History of Infertility and Plasma Markers of Inflammation, Cholesterol, and Adipokines Among Participants in the Nurses’ Health Study II

Introduction: There is increasing evidence that women who have experienced infertility are at greater risk for several chronic conditions. However, the mechanisms underlying these associations are not clear. Pathophysiology may be illuminated through observation of aberrant systemic biomarkers. However, there are limited data on infertility history and midlife biomarkers of inflammation, lipids, and adipokines. Materials and Methods: Among participants with biomarker measurements in the Nurses’ Health Study II, we used generalized linear models to assess history of infertility and plasma C-reactive protein (CRP, n = 3,518), interleukin-6 (IL-6, n = 3,145), soluble tumor necrosis factor-alpha receptor 2 (sTNFR2, n = 2,648), high-density lipoprotein-cholesterol (HDL-C, n = 1,387), low-density lipoprotein-cholesterol (LDL-C, n = 1,193), total cholesterol ( n = 4,427), leptin ( n = 2,228), and adiponectin ( n = 3,810). We investigated specific infertility diagnoses separately, as well as heterogeneity by body mass index (<25 kg/m 2 versus ≥25 kg/m 2 ), age at first infertility report, and primary versus secondary infertility. Results: On average, participants were 44 years at blood draw (range: 32–54 years). We observed no difference by infertility history in levels of CRP (% difference: 6.9, 95% confidence interval [−1.4,16.0]), sTNFR2 (−0.6% [−2.4,1.2]), HDL-C (0.2% [−3.1,3.6]), total cholesterol (0.6% [−0.5,1.8]), or adiponectin (−1.7% [−5.0,1.8]). Women who had experienced infertility had higher IL-6 (5.0% [0.1,10.1]) and leptin (6.5% [1.7,11.6]) and lower LDL-C (−3.7% [−7.0, −0.3]). Discussion: There was little evidence that women with a history of overall infertility have altered levels of inflammatory markers, total and HDL-C, or adiponectin compared with gravid women without infertility. In fully adjusted models, history of infertility was associated with higher IL-6 and leptin, as well as lower LDL-C levels.