Antibiotic Exposure and Early Reproductive Outcomes of In Vitro Fertilization (IVF) in a Chinese Couple-Based Preconception Cohort

Dietary antibiotic exposure is very common, and animal studies have suggested that environmental antibiotic exposure has harmful effects on human reproduction and embryo development. However, there are no population-based cohort studies on the effects of parental antibiotic exposure on early IVF outcomes. A total of 33 antibiotics and 1 metabolite with detection rates over 10% in both female and male partners were included. Couples' early IVF reproductive outcomes included the blastocyst numbers, best-quality embryo numbers, embryo numbers, best-quality embryo rates, two pronuclei (2PN) rates, and blastocyst rates. We applied the adaptive elastic net (AENET) with 10-fold cross-validation to identify antibiotics associated with early IVF outcomes in couples. According to the antibiotics identified by AENET, quantile-based g-computation (QGC) models, group-weighted quantile sum (GWQS) regression, and partitioning around medoids (PAM) algorithms were used to evaluate the joint associations of parental antibiotic mixtures with early IVF reproductive outcomes. The independent associations between antibiotics identified by AENET, antibiotic classes, and early IVF reproductive outcomes in couples were evaluated using the multivariate generalized linear mixed model (GLMM) with random intercepts. In this couple-based prospective cohort study, 739 couples with 947 fresh cycles were included between December 2020 and August 2023. The mean age (SD) was 34.08 (5.48) years for male partners and 33.09 (5.22) years for female partners. In couple-based analyses, sulfaclozine, roxithromycin, sulfamonomethoxine, erythromycin, and penicillin V were positively related to several early IVF reproductive outcomes, while sulfamethoxazole, penicillin G, chlorotetracycline, norfloxacin, florfenicol amine (FFA), sulfadiazine, cyadox, and sulfachloropyridazine were negatively related to early IVF outcomes. Among antibiotic classes, human antibiotics (HAs), β-lactams, chloramphenicols, and quinoxalines had positive effects on early IVF outcomes, while sulfonamides, preferred as veterinary antibiotics (PVAs), and lincosamides had inverse effects on early IVF outcomes. Similar results were also observed in male partners and female partners. The association between parental antibiotic exposure and IVF outcomes requires further validation in a larger cohort of couples. Additionally, the extrapolation of our results to the general childbearing-aged couples requires caution as infertile couples may be more susceptible to antibiotics.