Protective placental inflammatory and oxidative stress responses are attenuated in the context of twin pregnancy and chorioamnionitis in assisted reproduction

Purpose Assisted reproduction technologies (ART) are associated with increased risks of pregnancy complications and obstetric interventions. Here, we aimed to determine if ART affects placental inflammation and oxidative stress as a mechanism for unfavorable pregnancy outcomes. Methods The levels of six cytokines (IFN-γ, IL-1β, IL-6, IL-8, IL-10, TNFα) were measured using multiplex ELISA. The activity of four antioxidant enzymes (glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase, superoxide dismutase) and levels of two antioxidants (GSH, vitamin E) were measured using commercial/in-house assays. Markers were compared between ART and unassisted pregnancies, and then groups were stratified using ICD9/10 codes to determine differences in specific clinical contexts. Results In unassisted twin pregnancies, there was a trend of decreased cytokine levels (IL-1β, IL-6, IL-8, TNFα, p < 0.05), but cytokines in ART twins were the same or higher. Additionally, GST and GPx activities were lower in unassisted twins, and vitamin E levels were higher in ART twins ( p < 0.05). In pregnancies complicated by chorioamnionitis, there was a trend of increased cytokine levels in unassisted pregnancies (IL-1β, IL-6, and IL-8, p < 0.05). No increase was observed in ART, and IFN-γ and TNFα were decreased ( p < 0.05). Placental GST and GPx activities were higher in unassisted pregnancies with chorioamnionitis compared to ART ( p < 0.05). Conclusion Attenuation of protective placental inflammatory and oxidative stress responses may play a role in the underlying pathogenesis of negative birth outcomes in ART, expanding our understanding of adverse pregnancy outcomes when ART is used to conceive.