluate a priori purported methodological challenges: implementation of population-based sampling frameworks suitable for recruiting couples planning pregnancy;obtaining environmental data across sensitive windows of reproduction and development;home-based biospecimen collection; anddevelopment of a data management system for hierarchical exposome data. We used two sampling frameworks (i.e. fish/wildlife licence registry and a direct marketing database) for 16 targeted counties with presumed environmental exposures to persistent organochlorine chemicals to recruit 501 couples planning pregnancies for prospective longitudinal follow-up while trying to conceive and throughout pregnancy. Enrolment rates varied from <1% of the targeted population (n = 424 423) to 42% of eligible couples who were successfully screened; 84% of the targeted population could not be reached, while 36% refused screening. Among enrolled couples, ~85% completed daily journals while trying; 82% of pregnant women completed daily early pregnancy journals, and 80% completed monthly pregnancy journals. All couples provided baseline blood/urine samples; 94% of men provided one or more semen samples and 98% of women provided one or more saliva samples. Women successfully used urinary fertility monitors for identifying ovulation and home pregnancy test kits. Couples can be recruited for preconception cohorts and will comply with intensive data collection across sensitive windows. However, appropriately sized sampling frameworks are critical, given the small percentage of couples contacted found eligible and reportedly planning pregnancy at any point in time.

Time-to-Pregnancy Associated With Couples’ Use of Tobacco Products

“…Further details on the study design are provided elsewhere. 24 Following enrollment, couples were followed daily until a positive home pregnancy test or 12 months of trying. To be inclusive of the wide range of couples attempting pregnancy, only couples in which at least one partner had been told they would require medical assistance to become pregnant were excluded.…”

“…Together, the data from the fertility monitor and the daily diaries were used to define menstrual cycles used for determining TTP. 24 Women were provided with highly sensitive (25 IU/L) home pregnancy tests 25 that provide digital readouts of "pregnant" and "not pregnant" to ensure accuracy reading results 26 and were instructed to begin testing on the day of expected menses. A single positive pregnancy test denoted an human chorionic gonadotropin pregnancy.…”

Association between cigarette smoking behavior and infertility in women: a case-control study

“…Moreover, based on our results, 16% of infertile women have mentioned extreme dependency to nicotine, while none of the fertile women reported extreme dependency to nicotine. A laboratory study analyzed the impact of the different concentrations of nicotine on fertility in rats and showed that nicotine had a dose-dependent effect on fertility power (Louis et al, 2011).…”

“…According to one study, tobacco use likely increases infertility by 1.6-fold (Hatch et al, 2006). Berthiller and colleagues, however, reported that fertility did not decline in both male and female passive smokers (Louis et al, 2011;Oyeyipo et al, 2013).…”

A data‐driven search for semen‐related phenotypes in conception delay

“…We felt this choice was justified as conception delay has been empirically shown to be a very good marker of identifying which couples will need clinical evaluation and/or treatment. While there have only been a few studies that have followed couples from discontinuing contraception through 12 months of trying, the data demonstrate that 76–90% of couples who do become pregnant do so within the first 6 months of trying (Gnoth et al ., 2003; Wang et al ., 2003; Buck Louis et al ., 2009, 2011). Moreover, clinical guidance suggests that couples seek care if not pregnant within 6 months of trying when the female partner is 35+ years of age.…”