Analysis of the relationship of the serum vitamin D level with infertility and associated factors

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Methods: We retrospectively reviewed the data of 12,261 infertile patients who were treated with ART for the first time in the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University from June 2016 to December 2018. According to the serum 25(OH)D level, the patients were divided into the following two groups: the VD deficiency group (25(OH)D≤50 nmol/l) and VD nondeficiency group (25(OH)D>50 nmol/l). Results: Regression analysis showed that VD levels were not affected by BMI, PCOS, the blood type, family history or endometriosis (P>0.05). Advanced female age (>35 years) was a protective factor against VD deficiency; women under 35 years of age were more likely to develop VD deficiency than those over 35 years of age (P<0.05). The season of VD determination affected its level; the levels of VD in summer and autumn were significantly higher than those in winter and spring (P<0.05).They were obviously higher in spring than in winter (P<0.05). Insulin resistance affected VD levels; patients with insulin resistance were more prone to VD deficiency than those without insulin resistance (P<0.05). Conclusions: VD deficiency exists among infertile patients. The level of VD is affected by the woman's age, the season of determination and insulin resistance. BMI, PCOS, blood type, family history and endometriosis have no influence on vitamin D levels. Vitamin D Infertility 25(OH)D Assisted reproductive technology Insulin resistance 1. Introduction Vitamin D (VD) is a steroid hormone that is produced in the skin upon ultraviolet irradiation and is mainly known for its role in bone health and mineralization( 1 ). VD primarily contributes to the absorption of calcium and phosphate from the intestinal tract, which is necessary for bone mineralization. VD in blood circulation mainly exists in the form of 25(OH)D, whose concentration is the highest and 1000 times that of 1,25(OH)2D. The half-life of 25(OH)D is the longest, approximately 2 weeks, allowing it to last up to 25 days, and 25(OH)D is more stable than 1,25(OH)2D, whose half-life is approximately 7 hours. Therefore, the serum 25(OH)D level is often detected clinically as the most effective index to evaluate nutritional status in terms of in vivo VD levels. In modern society, owing to increases in work pressure, the rhythm of life has accelerated, and the childbearing age among women at the age of marriage is increasing. Furthermore, environmental pollution is worsening, poor lifestyle habits are influencing human health, and the national birth policy has been continually expanded. Consequently, the proportion of older pregnant women has increased, and the incidence of infertility has been increasing year by year. According to the estimation by the World Health Organization, globally, approximately 10%-15% of couples of childbearing age suffer from infertility, which affects approximately 48.5 million couples worldwide. Assisted reproductive technology (ART), as the main means to treat infertility in recent years, has developed rapidly and has become increasingly more mature. In recent years, research on the VD role in reproductive function has increased. The VD receptor is expressed in reproductive organs, such as the uterus, ovary and testis and has important biological effects on the growth and development of the endometrium and follicle and on sperm quality( 2 ). Therefore, studying the distribution of VD levels among infertile people and analyzing the relationship between VD levels and the basic conditions of infertile patients, as well as laboratory indicators, could provide helpful information for exploring interventions that involve related factors to improve VD levels and ART outcomes. 2. Materials And Methods This study was approved by the Ethics Committee of the Third Affiliated Hospital of Zhengzhou University. Because this study was retrospective and did not involve the patient's name, address or other identifying information, the Ethics Committee waived the requirement for patients to sign the informed consent form. 2.1 Research objects and grouping We retrospectively analyzed the records of infertile patients who received ART treatment for the first time in the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University from June 2016 to December 2018. ( 1 )Inclusion criteria: patients who accepted artificial insemination by husband (AIH), artificial insemination by donor (AID), in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), preimplantation genetic diagnosis (PGD), or preimplantation genetic screening (PGS) due to fallopian tube factors, ovulation disorder [luteinizing syndrome without follicle rupture or polycystic ovary syndrome (PCOS)], endometriosis, premature ovarian failure, recurrent abortion, male factors (severe oligospermia and azoospermia), and unknown reasons. ( 2 ) Exclusion criteria: those who had contraindications for ART; a history of VD supplementation in the past six months; and serious medical diseases, such as hypertension and diabetes.The patients were classified into three groups according to the clinically accepted criteria( 3 )as follows: adequate VD (25(OH)D ≥ 75 nmol/l), insufficient VD (25(OH)D 50–75 nmol/l) and deficient VD (25(OH)D ≤ 50 nmol/l) levels. They were then divided into the following two groups: the VD deficiency group (25(OH) D ≤ 50 nmol/l), comprising 10,077 cases, and the VD nondeficiency group (25(OH)D > 50 nmol/l), comprising 2184 cases. The diagnosis of insulin resistance (IR) was based on homeostasis model assessment of insulin resistance (HOMA-IR). The larger the HOMA-IR index of the steady-state model is, the worse the insulin sensitivity is and the higher the IR level is. The calculation method for HOMA-IR was as follows: HOMA-IR Index = fasting blood glucose level (mmol/l) x fasting insulin (µIU/ml)/22.5. IR was diagnosed when HOMA-IR was > 2.25( 4 ).The diagnosis of PCOS was based on the criteria formulated by the Rotterdam Conference in 2003( 5 )as follows: ( 1 ) rare ovulation or anovulation; ( 2 ) clinical and/or biochemical manifestations of hyperandrogenism; and ( 3 ) polycystic ovarian changes consistent with at least the above two items, when other diseases causing related symptoms were excluded. The excluded diseases included delayed congenital adrenal hyperplasia, Cushing's syndrome, hypogonadism and hypogonadism amenorrhea, androgen-secreting tumors of the ovary or adrenal gland, thyroid dysfunction and hyperprolactinemia. 2.2 Clinical data collection The following patient information was collected through the electronic medical record system of the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University: the woman's age, the man's age, the method of assisted pregnancy, number of years of infertility, family history, the woman’s body mass index (BMI), the woman’s number of years of infertility, infertility types and clinical diagnoses (including PCOS, IR and endometriosis). 2.3 Observational indexes Median cubital venous blood was collected on an empty stomach before pregnancy and centrifuged for 10 min at 3000 r/min. The specialist used an automatic biochemical immunoassay analyzer (Roche, Switzerland) and automatic biochemical analyzer (Olympus, Japan) to measure and record the serum 25(OH)D level and time, anti-Mullerian hormone (AMH) level, basic endocrine function, liver function, glucose level and fasting insulin level. 2.4 Multivariate analysis of factors associated with VD We analyzed the factors affecting VD levels and conducted logistic multivariate analysis on the factors that might affect VD levels. Based on the published literature and clinical experience, the following variables were included in the logistic regression: the woman's age, the woman's BMI, blood type, family history, VD determination season, IR, PCOS and endometriosis. 2.5 Statistical methods All the data were sorted and analyzed by using SPSS 21.0, and the main results are expressed as the mean and standard deviation (x ± s). The chi-squared test was used to compare the categorical variables between the groups. If the expected value of more than 20% was less than 5, Fisher’s exact test was used. For continuous variables, the Student's t-test or Mann–Whitney test was used depending on the normality of distribution and variance homogeneity, and logistic regression was used for multivariate analysis, with a = 0.05 as the level of significance. 3. Results 3.1 General clinical data of the two groups of patients There were no significant differences in BMI, blood type, family history or the rate of endometriosis between the VD deficiency group and the nondeficiency group (P > 0.05), but there were statistically significant differences in age, measuring season, IR and PCOS between the VD deficiency group and the nondeficiency group (P < 0.05) (see Table 1 for details). Table 1 Comparison of basic data between two groups factor VD deficiency group n(%) VD non-deficiency groupn(%) P Age ≤ 35 1513(16.97) 7405(83.03) < .0001* 36~ 671(20.07) 2672(79.93) BMI < 18.5 94(16.85) 464(83.15) 0.7496* 18.5~ 1285(17.99) 5857(82.01) 24.0~ 635(17.89) 2915(82.11) 28.0~ 170(16.82) 841(83.18) Blood type A 605(17.39) 2875(82.61) 0.2574* B 680(17.22) 3270(82.78) O 659(18.86) 2835(81.14) AB 240(17.95) 1097(82.05) Family history No family history of hypertension or diabete 2089(17.93) 9560(82.07) 0.1288* With family history of hypertension or diabetes 95(15.52) 517(84.48) Season of vitamin D determination Spring 318(7.47) 3937(92.53) < .0001* Summer 937(30.38) 2147(69.02) Autumn 773(33.64) 1525(66.36) Winter 156(5.95) 2468(94.05) Insulin resistance Without 1987(18.15) 8692(81.85) 0.0051* With 197(15.02) 1115(84.98) PCOS Without 1942(18.10) 8790(81.90) 0.0301* With 242(15.13) 1287(84.17) Enometriosis Without 2092(17.80) 9661(82.20) 0.8579* With 92(18.11) 416(81.89) *chi-spuare test, in which P < 0.05 indicates that the difference is statistically significant. 3.2 Proportions of patients between the groups with different vitamin D levels There were 10,077 cases in the VD deficiency group, accounting for 82.19% of the total population, and 2,184 cases in the nondeficiency group, accounting for 17.81% of the total population (see Table 1 for details). 3.3 Multivariate regression analysis of VD deficiency-associated factors (see Table 2 for details) ( 1 ) VD deficiency was not influenced by BMI, PCOS, blood type, family history or endometriosis (P > 0.05). ( 2 ) An advanced female age (> 35 years) was a protective factor against VD deficiency (P < 0.05). ( 3 ) The season of determination affected the VD level, which was significantly higher in summer and autumn than in winter and spring (P < 0.05) and significantly higher in spring than in winter (P < 0.05). ( 4 ) IR affected the VD level. Patients with IR were more prone to VD deficiency than those without IR (P < 0.05). Table 2 Logistic regression analysis of influencing factors of Vitamin D COR(95%CI) P AOR(95%CI) P Woman’s age 1.016(1.008–1.024) 0.000 1.021(1.012–1.029) 0.000 BMI 0.986(0.924–1.053) 0,685 0.998(0.927–1.073) 0.949 Blood type 0.258 0.422 Type A 1 1 Type B 0.988(0.876–1.115) 0.847 0.990(0.871–1.125) 0.877 Type O 1.105(0.978–1.248) 0.110 1.093(0.960–1.243) 0.179 Type AB 1.040(0.882–1.226) 0.644 1.034(0.868–1.231) 0.711 Family history 0.841(0.672–1.052) 0.129 0.834(0.658–1.057) 0.133 Season of vitamin D determination 0.000 0.000 Spring 1 1 Summer 5.403(4.708-6.200) 0.000 5.436(4.735–6.240) 0.000 Autumn 6.275(5.437–7.243) 0.000 6.353(5.502–7.335) 0.000 Winter 0.783(0.642–0.954) 0.015 0.785(0.644–0.957) 0.017 Insulin resistance 0.797(0.680–0.934) 0.005 0.830(0.694–0.992) 0.041 PCOS 0.851(0.736–0.985) 0.030 1.017(0.863–1.197) 0.842 Endometriosis 1.021(0.811–1.286) 0.858 0.913(0.716–1.164) 0.461 4. Discussion VD is a steroid hormone, and VD deficiency is prevalent in the general population. According to the statistics of the World Health Organization, the prevalence rate of infertility among couples of childbearing age ranges globally from 9–18%( 6 ), and the interaction between VD and its receptor can have a variety of biological effects( 7 ). Therefore, it is of great clinical significance to study the role of VD in infertile patients and the factors that influence VD levels. Over the past ten years, the proportion of VD-deficient people has increased to nearly 40%. Among them, in approximately 37.3% of the population, the VD level in the body does not reach 20 ng/ml( 8 , 9 ). Studies have shown that approximately 52% of women of childbearing age worldwide are in a state of VD deficiency, and the proportion is increasing year by year. Epidemiological data show that in North America, approximately 27% of infertile patients have VD deficiency and 79% of infertile women who receive ART treatment have VD insufficiency or deficiency( 9 ). In this study, VD deficiency accounted for 82.19% of the population. We suspect that VD receptor expression in reproductive organs such as the uterus and ovary has important biological effects on the growth and development of the endometrium and follicle and that general VD deficiency reduces the reproductive function of these tissues, resulting in infertility. 4.1 Relationship between the season or age and the vitamin D level One of the main sources of VD is the interaction between solar ultraviolet B radiation and the precursor molecule, 7-dehydrocholesterol, in the skin, which leads to VD synthesis in vivo ( 1 ). VD synthesis in the skin after sun exposure accounts for 80–90% of its total physiological amount, and therefore, any activity that reduces sunlight exposure reduces the level of VD ( 10 ). In this study, the proportion of patients with VD deficiency was 82.19%, which may have been related to both the race and skin color of the study population and to total sun exposure. The results of this study showed that the VD level was correlated with the season. Considering that Henan is located at a latitude of 31°23′- 36°22′north and a longitude of 110°21′- 116°39′east, it generally has a temperate monsoon climate, specifically, a subtropical monsoon climate. The subjects of this study were all native to Henan, and thus, there was little difference in the latitude or longitude between regions. However, the four seasons are distinct in Henan, and there are obvious differences in the sun illumination time and ultraviolet intensity during different seasons. Ultraviolet rays are the strongest in the summer and last until September and October, and the results of this study showed that the VD levels were significantly higher in summer and autumn than in winter and spring (P < 0.05). However, the VD level in the summer is still not the highest over the course of the year, which may be due to the excessive use of sunscreen products and the reduction in outdoor activities among women in the summer. Age is another important factor affecting VD levels. However, with increasing age, women's awareness of their health increases in terms of changes in their hormone levels, and they have good exercise habits and nutritionally balanced diets in daily life, which leads to increased VD levels among women over 30 years old. In this study, the oldest woman was 46 years old, and elderly individuals were not included in the study. In fact, among elderly individuals, with the increasing age, the skin ages and the functions of the liver, kidney and other organs that affect the synthesis of VD gradually decrease, which leads to a decrease in the ability to synthesize and transport active VD. VD deficiency is common in patients with PCOS. However, the conclusions of previous studies have not been completely consistent. For example, it remains unclear whether there is a relationship between VD deficiency status and PCOS in infertile women( 11 ).Comparison of the VD levels between patients with PCOS and in the control group showed no significant difference (11 vs. 17 ng/ml, respectively). In recent years, many related studies have shown that the VD content in patients with PCOS may be closely related to metabolic syndrome. For every 1 kg/m2 increase in BMI, the serum 25(OH)D concentration decreases by 0.75 nmol/l ( 12 ). Many studies have shown that the higher the proportion of obese patients is, the lower the VD content is; that is, BMI is negatively correlated with the VD content( 13 , 14 ). Some studies have used quantitative insulin sensitivity indicators to determine IR and concluded that in patients with PCOS, IR was related to their physiological VD content and that the 25(OH)D3 content can be used as an independent IR-influencing factor( 15 ). VD deficiency is a risk factor for IR and cardiovascular disease, which can further aggravate the metabolic abnormality of PCOS( 11 , 12 ). It has been found that VD deficiency is related to IR and type 2 diabetes and increases the risk of the disease. It has also been reported that VD supplementation plays a beneficial role in the treatment of metabolic syndrome-related conditions (such as dyslipidemia, IR, hyperglycemia, obesity and hypertension) ( 16 ). This effect may be based on the mechanism of VD effects on different physiological parameters (including improved arterial stiffness), such as decreases in renin-angiotensin-aldosterone system activity, parathyroid hormone levels and levels of inflammatory cytokines; an increase in lipoprotein lipase activity; and improvement of phospholipid metabolism and mitochondrial oxidation( 17 ). The positive correlation between VD levels and IR has been confirmed in a number of studies. Dastorani M conducted a randomized, double-blind, placebo-controlled trial of 40 infertile women aged 18–40 years( 18 ). The results showed that compared with placebo, VD supplementation led to significant decreases in serum AMH and insulin levels and a significant increase in a quantitative insulin sensitivity index. In addition, after VD supplementation, serum total cholesterol (5.1–12.6 vs. 2.9–10.9 mg/dl, p = 0.03) and low-density lipoprotein cholesterol (4.5–10.3 vs. 2.5–10.6 mg/dl, p = 0.04) levels significantly decreased. It has been concluded that VD supplementation may be beneficial for insulin and lipid metabolism in infertile women. In summary, a large number of studies on animals and humans have shown that there is a correlation between VD levels and female fertility. It has been determined that the season, age and abnormal islet function affect VD levels. There are many factors affecting VD levels, but the causal relationships between those are not completely clear. A large-sample prospective study is still needed to clarify the role of VD in fertility. 5. Conclusion VD deficiency is prevalent among infertile patients. The level of VD is affected by a woman's age, the measuring season and IR. VD levels are not influenced by BMI, PCOS, blood type, family history or endometriosis. Declarations Data availability statement All data are included in this article. i). Ethics approval and consent to participate This study was approved by the Ethics Committee of the Third Affiliated Hospital of Zhengzhou University. Because this study was retrospective and did not involve the patient's name, address or other identifying information, the Ethics Committee waived the requirement for patients to sign the informed consent form. we confirming that all methods were performed in accordance with the relevant guidelines and regulations. ii). Consent for publication Consent to publication not applicable. iii). Availability of Data and Material (ADM) The original data are available to all readers upon request.Please contact the first author at [email protected] for such supporting data. iv). Competing interests All authors declare no conflict of interest with regard to this study. v). Funding The Key Scientific Research Project of Colleges and Universities in Henan Province[20B320044] and the Medical Science and Technology Research Project of Henan Province (Joint Construction) [LHGJ20190365] vi). Authors' contributions LJH and LYJ selected the population to be included and excluded, completed data statistics and analysis and wrote the manuscript. GYC participated in the review and guidance of the research. LJH,DMZ,HX,JML,YB,ZYC and WXL participated in data entry and sorting. LJH participated in the research design, guidance, and manuscript revision. vii). Acknowledgment Not applicable. References Chiu K, Chu A, Go V, Saad M. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. The American journal of clinical nutrition. 2004;79(5):820–5. Chor J, Chico P, Ayloo S, Roston A, Kominiarek MA. Reproductive health counseling and practices: A cross-sectional survey of bariatric surgeons. Surgery for Obesity & Related Diseases. 2015;11(1):187–92. Chu J, Gallos I, Tobias A, Robinson L, Coomarasamy A. Vitamin D and assisted reproductive treatment outcome: a prospective cohort study. Reproductive Health. 2019;16(1). Dastorani M, Aghadavod E, Mirhosseini N, Foroozanfard F, Modarres SZ, Siavashani MA, et al. The effects of vitamin D supplementation on metabolic profiles and gene expression of insulin and lipid metabolism in infertile polycystic ovary syndrome candidates for in vitro fertilization. Reproductive Biology and Endocrinology. 2018;16(1). Faraji S, Alizadeh M. Mechanistic Effects of Vitamin D Supplementation on Metabolic Syndrome Components in Patients with or without Vitamin D Deficiency. Journal of Obesity & Metabolic Syndrome. 2020;29(4). Fatih, ?zkaya, Azam, Demirel. Vitamin D deficiency in infertile patients. Archivos Espanoles De Urologia. 2018. Ferreira P, Cangussu L, Bueloni-Dias F, Orsatti C, Schmitt E, Nahas-Neto J, et al. 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Rudick B, Ingles S, Chung K, Stanczyk F, Paulson R, Bendikson K. Characterizing the influence of vitamin D levels on IVF outcomes. Human Reproduction. 2012(11):3321–7. Wiersma T, Flikwert S, Leeuwen J, Daemers D. Vitamin D deficiency. Nederlands Tijdschrift Voor Geneeskunde. 2007;150(23):1315–6. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1702948","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":110617144,"identity":"2d4ae9a6-20c8-41dc-8a2b-47f7da9d327d","order_by":0,"name":"Jiaheng Li","email":"","orcid":"","institution":"The Third Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Jiaheng","middleName":"","lastName":"Li","suffix":""},{"id":110617146,"identity":"c9ceaa02-d147-4e9e-93ab-6e3e81a19d7b","order_by":1,"name":"Yijiang Li","email":"","orcid":"","institution":"The Third Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Yijiang","middleName":"","lastName":"Li","suffix":""},{"id":110617148,"identity":"1c386d5a-3bfd-4c44-9c95-104cdf8d0d97","order_by":2,"name":"Mingze Du","email":"","orcid":"","institution":"The Third Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Mingze","middleName":"","lastName":"Du","suffix":""},{"id":110617149,"identity":"780b0bda-27f8-4efd-83d7-7a027fb0f72a","order_by":3,"name":"Xuan Hou","email":"","orcid":"","institution":"The Third Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Xuan","middleName":"","lastName":"Hou","suffix":""},{"id":110617152,"identity":"6de24769-c703-48a5-bf46-f135171f2458","order_by":4,"name":"Menglu Ji","email":"","orcid":"","institution":"The Third Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Menglu","middleName":"","lastName":"Ji","suffix":""},{"id":110617153,"identity":"dcf73f65-a09a-490b-9746-b17923ece0ba","order_by":5,"name":"Bo Yang","email":"","orcid":"","institution":"The Third Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Bo","middleName":"","lastName":"Yang","suffix":""},{"id":110617155,"identity":"e1d7ac9a-6094-4c9f-9e49-f5fe492a2412","order_by":6,"name":"Yuchao Zhang","email":"","orcid":"","institution":"The Third Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Yuchao","middleName":"","lastName":"Zhang","suffix":""},{"id":110617156,"identity":"41f025cc-1341-413f-8e95-9f48c4eb7f53","order_by":7,"name":"Yichun Guan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA10lEQVRIiWNgGAWjYBACPmYEm/FBQkUNYS1sSFqYDR6cOUaEFmS25MMWZpwqEcrY2R9+ulFz2G7D8bPHKhIb2Bj427sTCDiMx1g659jh5A1n8tJuJO6QYZA4c3YDIS0M0jlsh5MNDuSY3Ug8w8ZgIJFLSAv74985/4Bazr8xK0hsYyZGC4OZdG7bYTuDGzlmDERq4TGzzu1LT5C88cZYIuHMMR6CfuHnP/74ds43a3u+8zmGH39U1Mjxt/fi1wIFzYkNUBYPMcpBoM6eWJWjYBSMglEwAgEAdhVGUwq64FwAAAAASUVORK5CYII=","orcid":"","institution":"The Third Affiliated Hospital of Zhengzhou University","correspondingAuthor":true,"prefix":"","firstName":"Yichun","middleName":"","lastName":"Guan","suffix":""},{"id":110617157,"identity":"641a1b06-528c-4336-b5cb-d3a8f38f77ab","order_by":8,"name":"Xingling Wang","email":"","orcid":"","institution":"The Third Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Xingling","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2022-05-28 14:14:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1702948/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1702948/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":30726335,"identity":"ab04142a-e6ff-4cb2-8842-191ace1db11e","added_by":"auto","created_at":"2022-12-23 20:29:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":374705,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1702948/v1/ec50ce38-761a-4518-92a9-c51cb0dc0f25.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Analysis of the relationship of the serum vitamin D level with infertility and associated factors","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eVitamin D (VD) is a steroid hormone that is produced in the skin upon ultraviolet irradiation and is mainly known for its role in bone health and mineralization(\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e). VD primarily contributes to the absorption of calcium and phosphate from the intestinal tract, which is necessary for bone mineralization. VD in blood circulation mainly exists in the form of 25(OH)D, whose concentration is the highest and 1000 times that of 1,25(OH)2D. The half-life of 25(OH)D is the longest, approximately 2 weeks, allowing it to last up to 25 days, and 25(OH)D is more stable than 1,25(OH)2D, whose half-life is approximately 7 hours. Therefore, the serum 25(OH)D level is often detected clinically as the most effective index to evaluate nutritional status in terms of in vivo VD levels.\u003c/p\u003e\n\u003cp\u003eIn modern society, owing to increases in work pressure, the rhythm of life has accelerated, and the childbearing age among women at the age of marriage is increasing. Furthermore, environmental pollution is worsening, poor lifestyle habits are influencing human health, and the national birth policy has been continually expanded. Consequently, the proportion of older pregnant women has increased, and the incidence of infertility has been increasing year by year. According to the estimation by the World Health Organization, globally, approximately 10%-15% of couples of childbearing age suffer from infertility, which affects approximately 48.5\u0026nbsp;million couples worldwide. Assisted reproductive technology (ART), as the main means to treat infertility in recent years, has developed rapidly and has become increasingly more mature. In recent years, research on the VD role in reproductive function has increased. The VD receptor is expressed in reproductive organs, such as the uterus, ovary and testis and has important biological effects on the growth and development of the endometrium and follicle and on sperm quality(\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e). Therefore, studying the distribution of VD levels among infertile people and analyzing the relationship between VD levels and the basic conditions of infertile patients, as well as laboratory indicators, could provide helpful information for exploring interventions that involve related factors to improve VD levels and ART outcomes.\u003c/p\u003e"},{"header":"2. Materials And Methods","content":"\u003cp\u003eThis study was approved by the Ethics Committee of the Third Affiliated Hospital of Zhengzhou University. Because this study was retrospective and did not involve the patient's name, address or other identifying information, the Ethics Committee waived the requirement for patients to sign the informed consent form.\u003c/p\u003e\n\u003cdiv id=\"Sec2\" class=\"Section2\"\u003e\n\u003ch2\u003e2.1 Research objects and grouping\u003c/h2\u003e\n\u003cp\u003eWe retrospectively analyzed the records of infertile patients who received ART treatment for the first time in the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University from June 2016 to December 2018. (\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e)Inclusion criteria: patients who accepted artificial insemination by husband (AIH), artificial insemination by donor (AID), in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), preimplantation genetic diagnosis (PGD), or preimplantation genetic screening (PGS) due to fallopian tube factors, ovulation disorder [luteinizing syndrome without follicle rupture or polycystic ovary syndrome (PCOS)], endometriosis, premature ovarian failure, recurrent abortion, male factors (severe oligospermia and azoospermia), and unknown reasons. (\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e) Exclusion criteria: those who had contraindications for ART; a history of VD supplementation in the past six months; and serious medical diseases, such as hypertension and diabetes.The patients were classified into three groups according to the clinically accepted criteria(\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e)as follows: adequate VD (25(OH)D\u0026thinsp;\u0026ge;\u0026thinsp;75 nmol/l), insufficient VD (25(OH)D 50\u0026ndash;75 nmol/l) and deficient VD (25(OH)D\u0026thinsp;\u0026le;\u0026thinsp;50 nmol/l) levels. They were then divided into the following two groups: the VD deficiency group (25(OH) D\u0026thinsp;\u0026le;\u0026thinsp;50 nmol/l), comprising 10,077 cases, and the VD nondeficiency group (25(OH)D\u0026thinsp;\u0026gt;\u0026thinsp;50 nmol/l), comprising 2184 cases.\u003c/p\u003e\n\u003cp\u003eThe diagnosis of insulin resistance (IR) was based on homeostasis model assessment of insulin resistance (HOMA-IR). The larger the HOMA-IR index of the steady-state model is, the worse the insulin sensitivity is and the higher the IR level is. The calculation method for HOMA-IR was as follows: HOMA-IR Index\u0026thinsp;=\u0026thinsp;fasting blood glucose level (mmol/l) x fasting insulin (\u0026micro;IU/ml)/22.5. IR was diagnosed when HOMA-IR was \u0026gt;\u0026thinsp;2.25(\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e).The diagnosis of PCOS was based on the criteria formulated by the Rotterdam Conference in 2003(\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e)as follows: (\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e) rare ovulation or anovulation; (\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e) clinical and/or biochemical manifestations of hyperandrogenism; and (\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e) polycystic ovarian changes consistent with at least the above two items, when other diseases causing related symptoms were excluded. The excluded diseases included delayed congenital adrenal hyperplasia, Cushing's syndrome, hypogonadism and hypogonadism amenorrhea, androgen-secreting tumors of the ovary or adrenal gland, thyroid dysfunction and hyperprolactinemia.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003ch2\u003e2.2 Clinical data collection\u003c/h2\u003e\n\u003cp\u003eThe following patient information was collected through the electronic medical record system of the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University: the woman's age, the man's age, the method of assisted pregnancy, number of years of infertility, family history, the woman\u0026rsquo;s body mass index (BMI), the woman\u0026rsquo;s number of years of infertility, infertility types and clinical diagnoses (including PCOS, IR and endometriosis).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n\u003ch2\u003e2.3 Observational indexes\u003c/h2\u003e\n\u003cp\u003eMedian cubital venous blood was collected on an empty stomach before pregnancy and centrifuged for 10 min at 3000 r/min. The specialist used an automatic biochemical immunoassay analyzer (Roche, Switzerland) and automatic biochemical analyzer (Olympus, Japan) to measure and record the serum 25(OH)D level and time, anti-Mullerian hormone (AMH) level, basic endocrine function, liver function, glucose level and fasting insulin level.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n\u003ch2\u003e2.4 Multivariate analysis of factors associated with VD\u003c/h2\u003e\n\u003cp\u003eWe analyzed the factors affecting VD levels and conducted logistic multivariate analysis on the factors that might affect VD levels. Based on the published literature and clinical experience, the following variables were included in the logistic regression: the woman's age, the woman's BMI, blood type, family history, VD determination season, IR, PCOS and endometriosis.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n\u003ch2\u003e2.5 Statistical methods\u003c/h2\u003e\n\u003cp\u003eAll the data were sorted and analyzed by using SPSS 21.0, and the main results are expressed as the mean and standard deviation (x\u0026thinsp;\u0026plusmn;\u0026thinsp;s). The chi-squared test was used to compare the categorical variables between the groups. If the expected value of more than 20% was less than 5, Fisher\u0026rsquo;s exact test was used. For continuous variables, the Student's t-test or Mann\u0026ndash;Whitney test was used depending on the normality of distribution and variance homogeneity, and logistic regression was used for multivariate analysis, with a\u0026thinsp;=\u0026thinsp;0.05 as the level of significance.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n\u003ch2\u003e3.1 General clinical data of the two groups of patients\u003c/h2\u003e\n\u003cp\u003eThere were no significant differences in BMI, blood type, family history or the rate of endometriosis between the VD deficiency group and the nondeficiency group (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), but there were statistically significant differences in age, measuring season, IR and PCOS between the VD deficiency group and the nondeficiency group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (see Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e for details).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eComparison of basic data between two groups\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003efactor\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eVD deficiency group n(%)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eVD non-deficiency groupn(%)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026le;\u0026thinsp;35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e1513(16.97)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7405(83.03)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;.0001*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36~\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e671(20.07)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2672(79.93)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBMI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;18.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e94(16.85)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e464(83.15)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003e0.7496*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18.5~\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e1285(17.99)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5857(82.01)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24.0~\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e635(17.89)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2915(82.11)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e28.0~\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e170(16.82)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e841(83.18)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBlood type\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e605(17.39)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2875(82.61)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003e0.2574*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eB\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e680(17.22)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3270(82.78)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eO\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e659(18.86)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2835(81.14)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAB\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e240(17.95)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1097(82.05)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eFamily history\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNo family history of hypertension or diabete\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2089(17.93)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e9560(82.07)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.1288*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eWith family history of hypertension or diabetes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e95(15.52)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e517(84.48)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003eSeason of vitamin D determination\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSpring\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e318(7.47)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3937(92.53)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;.0001*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSummer\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e937(30.38)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2147(69.02)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAutumn\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e773(33.64)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1525(66.36)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWinter\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e156(5.95)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2468(94.05)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eInsulin resistance\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWithout\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e1987(18.15)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8692(81.85)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.0051*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWith\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e197(15.02)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1115(84.98)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePCOS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWithout\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e1942(18.10)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8790(81.90)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.0301*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWith\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e242(15.13)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1287(84.17)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eEnometriosis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWithout\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e2092(17.80)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9661(82.20)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.8579*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWith\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e92(18.11)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e416(81.89)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\"\u003e*chi-spuare test, in which P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicates that the difference is statistically significant.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n\u003ch2\u003e3.2 Proportions of patients between the groups with different vitamin D levels\u003c/h2\u003e\n\u003cp\u003eThere were 10,077 cases in the VD deficiency group, accounting for 82.19% of the total population, and 2,184 cases in the nondeficiency group, accounting for 17.81% of the total population (see Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e for details).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n\u003ch2\u003e3.3 Multivariate regression analysis of VD deficiency-associated factors (see Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e for details)\u003c/h2\u003e\n\u003cp\u003e(\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e) VD deficiency was not influenced by BMI, PCOS, blood type, family history or endometriosis (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\n\u003cp\u003e(\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e) An advanced female age (\u0026gt;\u0026thinsp;35 years) was a protective factor against VD deficiency (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\n\u003cp\u003e(\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e) The season of determination affected the VD level, which was significantly higher in summer and autumn than in winter and spring (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and significantly higher in spring than in winter (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\n\u003cp\u003e(\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e) IR affected the VD level. Patients with IR were more prone to VD deficiency than those without IR (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eLogistic regression analysis of influencing factors of Vitamin D\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCOR(95%CI)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAOR(95%CI)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWoman\u0026rsquo;s age\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.016(1.008\u0026ndash;1.024)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.021(1.012\u0026ndash;1.029)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBMI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.986(0.924\u0026ndash;1.053)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0,685\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.998(0.927\u0026ndash;1.073)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e0.949\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBlood type\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.258\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e0.422\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eType A\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eType B\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.988(0.876\u0026ndash;1.115)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.847\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.990(0.871\u0026ndash;1.125)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e0.877\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eType O\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.105(0.978\u0026ndash;1.248)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.110\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.093(0.960\u0026ndash;1.243)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e0.179\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eType AB\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.040(0.882\u0026ndash;1.226)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.644\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.034(0.868\u0026ndash;1.231)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e0.711\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFamily history\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.841(0.672\u0026ndash;1.052)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.129\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.834(0.658\u0026ndash;1.057)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e0.133\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSeason of vitamin D determination\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSpring\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSummer\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.403(4.708-6.200)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.436(4.735\u0026ndash;6.240)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAutumn\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.275(5.437\u0026ndash;7.243)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.353(5.502\u0026ndash;7.335)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWinter\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.783(0.642\u0026ndash;0.954)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.015\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.785(0.644\u0026ndash;0.957)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e0.017\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eInsulin resistance\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.797(0.680\u0026ndash;0.934)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.005\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.830(0.694\u0026ndash;0.992)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e0.041\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePCOS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.851(0.736\u0026ndash;0.985)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.030\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.017(0.863\u0026ndash;1.197)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e0.842\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEndometriosis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.021(0.811\u0026ndash;1.286)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.858\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.913(0.716\u0026ndash;1.164)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e0.461\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eVD is a steroid hormone, and VD deficiency is prevalent in the general population. According to the statistics of the World Health Organization, the prevalence rate of infertility among couples of childbearing age ranges globally from 9\u0026ndash;18%(\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e), and the interaction between VD and its receptor can have a variety of biological effects(\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e). Therefore, it is of great clinical significance to study the role of VD in infertile patients and the factors that influence VD levels. Over the past ten years, the proportion of VD-deficient people has increased to nearly 40%. Among them, in approximately 37.3% of the population, the VD level in the body does not reach 20 ng/ml(\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e). Studies have shown that approximately 52% of women of childbearing age worldwide are in a state of VD deficiency, and the proportion is increasing year by year. Epidemiological data show that in North America, approximately 27% of infertile patients have VD deficiency and 79% of infertile women who receive ART treatment have VD insufficiency or deficiency(\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e). In this study, VD deficiency accounted for 82.19% of the population. We suspect that VD receptor expression in reproductive organs such as the uterus and ovary has important biological effects on the growth and development of the endometrium and follicle and that general VD deficiency reduces the reproductive function of these tissues, resulting in infertility.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.1 Relationship between the season or age and the vitamin D level\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOne of the main sources of VD is the interaction between solar ultraviolet B radiation and the precursor molecule, 7-dehydrocholesterol, in the skin, which leads to VD synthesis in vivo (\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e). VD synthesis in the skin after sun exposure accounts for 80\u0026ndash;90% of its total physiological amount, and therefore, any activity that reduces sunlight exposure reduces the level of VD (\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e). In this study, the proportion of patients with VD deficiency was 82.19%, which may have been related to both the race and skin color of the study population and to total sun exposure. The results of this study showed that the VD level was correlated with the season. Considering that Henan is located at a latitude of 31\u0026deg;23\u0026prime;- 36\u0026deg;22\u0026prime;north and a longitude of 110\u0026deg;21\u0026prime;- 116\u0026deg;39\u0026prime;east, it generally has a temperate monsoon climate, specifically, a subtropical monsoon climate. The subjects of this study were all native to Henan, and thus, there was little difference in the latitude or longitude between regions. However, the four seasons are distinct in Henan, and there are obvious differences in the sun illumination time and ultraviolet intensity during different seasons. Ultraviolet rays are the strongest in the summer and last until September and October, and the results of this study showed that the VD levels were significantly higher in summer and autumn than in winter and spring (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). However, the VD level in the summer is still not the highest over the course of the year, which may be due to the excessive use of sunscreen products and the reduction in outdoor activities among women in the summer.\u003c/p\u003e\n\u003cp\u003eAge is another important factor affecting VD levels. However, with increasing age, women\u0026apos;s awareness of their health increases in terms of changes in their hormone levels, and they have good exercise habits and nutritionally balanced diets in daily life, which leads to increased VD levels among women over 30 years old. In this study, the oldest woman was 46 years old, and elderly individuals were not included in the study. In fact, among elderly individuals, with the increasing age, the skin ages and the functions of the liver, kidney and other organs that affect the synthesis of VD gradually decrease, which leads to a decrease in the ability to synthesize and transport active VD.\u003c/p\u003e\n\u003cp\u003eVD deficiency is common in patients with PCOS. However, the conclusions of previous studies have not been completely consistent. For example, it remains unclear whether there is a relationship between VD deficiency status and PCOS in infertile women(\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e).Comparison of the VD levels between patients with PCOS and in the control group showed no significant difference (11 vs. 17 ng/ml, respectively). In recent years, many related studies have shown that the VD content in patients with PCOS may be closely related to metabolic syndrome. For every 1 kg/m2 increase in BMI, the serum 25(OH)D concentration decreases by 0.75 nmol/l (\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e). Many studies have shown that the higher the proportion of obese patients is, the lower the VD content is; that is, BMI is negatively correlated with the VD content(\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e). Some studies have used quantitative insulin sensitivity indicators to determine IR and concluded that in patients with PCOS, IR was related to their physiological VD content and that the 25(OH)D3 content can be used as an independent IR-influencing factor(\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e). VD deficiency is a risk factor for IR and cardiovascular disease, which can further aggravate the metabolic abnormality of PCOS(\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e). It has been found that VD deficiency is related to IR and type 2 diabetes and increases the risk of the disease. It has also been reported that VD supplementation plays a beneficial role in the treatment of metabolic syndrome-related conditions (such as dyslipidemia, IR, hyperglycemia, obesity and hypertension) (\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e). This effect may be based on the mechanism of VD effects on different physiological parameters (including improved arterial stiffness), such as decreases in renin-angiotensin-aldosterone system activity, parathyroid hormone levels and levels of inflammatory cytokines; an increase in lipoprotein lipase activity; and improvement of phospholipid metabolism and mitochondrial oxidation(\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e). The positive correlation between VD levels and IR has been confirmed in a number of studies. Dastorani M conducted a randomized, double-blind, placebo-controlled trial of 40 infertile women aged 18\u0026ndash;40 years(\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e). The results showed that compared with placebo, VD supplementation led to significant decreases in serum AMH and insulin levels and a significant increase in a quantitative insulin sensitivity index. In addition, after VD supplementation, serum total cholesterol (5.1\u0026ndash;12.6 vs. 2.9\u0026ndash;10.9 mg/dl, p\u0026thinsp;=\u0026thinsp;0.03) and low-density lipoprotein cholesterol (4.5\u0026ndash;10.3 vs. 2.5\u0026ndash;10.6 mg/dl, p\u0026thinsp;=\u0026thinsp;0.04) levels significantly decreased. It has been concluded that VD supplementation may be beneficial for insulin and lipid metabolism in infertile women.\u003c/p\u003e\n\u003cp\u003eIn summary, a large number of studies on animals and humans have shown that there is a correlation between VD levels and female fertility. It has been determined that the season, age and abnormal islet function affect VD levels. There are many factors affecting VD levels, but the causal relationships between those are not completely clear. A large-sample prospective study is still needed to clarify the role of VD in fertility.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eVD deficiency is prevalent among infertile patients. The level of VD is affected by a woman\u0026apos;s age, the measuring season and IR. VD levels are not influenced by BMI, PCOS, blood type, family history or endometriosis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data are included in this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ei). Ethics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of the Third Affiliated Hospital of Zhengzhou University. Because this study was retrospective and did not involve the patient\u0026apos;s name, address or other identifying information, the Ethics Committee waived the requirement for patients to sign the informed consent form. we confirming that all methods were performed in accordance with the relevant guidelines and regulations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eii). Consent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConsent to publication not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eiii). Availability of Data and Material (ADM)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe original data are available to all readers upon request.Please contact the first author at [email protected] for such supporting data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eiv). Competing interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare no conflict of interest with regard to this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ev). Funding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Key Scientific Research Project of Colleges and Universities in Henan Province[20B320044] and the Medical Science and Technology Research Project of Henan Province (Joint Construction) [LHGJ20190365]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003evi). Authors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLJH and LYJ selected the population to be included and excluded, completed data statistics and analysis and wrote the manuscript. GYC participated in the review and guidance of the research. LJH,DMZ,HX,JML,YB,ZYC and WXL participated in data entry and sorting. LJH participated in the research design, guidance, and manuscript revision.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003evii).\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eChiu K, Chu A, Go V, Saad M. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. The American journal of clinical nutrition. 2004;79(5):820\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChor J, Chico P, Ayloo S, Roston A, Kominiarek MA. Reproductive health counseling and practices: A cross-sectional survey of bariatric surgeons. Surgery for Obesity \u0026amp; Related Diseases. 2015;11(1):187\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChu J, Gallos I, Tobias A, Robinson L, Coomarasamy A. Vitamin D and assisted reproductive treatment outcome: a prospective cohort study. Reproductive Health. 2019;16(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDastorani M, Aghadavod E, Mirhosseini N, Foroozanfard F, Modarres SZ, Siavashani MA, et al. The effects of vitamin D supplementation on metabolic profiles and gene expression of insulin and lipid metabolism in infertile polycystic ovary syndrome candidates for in vitro fertilization. Reproductive Biology and Endocrinology. 2018;16(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFaraji S, Alizadeh M. Mechanistic Effects of Vitamin D Supplementation on Metabolic Syndrome Components in Patients with or without Vitamin D Deficiency. Journal of Obesity \u0026amp; Metabolic Syndrome. 2020;29(4).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFatih, ?zkaya, Azam, Demirel. Vitamin D deficiency in infertile patients. Archivos Espanoles De Urologia. 2018.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFerreira P, Cangussu L, Bueloni-Dias F, Orsatti C, Schmitt E, Nahas-Neto J, et al. Vitamin D supplementation improves the metabolic syndrome risk profile in postmenopausal women. Climacteric: the journal of the International Menopause Society. 2020;23(1):24\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGonz\u0026aacute;lez L, Ramos-Trautmann G, D\u0026iacute;az-Luquis G, P\u0026eacute;rez C, Palacios C. Vitamin D status is inversely associated with obesity in a clinic-based sample in Puerto Rico. Nutrition Research. 2015;35(4):287\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHang W, Brereton RE, Anderson RA, Wallace AM, Ho C. Vitamin D deficiency is common and associated with metabolic risk factors in patients with polycystic ovary syndrome. Metabolism Clinical \u0026amp; Experimental. 2011;60(10):1475\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e. !!! INVALID CITATION !!! (Holick, Binkley et al. 2011, Hilger, Friedel et al. 2013).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKeane K, Cruzat V, Calton E, Hart P, Soares M, Newsholme P, et al. Molecular actions of vitamin D in reproductive cell biology. Reproduction. 2017;153(1):R15-R27.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMizwicki MT, Menegaz D, Yaghmaei S, Henry HL, Norman AW. A molecular description of ligand binding to the two overlapping binding pockets of the nuclear vitamin D receptor (VDR): structure-function implications. Journal of Steroid Biochemistry \u0026amp; Molecular Biology. 2010;121(1\u0026ndash;2):98\u0026ndash;105.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMousa A, Naderpoor N, Wilson K, Plebanski M, Courten BD. Vitamin D supplementation increases adipokine concentrations in overweight or obese adults. European Journal of Nutrition. 2020;59(4).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNeil, Binkley, and, Diane, Krueger, and, et al. 25-Hydroxyvitamin D Measurement, 2009: A Review for Clinicians. Journal of Clinical Densitometry. 2009;12(4):417 \u0026ndash; 27.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNgo D, Chan WP, Rajendran S, Heresztyn T, Horowitz JD. Determinants of insulin responsiveness in young women: Impact of polycystic ovarian syndrome, nitric oxide, and vitamin D. Nitric Oxide. 2011;25(3):326\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNone. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Human Reproduction. 2004;81(1):19\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRudick B, Ingles S, Chung K, Stanczyk F, Paulson R, Bendikson K. Characterizing the influence of vitamin D levels on IVF outcomes. Human Reproduction. 2012(11):3321\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWiersma T, Flikwert S, Leeuwen J, Daemers D. Vitamin D deficiency. Nederlands Tijdschrift Voor Geneeskunde. 2007;150(23):1315\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Vitamin D, Infertility, 25(OH)D, Assisted reproductive technology, Insulin resistance","lastPublishedDoi":"10.21203/rs.3.rs-1702948/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1702948/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective: \u003c/strong\u003eThe aims of this study were to study the distribution of the serum VD levels among infertile people and to analyze the relationships between VD levels and the basic conditions of infertile patients, as well as laboratory indicators.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e We retrospectively reviewed the data of 12,261 infertile patients who were treated with ART for the first time in the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University from June 2016 to December 2018. According to the serum 25(OH)D level, the patients were divided into the following two groups: the VD deficiency group (25(OH)D≤50 nmol/l) and VD nondeficiency group (25(OH)D\u0026gt;50 nmol/l). \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eRegression analysis showed that VD levels were not affected by BMI, PCOS, the blood type, family history or endometriosis (P\u0026gt;0.05). Advanced female age (\u0026gt;35 years) was a protective factor against VD deficiency; women under 35 years of age were more likely to develop VD deficiency than those over 35 years of age (P\u0026lt;0.05). The season of VD determination affected its level; the levels of VD in summer and autumn were significantly higher than those in winter and spring (P\u0026lt;0.05).They were obviously higher in spring than in winter (P\u0026lt;0.05). Insulin resistance affected VD levels; patients with insulin resistance were more prone to VD deficiency than those without insulin resistance (P\u0026lt;0.05). \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eVD deficiency exists among infertile patients. The level of VD is affected by the woman's age, the season of determination and insulin resistance. BMI, PCOS, blood type, family history and endometriosis have no influence on vitamin D levels.\u003c/p\u003e","manuscriptTitle":"Analysis of the relationship of the serum vitamin D level with infertility and associated factors","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-06-08 15:41:27","doi":"10.21203/rs.3.rs-1702948/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"286deb3f-6444-418c-bb4a-cf988769803a","owner":[],"postedDate":"June 8th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-12-23T20:29:23+00:00","versionOfRecord":[],"versionCreatedAt":"2022-06-08 15:41:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1702948","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1702948","identity":"rs-1702948","version":["v1"]},"buildId":"WvIrzKhiLBfengagbw6Ux","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}