In a recent issue of Arthritis Care & Research, a very interesting study by Clowse et al assessed infertility in 113 female patients with systemic lupus erythematosus (SLE) using a reproductive history questionnaire from the National Data Bank for Rheumatic Diseases (1). Because 16% of women with SLE were found to be infertile, the authors concluded that women with SLE do not appear to have an increased rate of infertility compared to general population statistics.
Our group found that women with SLE have substantially decreased live birth rates compared to the general population, particularly after diagnosis (2). Multiple disease-related factors may explain reduced live birth rates in SLE (3), including infertility. Although Clowse et al did not observe increased infertility in their SLE sample, there are perhaps some methodologic considerations that may have influenced their results.
In the study by Clowse et al, infertility was defined based on a positive answer to one of the following questions: “Have you ever been unable to get pregnant after 12 months of trying?” and/or “Have you ever been diagnosed with infertility by a physician?” The first question relies on retrospective self-reported time to pregnancy (TTP) to define infertility. Self-reported TTP has been used as a proxy to fertility in several epidemiologic studies where subjects reported the number of calendar months or menstrual cycles required to achieve a pregnancy from the initiation of trying to get pregnant. A TTP >12 months is commonly used as a cutoff for infertility; however, only 2 studies have assessed the validity of retrospective self-reported TTP using prospective methods as the gold standard. Although good validity was shown when recall was limited to 3–20 months (4), poor validity was observed when recall was ∼1 decade later, with women who had longer observed TTP more likely to under-report their TTP (5). In the study by Clowse et al, the mean ± SD patient age was 54 ± 11 years, indicating that most women had their pregnancy or attempted conception more than a decade ago. This may have resulted in some recall bias, possibly leading to a conservative estimate of infertility.
Another potential issue is that, in asking a woman if she has “ever been unable to get pregnant after 12 months,” one might actually underestimate infertility by excluding those women who succeeded in achieving a pregnancy, but only after 12 months (classically, such cases of delayed pregnancy should actually be included when calculating infertility rates in SLE).
In summary, the authors attempted to answer a very important question, although methodologic considerations may limit the ability to draw final conclusions. Future studies will likely need to carefully consider these issues; possible directions might include, for example, assessing fertility in women with SLE by prospectively measuring TTP.