Associations of urinary N, N-dimethylformamide metabolite concentrations with ovarian reserve and in vitro fertilization outcomes based on a prospective cohort study in China.

BACKGROUND

N,N-Dimethylformamide (DMF) is a recognized reproductive toxicant based on animal studies and male occupational epidemiological data. However, no studies have investigated the association of DMF exposure with ovarian reserve or in vitro fertilization (IVF) outcomes in women.

OBJECTIVES

To explore the relationship of DMF exposure with ovarian reserve and IVF outcomes in women undergoing IVF treatment.

METHODS

This study included 737 women undergoing IVF treatment in Chongqing, China, between February and October 2023. One follicular fluid (FF) and three urine samples were prospectively collected from each participant, and the primary metabolite of DMF, N-acetyl-S-(N-methylcarbamoyl)-L-cysteine (AMCC), was measured. Associations between AMCC levels and ovarian reserve or IVF outcomes were assessed using generalized linear models and generalized estimating equations models.

RESULTS

AMCC (median: 57.4 ng/mL) was detected in over 99% of the urine samples across the three visits, but was undetectable in all the FF samples. Higher urinary AMCC concentrations were associated with several outcomes after adjustment for body mass index, age, ethnicity, smoking status, and reasons for infertility. For example, an interquartile range-fold increase in AMCC at the first visit was associated with higher basal serum estradiol levels (10.1% increase; 95% CI: 4.01-16.6%) but lower oocyte yield (3.24% decrease; 95% CI: -6.20 to -0.19%), mature oocytes (3.41% decrease; 95 %CI: -6.64 to -0.07%), and the proportion of day 3 good-quality embryos [rate ratio (RR): 0.87; 95% CI: 0.79 to 0.96]. Similarly, an interquartile range-fold increase in geometric mean urinary AMCC concentrations across the three visits was associated with decreases in the proportions of day 3 good-quality embryos (RR: 0.82; 95% CI: 0.74 to 0.92) and usable blastocysts (RR: 0.93; 95% CI: 0.87 to 0.999).

DISCUSSION: Urinary AMCC was positively associated with basal serum estradiol but negatively associated with the number of total and mature oocytes, and the proportions of day 3 good-quality embryos and usable blastocysts. Reducing AMCC-related exposure may help protect female reproductive capacity.