Self-reported Infertility Research Articles

Non-high-density to high-density lipoprotein cholesterol ratio and its association with infertility in U.S. women: a cross-sectional study.

To investigate the relationship between Non-High-Density Lipoprotein Cholesterol to High-Density Lipoprotein Cholesterol Ratio (NHHR) and infertility in US female adults aged 20 to 45. Our research team utilized data from the 2013-2018 National Health and Nutrition Examination Survey (NHANES) to conduct a cross-sectional study. Multivariable logistic regression was conducted to examine the association between NHHR and infertility, with trend tests providing additional insight into this relationship. Further, smoothed curve fitting was applied for a more detailed exploration. To ensure the robustness of our results, we conducted subgroup and sensitivity analyses. Between 2013 and 2018, our study included 2,947 participants, with 342(11.6%) self-reported infertility. A positive association was found between NHHR and infertility (OR=1.17,95%CI:1.07-1.27). Compared with the first trimester, the third trimester of NHHR was associated with an OR of 1.79(95% CI: 1.31-2.44) in model 3. The results of subgroup analyses revealed that the association between NHHR and infertility was nearly consistent. NHHR demonstrated a positive correlation with infertility among U.S. female adults. Further investigation is needed to explore their association better and the underlying mechanisms.

Association between fatty acids and female infertility: dual evidence from a cross-sectional study and Mendelian randomization analysis.

Background: Infertility poses a considerable threat to female reproductive health on a global scale. Dietary pattern, as a modifiable lifestyle factor, is frequently recommended as an important intervention for infertility-related diseases. Fatty acids play a crucial role in maintaining the health of the female reproductive system. However, the available evidence on the specific relationship between various types of fatty acids and infertility remains insufficient and controversial. Methods: Initially, a cross-sectional study was conducted utilizing the National Health and Nutrition Examination Survey (NHANES) database to collect data from women aged 18-45 years who met the inclusion criteria across the 2013-2020 cycles. Infertility was defined based on information gleaned from reproductive questionnaires. Fatty acid intake was determined by analyzing two 24 hour dietary recall interviews. Weighted logistic regression and weighted restricted cubic spline (RCS) analyses, incorporating covariate adjustments, were employed to preliminarily delineate the association between various types of fatty acids and proportions of fatty acid intake and female infertility risk. Model performance evaluation was carried out through receiver operating characteristic (ROC) curve analysis, complemented by the utilization of a nomogram diagram to gauge the infertility risk attributed to covariates. Genetic instrumental variables pertinent to diverse fatty acid profiles and female infertility were sourced from genome-wide association studies (GWAS). Mendelian randomization (MR), multivariable MR (MVMR) and reverse MR analyses were subsequently used to ascertain causality and reverse causality between distinct fatty acids and infertility, concurrently assessing for heterogeneity and horizontal pleiotropy. Results: In our NHANES analysis, a total of 3159 women were enrolled in the study, with a self-reported infertility prevalence of 11.49%. Infertile women exhibited significantly elevated intake of total omega-6 and omega-6/total fatty acids (TFA) compared to the controls. Weighted logistic regression models confirmed positive correlations between total omega-6 (continuous) and omega-6/TFA (categorical) and infertility risk, while omega-3 (continuous) intake demonstrated a negative correlation. Model 2, post rigorous multivariate covariate adjustment, showed improved predictive performance according to ROC curve analysis. Subgroup analysis suggested that the positive correlation between omega-6/TFA (continuous) and female infertility risk was not affected by stratification. Total omega-6 (continuous) emerged as a risk factor for infertile women aged 18-34 years. However, total saturated fatty acids (TSFAs, continuous), total omega-3 (continuous) and total polyunsaturated fatty acids (PUFAs, categorical) were protective factors only in the infertile women with a BMI ≥ 25 kg m-2. The positive associations between total omega-6 (Q4) and omega-6/TFA (continuous and Q3-Q4) and infertility risk were consistent across all BMI subgroups. MR analysis employing inverse variance weighted (IVW) as the primary method and Bonferroni correction revealed that genetically predicted TSFAs, monounsaturated fatty acids (MUFAs), omega-6 and MUFA/TFA were positively associated with female infertility risk, whereas PUFA/TFA showed a negative association. Importantly, the positive associations between MUFAs and omega-6 and infertility risk remained robust even after adjusting for potential confounders using MVMR analyses. Reverse MR analysis did not provide any evidence for reverse causality. The MR-Egger regression intercept and Cochran's Q test did not detect any heterogeneity or horizontal pleiotropy. Conclusions: This study presents compelling evidence to substantiate the link between diverse fatty acids, particularly omega-6 PUFAs, and the risk of female infertility. However, to fully comprehend the potential mechanisms and impact of distinct fatty acids and their compositional ratios on female infertility, extensive future research spanning fundamental and large-scale clinical inquiries is imperative.

Exposure to Environmental Chemicals and Infertility Among US Reproductive-Aged Women.

Environmental chemical exposure has been rising over the past few decades but its impact on fertility remains uncertain. We assessed exposures to 23 common chemicals across a range of sociodemographic characteristics and their relationship with self-reported infertility. The analytic sample was non-pregnant women aged 18-49 years without a history of hysterectomy or oophorectomy (n = 2579) from the National Health and Nutrition Examination Survey (2013-2016). Environmental chemical exposure was assessed with biospecimens and dichotomized as high and low levels of exposure based on the median. Logistic regression models estimated the adjusted odds ratio (aOR) and 95% confidence intervals (CIs) for the association between high levels of exposure and infertility, adjusted for age, race, education level, family income, and smoking status. We observed associations between infertility and cadmium [aOR: 1.88; 95% CI: 1.02-3.47] and arsenic [aOR: 1.88 (1.05-3.36)]. Two pesticides hexachlorobenzene [OR: 2.04 (1.05-3.98)] and oxychlordane [OR: 2.04 (1.12-3.69)] were also associated with infertility in unadjusted analyses. There were negative associations with two Per- and polyfluoroalkyl substances with n-perfluorooctanoic acid [aOR: 0.51: (0.30-0.86)] and n-perfluorooctane sulfonic acid [aOR: 0.51: (0.26-0.97). Specific chemicals may contribute to infertility risk, highlighting the need for targeted public health strategies to mitigate exposure.

Association of body roundness index with female infertility: 2013-2018 NHANES.

This study aims to understand the association between body roundness index (BRI) and female infertility prevalence. Infertility is a public health concern with significant implications for individuals' well-being and rights. All individuals who completed the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2018 were initially included in this cross-sectional study. Following the screening, 2,777 eligible participants were selected for analysis from the original pool of 10,375 participants. Trained operators conducted anthropometric measurements, including height, weight, and waist circumference. The BRI was then calculated based on established research. Data from infertility status questionnaires were gathered from the NHANES database for all participants, with self-reported infertility serving as the study outcome. Multivariable logistic regression and restricted cubic splines (RCS) were employed to investigate the relationship between BRI and infertility. Subgroup analyses were also conducted to further explore the association between BRI and infertility. Upon analyzing the baseline characteristics of all women in the study, notable distinctions were identified in the clinical and demographic features between fertile and infertile women. Our investigation revealed a positive correlation between BRI and the likelihood of infertility in both weighted and unweighted multiple logistic regression models. Additionally, BRI exhibited a significant association with infertility in both continuous and categorical forms. Utilizing RCS curves, we noted a linear escalation in the prevalence of infertility with rising BRI values. Subgroup analyses provided further clarity on these observations. Our study demonstrates a statistically significant positive correlation between BRI and the prevalence of infertility across diverse populations, suggesting potential implications for infertility prevention and treatment. Future prospective cohort studies will explore this association and understand the underlying mechanisms.

History of Infertility and Risk of Colorectal Cancer.

There has been limited prior research on the association between infertility and risk of colorectal cancer. Data from postmenopausal women in the Women's Health Initiative were used to estimate the association between self-reported infertility (12 months of trying to get pregnant without achieving a pregnancy) and the risk of colorectal cancer using Cox proportional hazard models. No association was observed between infertility and risk of postmenopausal colorectal cancer [RR, 0.97; 95% confidence interval (CI), 0.87-1.08], invasive colorectal cancer (RR, 0.99; 95% CI, 0.88-1.10), or colorectal cancer mortality (RR, 0.89; 95% CI, 0.71-1.12). Infertility was not found to be associated with colorectal cancer risk among postmenopausal women. Risk did not vary by specific infertility diagnoses. Infertility may not be associated with colorectal cancer risk.

Inflammatory markers are associated with infertility prevalence: a cross-sectional analysis of the NHANES 2013–2020

BackgroundInflammation exerts a critical role in the pathogenesis of infertility. The relationship between inflammatory parameters from peripheral blood and infertility remains unclear. Aim of this study was to investigate the association between inflammatory markers and infertility among women of reproductive age in the United States.MethodsWomen aged 20–45 were included from the National Health and Nutrition Examination Survey (NHANES) 2013–2020 for the present cross-sectional study. Data of reproductive status was collected from the Reproductive Health Questionnaire. Six inflammatory markers, systemic immune inflammation index (SII), lymphocyte count (LC), product of platelet and neutrophil count (PPN), platelet-lymphocyte ratio (PLR), neutrophil–lymphocyte ratio (NLR) and lymphocyte-monocyte ratio (LMR) were calculated from complete blood counts in mobile examination center. Survey-weighted multivariable logistic regression was employed to assess the association between inflammatory markers and infertility in four different models, then restricted cubic spline (RCS) plot was used to explore non-linearity association between inflammatory markers and infertility. Subgroup analyses were performed to further clarify effects of other covariates on association between inflammatory markers and infertility.ResultsA total of 3,105 women aged 20–45 was included in the final analysis, with 431 (13.88%) self-reported infertility. A negative association was found between log2-SII, log2-PLR and infertility, with an OR of 0.95 (95% CI: 0.78,1.15; p = 0.60), 0.80 (95% CI:0.60,1.05; p = 0.10), respectively. The results were similar in model 1, model 2, and model 3. Compared with the lowest quartile (Q1), the third quartile (Q3) of log2-SII was negatively correlation with infertility, with an OR (95% CI) of 0.56 (95% CI: 0.37,0.85; p = 0.01) in model 3. Similarly, the third quartile (Q3) of log2-PLR was negatively correlation with infertility, with an OR (95% CI) of 0.61 (95% CI: 0.43,0.88; p = 0.01) in model 3. No significant association was observed between log2-LC, log2-PPN, log2-NLR, log2-LMR and infertility in model 3. A similar U-shaped relationship between log2-SII and infertility was found (p for non-linear < 0.05). The results of subgroup analyses revealed that associations between the third quartile (Q3) of log2-SII, log2-PLR and infertility were nearly consistent.ConclusionThe findings showed that SII and PLR were negatively associated with infertility. Further studies are needed to explore their association better and the underlying mechanisms.

Prevalence of infertility and pregnancy loss among individuals with kidney disease in the Hispanic Community Health Study/Study of Latinos.

Hispanic/Latino individuals are less likely to receive optimal treatment for chronic kidney disease than non-Hispanic whites. This may be particularly detrimental for women of reproductive age as chronic kidney disease increases risk for infertility, menstrual irregularities, and pregnancy loss. While these maternal outcomes have been associated with advanced chronic kidney disease, their occurrence in early chronic kidney disease is unclear. Using baseline (2008-2011) and second study visit (2014-2017) data from the Hispanic Community Health Study/Study of Latinos, we retrospectively assessed the prevalence of chronic kidney disease as well as the association between chronic kidney disease and self-reported infertility, cessation of menses, hysterectomy, and nonviable pregnancy loss (experienced at less than 24 weeks gestation) in women of reproductive age (18-45 years). Multivariable survey logistic regression analyses determined the unadjusted and multivariable-adjusted prevalence odds ratios with 95% confidence intervals between chronic kidney disease and the separate outcomes. Among 2589 Hispanic/Latino women included (mean age = 31.4 years), 4.6% were considered to have chronic kidney disease. In adjusted analyses, women with chronic kidney disease did not have a significantly increased odds of infertility (odds ratio = 1.02, 95% confidence interval = 0.42-2.49), cessation of menses (odds ratio = 1.25, 95% confidence interval = 0.52-3.04), or hysterectomy (odds ratio = 1.17, 95% confidence interval = 0.61-2.25) compared to those without chronic kidney disease. In those with chronic kidney disease, the adjusted odds of a nonviable pregnancy loss occurring after baseline visit were increased (odds ratio = 2.11, 95% confidence interval = 0.63-7.02) but not statistically significance. The presence of early stage chronic kidney disease did not confer a significant risk of infertility, cessation of menses, or nonviable pregnancy loss.

Association between dietary inflammatory index and self-reported female infertility from the National Health and Nutrition Examination Survey 2013-2020.

To explore the association between the diet inflammatory index (DII) and infertility. Multivariable logistic regression was performed to investigate the relationship between infertility and DII, and restricted cubic spline (RCS) was utilised to test for nonlinear relationships in this cross-sectional study. Data of this study were collected from the 2013 to 2020 National Health and Nutrition Examination Survey (NHANES) database. Considering women's child-bearing age, we enrolled a total of 2066 women aged 20-45 years in this study. After all covariates were adjusted, a positive association was found between DII score and odds of infertility by multivariable logistic regression (odds ratio [OR] = 1.19, 95% confidence interval [CI] 1.03, 1.38; p = 0.027). Compared with participants with DII scores in the lowest quartile, those with DII scores in the highest quartile had significantly higher odds of infertility (OR = 2.42, 95% CI 1.09, 5.34; p = 0.034). The RCSs model suggested a linear relationship between DII and infertility (p for nonlinear = 0.1827). A positive association between a pro-inflammatory diet and self-reported infertility was detected. Our study extends the application of the DII scoring system to infertility prevention.

The effect of serum calcium on the association of depression with infertility among U.S. women

This study aimed to explored the association between depressive symptoms and infertility among U.S. women, and the effect of serum calcium on this association. We used data from the National Health and Nutrition Examination Survey (2013–2018), relating to women aged 20–45 years. Depressive symptoms were determined using the nine-item Patient Health Questionnaire (PHQ-9 scores ≥10), and interview data were used to identify self-reported infertility. Of 2708 women (mean age: 32.7 ± 7.5 years), 274 were depressed and 12.0 % self-reported being “ever-infertile.” Depressive symptoms were associated with infertility in multivariable logistic regression (OR, 1.62; 95 % CI, 1.11–2.38). Depressive symptoms were associated with infertility among participants who were obese (OR, 1.68; 95 % CI, 1.03–2.74), had not received psychological counseling (OR, 1.60; 95 % CI, 1.03–2.50), were antidepressant users (OR 3.22; 95 % CI, 1.15–9.00), and had high serum calcium levels (OR, 2.05; 95 % CI, 1.25–3.35). A significant interaction between serum calcium and depression was observed for infertility (P = .038, interaction likelihood ratio test). In sensitivity analyses, the association between depressive symptoms and infertility remained after excluding women aged ≥35 years (OR, 1.87; 95 % CI, 1.08–3.23), lowering the cut-off for PHQ-9 scores (≥5) (OR, 1.48; 95 % CI, 1.12–1.96), excluding women with some gynecological diseases (OR, 1.63; 95 % CI, 1.07–2.49), and using inverse probability of treatment weighting (OR, 1.64; 95 % CI, 1.17–2.31). ConclusionOur findings indicate that depression is associated with infertility among U.S. women and serum calcium may have an effect on the association. Interventions such as serum calcium reduction, weight management and psychosocial counseling for infertility treatment in individuals with depression may be integrated into routine clinical practice. Additionally, more caution could be exercised when using antidepressants.

The association between weight-adjusted-waist index and self-reported infertility among women of reproductive age in the United States.

This study aimed to determine whether the weight-adjusted-waist index (WWI) affected infertility in women of childbearing age in the United States. In this study, a database from the 2013 to 2018 National Health and Nutrition Examination Survey (NHANES) was used. We analyzed 3374 participants' data cross-sectionally. The survey used WWI and fertility status as independent and dependent variables. To determine the effect of WWI, an analysis of the independent relationship between WWI and infertility was conducted using weighted multivariable logistic regression and a generalized additive mode (GAM). A smooth curve fitting test was used to calculate whether there was a linear association between WWI and the incidence rate of infertility, as well as subgroup analyses and interaction tests. The prevalence of infertility was 10.19% among 3374 participants. Higher WWI quartiles were associated with higher infertility rates. Based on a fully adjusted model, the effects of WWI on fertility were positive (odds ratio = 1.39, 95% confidence interval: 1.17-1.66). As a result of smooth curve fitting, the association was linear across the entire WWI. Different characteristics were associated with different risks of infertility in subgroup analysis. Among women of reproductive age in the United States, WWI levels were positively associated with infertility. This relationship needs to be confirmed by further studies.

Elevated serum uric acid is associated with infertility in women living in America

Excessive uric acid levels may affect several organs and systems in the body. There is limited evidence of the effects of high serum uric acid levels on the female reproductive system. This study used the National Health and Nutrition Examination Survey (NHANES) database to explore the relationship between serum uric acid and female infertility. This cross-sectional study included a total of 2197 eligible subjects using data from NHANES 2013-March 2020 pre-pandemic data. Self-reported infertility (ever experiencing an inability to conceive after 12 months of trying to become pregnant) was the main outcome. Logistic regression models and restricted cubic spline were used to analyze the relationship between serum uric acid and female infertility, and stratified analysis was carried out. A total of 295 women self-reported infertility (13.43%). The median uric acid level for all study subjects was 4.4 mg/dL (interquartile range [IQR]: 3.7, 5.1). Serum uric acid levels were higher in the infertility group than in the control group (4.7 mg/dL [IQR: 4.0, 5.3] vs. 4.4 mg/dL [IQR: 3.7, 5.1], P < 0.001). After adjusting for age, race, marital status, smoking, alcohol, history of pregnancy, history of diabetes, history of hypertension, fasting glucose, total cholesterol, creatinine in refrigerated serum, low-density lipoprotein cholesterol, direct high-density lipoprotein cholesterol, glycohemoglobin, and body mass index confounders, women with serum uric acid levels at Q3 (4.4–5.1 mg/dL) had a 73% (odds ratio [OR] = 1.73, 95% confidence interval [CI] 1.18, 2.54, P = 0.005) higher risk of infertility, and women with uric acid levels at Q4 (5.1–18.0 mg/dL) had an 83% (OR = 1.83, 95% CI 1.22, 2.75, P = 0.003) increased risk of infertility compared to women at Q1 (1.6–3.7 mg/dL). The restricted cubic spline also showed that when serum uric acid levels exceeded the reference value, the risk of infertility gradually increased. We also performed a sensitivity analysis based on the complete dataset and found that the results were robust. Higher serum uric acid levels were significantly associated with an increased risk of female infertility. Women planning a pregnancy should have increased serum uric acid monitoring.

Association between serum Chlamydia trachomatis antibody levels and infertility among reproductive-aged women in the U.S.

Chlamydia trachomatis infection, the most prevalent sexually transmitted bacterial infection worldwide, is a significant cause of infertility. Many countries have introduced the widespread use of serologic assays for IgG seropositivity to chlamydial plasmid gene product 3 (Pgp3). However, data on the association between the level of Pgp3-IgG in the multiplex bead array assay (Pgp3AbMBA) and female infertility are still scarce. This cross-sectional analysis included 1,425 women from the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2016. In the fully adjusted logistic regression model, each standard deviation increments of Pgp3AbMBA (SD = 17,079.63) led to a 28% increase in the risk of infertility. The relationship remained consistent in women who had been pregnant and women who gave birth. Smooth curve fitting revealed that the association was linear across the entire range of Pgp3AbMBA. Subgroup analysis suggested that the association was significantly stronger in women who had ever used marijuana and lived in poverty. This study revealed a linear and independent association between the level of Pgp3AbMBA and self-reported infertility in U.S. women. Furthermore, we found that women who had ever used marijuana and lived in poverty were at the highest risk of infertility upon chlamydial infection.

Infertility and perceived chance of conception among men in Malawi

Infertility is a common experience among individuals and couples worldwide, but few studies focus on men’s reports of infertility or perceived chance of conceiving, particularly in high-fertility, pronatalist contexts where infertility is highly stigmatized. Using data from the fourth wave of the Umoyo wa Thanzi (UTHA) cohort study in rural Central Malawi (2017–2018), we examine the relationship between self-reported infertility, the perceived chance of conceiving within one year, and sociodemographic characteristics among men (N = 484). While 13% of men reported that they had experienced infertility, just 4% of men perceived that they were unlikely or there was no chance they would conceive with their partner within one year of having sex without contraception. In multivariable logistic regression models, older age was associated with experienced infertility (AOR: 1.06, p < 0.05) and higher parity was associated with lower odds of reporting that conception was unlikely or there was no chance of conception (AOR: 0.08; p < 0.05). We argue that additional research on infertility focusing on men is critical in gaining a more holistic and gender-equitable understanding of infertility. Including men in infertility research may also contribute to destigmatizing infertility among both women and men by acknowledging men’s roles in infertility.

Association between Perfluoroalkyl and Polyfluoroalkyl Substances and Women's Infertility, NHANES 2013-2016.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are widely used in consumer products. However, the role of PFAS in infertility is still poorly understood. A total of 788 women from the 2013-2016 nationally representative NHANES were included to explore the association between PFAS exposure and self-reported infertility. Six PFAS, including PFDE, PFNA, PFHxS, n-PFOA, n-PFOS, and Sm-PFOS, were detected by online SPE-HPLC-TIS-MS/MS. We used the generalized linear regression model (GLM), generalized additive models (GAM), and Bayesian kernel machine regression (BKMR) to assess the single effects, non-linear relationships, and mixed effects on women's infertility, respectively. The prevalence of self-reported infertility was 15.54% in this study. In GLM, n-PFOA showed a negative association with self-reported infertility in women for the Q3 (OR: 0.396, 95% CI: 0.119, 0.788) and Q4 (OR: 0.380, 95% CI: 0.172-0.842) compared with Q1 (p for trend = 0.013). A negative trend was also observed in n-PFOS and ∑PFOS (p for trend &lt; 0.05). In GAM, a non-linear relationship was revealed in Sm-PFOS, which exhibits a U-shaped relationship. The BKMR model indicated that there might be a joint effect between PFAS and women's infertility, to which PFNA contributed the highest effect (PIP = 0.435). Moreover, age stratification analysis showed a different dose-response curve in under and above 35 years old. Women under the age of 35 have a more noticeable U-shaped relationship with infertility. Therefore, the relatively low level of mixed PFAS exposure was negatively associated with self-reported infertility in women in general, and the impact of PFAS on infertility may vary among women of different age groups. Further studies are needed to determine the etiological relationship.

Associations of single and multiple organophosphate pesticide exposure with female infertility in the USA: data from the 2015-2018 National Health and Nutrition Examination Survey.

Substantial evidence has shown that organophosphate pesticide (OPP) exposure altered the reproductive system functions, such as prolonged menstrual cycles, sexual hormone imbalance, and changes in ovarian weight. However, the association of OPP exposure with female infertility is unclear. We explored the relationships of four single OPP metabolites and their mixed exposure with self-reported infertility among women aged 20-50 in the USA using the data from two cycles (2015-2016 and 2017-2018) of the National Health and Nutrition Examination Survey (NHANES) by multiple logistic regression, Bayesian kernel machine regression (BKMR), and quantile g-computation (QGC). Eventually, 659 females were included in our study. Among these females, 77 participants were ever infertile. Multiple logistic regression showed that the odds ratios (ORs) in the second and third tertiles of dimethylphosphate (DMP) for female infertility were 2.53 (95% confidence interval (95%CI): 1.20-5.32, P value = 0.016) and 2.96 (95%CI: 1.18-7.47, P value = 0.023) compared to the lowest tertile after adjusting for all covariates (P for trend = 0.022). A significantly positive association between the mixed OPP metabolites and infertility was observed in the BKMR model, in which DMP had the highest posterior inclusion probability (PIP = 0.741). The QGC model showed similar results, in which OPP metabolite mixtures increased the risk of female infertility, with DMP as a significantly positive contributor to the outcome. This study revealed the potential harm of OPP mixtures for female infertility in the USA, and DMP played the most critical role in female infertility risk among all OPP metabolites.

Infertility prevalence and the methods of estimation from 1990 to 2021: a systematic review and meta-analysis.

What is the contemporary prevalence of infertility in world populations and how do they differ by methodological and study characteristics? Pooled estimates of lifetime and period prevalence of 12-month infertility were 17.5% and 12.6%, respectively, but this varied by study population and methodological approach. Infertility affects millions of individuals worldwide. Accurate measures of its magnitude are needed to effectively address and manage the condition. There are distinct challenges and variation in how infertility is defined and measured, limiting comparability of estimates across studies. Further research is needed to understand whether and how differences in methodological approaches and study characteristics account for heterogeneity in estimates. We conducted a systematic review and meta-analysis. Six electronic databases, websites of relevant organizations, and conference proceedings were systematically searched. Searches were limited to those published between 1 January 1990 and 11 March 2021, with no language restrictions. Descriptive and random-effects meta-analysis models were used to examine range of estimates and generate estimates of pooled lifetime and period prevalence of 12-month infertility, respectively, among representative populations. Meta-regression using restricted maximum likelihood was applied to account for definitional and study characteristics and to obtain adjusted estimates. Risk of bias was assessed with a validated tool. The search yielded 12 241 unique records of which 133 studies met the criteria for the systematic review. There were 65 and 69 studies that provided data for lifetime and period prevalence of 12-month infertility, respectively. Five methodological approaches were identified: prospective time-to-pregnancy (TTP) design, current duration design, retrospective TTP design, self-reported infertility measure and constructed infertility measure. Ranges for lifetime (3.3-39.7%) and period estimates (1.6-34.0%) were similar and wide even after accounting for methodological and study characteristics. Pooled estimates of lifetime and period prevalence were 17.5% (95% CI: 15.0, 20.3, n = 37 studies, I 2 = 99.5%) and 12.6% (95% CI: 10.7, 14.6, n = 43 studies, I 2 = 99.8%), respectively, with some variation in magnitude by region and methodological approach, but with most CIs overlapping. Pooled estimates generated from meta-analysis were derived from 12-month infertility prevalence estimates that were heterogeneous across different domains, even after adjusting for definitional and study characteristics. The number of studies was small for certain strata from which pooled estimates were derived (e.g. there were only two studies for lifetime prevalence in Africa). While findings show a high prevalence of infertility globally and regionally, it also reveals variation in measures to ascertain and compare infertility prevalence. More systematic and comprehensive collection of data using a consistent definition is needed to improve infertility prevalence estimates at global, regional and country-levels. This work was supported by the World Health Organization. The authors have no conflicts of interest. PROSPERO CRD42020211704.

Lifetime infertility and environmental, chemical, and hazardous exposures among female and male US veterans

Veterans experience many potentially hazardous exposures during their service, but little is known about the possible effect of these exposures on reproductive health. This study aimed to assess the association between infertility and environmental, chemical, or hazardous material exposures among US veterans. This study examined self-reported cross-sectional data from a national sample of female and male US veterans aged 20 to 45 years separated from service for ≤10 years. Data were obtained via a computer-assisted telephone interview lasting an average of 1 hour and 27 minutes that assessed demographics, general and reproductive health, and lifetime and military exposures. Logistic regression models were used to evaluate associations between exposures to environmental, chemical, and hazardous materials and infertility as defined by 2 different definitions: unprotected intercourse for ≥12 months without conception and trying to conceive for ≥12 months without conception. Of the veterans included in this study, 592 of 1194 women (49.6%) and 727 of 1407 men (51.7%) met the unprotected intercourse definition for infertility, and 314 of 781 women (40.2%) and 270 of 775 men (34.8%) met the trying to conceive definition for infertility. Multiple individual exposure rates were found to be higher in women and men veterans with self-reported infertility, including petrochemicals and polychlorinated biphenyls, which were higher in both the men and women groups reporting infertility by either definition. Importantly, there was no queried exposure self-reported at higher rates in the noninfertile groups. Moreover, veterans reporting infertility reported a higher number of total exposures with a mean±standard deviation of 7.61±3.87 exposures for the women with infertility vs 7.13±3.67 for the noninfertile group (P=.030) and 13.17±4.19 for veteran men with infertility vs 12.54±4.10 for the noninfertile group (P=.005) using the unprotected intercourse definition and 7.69±3.79 for the women with infertility vs 7.02±3.57 for the noninfertile group (P=.013) and 13.77±4.17 for the veteran men with infertility vs 12.89±4.08 for the noninfertile group (P=.005) using the trying to conceive definition. The data identified an association between infertility and environmental, chemical, and hazardous materials that the veterans were exposed to during military service. Although this study was limited by the self-reported and unblinded data collection from a survey, and causation between exposures and infertility cannot be proven, it does show that veterans encounter many exposures during their service and calls for further research into the possible link between veteran exposures and reproductive health.

Sleep Behavior and Self-Reported Infertility: A Cross-Sectional Analysis Among U.S. Women.

ObjectiveTo investigate the associations between sleep behaviors and female infertility.MethodsWe conducted a cross-sectional study composed of 2175 U.S. women 18-44 years of age from the National Health and Nutrition Examination Survey (NHANES) (2015-2018). Bedtime/waketime and sleep duration were extracted from the sleep disorder questionnaire. Self-reported infertility was defined as a binary variable based on the participants’ response to the question, “Have you ever attempted to become pregnant over a period of at least a year without becoming pregnant?”. Multivariate logistic regression analyses were done to explore the relationship between sleep behaviors and female infertility.ResultsBedtime (OR=1.24; 95% CI, 1.10-1.40, P = 0.001) and waketime (OR=1.14; 95% CI, 1.01-1.28, P = 0.037) were associated with infertility. Waketime of 08:00 was the inflection point, above which the probability of infertility increased rapidly (OR=1.41; 95% CI, 1.11-1.79, P = 0.004). Sleep-wake behavior was significantly associated with infertility (OR=1.34; 95% CI, 1.16-1.53, P < 0.001) and participants with early-bed/early-rise behavior had the lowest risk.ConclusionsAmong U.S. women 18-44 years of age, bedtime and waketime were significantly linearly and non-linearly correlated with infertility, respectively. Early-bed/early-rise behavior was associated with the lowest infertility rate. Further study is needed because the timing of sleep behaviors are modifiable factors and could be a novel strategy to cope with infertility.

High-sensitivity C-reactive protein is not independently associated with self-reported infertility in National Health and Nutrition Examination Survey 2015–2018 data

ObjectiveTo study the association between high-sensitivity C-reactive protein (hs-CRP) and infertility among reproductive-age women while controlling for obesity and other metabolic markers. Previous studies found a link between infertility and cardiovascular diseases (CVDs). C-reactive protein is a sensitive marker of CVDs, and its levels are affected by obesity.Design/SettingWe conducted a cross-sectional study using national data from 2015 through 2018.PatientsA total of 940 women aged 20–45 years who self-reported infertility, had hs-CRP values measured, and did not have CRP >10 mg/L, asthma, arthritis, bronchitis, thyroid disease, bilateral oophorectomy, hysterectomy, and who were not breastfeeding or pregnant, premenarchal at the time of study or had menarche after the age of 20.InterventionsN/A.Main outcome measure(s)Infertility status (ever reporting inability to conceive with 12 months of trying to become pregnant).ResultsIn comparison to noninfertile women, self-reported infertile women had higher mean of hs-CRP (3.11 mg/L vs. 2.40 mg/L) and higher percentage of moderate/high hs-CRP values (77.0% vs 58.8%). However, after adjusting for metabolic markers, there was a nonsignificant association between moderate/high hs-CRP and self-reported infertility in the multivariable logistic regression analysis. Odds ratio estimates of the association between hs-CRP and infertility increased over 40% after removing obesity measures and/or high-density lipoprotein from regression models.ConclusionThere was no association between hs-CRP and self-reported infertility after controlling for obesity measures and other risk factors for CVDs in a sample of U.S. women aged 20–45 years.

Prevalence and characteristics of patients declined from pursuing in vitro fertilization with autologous oocytes

To determine the frequency of and factors associated with a patient being declined from pursuing a cycle of in vitro fertilization with autologous oocytes (IVF-AO). A cross-sectional study using a nationwide cohort of female respondents aged 35 or over, who visited a US fertility clinic from 1/2015 to 3/2020, responded to the online FertilityIQ questionnaire ( http://www.fertilityiq.com ). All respondents were asked if they were previously declined from pursuing a cycle of IVF-AO. Examined demographic and clinical predictors included age, race/ethnicity, education, income, clinic type, care received in a mandated state, insurance coverage for fertility treatment, and self-reported infertility diagnosis. Logistic regression was used to calculate the adjusted odds ratios for factors associated with being declined from pursuing IVF-AO. Of 8660 women who met inclusion criteria, 418 (4.8%) reported previously being declined a cycle of IVF-AO. In the multivariate analysis, predictors of being declined from pursuing IVF-AO included increasing age, income of less than $50,000, and diagnoses of poor oocyte quality and diminished ovarian reserve. Predictors of being less likely to report decline included some college or college degree and diagnoses of male factor, unexplained or tubal infertility. Notably, diagnosis of PCOS or residence in a state with mandated fertility coverage was not predictive of patients being declined from pursuing IVF-AO. Nearly 5% of patients who pursued IVF reported being declined from pursuing IVF-AO. Further studies are needed to confirm our findings and explore whether patients being declined treatment meet the criteria for futile or very poor prognosis.