The risk of infertility and dietary inflammatory index, a case-control study in Iran.

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Abstract

BackgroundInfertility is defined as the inability to conceive after 12 months of unprotected sexual intercourse and affects 15% of couples globally. Diet influences inflammatory factors, potentially affecting ovarian reserve and thus may have a role in infertility. The present study aimed to assess the association between infertility and the Dietary Inflammatory Index (DII).MethodsThis case-control study was conducted at Al-Zahra Hospital, Rasht, Iran, on 123 infertile women and 123 healthy participants. Food intake was assessed using a validated FFQ. The DII was calculated, and logistic regression analysis was performed to assess the relationship between DII and ovarian reserve.ResultsIndividuals with a higher DII had a greater risk of infertility compared to those with a lower DII (OR = 2.08, CI 95% = 1.024-4.248, P = 0.043) after adjustment for age, weight, body mass index, intake of anti-inflammatory supplements, suffering from underlying disease, smoking, alcohol consumption, and physical activity. Further adjustments for infertility duration, thyroid disorders, FSH, LH, and number of fertilities did not change the results.ConclusionThe dietary inflammatory index (DII) was positively associated with infertility. A higher inflammatory diet may increase the likelihood of infertility. Further research is needed to fully understand this connection.
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What

A pro-inflammatory diet, as indicated by a higher Dietary Inflammatory Index (DII), is associated with an increased risk of infertility in women, highlighting the potential role of dietary patterns in reproductive health.

Methods

This case–control study was conducted between 2023 and 2024 among infertile individuals attending the infertility clinic at Al-Zahra Hospital in Rasht, Iran. Participants aged 18–40 years with either primary or secondary infertility who provided informed written consent were included. The infertile group consisted of women with an anti-Müllerian hormone (AMH) < 1.1, diagnosed within the last 3 months, and exhibiting no signs of ovulatory, tubal, or male factor infertility. The healthy comparison group had an AMH level between 1.1 and 3.5, normal ovulation, and no history of tubal or male factor infertility. The exclusion criteria included taking medications that induce inflammation or impair nutrient absorption, illnesses that affect the intake and absorption of dietary nutrients, the use of anti-inflammatory supplements, and a history of endometriosis, chemotherapy, radiotherapy, and ovarian surgery. Sampling was done as consecutive incident cases. Following informed consent, 123 participants with reduced ovarian reserve were enrolled in the infertile group, and 123 participants of the same age with normal ovarian reserve were included in the healthy group. Reduced ovarian reserve was defined as AMH < 1.1 based on the Bologna criteria. The sample size was calculated using OPENEPI online software ( 12 ) and the odds ratio obtained in a previous similar study ( 13 ). Dietary intake was evaluated using a validated semi-quantitative Food Frequency Questionnaire (FFQ) tailored for the Iranian population which consists of 168 common food items and mixed dishes in Iran ( 14 ). The frequency of the consumption of food items over the past year was examined through a face-to-face interview. Household measures were taken into account for portion sizes and then were converted to grams. The food composition table (FCT) of the United States Department of Agriculture (USDA) was used to evaluate the intake of energy and nutrients. The Iranian FCT was considered for local foods that did not exist in the FCT. Data collected from the FFQ were processed using Nutritionist IV software (version 7.0; N-Squared Computing, Salem, OR, USA) to estimate macronutrient and micronutrient intake. The Dietary Inflammatory Index (DII) was used to estimate the inflammatory potential of the diet. To calculate the DII, a standardized global database containing mean consumption and standard deviation values for dietary parameters from 11 global populations was used ( 15 ). The intake of each nutrient was subtracted from the mean intake for that nutrient and then divided by the standard deviation to create a z-score. Subsequently, the z-scores were multiplied by the inflammatory effect score for each dietary parameter to obtain the final DII score. The scores were obtained based on the impact of nutrients on six major inflammatory biomarkers including IL-1β, IL-4, IL-6, IL-10, TNF-α, and CRP ( 16 ). Individual DII scores for all food components were summed to calculate the participant’s overall DII. A higher negative DII indicates a more anti-inflammatory diet.

Results

The average age and FSH level of the healthy group was significantly higher, and the average of FSH was significantly lower than the infertile group. There was no significant difference between the two groups in terms of height, weight, underlying diseases, thyroid disorders, history of in vitro fertilization (IVF) failure, average infertility duration, and average body mass index (BMI) (Table  1 ). Table 1 General characteristics of participants Infertile ( N  = 123) Healthy ( N  = 123) P -value Age a (year) 33.59 ± 5.01 37.31 ± 3.26  < 0.001 Underlying diseases b 10 (8%) (12%) 15 0.272 Thyroid disorders b 3 (2%) (6%) 7 0.347 History of IVF failure c 5 (4%) (2%) 3 0.186 Infertility duration (months) b 57.52 ± 42.95 49.49 ± 51.01 0.306 BMI a (Kg/m 2 ) 28.97 ± 16.49 26.62 ± 6.05 0.216 FSH a (mIU/ml) 17.57 ± 36.72 9.51 ± 6.94 0.045 LH a (mIU/ml) 5.94 ± 4.49 7.60 ± 8.56 0.157 Height a (cm) 157.36 ± 23.05 160.79 ± 30.65 0.319 Weight a (Kg) 71.65 ± 16.26 68.12 ± 13.57 0.064 a. Independent samples test, b. Pearson Chi-square, c. Fisher’s exact test BMI body mass index, FSH follicle-stimulating hormone, LH luteinizing hormone, IVF in vitro fertilization General characteristics of participants a. Independent samples test, b. Pearson Chi-square, c. Fisher’s exact test BMI body mass index, FSH follicle-stimulating hormone, LH luteinizing hormone, IVF in vitro fertilization Regarding the results on comparing demographic, pathologic, and clinical variables based on the dietary inflammatory index grouping (using the median DII), the history of IVF failure in people with a high DII was significantly higher than that of the participants with low DII (Table  2 ). Table 2 Distribution of demographic and clinical variables based on the median of the dietary inflammatory index (DII) DII ≥ 4.28 ( N  = 123) DII < 4.28 ( N  = 123) P -value Age a (year) 35.20 ± 4.64 36.32 ± 4.26 0.119 Underlying diseases b (n(%)) 6 (5%) 10 (8%) 0.223 Thyroid disorders b (n(%)) 4 (3%) 6 (5%) 0.373 History of IVF failure c (n(%)) 7 (6%) 1 (0.8%) 0.029 Infertility duration (months) b 47.40 ± 43.59 58.64 ± 51.51 0.148 BMI a (Kg/m 2 ) 28.78 ± 15.49 26.48 ± 5.60 0.222 FSH a (mIU/ml) 17.82 ± 38.65 10.72 ± 12.30 0.130 LH a (mIU/ml) 7.40 ± 8.52 6.38 ± 5.62 0.383 AMH a (ng/ml) 1.30 ± 1.09 1.30 ± 2.43 0.991 a. Independent samples test, b. Pearson Chi-square, c. Fisher’s exact test BMI body mass index, FSH follicle-stimulating hormone, LH luteinizing hormone, IVF in vitro fertilization, AMH: anti-Müllerian hormone Distribution of demographic and clinical variables based on the median of the dietary inflammatory index (DII) a. Independent samples test, b. Pearson Chi-square, c. Fisher’s exact test BMI body mass index, FSH follicle-stimulating hormone, LH luteinizing hormone, IVF in vitro fertilization, AMH: anti-Müllerian hormone According to the results on comparing dietary intake between infertile and healthy groups, the average eicosapentaenoic acid, docosahexaenoic acid, magnesium, vitamin C, total fiber, insoluble fiber, and crude fiber in the healthy group were higher than in the infertile group. In addition, the average cholesterol in the infertile group was higher than in the healthy group (Table  3 ). Table 3 Dietary intake among infertile and healthy groups Infertile ( N  = 123) Healthy ( N  = 123) P a Calorie (kcal/day) 1928.73 ± 420.88 2023.18 ± 548.47 0.249 Protein (g/day) 71.63 ± 12.73 71.97 ± 19.16 0.895 Carbohydrates (g/day) 305.64 ± 78.52 320.01 ± 103.87 0.352 Fats (g/day) 56.56 ± 14.15 59.91 ± 21.81 0.249 Cholesterol (mg/day) 237.18 ± 62.91 201.55 ± 68.78 0.001 SFA (g/day) 17.08 ± 4.98 17.25 ± 7.29 0.861 MUFA (g/day) 14.70 ± 4.86 16.72 ± 8.72 0.068 PUFA (g/day) 13.54 ± 3.98 14.30 ± 5.53 0.346 Oleic acid (g/day) 11.35 ± 4.03 12.95 ± 7.23 0.081 Linoleic acid (g/day) 11.14 ± 3.61 11.61 ± 5.17 0.527 Linolenic acid (g/day) 0.06 ± 0.05 0.06 ± 0.04 0.515 Eicosapentaenoic acid (g/day) 0.01 ± 0.01 0.02 ± 0.02 0.028 Docosahexaenoic acid (g/day) 0.03 ± 0.03 0.04 ± 0.06 0.037 Iron (mg/day) 17.14 ± 4.22 16.85 ± 5.18 0.712 Magnesium (mg/day) 182.91 ± 47.80 206.85 ± 78.52 0.020 Zinc (mg/day) 6.23 ± 1.56 6.53 ± 2.38 0.360 Selenium (μg/day) 0.02 ± 0.01 0.02 ± 0.01 0.102 Vitamin A (mg/day) 802.70 ± 397.63 896.98 ± 456.17 0.190 Beta-carotene (μg/day) 580.14 ± 321.34 604.35 ± 364.21 0.670 Vitamin E (mg/day) 2.74 ± 0.85 2.83 ± 0.79 0.490 Vitamin B1 (mg/day) 1.72 ± 0.43 1.69 ± 0.57 0.710 Vitamin B2 (mg/day) 1.20 ± 0.31 1.19 ± 0.45 0.991 Vitamin B3 (mg/day) 19.65 ± 4.65 19.64 ± 6.05 0.995 Vitamin B6 (mg/day) 1.04 ± 0.20 1.09 ± 0.29 0.204 Folate (μg/day) 211.68 ± 47.88 255.70 ± 73.21 0.153 Vitamin B12 (mg/day) 2.58 ± 0.83 2.78 ± 1.27 0.331 Pantothenic acid (mg/day) 3.86 ± 1.01 4.13 ± 1.58 0.197 Biotin (mg/day) 17.16 ± 5.15 16.62 ± 5.75 0.549 Vitamin C (mg/day) 117.23 ± 33.45 136.14 ± 54.44 0.009 Vitamin D (mg/day) 1.05 ± 0.70 1.19 ± 0.94 0.294 Vitamin K (mg/day) 131.83 ± 30.47 125.71 ± 45.67 0.321 Fiber (g/day) 12.92 ± 2.88 14.74 ± 4.44 0.002 Soluble fiber (g/day) 0.67 ± 0.19 0.75 ± 0.29 0.056 Insoluble fiber (g/day) 3.85 ± 1.30 4.75 ± 2.29 0.002 Crude Fiber (g/day) 4.29 ± 1.27 5.15 ± 1.98 0.001 Caffeine (mg/day) 123.53 ± 56.08 111.50 ± 45.18 0.144 a Independent samples T-test SFA saturated fatty acid, MUFA monounsaturated fatty acid, PUFA polyunsaturated fatty acid Dietary intake among infertile and healthy groups a Independent samples T-test SFA saturated fatty acid, MUFA monounsaturated fatty acid, PUFA polyunsaturated fatty acid The results on comparing the dietary intake based on the median DII showed that the average calorie, protein, carbohydrate, fat, saturated fatty acid, monounsaturated fat, polyunsaturated fat, oleic acid, linoleic acid, eicosapentaenoic acid, docosahexaenoic acid, iron, magnesium, zinc, selenium, vitamin A, beta-carotene, vitamin E, vitamin B2, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, vitamin C, vitamin D, vitamin K, fiber, soluble fiber, insoluble fiber, crude fiber, and caffeine in the group with a low dietary inflammatory index (less than 4.28) were higher than in the group with a high dietary inflammatory index (higher than 4.28) (Table  4 ). Table 4 Dietary intake of the participants based on the median DII DII ≥ 4.28 DII < 4.28 P a Calorie (kcal/day) 1825.09 ± 488.25 2149 ± 458.32  < 0.001 Protein (g/day) 67.64 ± 16.23 76.37 ± 15.92 0.001 Carbohydrates (g/day) 298.92 ± 103.68 330.69 ± 80.59 0.036 Fats (g/day) 48.81 ± 13.16 68.12 ± 19.23  < 0.001 Cholesterol (mg/day) 210.35 ± 75.53 223.29 ± 60.45 0.244 SFA (g/day) 14.29 ± 5.38 20.10 ± 6.07  < 0.001 MUFA (g/day) 12.47 ± 4.62 19.21 ± 8.16  < 0.001 PUFA (g/day) 12.04 ± 3.77 15.86 ± 5.26  < 0.001 Oleic acid (g/day) 9.38 ± 3.54 15.11 ± 6.84  < 0.001 Linoleic acid (g/day) 9.85 ± 3.55 12.89 ± 4.97  < 0.001 Linolenic acid (g/day) 0.05 ± 0.05 0.07 ± 0.04 0.067 Eicosapentaenoic acid (g/day) 0.01 ± 0.01 0.02 ± 0.03 0.025 Docosahexaenoic acid (g/day) 0.03 ± 0.03 0.05 ± 0.06 0.014 Iron (mg/day) 15.68 ± 4.88 18.33 ± 4.30  < 0.001 Magnesium (mg/day) 151.68 ± 28.12 242.66 ± 65.94  < 0.001 Zinc (mg/day) 5.16 ± 1.33 7.69 ± 1.87  < 0.001 Selenium (μg/day) 0.01 ± 0.01 0.02 ± 0.01 0.007 Vitamin A (mg/day) 588.86 ± 201.03 1128.92 ± 446.80  < 0.001 Beta-carotene (μg/day) 425.59 ± 160.40 765.86 ± 394.41  < 0.001 Vitamin E (mg/day) 2.33 ± 0.59 3.27 ± 0.73  < 0.001 Vitamin B1 (mg/day) 1.66 ± 0.57 1.76 ± 0.45 0.196 Vitamin B2 (mg/day) 0.99 ± 0.30 1.40 ± 0.39  < 0.001 Vitamin B3 (mg/day) 18.97 ± 5.89 20.38 ± 5 0.112 Vitamin B6 (mg/day) 0.90 ± 0.17 1.23 ± 0.23  < 0.001 Folate (μg/day) 175.59 ± 30.92 264.35 ± 57.62  < 0.001 Vitamin B12 (mg/day) 2.19 ± 0.80 3.18 ± 1.16  < 0.001 Pantothenic acid (mg/day) 3.20 ± 0.72 4.86 ± 1.36  < 0.001 Biotin (mg/day) 14.05 ± 3.75 19.68 ± 5.51  < 0.001 Vitamin C (mg/day) 98.69 ± 27.47 158.09 ± 45  < 0.001 Vitamin D (mg/day) 0.81 ± 0.62 1.43 ± 0.94  < 0.001 Vitamin K (mg/day) 113.43 ± 31.65 143.34 ± 42.14  < 0.001 Fiber (g/day) 11.47 ± 2.11 16.52 ± 3.76  < 0.001 Soluble fiber (g/day) 0.58 ± 0.14 0.86 ± 0.27  < 0.001 Insoluble fiber (g/day) 3.30 ± 0.99 5.45 ± 2.15  < 0.001 Crude fiber (g/day) 3.71 ± 0.95 5.87 ± 1.74  < 0.001 Caffeine (mg/day) 102.57 ± 39.91 130.31 ± 55.52 0.001 a Independent samples T-test SFA saturated fatty acid, MUFA monounsaturated fatty acid, PUFA polyunsaturated fatty acid Dietary intake of the participants based on the median DII a Independent samples T-test SFA saturated fatty acid, MUFA monounsaturated fatty acid, PUFA polyunsaturated fatty acid Regarding the association of DII as a quantitative variable with infertility without adjusting confounding variables (Model 1) and also after adjusting the effect of variables of infertility duration, thyroid disorders, FSH, LH, and number of fertilities (Model 2), a positive relationship was found between DII and infertility after adjusting the effect of the confounding variables ( P  = 0.033, OR = 1.214, CI 95% = 1.016–1.451) (Table  5 ). Table 5 Logistic regression of the relationship between infertility risk and the dietary inflammatory index as a continuous quantitative variable Model OR CI 95% P * Model 1 1.15 0.981–1.357 0.085 Model 2 1.214 1.016–1.451 0.033 * Logistic regression. Model 1: adjusted for age, weight, body mass index, intake of anti-inflammatory supplements, suffering from underlying disease, smoking, alcohol consumption, and physical activity. Model 2: further adjustments for infertility duration, thyroid disorders, FSH, LH, and number of pregnancies Logistic regression of the relationship between infertility risk and the dietary inflammatory index as a continuous quantitative variable * Logistic regression. Model 1: adjusted for age, weight, body mass index, intake of anti-inflammatory supplements, suffering from underlying disease, smoking, alcohol consumption, and physical activity. Model 2: further adjustments for infertility duration, thyroid disorders, FSH, LH, and number of pregnancies In addition, DII as a qualitative variable and based on the median DII had a significant relationship with infertility after adjusting the effect of confounding variables (P = 0.043, OR = 2.08, CI 95% = 1.024–4.248). Therefore, in people with a high dietary inflammatory index, the odds of infertility were 2.08 times more than in people with a low index (Table  6 ). Table 6 Logistic regression of the relationship between infertility risk and the dietary inflammatory index (DII) as a qualitative variable OR CI 95% P * Model 1 1.575 0.825–3.007 0.169 Model 2 2.08 1.024–4.248 0.043 * Logistic regression. Model 1: adjusted for age, weight, body mass index, intake of anti-inflammatory supplements, suffering from underlying disease, smoking, alcohol consumption, and physical activity. Model 2: further adjustments for infertility duration, thyroid disorders, FSH, LH, and number of pregnancies Logistic regression of the relationship between infertility risk and the dietary inflammatory index (DII) as a qualitative variable * Logistic regression. Model 1: adjusted for age, weight, body mass index, intake of anti-inflammatory supplements, suffering from underlying disease, smoking, alcohol consumption, and physical activity. Model 2: further adjustments for infertility duration, thyroid disorders, FSH, LH, and number of pregnancies

Conclusion

In summary, this study provides, to our knowledge, the first evidence of an association between ovarian reserve and DII in infertile individuals. The findings underscore the significance of maintaining a healthy diet to potentially mitigate infertility. If these results are corroborated in future studies, dietary interventions emphasizing foods with low DII could be recommended as a strategy to help reduce infertility risks. In addition, supplements containing anti-inflammatory nutrients can be recommended as a preventive and complementary treatment to reduce the risk of infertility in women. Nonetheless, further research is essential to fully understand the connection between infertility risk and DII.

Discussion

The results of this study indicate a significant positive association between the Dietary Inflammatory Index (DII) and infertility, even after controlling for potential confounding variables. The infertility risk increased two times in women who consume a diet with a high DII. Recent studies have increasingly explored the relationship between diet and infertility. For instance, the fertility diet (FD), first introduced in the Nurses’ Health Study II (NHSII) in 2007, emphasizes reduced intake of trans fats while promoting consumption of monounsaturated fatty acids, vegetable proteins, and full-fat dairy products, correlating with a lower risk of ovulatory infertility. In addition, a 2019 study found that adherence to a fertility diet was linked to improved live birth rates among women undergoing in vitro fertilization (IVF). A pro-fertility diet (PFD) consists of increased intake of whole grains, soy, seafood (over other animal protein sources), dairy products, and low pesticide foods ( 17 ). A growing body of evidence links lifestyle and diet to fertility outcomes, and research on dietary effects on ovarian reserve remains scarce ( 18 , 19 ). Indicators of ovarian reserve, such as anti-Müllerian hormone (AMH) levels and antral follicle count (AFC), serve as predictors of ovarian response to gonadotropins in women undergoing ovarian stimulation ( 20 – 22 ). In this regard, Kaboodmehri et al. (2021) found a relationship between AMH levels and dietary intake showing that serum AMH concentration was negatively correlated with the consumption of fast foods and saturated fats even after adjusting for menstrual age, menstrual pattern, and oral contraceptive use ( 23 ). In our study, the average cholesterol level in the reduced ovarian reserve group was higher than the healthy group, indicating that the consumption of fast food and saturated fats, associated with elevated DII, may contribute to a decrease in AMH and ovarian reserve. Conversely, the study by Carceles et al. (2020) examined dietary patterns in relation to AFC in 363 women receiving pre-pregnancy evaluations and treatments for infertility. Their findings indicated no association between dietary patterns and AFC in the women visiting the fertility center ( 18 ). However, it is important to note that this study did not specifically examine dietary inflammation. Moslehi et al. (2017) conducted a cross-sectional study to find a relationship between nutritional factors and ovarian reserves and menopause. A relationship was found between the serum concentration of 25 hydroxyvitamin (D(OH)25) and the intake of soy or soy products with ovarian reserve ( 21 ). In 2018, Souter et al. investigated the relationship between dietary antioxidants and AFC in women undergoing fertility treatments. They evaluated antioxidant intake—such as vitamins A, C, and E, and specific carotenoids—using a validated FFQ, concluding there was no significant relationship between vitamins A, C, and E and AFC. However, they did find a positive association between β-carotene from supplements and total lycopene intake with AFCs, suggesting possible beneficial effects of certain antioxidants on ovarian reserve ( 24 ). Our findings showed higher average levels of vitamin A, vitamin E, vitamin C, zinc, and selenium in the low DII (less than 4.28) group compared to those with high DII (more than 4.28), highlighting the role of antioxidants in protecting ovarian reserve. Using the DII instead of examining individual nutrients may yield different, more comprehensive insights regarding the relationship between infertility and dietary inflammation. In our study, the average intake of several nutrients, including vitamins A, E, C, various B vitamins, folate, and fibers, was notably higher among participants with a low DII (less than 4.28), emphasizing the potential of these substances to mitigate DII and preserve ovarian reserve. Moreover, a higher percentage of history of IVF failure was noted in the high DII group compared to the low DII group. The study by Vahid et al. (2021) assessed the relationship between maternal nutritional quality, dietary antioxidant index, and miscarriage risk, suggesting that recommending diets high in antioxidants, such as vitamins E, C, zinc, and selenium and a quality diet containing vitamins B12 and D can effectively reduce miscarriage risk in women with a history of repeated loss ( 25 ). In our study, apart from antioxidant substances (average vitamin A, vitamin E, vitamin C, zinc, and selenium), the level of vitamin D and vitamin B12 in the group with a low dietary inflammatory index (DII less than 4.28) was higher than the group with a high inflammatory diet index (DII more than 4.28), which suggests the importance of these substances in the success of IVF. Noli et al. (2020) investigated the role of diet in poor ovarian stimulation responses and found that greater dietary glycemic load, as well as carbohydrate and fiber intake, corresponded with unexpectedly poor ovarian responses among women undergoing IVF treatments ( 26 ). In alignment with these results, our study noted higher average levels of fiber in the low DII group and healthier patients, supporting Gaskins et al.’s original description of a “fertility diet,” characterized by higher intakes of fruits and vegetables, whole grains, seafood, dairy, and soy foods along with vitamins D, folic acid, and B12. Studies have shown that food patterns are related to endometriosis, infertility, and ovulation ( 5 , 7 – 9 , 27 ). In addition, new evidence suggests that improving lifestyle factors including adherence to specific dietary patterns is associated with improved fertility outcomes including clinical pregnancy, spontaneous abortion, and live birth rates in women undergoing in vitro fertilization (IVF) ( 10 , 17 ). Inflammation is a natural body process in response to infection or injury; however, long-term chronic inflammation can negatively affect fertility through menstrual cycle disorders, implantation failure, endometriosis, and recurrence of abortion. Furthermore, inflammation may interfere with cellular transmission pathways that are fundamental for the normal functioning of ovulation ( 28 ). Furthermore, in men, inflammation has a negative effect on sperm quality, which is a key factor in fertility ( 29 ). As a result, nutritional interventions aimed at reducing inflammation, such as anti-inflammatory diets, may improve fertility prospects for both men and women pre-pregnancy ( 30 ). However, the present study has several limitations. This research was conducted at only one therapeutic center and thus limited the generalizability of the study findings. The observational design of the study makes it challenging to establish definitive causal relationships. Data regarding dietary intake were collected using a Food Frequency Questionnaire (FFQ), and self-reporting can introduce bias and affect the accuracy of the information gathered. Therefore, the reliability of the dietary data may be limited. To enhance the robustness of future findings, it is recommended to conduct prospective multicenter studies with larger sample sizes. This would help in obtaining more comprehensive data and improving the generalizability of results. In addition, systematic reviews and meta-analyses should be undertaken to synthesize findings across different studies in this area, providing a clearer picture of the relationships being explored (Fig.  1 ). Fig. 1 The association between DII and infertility The association between DII and infertility

Statistical

Descriptive statistical methods (including mean and standard deviation, frequency, and percentage) were used to describe the data. To analyze the research hypotheses, the assumptions associated with parametric tests were first investigated. The normality of the research data was assessed using the Shapiro–Wilk test and kurtosis and skewness indices. The equality of variance between the groups was evaluated using Levene’s test. Independent t-tests were applied for quantitative variables, while Pearson’s Chi-square test was utilized for qualitative variables. If the assumptions for these tests were not satisfied, Fisher’s exact test was performed. Logistic regression was conducted to adjust for potential confounding factors. Confounding variables such as age, weight, body mass index, anti-inflammatory supplement use, underlying disease, smoking, alcohol consumption, and physical activity were adjusted in different regression models. The confounding variables were identified based on a thorough review of the literature and expert consensus in the field. Specifically, the factors known to influence the outcome of interest and that could differ between the case and control groups were considered. Statistical analysis was carried out using SPSS version 21, with a significance level of P  < 0.05 for all analyses.

Introduction

Infertility is a key public health concern defined as the inability to conceive after 12 months of unprotected sexual intercourse. It can be classified as either primary, referring to individuals who have never experienced pregnancy, or secondary, referring to those with a history of previous pregnancies ( 1 ). While infertility itself is not a life-threatening condition, its psychological and social repercussions can be severe. The diagnosis and treatment processes often impose significant stress on couples (2). Infertile couples face a variety of challenges, including sexual dysfunction, high treatment costs, and psychological burdens such as depression, anxiety, stress, decreased quality of life, and feelings of failure. Approximately 15% of couples of reproductive age worldwide experience infertility ( 3 ). In 2021, a study by Maharloui et al. assessed the prevalence of infertility in Iran, estimating the prevalence of primary infertility at 5% and secondary infertility at 2% ( 4 ). The causes of infertility are diverse and may include ovarian disorders such as polycystic ovary syndrome or diminished ovarian reserve, endocrine system disorders leading to hormonal imbalances ( 5 ), sperm dysfunction (30%), failure of ovulation (25%), anatomical abnormalities of the fallopian tubes (25%), unexplained infertility (25%), endometriosis (5%), improper or irregular intercourse (5%), cervical mucus dysfunction (3%), and uterine abnormalities such as fibroids (rare) ( 6 ). In addition to reducing ovarian reserve, the quality of eggs also decreases due to various factors throughout a person’s life, leading to an increase in aneuploidy rates ( 2 ). Ovarian reserve is influenced by multiple factors, one of which may be the level of inflammatory factors in the body. Emerging evidence suggests that chronic low-grade inflammation may impair reproductive function by affecting folliculogenesis, oocyte quality, and hormonal balance. Diet is a major modifiable factor influencing systemic inflammation. An unhealthy diet rich in fat and refined carbohydrates is associated with elevated levels of inflammatory markers, while a healthy diet rich in fruits, vegetables, fish, omega-3 fatty acids, and fiber exhibits anti-inflammatory properties. The Dietary Inflammatory Index (DII) quantifies the inflammatory potential of an individual’s diet. While DII has been linked to obesity and metabolic disorders, its relationship with reproductive health—particularly ovarian reserve—remains underexplored. The Dietary Inflammatory Index (DII) is a tool designed to assess the inflammatory potential of a diet based on the pro-inflammatory and anti-inflammatory properties of various dietary components ( 7 ). The DII includes factors such as energy, carbohydrate, protein, total fat, saturated fatty acids, monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), cholesterol, fiber, oleic acid, linoleic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), sodium, potassium, vitamin A, beta-carotene, lutein, lycopene, vitamin C, calcium, iron, vitamin D, vitamin E, vitamin B12, thiamine, riboflavin, niacin, vitamin B6, folate, biotin, pantothenic acid, vitamin K, magnesium, zinc, and selenium. Previous studies have shown a significant correlation between a high DII diet and BMI, waist circumference, and waist-to-height ratio ( 8 ). However, some recent studies have found no relationship between DII and obesity indices ( 9 ). In addition, while the DII has been used to assess the potential inflammatory effects of dietary intake in different populations, other studies have not found a significant relationship between DII and various diseases such as inflammatory bowel disease (IBD) ( 10 ) and high blood pressure ( 11 ). Given the limited and insufficient studies in this area and the contradictory results obtained, we decided to conduct a study to determine the relationship between ovarian reserve and the DII as an indicator of the inflammatory status of the diet in infertile individuals.

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