Celiac Disease and Infertility

Celiac disease is primarily an intestinal disorder that emanates from an abnormal immune system response to gluten, a common dietary protein encountered in bread, pasta, and other wheat-containing foods. The antibodies that develop in response to gluten are capable of cross-reacting with several normal body proteins, especially those of the digestive tract, and this can lead to a digestive disorder characterized by malabsorption, vitamin deficiencies (B-12, folate, iron), and abdominal distress (pain, bloating, cramping). The incidence of Celiac disease is estimated to be approximately 1 in 300 people.

There is increasing evidence of a link between Celiac disease and infertility related to abnormal immune response, increased rates of amennorhea, endometriosis, and earlier menopause in women with the condition.

Symptoms of Celiac Disease

The symptoms of Celiac Disease can be mild or misleading, thereby allowing its presence to go undetected or misinterpreted. To illustrate this point, I had a good friend who was told since childhood that his symptoms were due to lactose intolerance. So he dutifully stayed away from lactose as much as possible and took his lactase supplements for years. His symptoms of stomach upset were only minimally helped by such interventions and, despite eating like a horse, he could never gain weight. It was only when he was about 25 years old that someone considered he might have Celiac Disease, and testing revealed this to be the case. In his case, as in nearly all cases, the symptoms, antibodies, and intestinal damage disappeared within several months of gluten avoidance.

There is very limited published data currently that has investigated the effect of Celiac Disease upon fertility in women, but the preponderance of this data seems to support a negative effect. This is in line with what we know about the effect of other autoimmune disease upon fertility, especially that of autoimmune thyroiditis. There is a well-established link between the presence of anti-thyroid antibodies and recurrent miscarriage, and this association persists despite adequate thyroid hormone repletion. This suggests that an as yet to be understood facet of the immune flare-up itself is the actual culprit rather than the hormonal aberrations that can accompany it.

Celiac Disease and Gluten-free Diets

Although not all papers support a higher incidence of Celiac Disease in unexplained infertility patients, some have shown the incidence to be much higher, as high as 8% of those scrutinized. Several studies have reported that unexplained infertility can be successfully treated with a gluten-free diet, while others have shown that there are factors other than malabsorption of nutrients that result in infertility, delayed menarche and early menopause. In two large case-control studies examining women with Celiac Disease, researchers found that those women who were not on a gluten-free diet had their first menstruation up to 18 months later than those who were following the right diet. Moreover, nearly 39% of women not on the diet experienced bouts of amenorrhea, while only 9% of women who were on the gluten-free diet. Dramatically, those women who were not on the gluten-free diet were found to enter menopause up to 5 years earlier than women who avoided gluten. This suggests that the abnormalities stemming from Celiac Disease have both short and long term consequences, these being monthly ovulatory disturbances and a hastened diminution in the ovarian (or oocyte pool) lifespan, respectively.

Women diagnosed with Celiac Disease also seem to have a higher predilection towards developing endometriosis, another inflammatory condition in which an altered immune environment is present and perhaps causative.

Effects of Celiac Disease on Egg Quality

What is the effect of Celiac Disease on oocyte health and implantation potential? This would be best addressed by studying women with Celiac Disease who are undergoing IVF so their egg “quality”, embryo development, and implantation potential could be addressed. Unfortunately there are no such studies available. It would seem that if Celiac Disease can exert a negative effect on ovarian lifespan, i.e. oocyte count, then it would indeed be hurting egg quality and thereby diminish the number and competency of the eggs retrieved, but this requires large future studies to conclusively demonstrate.

Should women with infertility be screened for Celiac Disease? Researchers who have studied women with infertility have found that they test positive for celiac disease-related antibodies at a rate that is ten-fold higher than the normal population. In addition, women with Celiac Disease may not present classically with gastrointestinal symptoms; their symptoms can non-existent (about 4% of an asymptomatic adult population that has donated blood are positive for the Celiac antibodies) or even manifest as seemingly unrelated immunologically mediated illnesses such as dermatitis, alopecia, or apthous ulcers. Therefore it makes sense to consider screening infertile women for Celiac Disease as its presence is not infrequent, treatment is safe and simple, and its effects if left untreated can be subtle but profound.

Diagnosing Celiac Disease

The diagnosis of Celiac Disease begins by first performing blood tests that look for the presence of antibodies that develop in reaction to gluten such as tissue transglutaminase (tTG), anti-endomysial antibody (EMA), and deamidatedgliadin peptide (DGP). It is possible, however, to have positive results to these blood tests and to not have symptoms or tissue damage, and conversely also possible to have Celiac Disease but not have positive blood tests. For these reasons, most doctors also recommend endoscopy to assess for the physical damage caused by these antibodies, namely inflammation and “blunting” of the intestinal villi.

It is also important to note that gluten insensitivity occurs on somewhat of a spectrum, and there are those women with more mild gastrointestinal symptoms or physical findings, who, after ruling out other potential maladies, may also benefit from a trial of gluten avoidance.

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