The Relationship of Preconception and Early Pregnancy Isoprostanes with Fecundability and Pregnancy Loss.

Abstract

While redox stress likely plays an important role in reproductive health, the utility of peripheral biomarkers of oxidative stress, such as isoprostanes, during the periconception period remains underexplored. We evaluated the relationship between isoprostanes during preconception and gestational week 4 and women's reproductive health outcomes. The EAGeR trial (2007-2011) enrolled 1,228 women attempting pregnancy and followed them for up to 6 menstrual cycles and throughout pregnancy, if they became pregnant. We measured creatinine-adjusted, log-transformed isoprostanes 8-iso-PGF2α, its metabolite 2,3-dinor-iPF2α-III, and stereoisomers 5-iso-PGF2α-VI and 8,12-iso-iPF2α-VI in urine during preconception and 4 weeks' gestation. We evaluated pregnancy among participants in each menstrual cycle using hCG and defined pregnancy loss as observed loss following positive hCG. We calculated fecundability odds ratios (FOR) and 95% confidence intervals (CI) using discrete-time Cox proportional-hazards models and relative risk of pregnancy loss using adjusted log-binomial models. Higher preconception isoprostane levels were associated with lower fecundability (e.g. FOR 0.89, 95% CI 0.81-0.97 per interquartile range [IQR] increase in 8-iso-PGF2α). Among 797 pregnancies, isoprostane levels increased from preconception to 4 weeks' gestation (e.g. mean difference 0.12, 95% CI 0.10-0.14 ng/mL for 8-iso-PGF2α) and higher isoprostanes at 4 weeks' gestation were associated with lower risk of pregnancy loss (e.g. RR 0.79, 95% CI 0.62-1.00 per IQR increase in 8-iso-PGF2α). Preconception urinary isoprostanes may identify redox stress pathways associated with lower fecundability. However, the increase in isoprostanes into gestational week 4 and associated lower risk of pregnancy loss may suggest confounding by latent factors in early pregnancy.