Studying Time to Pregnancy by Use of a Retrospective Design

Abstract

Biologic fertility can be measured using time to pregnancy (TTP). Retrospective designs, although lacking detailed timed information about behavior and exposure, are useful since they have a well-defined target population, often have good response rates, and are simpler and less expensive to conduct than prospective studies. This paper reviews retrospective TTP studies from a methodological viewpoint and shows how methodological problems can be avoided or minimized by appropriate study design, conduct, and analysis. Sensitivity analyses using data from four European retrospective TTP studies are presented to explore the issues. Although the identified biases tend to have small impacts, the effects are not systematic across studies, and sensitivity analyses are recommended routinely. Planning bias can be checked by comparing propensity to report contraceptive failures in different exposure groups. Medical intervention bias can be avoided by censoring and inclusion of unsuccessful pregnancy attempts. Truncation bias can be a serious problem if unrecognized, but it is avoidable with appropriate study design and/or analysis. Behavior change bias can be minimized by assessing the covariates at the beginning of unprotected intercourse. More complete inference is possible if the study design covers the whole population, not just those who achieve a pregnancy. data collection; fertility; infertility; questionnaires; reproduction Abbreviation: TTP, time to pregnancy.Time to pregnancy (TTP) measures how long a couple takes to conceive. The TTP distribution in a population describes its degree of fertility. It is a functional measure, the final common path of a large number of biologic mechanisms in both sexes (1); its use is complementary to more mechanistic research on the biologic processes necessary for fertility and studies of specific medical conditions. Information about TTP is easy to obtain, and it has proven useful in descriptive epidemiology, for example, to identify time trends (2) and spatial variation (3) and to identify risk factors (4-7). Since the unit of study is the couple, covariates relating to both partners are required.TTP can be studied by use of either a prospective or retrospective design. Each has its strengths and weaknesses, and their roles are complementary. Prospective studies (the detailed discussion of which is beyond the scope of this paper) recruit couples at the start of their attempt, that is, couples who are prepared to undertake regular testing and to be followed up. These studies are therefore able to obtain detailed, timed information on key biologic events, including ovulation, implantation, and exposures, and on certain covariates, such as the frequency/timing of intercourse (8). They are becoming more sophisticated, and their feasibility has been demonstrated (8-11). The drawbacks are lack of a clear sampling frame (except in occupational studies) (12) and need for highly motivated participants, which might cause response bias and planning bias (see below). These drawbacks may ad...

Time to pregnancy among female greenhouse workers

“…Several types of bias specific for time-to-pregnancy studies (33,34) were evaluated, and we concluded that sterility bias and wantedness bias did not play a role in our study. Other types of bias mentioned by Weinburg et al (33) were excluded a priori, as we prevented medical intervention bias by censuring time to pregnancy at 14 months and did not expect many women in the Netherlands to change jobs, work habits, or behavior during their waiting time to pregnancy, which would lead to time trend bias and behavior modification bias.…”

“…Not everyone in the study was able to produce an adequate time-to-pregnancy value, but, in general, time-to-pregnancy data are considered valid estimates of the waiting time to pregnancy (34,37) and, therefore, lead only to nondifferential misclassification and an underestimation of the fecundability ratio. Concerning exposure, no distinctions could be made for the amount and kinds of pesticides used, as many different pesticides were reported, some of which may not be reproduction-toxic.…”

“…In addition, we investigated the different sources of bias that may occur in studies on time to pregnancy and that were relevant in our study (33,34).…”

“…Time to pregnancy in its strict meaning relates only to periods of unprotected intercourse that end in conception, excluding sterile couples and underrepresenting severely subfertile couples (34). If an exposure causes complete sterility rather than just reducing fecundability, retrospective time-to-pregnancy studies will not detect an adverse effect.…”

Misconceptions about falling sperm counts and fertility in Europe

“…The mean time to pregnancy of a population of couples trying to become parents has been extensively used in epidemiological studies to assess risk factors, differences between regions and trends over time. [6][7][8][9] What about male and female fecundity? The problem is that neither are separately assessable, being always dependent on the interaction between the partners.…”