Serum anti-mullerian hormone, sex hormone, and nutrient levels in reproductive age women with celiac disease

Abstract

Purpose

This study aimed to investigate the changes in serum Anti-Müllerian Hormone (AMH) levels, sex hormone levels, follicle-stimulating hormone (FSH)/luteinizing hormone (LH) ratio in patients with celiac disease (CeD), and their correlation with clinical characteristics and nutrient levels.

Methods

This cross-sectional study collected clinical and biochemical data from a total of 67 females diagnosed with CeD and 67 healthy females within the reproductive age range of 18–44 years. The study was conducted at a tertiary hospital between September 2016 and January 2024. Both groups underwent comprehensive clinical and laboratory assessments. Serum levels of AMH and sex hormones were quantified using chemiluminescence immunoassay, and their associations with CeD clinical features and nutrient levels were thoroughly analyzed.

Results

The study included 67 patients and 67 controls with a mean age of 36.7±7.6 years. No statistically significant differences were found between the two groups in mean age, BMI, FSH, LH, E₂, P levels, FSH/LH, menstrual irregularities, abortions history, parity, and gravidity (all P>0.05). However, AMH, T, FER, FA, Zn, and Se levels were significantly lower, and PRL levels were higher in the CeD group (all P<0.05). Spearman’s correlation analysis showed that AMH levels were negatively correlated with age, tTG level, disease duration, and Marsh grading (P<0.05).

Conclusions

This study highlights the association between impaired ovarian function in CeD patients and disease severity and nutrient levels. Early detection and intervention for ovarian function abnormalities are imperative to enhance fertility potential in CeD patients.

Introduction

Celiac disease (CeD) is a chronic autoimmune intestinal disorder triggered by the ingestion of gluten-containing grains such as wheat, barley, and rye in genetically predisposed individuals [1]. It is characterized by atrophy of the villi in the small intestinal mucosa, resulting in malabsorption of nutrients. Patients typically experience gastrointestinal symptoms such as diarrhea, abdominal pain, and bloating. Additionally, CeD can manifest in extra-intestinal symptoms, including anemia, dermatitis herpetiformis, osteoporosis, among other complications related to malabsorption, presenting a complex and varied clinical picture [2].

Recent studies have shown that CeD can affect reproductive health, with a reported prevalence of reproductive issues ranging from 1.10 to 1.54% [3, 4]. Women with CeD may experience symptoms such as hypogonadism, delayed puberty, amenorrhea, delayed onset of menstruation, infertility, recurrent miscarriages, and generally low fertility. Although the impact of CeD on female fertility is still debated, ovarian function is a crucial indicator of fertility in women of reproductive age. Previous research has demonstrated a strong connection between nutrient homeostasis and ovarian function, which is fundamental in the synthesis, secretion, and functioning of gonadal regulatory hormones [5, 6]. In women with CeD, nutrient malabsorption can lead to deficiencies of key nutrients vital for proper ovarian function, potentially resulting in reduced fertility. Nonetheless, the effects of nutrient malabsorption on fertility and pregnancy outcomes in CeD patients are inconsistent, suggesting that additional pathological factors may influence these reproductive challenges. Currently, the pathogenesis of CeD-associated reproductive disorders is thought to involve both immune and non-immune mechanisms, such as intestinal malabsorption, coagulation alterations, immune-mediated tissue damage, and endometrial inflammation [7]. Therefore, identifying serological markers that accurately assess ovarian function in CeD patients and understanding the factors influencing ovarian function are crucial for early detection and prevention of impaired fertility. Anti-Mullerian Hormone (AMH) levels reflect the total number of functional follicles, making it a valuable indicator for assessing ovarian function in women [8, 9].

This study aims to investigate the variations in serum reproductive hormone levels among newly diagnosed, untreated reproductive age women with CeD, explore their correlation with clinical characteristics and nutrient levels, and analyze ovarian function and its influencing factors to facilitate early detection of reduced fertility in female CeD patients.

Materials and methods

Research object

This individually matched, case-control cross-sectional study included 67 female patients with CeD and 67 healthy controls, all within the reproductive age of 18 to 44 years, from September 2016 to January 2024. Inclusion criteria were meticulously defined to ensure the presence of both ovaries in participants. The diagnosis of CeD was established through a comprehensive review of medical history, physical examinations, serological tests, and histological evaluation of biopsies obtained during upper-gastrointestinal endoscopy, adhering to the American College of Gastroenterology clinical guidelines [10]. Intestinal biopsies were graded according to the Marsh-Oberhuber classification: 0=normal mucosa, 1=increase in intraepithelial lymphocyte count, 2=crypt hyperplasia, 3a=partial villus atrophy, 3b=subtotal villus atrophy, and 3c=total villus atrophy [11]. Exclusion criteria were as follows: age less than 18 years old or more than 44 years old, diagnosed and treated with a gluten-free diet or a special diet (vegetarian, dairy-free diet), smoking, pregnancy, oral contraceptive taking history in the last 6 months, a gynecological and endocrine relevant surgical history, cytotoxic drugs history, pelvic radiotherapy history, diagnosed or potential polycystic ovary syndrome, autoimmune and inflammatory diseases history (rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, type 1 diabetes, thyroiditis, Sjögren’s Syndrome, Crohn’s disease, and ulcerative colitis), genetic diseases (William’s syndrome and Turner syndrome), hyperprolactinemia or other relevant diseases, severe somatic diseases such as liver, lung, or kidney diseases, diagnosed or potential malignancies or other gynecological organic diseases. The control group consists of individuals attending outpatient services and undergoing physical examinations during the same period, with the following inclusion criteria: women aged 18 to 44 years, presence of both ovaries; the exclusion criteria are the same as the CeD group. The control group is matched for age and body mass index (BMI) at a 1:1 ratio with the CeD patients.

Data collection

General and clinical data were collected from both groups. General Information included age, height, weight, BMI, and ethnicity. Health histories collected were smoking history, medication history, menstrual history, and history of previous diseases. Clinical information encompassed age at onset of CeD, duration of disease, gravidity, parity, number of abortions, and Marsh classification.

Venous blood samples were collected from each group during days 2–4 of their menstrual cycle after a 12-h fast. Serum samples were collected in anticoagulant-free vacuum tubes, gathering 5ml of blood, which was then allowed to sit at room temperature for 30–60 minutes or to be refrigerated at 2–8°C overnight. After centrifugation at a relative centrifugal force of 3000 rpm for 5 min, the upper layer of serum was separated and analyzed within 12 h of separation. All serum samples were immediately stored in polypropylene tubes at -80°C pending further analysis. The levels of serum E₂ (range: 11.20–225.00 pg/mL), FSH (range: 3.30–12.90 mIU/L), P (range: 0.29–1.55 ng/mL), T (range: 0.26–0.92 ng/mL), LH (range: 1.60–12.18 mIU/L), PRL (range: 3.27–26.81 ng/mL), folate (FA) (range: 5.21–20.00 ng/mL), ferritin (FER) (range: 13.00–232.00 ng/mL), zinc (Zn) (range: 65.65–126.72 μmol/L), and selenium (Se) (range: 100–340 μg/L) were determined using the chemiluminescence immunoassay method (Kangrun Biotech Co., Ltd., Guangzhou, China); serum AMH levels were measured with the ELISA kit (Kangrun Biotech Co., Ltd., Guangzhou, China). The detection range for AMH was 0.06 to 1.22 ng/mL; serum anti-tissue transglutaminase antibody (anti-tTG) -IgA levels were determined using the anti-tTG-IgA ELISA kit, and a detection value ≥20 CU is considered positive (Inova Diagnostics, San Diego, CA, USA). To minimize the potential for bias in the assays, all serum samples were processed on the same day, using the same measurement kits, and by the same operator, ensuring consistency and reliability in the results.

Endoscopy was performed on patients with positive serum specific antibodies using the upper gastrointestinal endoscopy (model Olympus Evis Lucera cv-290, Japan). Pathological tissue examinations were performed with biopsies taken from the bulb of the duodenum (at least two samples) and the descending part (at least four samples). The samples were preserved in a 5% solution of formalin and forwarded to the pathology department. Duodenal biopsies of patients with CeD were classified according to the Marsh-Oberhuber classification. The histopathological diagnosis was performed by three pathologists who had received professional training.

Statistical analysis

All statistical analysis in this study were performed using the SPSS Program, version 26.0 (Chicago, Illinois, USA). To assess the distribution of parameters, Kolmogorov-Smirnov test was applied. Quantitative data that conformed to the normal distribution are expressed as mean±standard deviation, the t test was used to compare two groups. When Quantitative data were not normally distributed, the comparison was made using the Mann-Whitney U test. Qualitative data are expressed as frequency (n) and percentage (%); the Chi-square (χ2) test was utilized to compare two groups. Additionally, Spearman’s rho correlation analysis was used for ordinal variables. The calculated P-values of less than 0.05 were considered statistically significant.

Results

Basic information and clinical characteristics of the study subjects

In our study, 67 patients with CeD and 67 control subjects were enrolled for the final analysis. The average duration of disease in the CeD group was 30.99 ± 54.45 months. Based on CeD histological Marsh classification, 17 (25.4%) were grade 2, 19 (28.4%) were grade 3a, 22 (32.8%) were grade 3b, and 9 (13.4%) were grade 3c. However, no statistically significant differences were observed between the two groups in terms of age at menarche, pregnancy, parity, history of menstrual irregularities, and history of miscarriage (all P>0.05). Additionally, the comparison of the ages and BMI between the two groups revealed no significant differences (P>0.05), indicating that the groups were comparable in this aspect. The baseline characteristics of both groups are detailed in Table 1.

Table 1.

Basic information and clinical characteristics of the study subjects

Variables	CeD (n=67)	Control (n=67)	t/Z/χ2-value	P-value
Age / years	37.2±6.4	36.8±3.8	-0.09	0.93
BMI / (kg/m2)	20.07 (19.34, 23.24)	22.6 (20.06, 24.63)	-1.42	0.16
Age of menarche / years	13 (13, 14.5)	14 (13, 15)	-0.38	0.83
Parity / n	1 (0, 2)	1 (0, 2)	-0.08	0.94
Gravidity/ n	1 (0, 2)	1 (0, 2)	-1.06	0.29
History of menstrual irregularities / n (%)			-1.81	0.07
yes	58 (43.3%)	64 (47.8%)
no	9 (6.7%)	3 (2.2%)
History of abortion / n (%)			-0.07	0.95
yes	12(13.4%)	6(8.9%)
no	55(47.8%)	50(74.6%)
Histology (Marsh degree) n (%)			-10.64	<0.001
Marsh 0	0	60(89.6%)
Marsh 1	0	2(3.0%)
Marsh 2	17(25.4%)	2(3.0%)
Marsh 3a	19(28.4%)	2(3.0%)
Marsh 3b	22(32.8%)	1(1.5%)
Marsh 3c	9(13.4%)	0

BMI body mass index

Comparison of laboratory indexes of the groups

Serum AMH, T levels in the CeD group were significantly lower than those in the control group, while PRL levels were significantly higher (all P<0.05). Meanwhile, levels of FA, FER, Zn, and Se were significantly lower in the CeD group compared to controls. In contrast, no statistically significant differences were found in serum FSH, LH, E₂, P levels, and the FSH/LH ratio between the patient and control groups (all P>0.05). The laboratory results of both groups are detailed in Table 2.

Table 2.

Comparison of AMH, sex hormone and nutrient levels of the groups

Variables	CeD (n=67)	Control (n=67)	Z-value	P-value
AMH / ng·mL-1	1.33(0.26, 2.3)	3.24(1.13, 4.095)	-3.702	<0.001
E2 / pg·ml-1	23.94(7.67, 63.98)	23.71(8.342, 120.58)	-0.299	0.767
FSH / mIU·L-1	12.31(6.35, 18.14)	7.234(4.46, 14.06)	-1.796	0.073
LH / mIU·L-1	8.57(4.89, 15)	8.856(5.006, 22.20)	-0.424	0.674
PRL / ng·mL-1	14.19(7.995, 21.09)	8.689(6.815, 12.532)	-4.151	<0.001
P / ng·mL-1	0.47(0.37, 0.61)	0.515(0.43, 0.57)	-0.891	0.374
T / ng·mL-1	0.36(0.18, 0.51)	0.55(0.38, 0.81)	-4.456	<0.001
FSH / LH	1.15(0.61, 1.80)	0.99(0.54, 1.33)	-1.873	0.061
FER / ng·mL-1	11.54(6.19, 46.31)	33.99(9.13, 119.63)	-2.714	0.007
FA / ng·mL-1	2.88(1.73, 5.30)	4.45(2.56, 6.47)	-2.922	0.004
Zn / μmol·L-1	82.75(75.66, 87.58)	89.8(80.32, 93.37)	-2.637	0.008
Se /μg·L-1	116.06(107.68, 129.43)	126(110, 139)	-2.228	0.026

AMH anti-Mullerian hormone, E₂ estradiol, FSH follicle-stimulating hormone, LH luteinizing hormone, PRL prolactin, P progesterone, T testosterone, FER ferritin, FA folate acid, Zn zinc, Se selenium

Correlation analysis of serum reproductive hormone levels with clinical characteristics and nutrient levels

The results indicated a negative correlation between AMH levels and age, disease duration, Marsh classification grade, and tTG levels (P<0.05). Additionally, the FSH/LH ratio was negatively correlated with FA and Zn levels (P<0.05). Conversely, this ratio was positively correlated with the age, tTG levels, and FER levels (all P<0.05). These results are shown in Table 3.

Table 3.

Correlation of serum AMH with disease-related indicators and nutrient levels

Variables	AMH / ng·mL-1		FSH / LH
	r-value	P-value	r-value	P-value
Age / years	-0.550	<0.001	0.469	<0.001
Disease duration/ months	-0.332	<0.001	0.151	0.061
Marsh grade	-0.3456	<0.001	0.007	0.934
anti-tTG / CU	-0.249	0.004	0.240	0.003
BMI / (kg/m2)	0.2	0.209	0.025	0.758
FER / ng·mL-1	-0.163	0.06	0.343	<0.001
FA / ng·mL-1	0.04	0.64	-0.185	0.021
Zn / μmol·L-1	0.156	0.09	-0.253	0.002
Se /μg·L-1	0.135	0.14	-0.09	0.337

AMH anti-Mullerian hormone, BMI body mass index, anti-tTG anti-tissue transglutaminase antibody, FSH follicle-stimulating hormone, LH luteinizing hormone, FER ferritin, FA folate acid, Zn zinc, Se selenium

Discussion

Celiac Disease (CeD) is an autoimmune disorder triggered by gluten consumption in genetically susceptible individuals. Its prevalence varies globally, with notable implications for reproductive health, particularly among women [12, 13]. Although the association of CeD with adverse obstetric and gynecological outcomes is recognized, the underlying mechanisms and correlations with reproductive hormone levels, disease severity, and nutrient status remain poorly understood [14]. Our study assessed serum reproductive hormone levels in CeD patients and healthy women of reproductive age using AMH, and other serum sex hormone levels (E₂, FSH, LH, T, P, and PRL). Our findings indicate that the serum AMH levels in CeD patients were significantly lower than the control group, suggesting a potential decline in ovarian function among the women with CeD. Meanwhile, the present study also found that serum T levels were significantly lower and PRL levels were higher in the CeD group compared to the control group. Serum levels of FER, FA, Zn, and Se were also statistically lower in the CeD group. Moreover, we observed that AMH level and ovarian reserve decreased with increasing disease duration, higher Marsh stage, and elevated serum tTG levels in CeD patients. Additionally, the FSH/LH ratio was negatively correlated with FA and Zn levels, while positively correlated with the age, serum tTG levels, and FER levels.

According to research, 30% of individuals with early-onset ovarian insufficiency also have an autoimmune disease [15–17]. Mont'Alverne showed that AMH levels and ovarian reserve were decreased in women with Behcet’s disease and that higher disease activity was substantially related to a decline in ovarian reserve [18]. Similarly, Cakmak et al. found that AMH levels and ovarian reserve in CeD patients decreased as disease duration increased [19]. These findings align closely with those of our study. In terms of the immune-related pathogenic mechanisms linking CeD with decreased ovarian function, it is widely believed that gluten proteins may trigger some autoimmune antibodies, such as tTG-IgA and anti-myocardial endothelial antibodies. These can induce a Th1-type immune response, characterized by macrophage activation and the involvement of CD8+ T-cells, interferon-γ (IFN- γ), and CD4+ T-cells[20]. Furthermore, gliadin can activate peripheral blood T cells, as evidenced by their proliferation, activation marker expression, and secretion of cytokines such as IFN-γ and interleukin-2, which may affect the intrauterine environment [21]. In fact, abnormal expression of angiogenic, pro-inflammatory, and anti-inflammatory cytokines during the implantation window is a crucial factor that negatively affects endometrial development, as indicated by the inadequate expression of various endometrial receptivity markers [22]. A study found that the rate of miscarriage in patients with CeD not treated with a gluten-free diet was six times higher than in treated patients, and the relative risk of miscarriage was 8.9 times higher than in treated patients [23]. An in vitro study showed that tTG-IgA antibodies could bind directly to uterine trophoblast cells and affect embryo implantation by decreasing trophoblast invasiveness through apoptotic damage [24]. In addition, an in vivo mouse model experiment confirmed the presence of tTG-IgA antibodies in endometrial cells, which reduced the proliferation and migration of trophoblast cells, increased apoptotic levels, and interfered with the clearance of apoptotic bodies through interactions involving the lacto lipoglobulin EGF factor. This interaction negatively impacts endometrial angiogenesis, potentially leading to intrauterine growth retardation, infertility, and early abortion [25]. In our study, we detected an inverse correlation between tTG levels and AMH levels in patients with CeD. Given that tTG can be expressed in endometrial cells, mesenchyme and placental trophoblast cells, an in vitro study concluded that anti-tTG antibodies may cause trophoblast damage and disrupt the phagocytosis process of apoptotic vesicles, thereby promoting a pro-inflammatory microenvironment in the uterus [26]. This suggests that tTG-IgA antibody may be a target for autoantibodies in pregnant women with CeD.

Studies have demonstrated that low T levels are prevalent in patients with endometriosis, are associated with the apoptosis of granulosa cells, which contributes to a reduced ovarian reserve [27]. It has been found that particularly low T levels, specifically below 1.115 nmol/L, negatively impact the rate of embryo implantation. Significant differences in implantation and pregnancy rates have been observed when subjects are categorized by basal T levels [28]. Our findings corroborate these studies, as we observed significantly lower serum T levels in the CeD group compared to the control group. Previous studies demonstrated that T facilitates follicular recruitment [29], promotes follicular growth and development [30], and increases the expression of insulin-like growth factor 1 (IGF-1) in primate ovaries, crucial for regulating follicular development [30]. It also heightens follicular responsiveness to FSH through androgen receptors [31, 32]. In vitro studies also indicate that while T depletion leads to apoptosis in granulosa cells, this process is inhibited by the administration of T [27]. Meanwhile, we found that serum PRL levels were significantly higher in the CeD group compared to the control group. In both animals and humans, excessive secretion of PRL suppresses the release of gonadotropin-releasing hormone (GnRH) and reduces the GnRH receptor's responsiveness, leading to lower LH pulse frequency and amplitude [33, 34]. As a result, elevated PRL levels in the blood and ovarian tissue can result in infertility due to anovulation or rare ovulation (oligo-ovulation) caused by hormonal imbalances [35, 36]. Clinical evidence strongly suggests a link between hyperprolactinemia and infertility, primarily through ovulatory disruptions stemming from the suppression of the hypothalamic-pituitary-ovarian (HPO) axis by blocking pulsatile GnRH secretion [37]. These findings suggest that low T levels and elevated PRL levels in female patients of reproductive age with CeD may contribute to obstetric adverse events such as recurrent miscarriages by affecting granulosa cell apoptosis, ovarian ovulation, decreased estrogenic activity, and other processes. Moreover, while FSH acts synergistically with LH to promote estrogen secretion, follicular maturation, and ovulation, it was noted that a high FSH/LH ratio, even when basal FSH levels are normal, could indicate a decline in ovarian function [38]. Although the FSH/LH ratio in the CeD group was higher than in the control group, the difference was not statistically significant, possibly due to the relatively small sample size of this study. Furthermore, the FSH/LH ratio was negatively correlated with FA and Zn levels, and positively correlated with age, tTG levels, and FER levels. It has been suggested that serum AMH can be an earlier and more accurate predictor of changes in ovarian function compared to early follicular phase FSH, INHB, and E₂ [9, 39]. Our study’s findings align with this, confirming that changes in serum AMH levels precede those in FSH and E₂, suggesting AMH is a sensitive indicator for assessing ovarian function in women with CeD.

Nutrient deficiency, frequently found in active CeD, have been identified as the primary contributors to gynecological disorders and adverse pregnancy outcomes linked to the condition. Typically, the altered villous architecture in the small intestine leads to malabsorption, which may cause mild hematologic irregularities, anemia, and specific nutrient deficiency like Zn, Se, and FA [5, 40–42], which play significant roles in pregnancy and fetal development. In the present study, FA levels were found to be significantly lower in the CeD group compared to the control group. Chavarro et al. [43] showed that daily intake of 700 μg of FA reduces the risk of ovulation disorders by 40–50%. Women from the highest tertile of folate consumption (270.6 μg/d) had 64% lower chances of developing anovulation compared to women from the lowest tertile (100.9 μg/d). The mechanism through which FA exerts a beneficial effect on female fertility primarily stem from its role in reducing oxidative stress and diminishing proinflammatory cytokine production, crucial for ovulation and oocyte development. Another possible mechanism through which FA influences the course of ovulation is related to the lower response of ovaries to FSH stimulation in cases of low FA concentrations in the blood serum [44]. Zn is vital for human health, participating in many enzymatic processes, biochemical functions, and immune system responses [45]. Two separate studies found a high zinc deficiency rate of 71,6% (<10,7 mmol/l) in 134 and 109 children with CeD in India and Turkey respectively [46, 47]. In our study, we also found that Zn level was significantly lower in the CeD group compared to the control group. Zn deficiency has been shown to impair synthesis and secretion of LH and FSH, potentially causing abnormalities in the ovarian axis, secondary amenorrhea, spontaneous abortions, and pre-eclampsia [48]. Se is an essential trace element of importance to human biology and health [49]. Previous studies have reported that Se deficiency was common in CeD patients [50]. In our study, serum Se levels were significantly lower in the CeD group compared to the control group. Numerous reports implicate Se deficiency in several reproductive and obstetric complications including male and female infertility, miscarriage, and obstetric cholestasis. Several studies indicated a positive correlation between serum Se and antioxidant concentration in the follicular fluid, and improvements in oocyte production and follicle number [48, 49].

As regards minerals, iron seems the most important. Ferritin (FER), an important iron storage protein in the body, plays a crucial role not just in iron metabolism but also in the oxidative phosphorylation process of cells [51]. Deficiencies in ferritin are frequently observed in women of reproductive age due to menstruation-related losses. A cohort study conducted over a decade found that both FER and iron deficiencies were most prevalent among children with CeD, with average frequencies of 21.9% and 33%, respectively, showing a decreasing trend over time [52]. Meanwhile, our study also suggested that serum FER levels were lower in the CeD group than in the control group. Granulosa (or follicular) cells surround the mature egg during the ovarian cycle, secrete reproductive hormones, and contribute to forming the corpus luteum. Proliferating granulosa cells require iron to function, and transferrin rises in concentration in follicular fluid as the follicle develops [53]. Despite the localized production of transferrin within follicular cells, transferrin concentrations in follicular fluid correlates with serum levels, suggesting that global iron status and iron-binding capacity contribute more to total concentrations than does local transferrin synthesis within the ovary [54]. This suggests that iron status may play a role in egg maturation, thereby impacting the overall fecundity of women with CeD. To further elucidate the association between clinical features, nutrient levels, and reproductive hormone levels in women of reproductive age with CeD, Spearman’s correlation analysis was performed. The analysis revealed that AMH levels in the CeD group were negatively correlated with disease duration, Marsh grading, and tTG levels. Additionally, the FSH/LH ratio was negatively correlated with FA and Zn levels, while positively correlated with the tTG levels and FER levels. This finding confirms that the decline in ovarian function in CeD patients is associated with disease progression and nutrient deficits, becoming more pronounced with increasing tTG levels, disease duration and Marsh grading. In conclusion, abnormalities in nutrient levels are associated with the pathophysiological basis of decreased ovarian function in CeD. Further studies are needed to determine the role and mechanisms of nutrient levels in decreased ovarian function in patients with CeD.

Our study’s cross-sectional design and relatively small sample size limit the ability to draw definitive conclusions about the etiology of CeD and its impact on ovarian function. Future large-scale prospective cohort studies are warranted to further elucidate these relationships. Additionally, exploring the molecular mechanisms underlying reproductive dysfunction associated with CeD and evaluating the efficacy of targeted interventions, such as gluten-free diets and nutritional supplementation, could provide valuable insights into improving reproductive outcomes for CeD patients.

Conclusion

In summary, ovarian function is reduced in CeD women of reproductive age. AMH can predict ovarian function more sensitively, offering valuable insights for clinical fertility treatments. Meanwhile, serum ferritin, folic acid, and zinc and selenium levels are generally lower in CeD patients than in normal women of reproductive age, so assessment of serum nutrients level can be considered a routine part of examination of CeD patients. There is no definitive method to improve ovarian function. It is recommended that CeD women of reproductive age undergo ovarian function assessment during early diagnosis and pay attention to nutrient screening and appropriate supplementation before and during early pregnancy to reduce the occurrence of adverse reproductive outcomes.

Author contribution

Ailifeire Tuersuntayi: experimental design, data collection and collation, statistical analysis, paper writing; Tian Shi: experimental design, article content guidance, data collection; Beiyao Gao: statistical analysis, data collection; Yan FENG: experimental design, data collection; Ting LI: experimental design, data collection; Wenjia HUI: experimental design, data collection; Shenglong XUE: statistical analysis, data collection; Feng Gao: experimental design, trial process supervision and quality control.

Funding

This work was supported by the National Natural Science Foundation of China (82260116).

Declarations

Ethical approval

Legal representatives of patients signed an informed consent form for inclusion in the study. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Ethics Committee of the People's Hospital of Xinjiang Uygur Autonomous Region (KY2023060173).

Consent to participate

Informed consent was obtained from all individual participants included in the study.

The manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously and is not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed.

Conflict of interest

The authors declare no competing interests.