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Serum uric acid and its association with intrauterine insemination outcomes in women with polycystic ovarian syndrome
For correspondence: Dr Yehao Dong, Department of Center for Reproductive Medicine, Affiliated Hospital of Jining Medical University, Jining, 272 029, Shandong, China e-mail: micedong@sjtu.edu.cn
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Received: ,
Accepted: ,
How to cite this article: Zhang X, Qin Q, Yang H, Yu L, Li Y, Sun R, et al. Serum uric acid and its association with intrauterine insemination outcomes in women with polycystic ovarian syndrome. Indian J Med Res. 2026;163:406-14. doi: 10.25259/IJMR_1973_2025.
Abstract
Background and objectives
Uric acid is associated with many systemic diseases. Recent evidence demonstrated that high serum uric acid levels in polycystic ovary syndrome (PCOS) could lead to a poor prognosis of in-vitro fertilisation. The objective of this study was to explore the association between serum uric acid levels and reproductive outcomes in women with PCOS undergoing intrauterine insemination (IUI) treatment.
Methods
We included 682 patients with PCOS who underwent IUI treatment between 2015 and 2024. They were stratified into three groups according to the level of serum uric acid: normal (251-360 µmol/L), low (≤250 µmol/L), and high (>360 µmol/L). Pregnancy and obstetric outcomes of patients were evaluated and linked to serum uric acid levels. The primary outcome measures of this study were the clinical pregnancy rate and live birth rate. Secondary outcome measures included the rates of biochemical pregnancy, ectopic pregnancy, miscarriage, and low birth weight.
Results
There was no significant difference between the three groups with respect to clinical pregnancy rate (23.3% vs. 26.2% vs. 30.4%) and live birth rate (86.2% vs. 81.5% vs. 93.6%). Biochemical pregnancy rate (25.1% vs. 28.2% vs. 35.3%), ectopic pregnancy rate (3.5% vs. 1.9% vs. 3.2%), miscarriage rate (10.4% vs. 16.7% vs. 3.2%), and low-birth-weight rate (14.6% vs. 12.5% vs. 19.4%) were comparable among the three groups.In terms of birth weight, the three study groups showed comparable values (3122.8±81.10 vs. 3095.6±68.96 vs. 3099.5±162.09 g), and no significant difference was observed. These results remained the same after adjusting for baseline clinical characteristics and in-hospital treatment.
Interpretation and conclusions
Our findings demonstrated that maternal pre-pregnancy serum uric acid level was not significantly related to pregnancy and obstetric outcomes following IUI treatment in women with PCOS.
Keywords
Infertility
Intrauterine insemination
Polycystic ovary syndrome
Reproductive outcomes
Uric acid
Uric acid is the final product of purine metabolism in the human body, which possesses dual biological properties of antioxidant and pro-oxidant activities.1 Growing evidence indicates that serum uric acid levels tend to be higher in women with polycystic ovary syndrome (PCOS) and correlate with clinical severity.2,3 The prevalence of hyperuricemia in the PCOS population is approximately three times higher than that in those without PCOS.4 A recent study demonstrated that each 50 µmol/L serum uric acid increase correlated with a 16 g reduction in neonatal birth weight and a 0.06 wk decrease in gestational age in women undergoing IVF/ICSI.5 However, there are no studies evaluating the impact of pre-pregnancy serum uric acid levels on intrauterine insemination (IUI) outcomes among the PCOS population. We aimed to explore the relationship between serum uric acid in infertile females with PCOS and their reproductive outcomes of IUI cycles.
Methods
This retrospective study was undertaken by the Department of Reproductive Medicine, Affiliated Hospital of Jining Medical University, China. The present work was carried out in accordance with the principles of the Declaration of Helsinki and was approved by the ethics committee of the hospital. No informed consent was required as this was a retrospective study without any intervention or influence on clinical treatment.
Study population
A total of 682 cycles of IUI conducted in the reproductive centre of the Affiliated Hospital of Jining Medical University from 2015 to 2024 were retrospectively analysed. The inclusion criteria of this study were as follows: (i) participant (recipient) age between 20 and 40 yr; (ii) duration of infertility ≥1 yr; (iii) more than 10 million motile sperm per ejaculate (in donor); (iv) at least one patent fallopian tube (in recipient). The exclusion criteria were the following: (i) women without PCOS; (ii) recipient’s body mass index (BMI) more than 30 kg/m2; (iii) using sperm from a sperm bank; (iv) uterine malformations (single-horned uterus, double uterus, and septate uterus); (v) endocrine abnormalities such as thyroid dysfunction, hyperprolactinemia, and hypogonadotropic hypogonadism; and (vi) chronic diseases including diabetes, hypertension, and autoimmune diseases.
According to the diagnostic criterion, serum uric acid level ≤360 µmol/L in premenopausal women was regarded as normal, while >360 µmol/L was clinically defined as hyperuricemia.6,7 However, recent studies revealed that low serum uric acid concentration (≤250 µmol/L) diminished the antioxidant capacity of plasma and appeared to be related to adverse clinical outcomes.8-10 Thus, 250 µmol/L was used as the lower cut-off value of the normal range of serum uric acid in our research. Based on serum uric acid level, the study population was categorised into three groups: normal (251-360 µmol/L), low (≤250 µmol/L), and high (>360 µmol/L).
Data collection
Hospital information system and patient records were used to identify all PCOS patients undergoing IUI treatment. The baseline demographic information, including age, BMI, education level, and smoking status, was collected. Detailed patient data, like history of infertility and number of IUI cycles, were retrieved. The laboratory parameters, including levels of circulating serum follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol, prolactin (PRL), testosterone, progesterone, anti-Müllerian hormone (AMH), thyroid-stimulating hormone (TSH), fasting blood glucose (FBG), and uric acid, were also noted. Data on endometrial thickness and antral follicle count (AFC) was extracted from the ultrasound reports.
The natural cycle was adopted for women with regular menstrual cycles. Patients having irregular menstruation, ovulation disorders, or unexplained subfertility underwent ovarian stimulation. The detailed description of these protocols and procedures can be found in our previous publication.11 Operational records provided the clinically relevant semen parameters, ovarian stimulation, and IUI protocol for each patient.
Pregnancy outcome assessment
A biochemical pregnancy test (positive human chorionic gonadotropin test) was initially administered 14 days after IUI to determine if the woman was pregnant. Once the test result was positive, transvaginal sonography at the seventh week of gestation was performed to confirm clinical pregnancy by detecting the presence of a gestational sac and foetal heartbeat. The termination of a pregnancy before 28 wk of gestation or foetal weight less than 1000 g was considered a miscarriage. Ectopic pregnancy refers to the presence of one or more gestational sacs outside the uterine cavity. A live birth was defined as the delivery of an infant exhibiting vital signs such as heartbeat, breathing, umbilical cord pulsation, or voluntary muscle contraction at 28 wk or more of gestation. Low-birth-weight (LBW) was regarded as the birth weight of an infant less than 2500 g.
Statistical analysis
Continuous variables are presented as mean±standard error (SE), and assumption testing was performed using Kruskal-Wallis to compare statistically significant differences among multiple groups. Categorical variables were expressed as numbers (n) and percentages (%), and the chi-square test or Fisher’s exact test was conducted for comparison of proportions. Median values were used to replace missing values for continuous variables, and modes were used to replace missing categorical variables. All covariates identified as statistically significant in the univariate analysis were included in the logistic regression to adjust for the relationship between serum uric acid levels and reproductive outcomes. Before logistic regression, we examined the collinearity between independent variables by calculating the tolerance and the variance inflation factor. The results showed that the tolerance of each variable was greater than 0.1, and the variance inflation factor was less than 10, indicating that there was no multicollinearity among the variables. The following adjustments were made: Model 1: no adjustment; Model 2: adjusted for age and BMI in women; Model 3: additionally adjusted for age at menarche, type of infertility, indication for IUI, basal LH, basal testosterone, FBG, SBP, normal sperm morphology, total motility, progressive motile sperm, treatment protocol, and ovarian stimulation protocol. The odds ratio (OR) and corresponding 95 per cent confidence interval (CI) were calculated to indicate the effect size and assess the reliability of the model. All data analyses were performed using SPSS version 27.0 (IBM Corp., Armonk, NY, USA). P less than 0.05 was regarded as significant.
Results
Figure shows the flowchart of the study.
- Flow chart of the study. IUI, intrauterine insemination; BMI, body mass index; PCOS, polycystic ovary syndrome.
Baseline characteristics of study population
Table Ⅰ compares the demographic and clinical characteristics of study participants categorised by serum uric acid levels.
| Variable | Normal serum uric acid group (n=374) | Low serum uric acid group (n=206) | High serum uric acid group (n=102) | P value |
|---|---|---|---|---|
| Serum uric acid, μmol/L | 299.8 ± 1.53 | 213.4 ± 1.86 | 406.7 ± 4.24 | |
| Female | ||||
| Age, yr | 28.7 ± 0.19 | 29.0 ± 0.23 | 27.5 ± 0.37 | 0.008 |
| BMI, kg/m2 | 23.7 ± 0.16 | 22.6 ± 0.21 | 26.1 ± 0.24 | <0.001 |
| Education | 0.641 | |||
| Less than high school | 24.6% (92/374) | 25.2% (52/206) | 28.4% (29/102) | |
| High school | 21.1% (79/374) | 16.5% (34/206) | 17.7% (18/102) | |
| More than high school | 54.3% (203/374) | 58.3% (120/206) | 53.9% (55/102) | |
| Age at menarche, yr | 13.7 ± 0.06 | 13.9 ± 0.09 | 13.3 ± 0.13 | 0.002 |
| Menstrual cycle, d | 55.2 ± 1.76 | 53.5 ± 1.66 | 56.7 ± 3.21 | 0.673 |
| Endometrial thickness, mm | 5.7 ± 0.11 | 5.6 ± 0.12 | 5.9 ± 0.19 | 0.400 |
| Duration of infertility, yr | 2.5 ± 0.08 | 2.5 ± 0.11 | 2.2 ± 0.16 | 0.098 |
| Type of infertility | 0.002 | |||
| Primary | 58.6% (219/374) | 61.7% (127/206) | 77.5% (79/102) | |
| Secondary | 41.4% (155/374) | 38.4% (79/206) | 22.6% (23/102) | |
| Indication for IUI | 0.014 | |||
| Female factor | 19.3% (72/374) | 25.2% (52/206) | 15.7% (16/102) | |
| Male factor | 26.2% (98/374) | 22.3% (46/206) | 29.4% (30/102) | |
| Both factor | 13.6% (51/374) | 6.3% (13/206) | 5.9% (6/102) | |
| Unexplained | 40.9% (153/374) | 46.1% (95/206) | 49.0% (50/102) | |
| Number of IUI cycles, n | 1.6 ± 0.04 | 1.5 ± 0.05 | 1.7 ± 0.10 | 0.383 |
| Basal FSH, mIU/mL | 6.79 ± 0.08 | 6.97 ± 0.13 | 6.66 ± 0.15 | 0.384 |
| Basal LH, mIU/mL | 10.26 ± 0.40 | 11.82 ± 0.68 | 10.18 ± 0.82 | 0.016 |
| Basal oestradiol, pg/mL | 70.19 ± 10.63 | 86.27 ± 15.67 | 58.53 ± 8.38 | 0.097 |
| Basal PRL, ng/mL | 14.05 ± 0.35 | 14.36 ± 0.51 | 16.14 ± 0.87 | 0.148 |
| Basal testosterone, ng/mL | 0.59 ± 0.02 | 0.54 ± 0.02 | 0.65 ± 0.03 | <0.001 |
| Basal progesterone, ng/mL | 0.67 ± 0.03 | 1.09 ± 0.31 | 0.89 ± 0.13 | 0.429 |
| AMH, ng/mL | 9.68 ± 0.27 | 9.42 ± 0.34 | 8.43 ± 0.46 | 0.098 |
| TSH, mIU/L | 2.31 ± 0.06 | 2.19 ± 0.07 | 2.46 ± 0.13 | 0.540 |
| AFC, n | 30.5 ± 0.61 | 28.1 ± 0.64 | 29.2 ± 0.86 | 0.058 |
| FBG, mmol/L | 5.0 ± 0.03 | 4.9 ± 0.04 | 5.1 ± 0.05 | 0.007 |
| DBP, mmHg | 74 ± 0.39 | 74 ± 0.48 | 75 ± 0.73 | 0.108 |
| SBP, mmHg | 115 ± 0.54 | 115 ± 0.63 | 119± 1.00 | <0.001 |
| Male | ||||
| Age, yr | 29.5 ± 0.19 | 29.6 ± 0.25 | 28.8 ± 0.34 | 0.302 |
| BMI, kg/m2 | 25.7 ± 0.22 | 25.9 ± 0.29 | 25.6 ± 0.46 | 0.536 |
| Smoking | 11.0% (41/374) | 14.1% (29/206) | 9.8% (10/102) | 0.433 |
| Raw semen | ||||
| Semen volume, mL | 2.7 ± 0.03 | 2.7 ± 0.04 | 2.8 ± 0.05 | 0.054 |
| Semen concentration, ×106 per mL | 33.5 ± 0.63 | 33.1 ± 0.88 | 31.8 ± 0.91 | 0.812 |
| Total motility, % | 58.5 ± 0.56 | 58.4 ± 0.70 | 58.0 ± 1.10 | 0.994 |
| Variable | Normal serum uric acid group (n=374) | Low serum uric acid group (n=206) | High serum uric acid group (n=102) | P value |
| Progressive motile sperm, % | 34.7 ± 0.46 | 35.0 ± 0.51 | 34.2 ± 0.87 | 0.781 |
| Normal sperm morphology, % | 4.2 ± 0.11 | 4.4 ± 0.14 | 4.1 ± 0.12 | 0.006 |
| Prepared semen | ||||
| Semen volume, mL | 0.4 ± 0.00 | 0.4 ± 0.00 | 0.4 ± 0.00 | 0.487 |
| Semen concentration, ×106 per mL | 62.6 ± 1.11 | 63.9 ± 1.49 | 64.1 ± 1.76 | 0.247 |
| Total motility, % | 82.0 ± 0.43 | 82.5 ± 0.58 | 79.4 ± 1.05 | 0.018 |
| Progressive motile sperm, % | 68.4 ± 0.44 | 69.3 ± 0.59 | 65.8 ± 1.04 | 0.006 |
| Normal sperm morphology, % | 7.7 ± 0.27 | 7.8 ± 0.32 | 6.9 ± 0.20 | 0.081 |
BMI, body mass index; IUI, intrauterine insemination; FSH, follicle-stimulating hormone; LH, luteinizing hormone; PRL, prolactin; AMH, anti-Müllerian hormone; TSH, thyroid-stimulating hormone; AFC, antral follicle count; FBG, fasting blood glucose; DBP, diastolic blood pressure; SBP, systolic blood pressure
Comparisons of ovarian stimulation protocols
A total of 317 natural cycles and 365 stimulated cycles were enrolled in the analysis. In stimulated cycles, patients were given clomiphene citrate (CC), letrozole (LE), human menopausal gonadotropin (HMG), or FSH before the operation. As shown in Table Ⅱ, the percentage of women who underwent stimulation cycles was significantly lower in the low uric acid group compared to those with high uric acid. Based on the medication scheme, all ovarian stimulation protocols were divided into three categories: LE/LE + HMG, CC/CC + HMG, and FSH/HMG. Treatment and ovarian stimulation protocols in these groups are compared in Table II.
| Variable | Normal serum uric acid group (n=374) | Low serum uric acid group (n=206) | High serum uric acid group (n=102) | P value |
|---|---|---|---|---|
| Treatment protocol | 0.027 | |||
| Natural cycle | 46.8% (175/374) | 51.5% (106/206) | 35.3% (36/102) | |
| Ovarian stimulation cycle | 53.2% (199/374) | 48.5% (100/206) | 64.7% (66/102) | |
| Ovarian stimulation protocol | 0.037 | |||
| LE/LE + HMG | 68.3% (136/199) | 82.0% (82/100) | 72.7% (48/66) | |
| CC/CC + HMG | 20.6% (41/199) | 12.0% (12/100) | 24.2% (16/66) | |
| FSH/HMG | 11.1% (22/199) | 6.0% (6/100) | 3.0% (2/66) |
HMG, Human menopausal gonadotropin; LE, Letrozole; CC, Clomiphene citrate
Pregnancy and obstetric outcomes in women with PCOS
Table Ⅲ shows the proportions of different reproductive outcomes of our participants. There was no ascending or descending trend in the biochemical pregnancy rate with the alteration of serum uric acid. Other pregnancy outcomes, such as clinical pregnancy rate, ectopic pregnancy rate, and birth weight, were consistent with this result. To confirm the stability of results, we used logistic regression to evaluate the association between serum uric acid levels and reproductive outcomes in the unadjusted model and adjusted models (Table Ⅳ). No significant differences in terms of pregnancy and obstetric outcomes were noted between the groups.
| IUI outcomes | Normal serum uric acid group (n=374) | Low serum uric acid group (n=206) | High serum uric acid group (n=102) | P value |
|---|---|---|---|---|
| Biochemical pregnancy rate | 25.1% (94/374) | 28.2% (58/206) | 35.3% (36/102) | 0.123 |
| Clinical pregnancy rate | 23.3% (87/374) | 26.2% (54/206) | 30.4% (31/102) | 0.314 |
| Ectopic pregnancy rate | 3.5% (3/87) | 1.9% (1/54) | 3.2% (1/31) | 1.000 |
| Miscarriage rate | 10.4% (9/87) | 16.7% (9/54) | 3.2% (1/31) | 0.166 |
| Live birth rate | 86.2% (75/87) | 81.5% (44/54) | 93.6% (29/31) | 0.325 |
| Pregnancy type | 1.000 | |||
| Single on Pregnancy | 78.2% (68/87) | 74.1% (40/54) | 87.1% (27/31) | |
| Multiple | 8.1% (7/87) | 7.4% (4/54) | 6.5% (2/31) | |
| Birth weight, g | 3122.8 ± 81.10 | 3095.6 ± 68.96 | 3099.5 ± 162.09 | 0.450 |
| LBW rate | 14.6% (12/82) | 12.5% (6/48) | 19.4% (6/31) | 0.703 |
LBW, low-birth-weight
| IUI outcomes | OR (95% CI) | P value | ||
|---|---|---|---|---|
| Normal serum uric acid group | Low serum uric acid group | High serum uric acid group | ||
| Biochemical pregnancy | ||||
| Model 1 | Ref | 1.17 (0.80-1.71) | 1.63 (1.02-2.60) | 0.125 |
| Model 2 | Ref | 1.15 (0.78-1.70) | 1.67 (1.02-2.74) | 0.120 |
| Model 3 | Ref | 1.24 (0.83-1.85) | 1.83 (1.09-3.07) | 0.064 |
| Clinical pregnancy | ||||
| Model 1 | Ref | 1.17 (0.79-1.74) | 1.44 (0.89-2.34) | 0.316 |
| Model 2 | Ref | 1.15 (0.77-1.72) | 1.50 (0.90-2.50) | 0.284 |
| Model 3 | Ref | 1.22 (0.81-1.84) | 1.62 (0.95-2.76) | 0.182 |
| Miscarriage | ||||
| Model 1 | Ref | 1.73 (0.64-4.68) | 0.29 (0.04-2.38) | 0.197 |
| Model 2 | Ref | 2.13 (0.76-5.96) | 0.22 (0.03-1.84) | 0.081 |
| Model 3 | Ref | 2.11 (0.49-9.13) | 0.17 (0.01-2.18) | 0.106 |
| Live birth | ||||
| Model 1 | Ref | 0.70 (0.28-1.76) | 2.32 (0.49-11.01) | 0.325 |
| Model 2 | Ref | 0.59 (0.23-1.53) | 3.14 (0.63-15.54) | 0.135 |
| Model 3 | Ref | 0.59 (0.16-2.21) | 4.69 (0.68-32.32) | 0.089 |
| LBW | ||||
| Model 1 | Ref | 0.83 (0.29-2.39) | 1.40 (0.48-4.13) | 0.705 |
| Model 2 | Ref | 0.84 (0.29-2.42) | 1.41 (0.45-4.35) | 0.736 |
| Model 3 | Ref | 1.14 (0.27-4.78) | 0.77 (0.15-4.09) | 0.919 |
OR, odds ratio; CI, confidence interval; Ref, reference; LBW, low-birth-weight
Model 1: unadjusted model; Model 2: adjusted for age and BMI; Model 3: adjusted for the variables in Model 2 plus age at menarche, type of infertility, indication for IUI, basal LH, basal testosterone, FBG, SBP, normal sperm morphology, total motility, progressive motile sperm, treatment protocol, and ovarian stimulation protocol
Discussion
In the present study, we did not find any correlation between pre-pregnancy serum uric acid levels in patients with PCOS and the rates of biochemical pregnancy, clinical pregnancy, ectopic pregnancy, and miscarriage following IUI. Currently, there are scarce and controversial data on whether uric acid affects delivery outcomes in women with PCOS undergoing in-vitro fertilisation (IVF) treatment.5,12,13 A study by Yang et al12 showed that as the serum uric acid level increased, the live birth rate of women undergoing their first fresh-embryo transfer cycles exhibited an overall decreasing trend both in the unadjusted and adjusted generalised additive models. Wu et al5 found that the impact of serum uric acid on live birth in PCOS is not universal. In our study, no difference in live birth rate was observed among groups of women undergoing IUI, and the result remained the same after adjusting for potential confounders. Elevated levels of serum uric acid have been shown to increase the risk of LBW in women with PCOS following IVF.12 We did not observe any such risk.
In 2024, Gong et al2 observed significant positive correlations between serum uric acid levels and FBG, fasting insulin, and homeostatic model assessment of insulin resistance, and our results are consistent with this finding. In our study, patients with hyperuricemia had the highest levels of FBG, far exceeding those in other groups. A previous retrospective cross-sectional study performed at a large reproductive medicine centre reported that 25.5% of women with PCOS suffered from hyperuricemia,4 slightly higher than that in our study (15.0%). This difference might be attributed to our exclusion of obese individuals (BMI >30 kg/m2). Local hypoxia in adipose tissue of obese patients could augment uric acid production by enhancing xanthine oxidoreductase activity.14 The accumulation of visceral fat induces a large influx of plasma free fatty acids into the portal vein and liver, thereby stimulating triglyceride production and subsequently elevating uric acid secretion by activating the uric acid synthesis pathway.15 It was reported that 58.8% of obese women with PCOS had hyperuricemia, which was almost three times higher than that in those with a normal BMI.4 Thus, we had to rule it out as a confounding factor in our study.
Existing evidence on the association between serum uric acid levels and sex hormones is limited and inconclusive. The generally prevailing opinion is that high levels of testosterone are closely correlated with elevated serum uric acid levels and prevalence of hyperuricemia. A 1H nuclear magnetic resonance-based plasma metabolomics analysis indicated that PCOS patients with hyperandrogenism had higher serum uric acid levels than those with polycystic ovaries and anovulation.16 Furthermore, some reports have shown that serum uric acid levels increase with increasing testosterone levels in postmenopausal women.17,18 This effect may be due to testosterone-induced functional modifications in the renal uric acid reabsorption system via upregulation of sodium-coupled monocarboxylate transporter 1.19 Previous animal studies also suggested that testosterone might increase serum uric acid levels by affecting the normal liver cell function, purine nucleotide, and nucleic acid metabolism.20,21 However, a recent study by Tan et al22 claimed that genetically predicted total testosterone levels were negatively associated with serum uric acid levels. In patients undergoing controlled ovarian hyperstimulation during IVF cycles, Yan et al23 did not find any correlation between levels of serum uric acid and testosterone. Our present results showed that serum uric acid levels exhibited a positive relationship with testosterone in women with PCOS. These differences are probably caused by the different populations examined and require further research to reveal this relationship. In addition, Jung et al24 examined the impacts of different types of hormone therapy on serum uric acid levels and ascribed the reduction to the effects of other reproductive hormones rather than oestradiol, which is consistent with our result showing that oestradiol is not linked to serum uric acid in women with PCOS.
To the best of our knowledge, this is the first study to explore the effect of serum uric acid level on reproductive outcomes following IUI in women with PCOS. Some limitations should also be considered. The retrospective cohort design relies on the accuracy and completeness of recorded data, which may introduce inherent bias. Despite adjustment for multiple potential confounders, there may still be hidden confounding factors that could influence the results. Results are from a single centre, which might restrict the generalisability of the findings. Therefore, it will be necessary to perform further research with large multicentre samples and evaluate additional confounding factors to confirm the results of our study.
To conclude, serum uric acid levels are not correlated with pregnancy or obstetric outcomes in women with PCOS undergoing IUI. This evidence-based finding optimises clinical decision-making, alleviates patient anxiety, and avoids unnecessary uric acid monitoring.
Acknowledgment
Authors acknowledge all working staff at the Centre for Reproductive Medicine of the Affiliated Hospital of Jining Medical University for their active involvement and collaboration in project administration. Moreover, the authors are sincerely grateful for the participants in this study.
Author contributions
XZ: Concepts, study design, data acquisition, provided clinical samples; QQ: Concepts, study design, data acquisition, provided clinical samples; HY: Data analysis, manuscript writing, data interpretations; LY: Data analysis and interpretations, manuscript writing; YL: manuscript writing; RS: manuscript writing; SW: manuscript writing; XW: manuscript writing; FC: Concepts, study design, data analysis, data interpretations; YD: Concepts, study design, data acquisition, provided clinical samples, data interpretations. All authors have read and approved the final printed version of the manuscript.
Financial support and sponsorship
The study received funding support from the Excellent Youth Innovation Team Project of Shandong Higher Education Institutions (project no 2024KJJ006) awarded to ninth author (FC).
Conflicts of Interest
None.
Use of Artificial Intelligence (AI)-Assisted Technology for manuscript preparation
The authors confirm that there was no use of AI-assisted technology for assisting in the writing of the manuscript and no images were manipulated using AI.
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