Prevalence and Contributors to Low‐grade Inflammation in Three U.S. Populations of Reproductive Age Women

Abstract

Background: Inflammation, measured by high-sensitivity C-reactive protein (hsCRP), is linked to adverse reproductive outcomes. However, prevalence and predictors of low-grade inflammation are poorly understood among reproductive age women. Therefore, the current aim was to characterize: (i) the prevalence of elevated hsCRP and (ii) whether the association of various demographic, anthropometric, life style, and metabolic characteristics with higher hsCRP varies across populations of reproductive age women with varying risk profiles for adverse reproductive outcomes. Methods: Bivariate analysis of characteristics among women ages 18-40 having hsCRP <2.0 vs. ≥2.0 mg/L in the BioCycle Study (N = 259), the Effects of Aspirin in Gestation and Reproduction Trial (EAGeR) (N = 1228), and the National Health and Nutrition Examination Survey (NHANES; N = 2173) were conducted. Multivariable regression analysis estimated the association of all characteristics to hsCRP within each cohort. Results: Prevalence of hsCRP≥2 mg/L ranged from 20 to 40%. Age, BMI, waist circumference, blood pressure, lipids, glucose, and insulin were frequently higher in women with hsCRP ≥2 mg/L. In multivariable models, however, only adiposity (BMI, waist circumference) was independently associated with hsCRP within all three cohorts. Some variables showed cohort-specific associations with higher hsCRP: white race (EAGeR), higher fasting glucose (BioCycle), and lesser education and employment (NHANES). The total characteristics explained 28-46% of the variation in hsCRP across the three cohorts. Conclusions: Low-grade inflammation was common, including among predominantly non-obese women, affecting from 20 to 40% of reproductive age women. Given the potential to reduce inflammation through inexpensive, widely available therapies, examination of the impact of chronic inflammation on reproductive and pregnancy outcomes, as well as preventive interventions, are now needed.

The Role of Inflammatory Hematological Markers in Predicting IVF Success

“…Inflammation caused by organic diseases, such as endometriosis, polycystic ovary syndrome (PCOS) or obesity, is a well-known cause of infertility ( Cho et al, 2008 ; Çakıroğlu et al, 2016 ) . However, Sjaarda et al (2018) tested the inflammatory status by high-sensitive C-reactive protein (hs-CRP) and found that low-grade inflammation is very common (20-40%) in reproductive-age women, including normal-weight women. Apart from hs-CRP, systemic inflammatory status could be assessed by NLR, MLR, and PLR ( Mertoglu et al, 2019 ; Madendag et al, 2018 ) .…”

High-sensitivity C-reactive protein levels and pregnancy outcomes in women with unexplained infertility after ovarian stimulation with intrauterine insemination in a multicenter trial

“…Using PASS 16 software (NCSS, LLC, Kaysville, Utah), power calculations for the sample of 781 patients indicated the study would have 80% power to detect a RR for live birth of 0.59 for hs-CRP ≥3.0, given a 5% type I error rate for false-positive conclusions (two-sided alpha = 0.05) and an R 2 of 0.2 for the degree of correlation between the hs-CRP levels and the other covariates. For these calculations, we assumed a 25% live birth rate among women with normal hs-CRP (<3.0 mg/L) corresponding to the birth rate observed in the AMIGOS trial and assumed a 30% prevalence of elevated hs-CRP given reports of low-grade inflammation in 20%–40% of reproductive age women ( 3 ). This study received approval from the University of Oklahoma Health Science Center’s Institutional Review Board.…”

“…No readily identifiable cause is found for 15%–30% of couples following a standard evaluation, leading to a diagnosis of unexplained infertility ( 1 ). Chronic inflammation, frequently assessed by serum high-sensitivity C-reactive protein (hs-CRP) levels, has been linked to adverse reproductive outcomes, including reduced fecundability, recurrent miscarriage, and recurrent in vitro fertilization (IVF) failures ( 2 , 3 ). The hs-CRP is an acute phase reactant protein released from the liver and serves as a marker to identify inflammation.…”

“…There are several factors known to be associated with higher baseline hs-CRP levels that may be associated with infertility, including obesity, endometriosis, and polycystic ovarian syndrome ( 6 , 7 , 8 ). While low-grade inflammation is found in 20%–40% of reproductive age women, hs-CRP is not a routine diagnostic or therapeutic marker used as part of an infertility evaluation ( 3 ). The prevalence of subclinical inflammation in women with unexplained infertility and the role of elevated hs-CRP levels in the prediction of treatment success following ovarian stimulation-intrauterine insemination (OS-IUI), typically the first-line treatment for unexplained infertility, remains unknown.…”

High-Sensitivity C-Reactive Protein (Hs-Crp) Level and Pregnancy Outcomes in Women With Unexplained Infertility Undergoing Ovarian Stimulation With Intrauterine Insemination (Os-Iui) in a Multicenter Trial

“…SUPPORT FERTILITY & STERILITY Ò e103 MATERIALS AND METHODS: Of the 900 AMIGOS participants, 778 were available for analysis after excluding patients with hsCRP levels R10 indicative of infection, ectopic pregnancies and those missing pregnancy outcome or baseline hs-CRP serum measures. Hs-CRP concentration was evaluated using two definitions: first by hs-CRP categories of < 2mg/L and 2 -9.9 mg/L as previously defined in the literature, and second, by tertiles (tertile 1 % 0.725 mg/L, tertile 2 0.725 to 2.42 mg/L, and tertile 3 > 2.42 mg/ L) 1 . Risk ratios (RR) and 95% confidence intervals for the outcomes of live birth, clinical pregnancy, and pregnancy loss were estimated using modified Poisson regression models with robust standard errors.Adjustment for covariates were examined in multivariable models.…”