Haloacetic Acid Disinfection Byproducts in Follicular Fluid and In Vitro Fertilization Outcomes: A Prospective Cohort Study in China.

Drinking water disinfection byproducts (DBPs), particularly haloacetic acids (HAAs), can exert adverse effects on oocyte quality and embryo development. However, there has been a paucity of human evidence. We included 1176 women who underwent 1306 in vitro fertilization (IVF) cycles from the Tongji Reproductive and Environmental cohort (2018-2021). Dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) concentrations in follicular fluid were assessed. Elevated quartiles of DCAA and TCAA concentrations in follicular fluid had significant inverse exposure-response associations with all IVF outcomes (e.g., 16.67% and 10.14% reductions in proportion of clinical pregnancy for the highest vs lowest quartiles of DCAA and TCAA concentrations, respectively; both P for trend <0.01). The effects were more pronounced in women undergoing non-long GnRH agonist regimens and IVF insemination technology. The serial mediation analyses identified that a sequential pathway (oocyte → mature oocyte → zygotes with two pronuclei → good-quality embryos) mediated 21.1%-33.9% of HAA exposure-related inferior clinical pregnancy outcomes (implantation, clinical pregnancy, and live birth). Our findings suggest that elevated levels of HAAs in follicular fluid are associated with decreased oocyte quality and subsequent inferior IVF outcomes, strengthening human evidence that exposure to drinking water DBPs has detrimental effects on early reproductive outcomes.