Validity Issues Relating to Time-to-Pregnancy Studies of Fertility

Abstract

Circumstantial evidence regarding the deterioration of male fecundity, together with the fact that the majority of infertility cases have unknown causes, make it important to identify risk factors that can be eliminated and thus pave the way for prevention of infertility. Rapidly increasing costs of artificial fertilization and cumbersome lengthy treatments of infertile couples with limited success rates add to the importance of such studies and contribute to a wider acceptance of epidemiologic studies of fertility. Worldwide fertility is now close to replacement level, and the previous fear of uncon trolled population growth should no longer stand in our way for studying environmental causes that impair fecundity. More than 20 years ago, a seminal paper1 on subfecundity and infertility examined occupational risk factors in the Danish workplace. During the late 1980s, the use of time-to-pregnancy (TTP) was introduced and elaborated. TTP is the number of months or menstrual cycles it takes a couple to conceive and covers the entire distribution of waiting times from 0 (high-level fecundity) to several years (low-level fecundity).2'3 Valid information about TTP is easy and inexpensive to obtain by questionnaires and interview. With increasing interest in reproductive issues in public health, TTP soon became a widely used measure in epidemiologic studies. As time went on, it became clear that TTP studies needed to take several population characteristics into consideration, especially if the compared populations differed in such factors as desired family size, use of contraceptive methods, and sexual activity. Many specific pitfalls inherent in the TTP methodology were identified,4'5 and new types of biases have been added to the list in recent years.6 Lately, we have witnessed discussions on costly prospective designs versus inexpensive retro spective designs.7 Also, we have seen differing opinions as to whether it is possible to obtain valid retrospective information on secular trends in fecundity by the TTP meth odology8'9 or on fecundity among different cultures.' 0 " Is the TTP design option still to be considered a valid method for obtaining knowledge about fecundity in humans? To obtain a direct measure of human fecundity, couples must attempt to use their reproductive capability. This is where the troubles start. First, not all persons get to try, even if they want children (for example, if they never find a partner). Second, some couples get pregnant while using contraception or by accident. Such pregnancies have no TTP value but provide important information. These couples may be more fecund than others, but how much more we do not know. As a result, those who provide a measurable TTP may underrepresent highly fecund couples. Third, not all couples succeed in conceiving, and TTP distributions that include only those who succeed will underrepresent less fertile couples, thus indicating the need for collecting data on unprotected intercourse