
OBJECTIVE:We aim to clarify the comparative clinical efficacy of ovulation induction and artificial cycle (AC) protocols for frozen-thawed embryo transfer (FET) in reproductive-aged women with polycystic ovary syndrome (PCOS), given the conflicting findings and ongoing controversy surrounding this issue in existing studies. METHODS:This was a retrospective cohort study conducted at a public fertility center in China, which included a total of 1331 women with PCOS who underwent FET between January 2021 and December 2024; the study compared the efficacy of two endometrial preparation interventions during FET, ovulation induction cycles (n = 543) and AC (n = 788). The primary outcome measure was live birth rate, while the secondary outcome measures were categorized into three types: clinical outcomes, maternal outcomes and perinatal outcomes. RESULTS:Endometrial thickness on the day of progesterone administration was significantly greater in the ovulation induction group (10.3 (9.0-12.2) vs. 9.2 (8.0-10.8), p < 0.001) than in the AC group. Following adjustment for potential confounding factors, the ovulation induction cycle group exhibited a significantly higher clinical pregnancy rate (59.5% vs. 51.5%, aOR = 1.3, 95%CI: 1.1-1.7) and live birth rate (48.8% vs. 39.7%, aOR = 1.4, 95%CI: 1.1-1.7) relative to the artificial cycle group. Perinatal outcomes were comparable between AC and ovulation induction. CONCLUSIONS:In conclusion, ovulation induction significantly improves live birth rates over artificial cycles in PCOS women undergoing FET, with comparable perinatal safety. Despite the limitations of retrospective, single-center data, this study provides real-world evidence to guide endometrial preparation. Prospective randomized trials are warranted to confirm these findings.
OBJECTIVE:To examine the effect of DT56a (Femarelle®), a non-hormonal oral treatment for the management of menopause, on symptoms of vulvovaginal atrophy (VVA)/genitourinary syndrome of menopause (GSM) in postmenopausal women. METHODS:Twelve (n = 12) postmenopausal women with severe VVA (100% parabasal cells on cervical cytology) and at least one severe VVA symptom were recruited for a 12-week open-label pilot study. At baseline and week 12, participants underwent physical examination, Pap smear, vaginal ultrasound, vaginal cultures, vaginal pH assessment, and vaginal maturation index evaluation. Subjects also completed questionnaires assessing atrophy symptoms and quality of life using the Utian Quality of Life (UQoL) scale. Follow-up at 24 months was available for several participants. RESULTS:After 12 weeks of treatment, all patients showed a significant reduction in vaginal pH. In addition, 11 of the 12 women demonstrated significant improvement in the vaginal maturation index and UQoL questionnaire scores. CONCLUSIONS:DT56a significantly improved subjective and objective parameters of VVA/GSM, including vaginal pH, vaginal maturation index, and quality of life. These findings support its potential role as a non-hormonal systemic treatment option for women with VVA/GSM.
OBJECTIVE:Endometriosis faces diagnostic delays due to the lack of tools for diagnostic evaluation. The value of miR-4677-3p combined with ultrasound in the diagnosis of endometriosis. METHODS:110 healthy subjects and 110 endometriosis patients were recruited. miR-4677-3p level was detected by qRT-PCR. Color Doppler ultrasound was used to measure uterine artery blood flow parameters. Pearson analysis was applied to explore the correlation between miR-4677-3p and blood flow parameters. ROC curve was used to evaluate the diagnostic value. Logistic regression analysis was performed to identify risk factors. RESULTS:miR-4677-3p serum expression in endometriosis patients was upregulated, EDV and PSV were decreased, while PI and RI were increased. miR-4677-3p level was negatively correlated with RI and PI, and positively correlated with EDV and PSV. miR-4677-3p has diagnostic value for endometriosis, with an AUC of 0.863. After combination with ultrasound parameters, the AUC increased to 0.925, indicating a superior diagnostic value for endometriosis. Aberrantly expressed miR-4677-3p, dysmenorrhea, and CA125 as risk factors. CONCLUSION:The combined application of serum miR-4677-3p and ultrasound parameters can improve the diagnostic efficiency of endometriosis, providing a clinical tool for the accurate identification of the disease.
OBJECTIVE:Circular RNAs (circRNAs) are important regulators of human disease, yet their specific mechanistic role in postmenopausal osteoporosis (PMOP) remains unclear. This study aimed to investigate the expression pattern, diagnostic value, and biological function of hsa_circ_0003254. METHODS:This study enrolled 207 postmenopausal females grouped into osteopenia (OPn, n = 72), osteoporosis (OP, n = 85), and healthy controls (Health, n = 50). RT-qPCR was employed to detect expression differences of hsa_circ_0003254, receiver operating characteristic (ROC) analysis, and logistic regression were utilized to assess its diagnostic value. The functional role of hsa_circ_0003254 in osteogenesis was assessed by transfecting hBMSCs with pcDNA-circ or si-circ. Western blot analysis was performed to determine the protein levels of RUNX2, ALP, and OCN. RESULTS:Analysis of the clinical cohort revealed that the expression of hsa_circ_0003254 was significantly elevated in patients with OPn and OP compared to healthy controls. Its expression level showed a significant positive correlation with both the PINP and the CTX-1. ROC analysis confirmed the diagnostic efficacy of hsa_circ_0003254 for PMOP, distinguishing healthy controls from OP patients (AUC = 0.876) and differentiating OPn from OP patients (AUC = 0.934). Multivariate logistic regression analysis confirmed hsa_circ_0003254 as a risk factor for PMOP (OR = 18.507, p < 0.001). Functionally, Osteogenic induction downregulated hsa_circ_0003254. Overexpression suppressed ALP activity, cell viability, and osteogenic gene expression (ALP, RUNX2, OCN), while knockdown enhanced all these parameters. CONCLUSIONS:Hsa_circ_0003254 may serve as a potential circulating biomarker for PMOP. Its elevated expression might participate in osteoporosis progression by regulating osteogenic differentiation.
Objective This study aimed to examine the association between body roundness index (BRI) and female infertility.Method This cross-sectional study utilized data from the National Health and Nutrition Examination Survey from 2013 to 2020. BRI was calculated using standardized measurements of height and waist circumference. Multivariable logistic regression models assessed the relationship between BRI and infertility, adjusting for potential confounders. Subgroup analyses examined the stability of the relationship between BRI and infertility, and smooth-fitting curves were applied to explore the linear or non-linear relationship between them.Results Among the participants, 483 (13.43%) women were diagnosed with infertility. BRI was positively related to infertility (adjusted odds ratio [OR] 1.09; 95% confidence interval [CI] 1.05, 1.13). When categorized into tertiles, women in the highest BRI tertile had a 78% higher risk of infertility (OR 1.78; 95% CI 1.37, 2.32) compared with the lowest tertile. Subgroup analyses revealed potential interactions of age and pregnancy history regarding the association between BRI and infertility, showing an S-shaped relationship in women under 36 years and those without a pregnancy history.Conclusion BRI is positively correlated with infertility in United States women. This finding suggests that BRI could serve as a valuable predictor in female infertility assessment.
Objective Female infertility is an escalating global health challenge. Utilizing data from the Global Burden of Disease Study 2021, this study analyzed the spatiotemporal distribution of female infertility (1990–2021) and projected trends through 2050.Methods We evaluated prevalence, disability-adjusted life years (DALYs), and age-standardized rates across 204 countries, stratified by Socio-demographic Index (SDI). Temporal trends were quantified using Estimated Annual Percentage Change (EAPC), and future burdens were forecasted via Bayesian Age-Period-Cohort models.Results Global female infertility cases surged by 84.4%, rising from 59.69 million in 1990 to 110.09 million in 2021, with the age-standardized prevalence rate (ASPR) trending upward (EAPC=0.70). While High-middle and Middle SDI regions bore the largest absolute burden—driven by persistent infections and metabolic risks—High SDI regions exhibited the steepest increase (EAPC=1.43). This rapid rise in developed nations aligns with delayed childbearing, evidenced by a peak prevalence shift to the 40–44 age group, contrasting with the global peak at 35–39 years. Projections indicate a continued ascent in burden across all cohorts through 2050.Conclusions The global burden of female infertility is rising and spatially distinct. Transitioning economies face high baseline rates, yet developed nations show the fastest growth, demanding urgent action. Strategies must be tailored to regional drivers: prioritizing infection control and metabolic health in middle-income settings, and fertility support policies in high-income regions.
Background Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder whose terminology inadequately reflects its systemic nature. The proposed renaming to polyendocrine metabolic ovary syndrome (PMOS) aims to better represent its pathophysiology.Objective To present the European Society of Gynaecology (ESG) position regarding the proposed terminology change and its implementation.Methods Expert consensus and narrative synthesis of current scientific evidence and international recommendations.Results ESG supports a structured, patient-centered transition strategy. Recommendations include prioritizing patient communication, implementing a gradual transition with prolonged dual terminology use, and integrating the new terminology systematically into scientific and educational frameworks. The importance of interdisciplinary clarity and the central role of gynecological endocrinology are emphasized.Conclusion A phased and clearly communicated transition will enhance conceptual accuracy while preserving patient understanding, continuity of care, and clinical coordination.
Peripheral precocious puberty (PPP) is a rare condition in early childhood, particularly among girls under 3 years of age. One cause of PPP is functional ovarian cysts that secrete estrogen at levels sufficient to trigger the development of premature secondary sexual characteristics. Unilateral ovarian agenesis is an uncommon congenital anomaly. The coexistence of both conditions in a single patient is extremely rare and poses unique diagnostic and management challenges. We report the case of a 2-year and 10-month-old girl presenting with concurrent breast development, pubarche, and recurrent vaginal bleeding. Pelvic imaging revealed a cyst in the left ovary and agenesis of the right ovary. Laparoscopy confirmed absence of the right ovary and ipsilateral fallopian tube. Based on clinical, hormonal, and radiologic findings, a diagnosis of PPP due to a functional ovarian cyst was made. Given the rapid progression of symptoms, increase in cyst size, and concern for torsion, a short observation period of three months was followed by ovarian-preserving laparoscopic cystectomy. Histopathology confirmed a benign follicular cyst. Postoperatively, the patient experienced partial regression of pubertal signs and complete resolution of vaginal bleeding. This case highlights the importance of individualized decision-making in managing PPP,especially in the presence of congenital anomalies.
OBJECTIVE:Women with Turner syndrome (TS) are at increased risk of reduced bone mineral density (BMD) due to primary ovarian insufficiency. This study aimed to assess longitudinal changes in BMD in TS patients receiving oral or transdermal hormone replacement therapy (HRT) and to identify factors associated with bone density decline. METHODS:This retrospective pilot study included 40 TS patients treated with oral or transdermal estradiol. The median age was 22 years in both the transdermal (20-30) and oral (20-27) groups. Median BMI was 23.1 (21.1-25.5) and 25.4 (22.1-29.1), respectively. Dual-energy X-ray absorptiometry (DEXA) of the lumbar spine and femoral neck was performed at baseline and follow-up. The primary outcome was the t-score at both sites. Univariable and multivariable logistic regression analyses were used to identify factors associated with declining t-scores. RESULTS:At baseline, 38.3% of patients had osteopenia, and 3.3% had osteoporosis. During follow-up, a decline in t-scores at at-least one skeletal site was observed in 47.5% of patients. No significant differences were found between oral and transdermal estradiol therapy regarding absolute t-scores, t-score changes, or the proportion of patients with declining t-scores (all p > 0.05). In multivariable analysis, lower vitamin D levels at follow-up were independently associated with declining t-scores. CONCLUSIONS:In TS patients, the route of estradiol administration did not significantly affect long-term BMD outcomes. Despite HRT, a substantial proportion of patients experienced bone loss. Vitamin D status has emerged as the most relevant modifiable factor associated with declining BMD, highlighting the need for bone health management beyond HRT.
OBJECTIVE:To review recent evidence on the association between progestin exposure and meningioma risk and to propose practical recommendations for hormonal management in women requiring progestin therapy. METHODS:A narrative review of studies published between 2015 and 2025 evaluating the relationship between exogenous progestins and meningioma development, growth, or progression was performed. Evidence regarding different progestin compounds, cumulative exposure, reversibility after discontinuation, and implications for gynecologic practice was analyzed. RESULTS:Meningiomas account for more than one-third of intracranial tumors and occur two to three times more frequently in women, supporting a potential hormonal influence mediated by progesterone receptors, which are expressed in most tumors. The increasing use of MRI has led to more frequent detection of incidental meningiomas in premenopausal women using progestins for contraception or gynecologic conditions such as endometriosis and heavy menstrual bleeding. Consistent associations with increased meningioma risk were observed for high-dose or prolonged exposure to cyproterone acetate, chlormadinone acetate, nomegestrol acetate, and medroxyprogesterone acetate. Risk appeared to increase with cumulative exposure and decrease after treatment discontinuation. Evidence for other progestins, including desogestrel, dienogest, levonorgestrel, and the levonorgestrel-releasing intrauterine system, remains limited and less conclusive. CONCLUSIONS:Women's health specialists should systematically assess a history of meningioma before prescribing progestins. In patients with incidental meningioma, discontinuation of high-risk progestins should be considered, followed by MRI reassessment within 3-6 months. When hormonal treatment remains necessary, the lowest effective dose and regular neuro-oncologic monitoring are recommended. Increased awareness and individualized counseling are essential to optimize hormonal management in women at risk of meningioma.
Background Adenomyosis is a benign uterine disease that has been associated with endometrial proliferative disorders. Adenomyosis and endometrial cancer (EC) are sex-steroid-dependent conditions that may coexist, but their estrogen receptor (ER) and progesterone receptor (PR) signaling landscape is poorly defined.Objective The present multicenter study aimed to characterize the expression of estrogen (ESR1/ESR2 plus the coregulators NCOA1, CCND1, BRCA1) and progesterone (PGR plus FOXO1, and CYP26A1) receptor pathway-related genes in hysterectomy specimens of patients with adenomyosis and coexisting EC.Methods Specimens from three groups of patients (n = 10 per group) referred to two tertiary hospitals were studied: adenomyosis plus EC (Group 1), only adenomyosis (Group 2), and only EC (Group 3). Gene expression was assessed by droplet digital PCR using a compartment-matched design. Analysis was compartment-specific, and no cross-compartment comparisons were performed.Results Compared with isolated adenomyosis, adenomyotic lesions from uteri with coexisting EC showed higher ESR2 (p = 0.0082) and BRCA1 (p = 0.0007) expression, with no differences in ESR1, NCOA1, or CCND1. PR-related gene expression (PGR, FOXO1, and CYP26A1) did not differ between adenomyosis groups.Conclusion Although preliminary, the present findings indicate that adenomyosis coexisting with EC is characterized by elevated expression of ESR2 and BRCA1, suggesting an enriched ER-related microenvironment that may be relevant to local estrogen responsiveness.
OBJECTIVES:To evaluate the reliability and clinical utility of the modified Ferriman-Gallwey (mFG) score in routine practice when applied by clinicians with differing experience and by patients for self-assessment. METHODS:In this cross-sectional reliability study, 43 reproductive-aged women were assessed for hirsutism. Three clinicians (reproductive endocrinologist, general gynecologist, and resident) independently scored participants using the mFG scale, and patients self-graded their hirsutism. Inter-rater reliability was examined using intraclass correlation coefficients (ICC) and weighted kappa statistics by body area. Clinical agreement was assessed with Bland-Altman limits of agreement (LOA). RESULTS:Inter-rater reliability was good (ICC = 0.649), higher between experienced clinicians (ICC = 0.723) and lower when the resident was included (ICC = 0.588). Weighted kappa ranged from 0.118 to 0.832 (highest for chin, lowest for upper back). Bland-Altman analysis showed substantial disagreement: experienced pair bias -0.74 (LOA -6.94 to + 5.46) and less-experienced pair bias + 0.44 (LOA -7.22 to + 8.11). Patient self-scoring showed poor agreement with clinician scoring (ICC = 0.20). CONCLUSIONS:Although clinician scoring demonstrated good statistical reliability, inter-rater differences remained clinically meaningful, with LOA exceeding diagnostic thresholds for hirsutism. Greater experience improved agreement but did not eliminate variability. Patient self-scoring showed low agreement with experts and tended to overestimate severity; however, it may function as a high-sensitivity screening adjunct rather than a substitute for clinician assessment.
OBJECTIVE:Female infertility is a common reproductive disorder influenced by metabolic dysfunction. The glycolipid metabolism 7 factors (GLM7) is a composite metabolic index integrating age, BMI, glucose, insulin, and lipid profiles. This study aimed to examine its association with female infertility in a nationally representative population. METHODS:Data from 1,405 female participants aged 18-45 years from the 2013-2018 cycles of the National Health and Nutrition Examination Survey were analyzed. We used survey-weighted logistic regression models and restricted cubic splines to assess the association between GLM7 and infertility. Receiver operating characteristic (ROC) curves were used to assess the diagnostic accuracy. RESULTS:A total of 167 participants (11.9%) reported infertility. After full adjustment, higher GLM7 levels were independently associated with increased odds of infertility (odds ratio (OR) = 1.401, 95% CI: 1.028-1.909, p = 0.034). A positive linear association was observed, with a potential plateau effect at GLM7 ≈ 6.98. GLM7 showed modest discriminative ability (AUC = 0.596, 95%CI: 0.552-0.639). CONCLUSIONS:GLM7 was positively associated with female infertility. As a multidimensional metabolic indicator, GLM7 may provide complementary information for reproductive health research. However, its modest discriminative performance suggests limited value as a standalone screening tool, warranting further validation in longitudinal and clinical studies.
OBJECTIVE:Aging and menopause negatively affect women's sexual quality of life, and midlife women often report sleep difficulties. The aim of the present study was to investigate the relationship between sleep quality and sexual quality of life in postmenopausal women. METHODS:A total of 303 postmenopausal women attending the Gynecology and Menopause Clinics of a university-affiliated training hospital completed the sexual quality of life questionnaire-female (SQoL-F) and the Pittsburgh sleep quality index (PSQI). SQOL-F and PSQI scores were compared by time since menopause, educational level, and age in decades. Correlations between SQoL-F and PSQI domain scores were analyzed. RESULTS:One hundred thirteen women (37.3%) had good sexual quality of life (SQoL-F > 84). SQoL-F and PSQI domain scores did not differ by time since menopause. Sexual and relationship satisfaction were higher among women aged 40-49 years, while other SQoL-F domains showed similar scores across age groups. PSQI domains were also comparable between age categories. Demographic characteristics did not differ between women with good versus poor sleep quality. Correlations between SQoL-F and PSQI domains were negligible to low, including total scores. The correlations reported are unadjusted. The Spearman rho values between the four domains of SQoL-F and seven domains of PSQI ranged between -0.181 and 0.033 (95% CI: -0.281 to 0.129), -0.144 and 0.026 (95% CI: -0.256 to 0.173), -0.159 and 0.043 (95% CI: -0.270 to 0.170), -0.087 and 0.009 (95% CI: -0.207 to 0.140), respectively. CONCLUSION:Younger and better-educated postmenopausal women showed a better overall sexual quality of life. No meaningful association was found between sleep parameters and sexual outcomes.
OBJECTIVE:Up to 50% of women with functional hypothalamic amenorrhea (FHA) exhibit polycystic ovarian morphology (PCOM) on ultrasound. We aimed to compare the hormonal response to ovulation induction with pulsatile GnRH therapy in FHA patients with and without PCOM. METHODS:In this single-center observational study, 41 patients with FHA underwent 3 months of pulsatile GnRH therapy to induce ovulation. Patients were categorized into a PCOM group (n = 24) and a non-PCOM group (n = 17). Serum levels of Anti-Muellerian-hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin, sex hormone-binding globulin (SHBG), testosterone, and thyroid-stimulating hormone (TSH) were assessed at baseline and after 3 months of treatment. RESULTS:At baseline, median AMH levels were significantly higher in the PCOM group (6.21 ng/ml [IQR 4.03-8.87]) compared to the non-PCOM group (1.7 ng/ml [IQR 1.14-2.20]; p < 0.001). After 3 months of pulsatile GnRH therapy, AMH levels significantly increased in the non-PCOM group (1.94 [IQR 1.39-2.49], p < 0.001), whereas no significant change was observed in the PCOM group (p = 0.218). LH, FSH, and estradiol levels increased in both groups. Pulsatile GnRH therapy effectively induced ovulation (1 dominant follicle in each patient), irrespective of ovarian morphology. CONCLUSION:The significant AMH rise in women with FHA without PCOM likely reflects restored folliculogenesis. In contrast, the absence of an AMH rise in the PCOM group was expected, given their already elevated baseline levels. Importantly, these findings suggest that pulsatile GnRH therapy does not exacerbate AMH levels in most patients.
Objective Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age. While diagnostic criteria have historically varied, the Rotterdam criteria, established in 2003, are now the standard. This classification identifies four PCOS phenotypes based on the presence and/or absence of three key features: ovulatory dysfunction (OD), hyperandrogenism (HA), and polycystic ovarian morphology (PCOM). Despite phenotypic differences, current clinical guidelines treat PCOS as a homogeneous condition when assessing pregnancy risks. Therefore, this narrative review examines variations in gestational outcomes across PCOS phenotypes in both natural and assisted reproductive technology (ART)-conceived pregnancies.Methods A search of three databases (PubMed, Cochrane, and Google Scholar) using key terms identified 13 eligible retrospective and prospective studies reporting gestational outcomes in PCOS phenotypes.Results Findings indicate that phenotypes characterized by HA (A, B, and C) are at higher risk for preeclampsia, gestational diabetes, and miscarriage in natural pregnancies. However, in ART-conceived pregnancies, Phenotypes A and D exhibited higher risks of adverse outcomes, while Phenotypes A and C showed significantly lower live birth and cumulative live birth rates.Conclusion These results reveal inconsistencies in pregnancy risks across phenotypes and conception methods, suggesting differences in the underlying mechanisms. The findings challenge the one-size-fits-all approach to pregnancy counseling in PCOS. Incorporating phenotype-specific risk stratification into clinical guidelines could enhance maternal and neonatal outcomes, particularly for high-risk phenotypes. Further research is needed to refine pregnancy care strategies tailored to individual PCOS phenotypes.
OBJECTIVE:To compare the efficacy of different COH protocols on pregnancy outcomes in adenomyosis patients. STUDY DESIGN:A real-world retrospective cohort study analyzed 1486 IVF-ET cycles in adenomyosis patients who received COH regimens between 2018 and 2021. Pregnancy outcomes were compared among patients under different COH protocols. RESULTS:The short-acting long protocol achieved the highest live birth (47.92%) and cumulative clinical pregnancy (68.84%) rates. The antagonist protocol showed lower fresh-cycle pregnancy (36.63% vs. 52.10%, p = 0.036), live birth (21.78% vs. 36.55%, p = 0.009), and cumulative clinical pregnancy rates (39.31% vs. 53.29%, p < 0.001) compared to the long/ultra-long protocol. Multivariable logistic regression confirmed that the COH protocol was an independent predictor of both clinical pregnancy (Wald χ² = 8.127, p = 0.043) and cumulative clinical pregnancy (Wald χ² = 40.344, p < 0.001). In patients <35 years with a normal ovarian reserve (anti-Müllerian hormone ≥ 1.2 ng/mL), live birth rates and cumulative clinical pregnancy rates were similar between the antagonist protocol and long/ultra-long protocols (27.59% vs. 44.94%, p = 0.098; 63.83% vs. 63.87%, p = 0.995), with significantly less gonadotropin used in the antagonist protocol. CONCLUSIONS:In adenomyosis patients, the long/ultra-long provided better fresh-cycle outcomes. While the antagonist protocol had lower overall pregnancy rates, it preserved cumulative pregnancy rates in young patients with normal ovarian reserves and reduced gonadotropin exposure.
BACKGROUND:Female infertility is multifactorial, with adiposity and regional fat distribution hypothesized as contributors, though evidence using detailed fat measures is limited. This study aims to examine the association between fat distribution indicators and female infertility in a nationally representative sample. METHODS:This retrospective cross-sectional study analyzed NHANES 2013-2018 data from 2,531 women aged 20-45. Infertility was defined by self-reported difficulty conceiving ≥ 12 months or seeking fertility care. Exposures included body mass index (BMI) and DXA-based measures: total percent fat (TPF), android percent fat (APF), gynoid percent fat (GPF), android fat/gynoid fat ratio (AGR), visceral fat/total fat (VPF), subcutaneous fat/total fat (SPF), and visceral fat/subcutaneous fat ratio (VSR). Multivariable logistic regression was used to assess associations, and sensitivity analyses were performed to evaluate robustness. RESULTS:In multivariable-adjusted models, TPF, APF, AGR, and BMI were modestly associated with higher odds of infertility (TPF: OR = 1.02, 95%CI: 1.00-1.05; APF: OR = 1.03, 95%CI: 1.01-1.04; AGR: OR = 1.02, 95%CI: 1.01-1.03; BMI: OR = 1.02, 95%CI: 1.01-1.04). Smooth curve fitting suggested a generally monotonic positive pattern for these associations. Associations were broadly similar across subgroups, although some subgroup interactions were observed. CONCLUSION:In this analysis, TPF, APF, AGR, and BMI showed modest associations with infertility, which should not be interpreted causally. Although associations were generally consistent across subgroups, subgroup-specific heterogeneity cannot be excluded.