Celiac Disease and Infertility – When Should We Test?
Celiac disease is a systemic autoimmune disease that occurs in genetically predisposed individuals, triggered by the ingestion of certain proteins found in wheat, rye, and barley. This chronic autoimmune-mediated disease has both intestinal and extra-intestinal manifestations. While the classic presentation is diarrhea, malabsorption, and weight loss, these gastrointestinal (GI) symptoms become less common with those who acquire the disease as adults. One the many extra-intestinal manifestations of celiac disease is impaired fertility.
The incidence of celiac is rising at an alarming rate; In the past 25yrs, there has been a 5-fold increase in the United States with an overall prevalence of 1%. Even more disturbing, is that given the protean nature of this disease, especially when presenting in adults, it is estimated that an astounding 95% of individuals with celiac disease remain undiagnosed. Over half of adult patients with celiac disease have no GI manifestations. The diagnosis of celiac disease is typically made by a blood test looking for specific antibodies usually followed by a confirmatory endoscopic examination of the upper portion of the small intestine.
John Morris, first described the impact of celiac disease on fertility in a report published in the journal The Lancet in 1970 where he described 3 cases of infertility reversed with the use of a gluten-free diet. Of note is that one of these cases involved a woman who had children and presented with secondary infertility. Since this original report, there have been numerous studies looking at the association between celiac disease and infertility. The results have been conflicting with some showing a positive association and while others have failed to show an association. Given these conflicting results, there currently are no gynecologic or gastrointestinal Association guidelines recommending the screening women with infertility for celiac disease.
A recent meta-analysis to be published in the Journal of Clinical Gastroenterology sheds a new light on this question. The authors pooled the results of 9 studies selected from an original group of 105 reports on celiac disease. They excluded studies where the diagnosis of celiac disease was based on serology alone. This analysis found that women presenting with “all-cause” infertility had prevalence of 2.3%, and a 3.5x increased odds of having celiac disease. Those women diagnosed with “unexplained” infertility had a prevalence of 3.2% and a dramatic, 6x increased odds of having celiac disease. Based on these findings the authors recommend screening all infertility patients for celiac disease.
Besides infertility, celiac disease is associated with a host of gynecological problems including delayed menarche, early menopause, endometriosis, and recurrent early pregnancy loss. While the data is conflicting, several large studies have found that untreated celiac disease is associated with adverse obstetrical outcomes, namely intrauterine growth retardation, preterm, small for gestational age babies and postpartum hemorrhage. Both patients with celiac disease and their first-degree relatives are at increased risk of other, autoimmune disorders. It goes without saying that first-degree relatives are also at increased risk of having celiac disease. While screening all infertility patients for celiac disease in not currently standard practice, we should have a very low threshold for looking for this disease in our infertile population.
Murray, J. A., Van, Dyke C., Plevak, M. F., Dierkhising, R. A., Zinsmeister, A. R., and Melton, L. J., III. Trends in the identification and clinical features of celiac disease in a North American community, 1950-2001. Clin.Gastroenterol.Hepatol. 1(1), 19-27. 2003.
Dhalwani, Nafeesa N., West, Joe, Sultan, Alyshah Abdul, Ban, Lu, and Tata, Laila J. Women With Celiac Disease Present With Fertility Problems No More Often Than Women in the General Population. Gastroenterology. Gastroenterology 147(6), 1267-1274. 2014. Elsevier. 12-7-2014.
Tersigni, C., Castellani, R., de, Waure C., Fattorossi, A., De, Spirito M., Gasbarrini, A., Scambia, G., and Di, Simone N. Celiac disease and reproductive disorders: meta-analysis of epidemiologic associations and potential pathogenic mechanisms. Hum.Reprod.Update. 20(4), 582-593. 2014.
Ehsani-Ardakani, M. J., Fallahian, M., Rostami, K., Rostami-Nejad, M., Lotfi, S., Mohaghegh-Shalmani, H., Dabiri, R., Norouzinia, M., Azizpour-Shoobi, F., and Zali, M. R. Celiac disease and dysfunctional uterine bleeding; the efficiency of gluten free diet. Bratisl.Lek.Listy 115(1), 19-21. 2014
Empowering Fertility: An educational blog for patients & healthcare professionals that empowers individuals to take charge of their fertility. Visit us at http://empoweringfertility.com.