Association of ambient air pollutant mixtures with IVF/ICSI-ET clinical pregnancy rates during critical exposure periods.

Study question: Does exposure to a mixture of ambient air pollutants during specific exposure periods influence clinical pregnancy rates in women undergoing IVF/ICSI-embryo transfer (ET) cycles?

Summary answer: The specific exposure period from ET to the serum hCG test was identified as a critical exposure window as exposure to sulfur dioxide (SO₂) or a combination of air pollutants was associated with a decreased likelihood of clinical pregnancy.

What is known already: Exposure to a single pollutant may impact pregnancy outcomes in women undergoing ART. However, in daily life, individuals often encounter mixed pollution, and limited research exists on the effects of mixed air pollutants and the specific exposure periods.

Study design size duration: This retrospective cohort study involved infertile patients who underwent their initial IVF/ICSI-ET cycle at an assisted reproduction center between January 2020 and January 2023. Exclusions were applied for patients meeting specific criteria, such as no fresh ET, incomplete clinical and address information, residency outside the 17 cities in the Sichuan Basin, age over 45 years, use of donor semen, thin endometrium (<8 mm) and infertility factors unrelated to tubal or ovulation issues. In total, 5208 individuals were included in the study.

Participants/materials setting methods: Daily average levels of six air pollutants (fine particulate matter (PM_2.5), inhalable particulate matter (PM₁₀), SO₂, nitrogen dioxide (NO₂), carbon monoxide (CO), and ozone (O₃)) were acquired from air quality monitoring stations. The cumulative average levels of various pollutants were determined using the inverse distance weighting (IDW) method across four distinct exposure periods (Period 1: 90 days before oocyte retrieval; Period 2: oocyte retrieval to ET; Period 3: ET to serum hCG test; Period 4: 90 days before oocyte retrieval to serum hCG test). Single-pollutant logistic regression, two-pollutant logistic regression, Quantile g-computation (QG-C) regression, and Bayesian kernel machine regression (BKMR) were employed to evaluate the influence of pollutants on clinical pregnancy rates. Stratified analyses were executed to discern potentially vulnerable populations.

Main results and the role of chance: The clinical pregnancy rate for participants during the study period was 54.53%. Single-pollutant logistic models indicated that for PM_2.5 during specific exposure Period 1 (adjusted odds ratio [aOR] = 0.83, 95% CI: 0.70-0.99) and specific exposure Period 4 (aOR = 0.83, 95% CI: 0.69-0.98), and SO₂ in specific exposure Period 3 (aOR = 0.92, 95% CI: 0.86-0.99), each interquartile range (IQR) increment exhibited an association with a decreased probability of clinical pregnancy. Consistent results were observed with dual air pollution models. In the multi-pollution analysis, QG-C indicated a 12% reduction in clinical pregnancy rates per IQR increment of mixed pollutants during specific exposure Period 3 (aOR = 0.89, 95% CI: 0.79-0.99). Among these pollutants, SO₂ (33.40%) and NO₂ (33.40%) contributed the most to the negative effects. The results from BKMR and QG-C were consistent. Stratified analysis revealed increased susceptibility to ambient air pollution among individuals who underwent transfer of two embryos, those with BMI ≥ 24 kg/m² and those under 35 years old.

Limitations reasons for caution: Caution was advised in interpreting the results due to the retrospective nature of the study, which was prone to selection bias from non-random sampling. Smoking and alcohol, known confounding factors in IVF/ICSI-ET, were not accounted for. Only successful cycles that reached the hCG test were included, excluding a few patients who did not reach the ET stage. While IDW was used to estimate pollutant concentrations at residential addresses, data on participants' work locations and activity patterns were not collected, potentially affecting the accuracy of exposure prediction.

Wider implications of the findings: Exposure to a mixture of pollutants, spanning from ET to the serum hCG test (Period 3), appeared to be correlated with a diminished probability of achieving clinical pregnancy. This association suggested a potential impact of mixed pollutants on the interaction between embryos and the endometrium, as well as embryo implantation during this critical stage, potentially contributing to clinical pregnancy failure. This underscored the importance of providing women undergoing ART with comprehensive information to comprehend the potential environmental influences and motivating them to adopt suitable protective measures when feasible, thereby mitigating potential adverse effects of contaminants on reproductive health.

Study funding/competing interests: This work received support from the National Key Research and Development Program of China (No. 2023YFC2705900), the National Natural Science Foundation of China (Nos. 82171664, 81971391, 82171668), the Natural Science Foundation of Chongqing Municipality of China (Nos. CSTB2022NSCQ-LZX0062, CSTB2023TIAD-KPX0052) and the Foundation of State Key Laboratory of Ultrasound in Medicine and Engineering (No. 2021KFKT013). The authors report no conflicts of interest.

Trial registration number: N/A.