Tingen, C., Stanford, J. B., & Dunson, D. B. (2004). Methodologic and statistical approaches to studying human fertility and environmental exposure. Environmental Health Perspectives, 112(1), 87-93. https://doi.org/10.1289/ehp.6263
Tingen C, Stanford JB, Dunson DB. Methodologic and statistical approaches to studying human fertility and environmental exposure. Environ Health Perspect. 2004;112(1):87-93. doi:10.1289/ehp.6263
Tingen, Candace, et al. "Methodologic and statistical approaches to studying human fertility and environmental exposure." Environmental Health Perspectives, vol. 112, no. 1, 2004, pp. 87-93.
For EndNote, Zotero or Mendeley:
Open access
No open license is recorded for this paper. Reuse terms are set by the publisher.
National Institute of Environmental Health Sciences00j4k1h63
Linked to ROR, the Research Organization Registry
RRM Academy Synopsis
Authors call daily cycle records gold standard for exposure studies
The authors call detailed prospective studies the gold standard for studying fertility exposures. This 2003 methods review compares three study designs. The detailed design records bleeding, intercourse and ovulation day every cycle. Researchers can then estimate pregnancy chances for each day.
Study at a glance, narrative review: Detailed daily cycle records are the gold standard for exposure studies. Source: Tingen C et al., 2003, PMID 14698936.
Key Findings
Retrospective time to pregnancy studies are open to recruitment, recall, behavior and exposure-trend biases. The authors say they cannot be used to establish effects of environmental exposures on human fertility.
Conventional prospective studies follow women from the time they stop contraception. They have fewer biases than retrospective studies but cannot adjust for the timing of intercourse.
In Wilcox et al. 1995, conception was unlikely unless intercourse fell within the 6-day interval ending on ovulation day.
Barrett and Marshall followed 221 married British couples. Conception probabilities peaked 2 days before the estimated day of ovulation and fell to near zero afterward.
As a rule of thumb, the authors advise against day-specific studies of under 100 couples without Bayesian methods. The European Study of Daily Fecundability had 881 couples, 7,017 cycles.
Interpretation
The paper is a narrative review by authors at the National Institute of Environmental Health Sciences and the University of Utah. It reports no new study results. The design advice rests on earlier studies and the authors' statistical judgment. Sample-size guidance is a rule of thumb. Most exposure findings cited came from small retrospective studies. The detailed design may cost more, asks more of participants, and might enroll volunteers who differ from the wider population.
RRM Context
Day-specific conception chances tie pregnancy to the timing of ovulation, the logic behind fertility awareness charting. The review lists mucus observation and basal body temperature as ways to mark ovulation day. Mucus also tells researchers about sperm survival. The authors mark an ovulation marker as an essential core data element.
Our editorial summary of this paper, not the article's abstract.
Abstract
Although there has been growing concern about the effects of environmental exposures on human fertility, standard epidemiologic study designs may not collect sufficient data to identify subtle effects while properly adjusting for confounding. In particular, results from conventional time to pregnancy studies can be driven by the many sources of bias inherent in these studies. By prospectively collecting detailed records of menstrual bleeding, occurrences of intercourse, and a marker of ovulation day in each menstrual cycle, precise information on exposure effects can be obtained, adjusting for many of the primary sources of bias. This article provides an overview of the different types of study designs, focusing on the data required, the practical advantages and disadvantages of each design, and the statistical methods required to take full advantage of the available data. We conclude that detailed prospective studies allowing inferences on day-specific probabilities of conception should be considered as the gold standard for studying the effects of environmental exposures on fertility.
