Abstract
Neonicotinoid insecticides (NEOs), recognized endocrine-disrupting compounds, are extensively utilized in agricultural and livestock practices, exhibiting global environmental persistence and bioaccumulation in human populations and wildlife. Accumulating experimental and epidemiological evidence implicates NEO exposure in reproductive dysfunction. This study investigated paired NEO concentrations in serum, female follicular fluid, and male seminal plasma from 211 couples undergoing assisted reproductive technology (ART), evaluating associations with reproductive outcomes. NEO concentrations were quantified using liquid chromatography-tandem mass spectrometry (LC–MS/MS), and associations with ART parameters, considering partner exposure metrics, were examined utilizing covariate-adjusted generalized linear models. Results revealed N-demethyl-acetamiprid (N-dm-ACE) was commonly detected across all matrices. Female serum clothianidin (CLO) demonstrated a significant inverse correlation with fertilization potential and good-quality embryo yield, while elevated serum N-dm-ACE concentrations were linked to diminished biochemical pregnancy probability. Within follicular fluid, CLO presence impaired fertilization and cleavage rates, and higher N-dm-ACE levels compromised good-quality embryo developmental competence. Additionally, THX detection in seminal plasma was linked to reduced cleavage rates and lower biochemical and clinical pregnancy rates. Negative dose–response relationships were observed between N-dm-ACE exposure in female serum and both biochemical and clinical pregnancies, and between N-dm-ACE levels in follicular fluid and cleavage rate and biochemical pregnancy. These results demonstrate that partner NEO exposure detrimentally influences pivotal ART success metrics, highlighting the critical importance of dual parental biomonitoring in reproductive toxicology research for clinical risk assessment. Comprehensive longitudinal cohort studies are warranted to substantiate these associations and elucidate mechanistic pathways. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12940-025-01242-y.