There is an established relationship between overt CD and adverse reproductive consequences, including infertility. The relationship between silent CD and infertility has been more controversial.
Studies evaluating the relationship between CD and adverse reproductive experiences—including infertility, recurrent pregnancy loss, and poor obstetric outcome—have a number of limitations, including inconsistent and incomplete criteria for the diagnosis of CD and infertility. They have often involved small and underpowered sample sizes and have combined patients who presented with typical gastrointestinal symptoms and those with silent disease. Several reports have had inappropriate control groups or no control groups at all.
Several studies primarily involving Europe and the Mideast have suggested that CD is associated with infertility in 4% to 8% of cases, compared with a background incidence in those populations of approximately 1%.8-10 A cohort study involving Northern California women with unexplained infertility screened with serologic markers reported that fewer than 1% were affected.11 A more recent series of 191 patients with unexplained infertility screened in New York found a 6% prevalence of histologically confirmed cases of previously undiagnosed CD.12
The contradictory conclusions may be because of differences in the ethnicity of the study populations. A Swedish nationwide population-based study that evaluated the fertility experience of patients with known histologically confirmed CD concluded that women with CD overall had normal fertility but did have decreased fecundity in the 2 years before their diagnosis.13
More compelling evidence of a role for CD in unexplained infertility may be suggested by a positive response to therapy in those with yet-untreated disease. There are several reports of successful pregnancy after adoption of a gluten-free diet, but the number of CD cases detected by screening has been too small and the concomitant use of other effective interventions limits conclusions about causality.14 To date, efficacy of a gluten-free diet as part of an infertility treatment regimen has not been tested in a systematic manner.
Celiac disease also has been suggested as a contributor to recurrent pregnancy loss. In a small series, 8% of affected patients had positive serology and the diagnosis of CD was confirmed by biopsy in 88%.15 Benefit of treatment was not determined. A large Italian population-based study of patients with serologically detected but not histologically confirmed CD found a higher incidence of anemia but not of spontaneous abortion, premature delivery, low birth weight, or intrauterine growth restriction (IUGR) in affected patients.16 In the absence of maternal symptoms, screening for occult CD is not currently recommended in the workup of recurrent spontaneous abortion.
The benefit of a gluten-free diet is more conclusively proven to improve birth outcomes in women previously diagnosed with CD. A large Danish cohort study noted that before institution of a gluten-free diet, mean birth weight of newborns of mothers with CD was 8.39 oz less than controls, and they had a 3-fold greater risk of IUGR, but these differences disappeared in subsequent pregnancies with treatment.17 These findings have been confirmed with expanded follow-up studies and in other populations, and reduction in risk of preterm delivery has been confirmed as well.18,19