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

Abstract

Background: Inflammation 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.

Methods: Women 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.

Results: A 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.

Conclusion: The findings showed that SII and PLR were negatively associated with infertility. Further studies are needed to explore their association better and the underlying mechanisms.

Keywords: Infertility; Inflammatory markers; Lymphocyte count (LC); Lymphocyte-monocyte ratio (LMR); National Health and Nutrition Examination Survey (NHANES); Neutrophil-lymphocyte ratio (NLR); Platelet-lymphocyte ratio (PLR); Product of platelet and neutrophil count (PPN); Systemic immune inflammation index (SII).

Fig. 1

Flowchart of participants selection. Legend: Abbreviations: NHANES, National Health and Nutrition Examination Survey

Fig. 2

Restricted cubic spline plot of the association between inflammatory markers and infertility. Legend: A log2-transformed SII; B log2-transformed LC; C log2-transformed PPN; D log2-transformed PLR; E log2-transformed NLR; F log2-transformed LMR. Abbreviation: SII, systemic immune inflammation index; LC, lymphocyte count; PPN, product of platelet and neutrophil count; PLR, platelet to lymphocyte ratio; NLR, neutrophil to lymphocyte ratio; LMR, lymphocyte to monocyte ratio