Celiac disease: a hidden cause of infertility and pregnancy complications?

Lopes, Ana Clara Abdo; Sepulveda, Grazielle Malca; Dall’Oglio, Nicole; Cardoso, Daniela Medeiros Milhomem; Castro, Jorge Marcelo Mura; Campos, Sandra Martin Siqueira

doi:10.55684/2026.84.pt.e00011

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Review Article • BioSCI. (Curitiba) 84 • 2026 • https://doi.org/10.55684/2026.84.pt.e00011 linkcopy

Celiac disease: a hidden cause of infertility and pregnancy complications?

Authorship SCIMAGO INSTITUTIONS RANKINGS

Introduction: Celiac disease is a chronic and autoimmune enteropathy that manifests itself in individuals who are genetically susceptible to the action of environmental factors, in which the main one is gluten. In addition to symptoms such as chronic diarrhea and abdominal pain, the disease is also associated with extraintestinal symptoms, such as infertility and gestational impacts.

Objectives: To synthesize the main aspects of celiac disease and its implications for female fertility and the gestational period.

Method: Review made with material and analysis selected from searches on the virtual platforms SciELO, Google Scholar and PubMed, through the descriptors: "celiac disease", "gestational period" and "infertility" and their correspondents in English and Spanish, and in the book Treaty of Gastroenterology from Undergraduate to Graduate Studies (2nd edition).

Results: A total of 24 articles were included.

Conclusion: Celiac disease has a significant impact on fertility and pregnancy; however, the effects can be reduced or even eradicated with the implementation of a gluten-free diet. However, the greatest challenge persists in the identification and diagnosis of celiac women who are of childbearing age, due to the lack of clinical specificity, genetic variability, and the extent of environmental factors that impact the disease.

KEYWORDS:
Celiac disease; Pregnancy; Infertility

Author(s) and year	Type of study	Objectives	Method	Conclusion
Lindfors et al.¹ (2019)	Narrative review	Synthesize the main aspects of celiac disease, including epidemiology, pathophysiology, clinical manifestations, diagnosis, treatment, and impact on quality of life.	Broad review of the scientific literature on celiac disease, with an integrated approach to immunological, genetic, environmental, diagnostic and therapeutic mechanisms.	Celiac disease is immune-mediated enteropathy triggered by gluten in genetically predisposed individuals, with intestinal and extraintestinal manifestations. The diagnosis depends on the association between clinical, serology and histology, with a gluten-free diet being the established treatment.
Lebwohl et al.² (2018)	Narrative review	Review epidemiology, pathogenesis, clinical presentation, diagnosis, complications, and management of celiac disease.	Critical review of the literature in the format of a clinical update article published in the Lancet.	Celiac disease affects about 1% of the population in many countries, with increasing incidence and varied clinical manifestations. Early recognition and adherence to the gluten-free diet are key to reducing complications.
Fasano and Catassi.³ (2012)	Clinical review	To present a practical approach to the diagnosis, treatment and follow-up of patients with celiac disease.	Evidence-based clinical review, with discussion of clinical presentation, serology, intestinal biopsy, and dietary management.	Celiac disease has a broad clinical spectrum and may course with gastrointestinal or extraintestinal symptoms. The diagnosis requires adequate investigation even during gluten consumption, and the treatment consists of a gluten-free diet.
Kotze⁴ (2004)	Descriptive observational study	OBJECTIVE: To evaluate gynecological and obstetric changes in Brazilian patients with celiac disease, relating them to nutritional status and adherence to the gluten-free diet.	Analysis of adult celiac patients according to nutritional status and evaluation of children/adolescents according to adherence to the gluten-free diet.	Patients with celiac disease had gynecological and obstetric alterations, such as late menarche, amenorrhea, and miscarriages. Severity was related to poorer nutritional status and non-adherence to the gluten-free diet.
Di Simone et al.⁵ (2021)	Narrative review	Update pathogenic mechanisms that relate celiac disease to reproductive failure, infertility, and obstetric complications.	Review of evidence on immunological, inflammatory, nutritional, and placental mechanisms involved in the association between celiac disease and reproductive failure.	Celiac disease can compromise fertility and pregnancy by nutritional and immunological mechanisms, especially by the action of anti-tissue transglutaminase autoantibodies on the endometrium, trophoblast, and placenta.
Casella et al.⁶ (2016)	Narrative review	To review the contribution of celiac disease to gynecological and obstetric changes.	Review of the literature on celiac disease in women of childbearing age, infertility, miscarriages, fetal growth and gestational outcomes.	Celiac disease is more prevalent in women during the fertile period and should be investigated in cases of infertility, recurrent miscarriages, and unfavorable obstetric outcomes without a defined cause.
Ludvigsson and Murray.⁷ (2019)	Epidemiological review	Describe the epidemiology of celiac disease, including prevalence, incidence, population factors and geographic distribution, prevalence, incidence, population factors, and geographic distribution.	Review of epidemiological studies on celiac disease in different populations, with analysis of variations by age, sex, region, and diagnostic methods.	Celiac disease is a common chronic inflammatory condition of the small intestine, triggered by gluten in genetically susceptible individuals, with relevant global prevalence and variation according to population and diagnostic strategy.
Marinho et al.⁸ (2016)	Textbook	Present clinical, pathophysiological, diagnostic and therapeutic foundations of gastroenterological diseases, including celiac disease.	Gastroenterology textbook chapter aimed at undergraduate and graduate studies, with didactic synthesis of consolidated knowledge.	The treatise provides a conceptual basis for understanding celiac disease, including pathophysiology, clinical manifestations, diagnosis by serology and biopsy, and treatment with a gluten-free diet.
Pereira.⁹ (2020)	Narrative literature review	Analyze the pathophysiology of celiac disease, elucidate its diagnostic methods, and highlight the importance of proper food labeling.	Narrative review prepared between July and December 2020, with a search in MEDLINE, SciELO, PubMed, Virtual Health Library and books, using descriptors related to celiac disease, treatment, signs, symptoms and diagnosis.	Celiac disease results from an inflammatory response to gluten in genetically predisposed individuals, leading to villous atrophy and malabsorption. Diagnosis is based on clinical evaluation, serological markers and endoscopic biopsy, with a gluten-free diet being the only proven treatment.
Iversen and Sollid.¹⁰ (2022/2023)	Narrative review	Describe the immunobiological and pathogenic mechanisms of celiac disease.	Review of evidence on HLA-DQ2/DQ8, gluten peptide presentation, T lymphocytes, transglutaminase 2, and autoantibodies.	Celiac disease has a well-characterized pathophysiology, involving immune response to gluten, HLA predisposition, and production of autoantibodies against transglutaminase 2.
Nieto et al.¹¹ (2020)	Narrative review	To review causes, pathology, and nutritional assessment of the gluten-free diet in celiac disease.	Literature review on pathophysiology, nutritional deficiencies, and gluten-free diet composition.	Celiac patients may have nutritional deficiencies before and during the gluten-free diet, requiring adequate nutritional monitoring.
Caio et al.¹² (2019)	Comprehensive narrative review	To update knowledge on the pathophysiology, diagnosis, clinical manifestations, treatment and therapeutic perspectives of celiac disease.	Comprehensive review of the scientific literature on different aspects of celiac disease.	Celiac disease remains a challenging condition, with diverse phenotypes and the need for a better understanding of potential, seronegative, and refractory forms.
Gujral et al.¹³ (2012)	Narrative review	To review the prevalence, diagnosis, pathogenesis, and treatment of celiac disease.	Review of studies on genetic, environmental, immunological and therapeutic factors.	Celiac disease results from the interaction between gluten, genetic predisposition, and immune response; Its prevalence is estimated to be about 0.5% to 1%, and the treatment is a gluten-free diet.
Husby et al.¹³ (2020)	Clinical guideline / guideline	Update the ESPGHAN recommendations for diagnosis of celiac disease in children and adolescents.	Evidence review and expert consensus for diagnostic criteria, including serology, biopsy, and biopsy-free approach in selected cases.	Pediatric diagnosis should use specific serology, especially anti-TG2 IgA and total IgA; In specific situations, it can be diagnosed without biopsy according to established criteria.
Rubin and Crowe.¹⁴ (2020)	Clinical review	Present practical updates on the diagnosis, clinical manifestations, and management of celiac disease.	Clinical review in didactic format, focused on medical practice.	Recognition of intestinal and extraintestinal manifestations is essential for timely diagnosis and for the institution of a gluten-free diet.
Oberhuber et al.¹⁵ (1999)	Histopathological review / classification proposal	To review histological findings of celiac disease and to propose standardization of the anatomopathological report.	Review of histological changes in celiac disease based on Marsh’s classification.	Histopathological standardization allows the classification of lesions of the intestinal mucosa, including increased intraepithelial lymphocytes, crypt hyperplasia, and villous atrophy.
Harris et al.¹⁷ (2012)	Narrative review	To review the clinical, endoscopic and histopathological aspects of celiac disease.	Review of the literature on clinical manifestations, endoscopic diagnosis, and histological alterations of CD.	The diagnosis of CD requires integration between clinical, serological, endoscopic and histopathological findings for greater diagnostic accuracy.
Skoracka et al.¹⁸ (2021)	Narrative review	To assess the influence of nutrition on female fertility.	Review of studies on female fertility and associated nutritional factors.	Nutritional deficiencies can compromise female fertility, and adequate micronutrient intake is essential for reproductive function.
Freeman.¹⁹ (2010)	Narrative review	To analyze reproductive changes associated with celiac disease.	Review of the literature on fertility, pregnancy and obstetric complications in celiac women.	Untreated CD is associated with infertility, recurrent miscarriages, and adverse pregnancy outcomes, and can be reversed with a gluten-free diet.
Tonai et al.²⁰ (2020)	Experimental study in animals	To investigate the effects of iron deficiency on female fertility.	Experimental model in mice subjected to iron deficiency, with evaluation of follicular development.	Iron deficiency impairs follicular development and reduces female fertility.
Sóñora et al.²¹ (2014)	In vitro experimental study	To evaluate the effect of anti-tissue transglutaminase antibodies on human trophoblastic cells.	Culture of human trophoblastic cells exposed to anti-tTG antibodies.	Anti-tTG antibodies reduce proliferation and trophoblastic migration and increase apoptosis, contributing to gestational complications in CD.
Butler et al.²² (2011)	Narrative review	To review the relationship between celiac disease and pregnancy outcomes.	Review of observational studies on pregnancy in women with CD.	Women with undiagnosed CD are at increased risk of miscarriage, prematurity, and fetal growth restriction
Boers et al.²³ (2019)	Case report	OBJECTIVE: To describe the gestational course in a patient with celiac disease.	Clinical report and brief review of the literature.	Early diagnosis and adherence to the gluten-free diet contribute to better maternal and fetal outcomes.
Tack et al.²⁴ (2010)	Narrative review	To review the epidemiology, clinical manifestations, and treatment of celiac disease.	Comprehensive review of the literature.	CD has a broad clinical spectrum and treatment based on a gluten-free diet remains the main therapeutic strategy.

TYPE	FEATURES
TYPE 0	Normal mucosa
TYPE I	Increased number of ISL and infiltrative lesion
TYPE II	Crypt hyperplasia and increase in the number of ILLs with hyperplastic lesions
TYPE III	Villous atrophy and crypt hyperplasia with destructive injury	III a - Partial III b - Subtotal III c - Total

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[TFN2n] Adapted from Harris et al.¹⁷