Recurrent miscarriages and celiac disease: case report

¹Department of Gynecology and Obstetrics, Maternity Souissi, University Hospital Center Ibn Sina, University Mohammed V, Rabat, Morocco

^&Corresponding author
Chourouk Elkarkri, Department of Gynecology and Obstetrics, Maternity Souissi, University Hospital Center Ibn Sina, University Mohammed V, Rabat, Morocco

Introduction    

Celiac disease is a common immune-based disease that often affects the small intestine, which is also known as gluten sensitive enteropathy. It affects genetically predisposed patients (HLA DQ2/DQ8). Its prevalence is estimated at around 1% of the general population. It is associated with a high risk of fertility problems and complications during pregnancy, including recurrent miscarriages. We report the case of a patient with several miscarriages whose etiology has finally been linked to celiac disease.

Patient and observation     

A 34-year-old patient with no significant pathological history, blood grouping B+, nulliparous, who consults for repeated early abortions without other associated clinical anomalies. Clinical evaluation for recognized causes of recurrent pregnancy loss (RPL) was performed at the discretion of the physician and included a hysterosalpingography, a spermogram, infectious assessment, the search for thrombophilia (circulating anticoagulants, anti-thrombin deficiency, anti-native DNA antibody, anti-nuclear antibody, protein C deficit, protein S deficit, search for antiphospholipid antibody syndrome, search for hyperhomocysteinemia), endocrinopathy (search for diabetes, thyroid check-up), karyotypic abnormalities and everything was negative. Furthermore, there were no clinical digestive abnormalities or biological malabsorption syndrome. The search for anti-transglutaminase antibodies and anti-endomysium IgA antibodies was positive at a very high rate. The jejunal biopsy showed the presence of subtotal villous atrophy with cryptic hyperplasia and 45% intraepithelial lymphocytosis compatible with celiac disease. The patient has since started to follow the gluten-free diet. 8 months later, the patient had a pregnancy, she continued her diet throughout the pregnancy. The pregnancy was uneventful and she gave birth to a newborn baby in good condition with normal birthweight.

Discussion     

In 1970, Moriss et al were the first to report the case of three infertile women in whom the discovery and treatment of celiac disease led to normal pregnancies and childbirth [1-3]. Reproductive disorders and pregnancy complications are frequent symptoms of the celiac disease which rarely make seek this pathology [2,4,5]. Indeed, 19.4% of women with this disease have amenorrhea but also, oligo-hypo-menorrhea, dysmenorrhea and metrorrhagia [6]. There is also a strong correlation between celiac disease and early miscarriages, threat of abortion, preeclampsia and intrauterine growth restriction (IUGR) [7]. The pathogenesis of all these gyneco-obstetric problems is not completely clear. However, two main hypotheses can be made, autoimmune origin and malnutrition [8]. As part of the research into the physiolopathology of these disorders, some authors are interested in vitamins and trace elements such as folic acid, selenium and zinc. These are essential nutrients for a woman's reproductive function, and are poorly absorbed in celiac disease [2]. These authors have shown, among other things, that the zinc deficiency causes a disorder in the secretion and the action of LH and that of FSH which disturbs the ovarian functioning. This may partly explain the problems of infertility and early miscarriages caused by celiac disease. Based on this physiopathogenic hypothesis, some authors have managed to restore good reproductive function by correcting these deficits alongside a gluten-free diet in infertile women with celiac disease [9]. However, other studies have shown that simply correcting this nutrient deficit, without combining a gluten-free diet, is not enough to achieve pregnancies. The authors concluded that the infertility problem associated with celiac disease is more complex than a simple deficiency in vitamins and trace elements [10,11].

The other physiopathological path explored to try to understand the mechanism of these disturbances of the genital life associated with celiac disease is that of autoimmunity. In this sense, some authors have compared the serum of healthy women to those of women with active celiac disease with gyneco-obstetrical manifestations. They have shown that woman with CD often show increased levels of serum auto-antibodies, including anti-transglutamines and anti-thyroid antibodies [12]. The gluten-free diet significantly reduces the risk of developing recurrent pregnancy loss. In a prospective study, 13 women with CD who had 22 RPL were followed for ten years after their gluten-free diet, six of them carried pregnancies to term without any RPL [12]. A before-after type study comparing 12 untreated pregnant women with celiac disease to 12 treated with a gluten-free diet found a risk of RPL reduced by 9.18 (95% CI = 1.05-79.9) (117). The efficiency of the gluten-free diet therefore underlines the importance of detection for celiac disease in women prone to spontaneous recurrent miscarriage, even asymptomatic. This clinical case, illustrates the association between celiac disease and recurrent miscarriages. It also clearly shows the clinician´s difficulty in relating the symptom “abortive disease” to this pathology. Finally, the case we present supports the opinion of many authors who consider that untreated celiac disease is more likely to provide these complications [13]. Indeed, it has been shown a correlation between the higher rate of antibodies in the case of active celiac disease and the clinical gyneco-obstetrical manifestations [14,15].

Conclusion     

Fertility abnormalities and gyneco-obstetric disorders are part of the extra-digestive manifestations of celiac disease. Its research is therefore necessary in the etiological assessment of recurrent miscarriages.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

CE wrote the paper. SA, AN, NZ, AL, AB contributed by correction of this paper. All the authors read and approved the manuscript.

References