Dynamic Associations between Ambient PM2.5 and Its Components and Transitions of Clinical Pregnancy and Adverse Reproductive Outcomes among Participants Treated with ART.

This study included participants with infertility who underwent first fresh embryo transfer using personalized embryo transfer protocols in Jinxin Xi’nan Women’s and Children’s Hospital in Sichuan, China between January 7, 2019 and July 5, 2022. Detailed clinical data were collected for all participants. Among the 13,157 initially recruited participants, we excluded 170 participants below 20 or above 40 years of age to focus on the core reproductive population and minimize age-related bias. We further excluded 270 with severe uterine malformations, chromosomal abnormalities, severe medical disorders (e.g., hypertension, diabetes, etc.), severe endocrine disorders (thyroid disorders, endometriosis, adenomyosis, etc.), and other disorders. The above exclusion criteria were based on the presence or absence of clinically diagnosed diseases. Additionally, 1270 participants with missing air pollution exposure data were excluded. The remaining 11,447 participants were finally included in the analysis ( Figure S1 ). The baseline characteristics of included and excluded participants were comparable ( Table S1 ). This study was approved by the Research Ethics Committee of the Sichuan Jinxin Xi’nan Women’s and Children’s Hospital (Ethics number 202309) and the informed consent was exempted from all included participants. The study collected detailed residential addresses of the participants, accurate to the natural village and community level. These addresses were converted to geographic coordinates (latitude and longitude) using geocoding systems. PM 2.5 and its component data were taken from the Tracking Air Pollution (TAP, http://tapdata.org.cn/ ) database in China, which provides daily full-coverage data on atmospheric component concentrations. The TAP project constructed a multiscale, near-real-time aerosol and gaseous pollutant concentration data set for China by integrating multisource data from ground observations, satellite remote sensing, emission inventories, and model simulations. PM 2.5 and its components, including BC, NO 3 – , sulfate SO 4 2– , ammonium NH 4 + and OM, with a spatial resolution of 10 km. The TAP estimates (2000–2020) were verified by real-time monitoring observations, and the correlation coefficients between the observed and estimated concentrations of BC, OM, NO 3 – , SO 4 2– , and NH 4 + were 0.64, 0.72, 0.75, 0.70, and 0.75, respectively. The TAP data set has been widely used in many environmental epidemiological studies. − The study set up multistage exposure assessment windows of 1 year, 3 months, 1 month and 14 days prior to embryo transfer, as well as post-transfer to confirmation of reproductive outcomes. The acquisition of stage-specific exposure levels first employs bilinear interpolation to estimate daily concentrations within the exposure window, followed by calculation of the mean concentration across the entire exposure period. These windows were selected on the basis of their coverage of the key sensitive stages of gamete and oocyte development, endometrial tolerance establishment, ovarian response, embryo implantation and pregnancy maintenance. − All participants were followed up from the date of fresh embryo transfer until occurrence of the outcomes or the end of the study period (July 6, 2023). During the follow-up period, we documented multiple outcomes, including clinical pregnancy, pregnancy complications, PTB, and miscarriage. Clinical pregnancy is a condition in which a visible gestational sac is confirmed by vaginal ultrasound in the fifth week of gestation on the basis of a positive serum β-hCG. The pregnancy complications mainly include gestational diabetes mellitus, gestational hypertension, premature rupture of membranes, amniotic fluid abnormalities, thyroid disorders, umbilical cord abnormalities and intrauterine fetal abnormalities. PTB is defined as delivery between 28 weeks and 37 weeks of gestation, while miscarriage is defined as termination of pregnancy before 28 weeks of gestation. , We developed a directed acyclic graph (DAG) to identify variables for adjustment ( Figure S2 ). , We first included sociodemographic factors, including age, region (Chengdu, southwest China, and other regions of China), socio-economic status, and body mass index (BMI) of pregnant women. Socio-economic status was derived by summing the scores for education and occupation for both partners. Educational attainment: high school and below = 1, specialist or bachelor’s degree = 2, master’s degree and above = 3. Occupations: manual labor occupations and unemployed = 1, special occupations/others = 2, administrative and office occupations = 3, management and professional occupations = 4. Total scores (4–14) were classified as low (4–7), medium (8–10), or high (11–14) socio-economic status. Relevant reproductive factors were also considered, including sperm concentration, sperm survival rate, the number of high-quality embryos transferred, endometrial thickness, antimüllerian hormone (AMH) levels, follicle-stimulating hormone (FSH) levels, antral follicle count (AFC), fertilization methods [IVF or intracytoplasmic sperm injection (ICSI)], embryo transfer protocols (single embryo transfer or double embryo transfer), season of embryo transfer, infertility type (primary or secondary). High-quality embryos under microscopy. These factors were included to account for their potential influence on reproductive outcomes. The characteristics of the participants were described using mean and standard deviation for continuous variables and frequencies and proportions for categorical variables. We used multistate regression models to estimate the dynamic associations between PM 2.5 and its components exposure and IVF outcomes based on a clock-forward approach ( Figure ). The multistate model consisted of four states (clinical pregnancy, pregnancy complications, PTB, miscarriage) with six transitions between these states: (a) a transition from infertility to clinical pregnancy, (b) a transition from clinical pregnancy to pregnancy complications, (c) a transition from clinical pregnancy to PTB, (d) a transition from clinical pregnancy to miscarriage, (e) a transition from pregnancy complications to PTB, and (f) a transition from pregnancy complications to miscarriage. The assessment details of the multistate model can be found in Figure S3 with Table S2 in the Supporting Information, covering proportional risk assumption testing and goodness-of-fit analysis. Assuming all PM 2.5 components are harmful, we used quantile g computation (QGC), a more suitable approach than WQS for survival analysis, to estimate the mixtures joint effect per quartile increase. , Restricted cubic spline modeling was used to assess potential nonlinear relationships between PM 2.5 and its components and the progression of reproductive outcomes at the 10th, 50th, and 90th percentiles in 3-segment increments. To control the false discovery rate (FDR) for association tests between pollutants and outcomes, this study applied the Benjamini-Hochberg (BH) method to correct all raw p -values and reported the adjusted q -values. Transitions from infertility to clinical pregnancy and from clinical pregnancy to adverse outcomes among infertile participants ( n = 11,447). Considering that reproductive parameters (the number of high-quality embryos at the cleavage stage, endometrial thickness, AMH, AFC, FSH, sperm concentration, and sperm survival rate) may mediate the association between PM 2.5 and its components and assisted reproductive outcomes, we further performed mediation analyses to examine whether reproductive parameters could mediate the association between PM 2.5 and its components and clinical pregnancy, pregnancy complications, PTB and miscarriage. High-quality embryos under microscopy, endometrial thickness by transvaginal ultrasound, AMH and FSH via immunoassays, AFC by early follicular phase ultrasound, sperm concentration using computer-assisted sperm analysis (CASA), and sperm survival rate is measured by eosin-aniline black staining and microscopic counting of viable spermatozoa, with a normal reference value of ≥58% (WHO fifth ed.). The mediation analysis was based on standard assumptions: no unmeasured confounding exists for the relationships of exposure with mediator, exposure with outcome, and mediator with outcome, and no confounders related to the mediator-outcome relationship are affected by the exposure. We performed several sensitivity analyses to test the robustness of the results. First, mean air pollution exposure levels were calculated for 2 and 4 months prior to embryo transfer to assess whether the exposure window was different. Second, the ICSI and IVF groups, as well as the single and double embryo transfer groups, were analyzed to in each group separately. Third, we further employed a mixed-effects model (Cox frailty model), incorporating region as a random effect, to assess and control for potential clustering effects. All statistical tests were two-sided and p < 0.05 was used as the criterion for determining statistical significance. The multistate model was constructed using the mstate package, and mediation analysis performed with the mediator package in R (version 4.4.1).

Among 11,447 infertile participants with IVF, 6049 (52.84%) developed clinical pregnancy; 791 (13.08%) further developed PTB and 798 (13.19%) developed miscarriage ( Table ). The mean age of participants with successful clinical pregnancy was 30.59 years (standard deviation 3.88 years), and 3567 (59.0%) were from southwest China ( Figure ). Geographic distribution of IVF participants ( n = 11,447). IVF, in vitro fertilization. The map was drawn based on the standard Chinese map. Study samples cover 31 provincial administrative regions of China (excluding Taiwan, Hong Kong and Macao), with the majority originating from Southwest China. Map elements are labeled as follows: black dashed lines denote the undetermined national boundary of the Xinjiang Uygur Autonomous Region; islands such as the Nanhai Islands and the Diaoyu Island were marked in red; blue dots represent the geographic distribution of study samples. Note: Continuous variables were tested by analysis of variance and rank sum test, and categorical variables were tested by chi-square test. SD, standard deviation; IQR, interquartile range. AMH, Antimullerian hormone; FSH, Follicle Stimulating Hormone; AFC, Antral Follicle Count. Southwest China includes Sichuan (excluding Chengdu), Chongqing, Guizhou, Yunnan, and Tibet. Women’s age, region, BMI, blood pressure, bilirubin, blood glucose, AMH, years of infertility, and type of infertility, as well as their spouses’ sperm concentration and sperm survival rate are documented during the IVF pretreatment assessment (approximately 30–60 days prior to embryo transfer). Women’s FSH and AFC are assessed on days 2–4 of the menstrual cycle. Endometrial thickness is evaluated 1–3 days prior to embryo transfer. The fertilization methods were confirmed on the day of egg collection and the number of high-quality embryos at the cleavage stage was assessed on day 3 of embryo development. The number of high-quality embryos transferred, embryo transfer protocols, and the season of embryo transfer are determined on the day of embryo transfer. The results of the study showed that participants with PTB, or miscarriage had higher levels of PM 2.5 and its components exposure in the 3 months prior to embryo transfer than participants with clinical pregnancy ( Table ). Further analyses showed significant positive correlations between PM 2.5 and its components ( Table S3 ). Furthermore, the concentrations of PM 2.5 exceed China’s national air quality secondary standards. Note: Continuous variables were tested by analysis of variance and rank sum test. SD, standard deviation. PM 2.5 , particulate matter ≤2.5 μm in diameter; BC, black carbon; OM, organic matter; SO 4 2– , sulfate; NO 3 – , nitrate; NH 4 + , ammonium. The multistate modeling analyses showed that exposure to PM 2.5 and its components was significantly negatively associated with the transition from infertility to clinical pregnancy among participants, and positively associated with transitions from clinical pregnancy to PTB or miscarriage ­( Figure ). Figure and Table S4 demonstrate the estimated effect of the association between PM 2.5 and its components and reproductive outcomes under different exposure windows. Exposure to PM 2.5 and its components in the 3 months prior to embryo transfer was negatively associated with progression from infertility to clinical pregnancy and positively associated with transition from clinical pregnancy to PTB in participants, with the effect being most pronounced at the stage of clinical pregnancy to PTB. Notably, only BC and OM exposure were significantly associated with transition from clinical pregnancy to miscarriage. As an example, for every 1 interquartile range (IQR) increase in OM exposure, the HR associated with progression of infertility to clinical pregnancy was 0.956 (95% CI: 0.927, 0.985), the HR for progression of clinical pregnancy to PTB was 1.176 (95% CI: 1.083, 1.276), and the HR for progression of clinical pregnancy to miscarriage was 1.115 (95% CI: 1.025, 1.217). After FDR correction, the association between pollutant exposure in the 3 months prior to embryo transfer and outcomes remained stable ( Table S5 ). For instance, in the association between BC exposure and clinical pregnancy to PTB and miscarriage, the q -values were all less than 0.05. Association of each IQR increase in exposure to PM 2.5 and its components with clinical pregnancy, adverse reproductive outcomes in IVF participants ( n = 11,447). IQR, interquartile range; IVF, in vitro fertilization; ET, embryo transfer; PM 2.5 , particulate matter ≤2.5 μm in diameter; BC, black carbon; OM, organic matter; SO 4 2– , sulfate; NO 3 – , nitrate; NH 4 + , ammonium. IQR increments are 20.990 μg/m 3 for PM 2.5 , 0.927 μg/m 3 for BC, 5.286 μg/m 3 for OM, 3.858 μg/m 3 for SO 4 2– , 6.611 μg/m 3 for NO 3 – , and 4.135 μg/m 3 for SO 4 2– . Multistate models were adjusted for age, region, socio-economic status, body mass index, number of high-quality embryos transferred, endometrial thickness, AMH, FSH, AFC, fertilization methods, embryo transfer protocols, season of embryo transfer, types of infertility for the women, and for sperm concentration and sperm survival rate for the spouse. Variance inflation factor analysis showed that the VIF values for all independent variables were less than 5 (1.02–4.40), indicating an acceptable level of covariance. Quartile g-computation estimates represent the health effect value for a simultaneous increase of one quartile in the PM 2.5 component mixtures. The results showed that each quartile increase in mixtures was negatively associated with participants’ transition from infertility to clinical pregnancy (HR: 0.836, 95%CI: 0.747, 0.950) and positively associated with the transition from clinical pregnancy to PTB (HR: 1.990, 95%CI: 1.351, 2.670). See Figure with Table S6 for details. Joint association of PM 2.5 component mixtures exposure with clinical pregnancy, adverse reproductive outcomes in IVF participants ( n = 11,447). IVF, in vitro fertilization; ET, embryo transfer. The estimates produced by the quantile g-computation represent the health effect value of a simultaneous increase in the concentration of five pollutants by one quantile. Cox regression models using the quantile g-computation approach were adjusted for age, region, socio-economic status, body mass index, number of high-quality embryos transferred, endometrial thickness, AMH, FSH, AFC, fertilization methods, embryo transfer protocols, season of embryo transfer, types of infertility for the women, and for sperm concentration and sperm survival rate for the spouse. Variance inflation factor analysis showed that the VIF values for all independent variables were less than 7 (1.21–6.84), indicating an acceptable level of covariance. By using a multistate model ( n = 11,447), we examined the association between air pollution and infertility participants in six transition states. Hazard ratios are indicated by thick lines and 95% confidence intervals are indicated by shaded areas. The dose–response curves of PM 2.5 and its components with clinical pregnancies were all tested for nonlinearity with p -values <0.05, indicating a nonlinear relationship, with inflection points of 35.76, 1.72, 8.19, 6.31, 7.93, and 5.82 μg/m 3 . Note: ET, embryo transfer; PM 2.5 , particulate matter ≤ 2.5 μm in diameter; BC, black carbon; OM, organic matter; SO 4 2– , sulfate; NO 3 – , nitrate; NH 4 + , ammonium. Models were adjusted for age, region, socio-economic status, body mass index, number of high-quality embryos transferred, endometrial thickness, AMH, FSH, AFC, fertilization methods, embryo transfer protocols, season of embryo transfer, types of infertility for the women, and for sperm concentration and sperm survival rate for the spouse. Variance inflation factor analysis showed that the VIF values for all independent variables were less than 5 (1.02–4.91), indicating an acceptable level of covariance. Logistic regression assessed PM 2.5 and its components with assisted reproductive outcomes, followed by linear regression for their relationships with reproductive parameters (number of high-quality embryos at cleavage stage, endometrial thickness, AMH, AFC, FSH, sperm concentration, sperm survival rate). We found that only the number of high-quality embryos at the cleavage stage was associated with both PM 2.5 and its components and clinical pregnancy ( Tables S7 ). Through mediation effects analysis ( Figure ), we further examined the potential mediating role of the number of high-quality embryos at the cleavage stage in the relationship between PM 2.5 and its components and clinical pregnancy. The findings suggest that the associations of PM 2.5 and its components with clinical pregnancy are mediated in part by the number of high-quality embryos at the cleavage stage. The mediating effect of the number of high-quality embryos at the cleavage stage accounted for 2.41%, 3.25%, 1.54%, 2.20%, 1.52%, and 1.09% respectively. Mediation analysis of the relationship between PM 2.5 and its components with clinical pregnancies by the number of high-quality embryos at the cleavage stage ( n = 11,447). The role of the number of high-quality embryos at the cleavage stage in the relationship between PM 2.5 and its components with clinical pregnancies was analyzed using a mediation effects model. Oval boxes indicate exposure factors, quadrilateral boxes indicate mediators, and hexagonal boxes indicate study outcomes. β, regression coefficient; PM 2.5 , particulate matter ≤2.5 μm in diameter; BC, black carbon; OM, organic matter; SO 4 2– , sulfate; NO 3 – , nitrate; NH 4 + , ammonium. * p < 0.05, ** p < 0.017, *** p < 0.001, p values <0.05 were considered statistically significant. Models were adjusted for age, region, socio-economic status, body mass index, number of high-quality embryos transferred, fertilization methods, embryo transfer protocols, season of embryo transfer, types of infertility for the women. Variance inflation factor analysis showed that the VIF values for all independent variables were less than 5 (1.05–4.52), indicating an acceptable level of covariance. First, in the sensitivity validation of the exposure window, the strongest association with assisted reproductive outcomes was observed in the 3 months prior to embryo transfer compared with the exposure assessments in the 2 months and 4 months prior to embryo transfer ( Table S8 ). Second, the main findings of the IVF and ICSI groups were consistent, showing that exposure to PM 2.5 and its components was negatively associated with the transition of IVF participants from infertility to clinical pregnancy and positively associated with the progression from clinical pregnancy to PTB ( Table S9 ). Third, after incorporating regional random effects, the association between pollutants and reproductive outcomes remained largely unchanged. In most models, the random-effects variance was not significant ( Table S10 ). A few combinations (e.g., PM 2.5 exposure prior to transfer 3 months and clinical pregnancy, variance = 0.003, p < 0.01) exhibited heterogeneity without significant changes in effects, indicating that results were either unaffected or weakly influenced by regional clustering.

Our results showed that exposure to higher PM 2.5 and its components prior to fresh embryo transfer was negatively associated with progression from infertility to clinical pregnancy and positively associated with progression from clinical pregnancy to PTB or miscarriage in IVF participants, with the effect being most pronounced at the stage of clinical pregnancy to PTB. Notably, only BC and OM exposure were significantly associated with transition from clinical pregnancy to miscarriage. In addition, the number of high-quality embryos at the cleavage stage mediated the association between pollution and clinical pregnancy. Although air pollution is known to negatively affect reproductive outcomes, this study provides novel epidemiological evidence that PM 2.5 and its components may specifically compromise the dynamic reproductive outcomes of IVF by impairing gametogenesis. By analyzing the outcomes of fresh embryo transfer, we were able to comprehensively assess the dynamic effects of PM 2.5 and its components on gametogenesis and pregnancy. Epidemiological studies have reported that increased concentrations of PM 2.5 , PM 10 , O 3 and NO 2 are associated with reduced natural fertility. − However, relevant data for ART patients are limited. It has been suggested that acute exposure to high levels of environmental pollutants from wildfires may lead to reduced blastocyst formation. Another study found that increased PM exposure during the follicular phase of the fertile cycle in ART patients may be associated with an increased risk of miscarriage. A recent meta-analysis also showed that exposure to higher concentrations of PM 2.5 in the ART population during the 85 days prior to egg retrieval was associated with lower live birth rates. Recently, a study conducted in Australia on the association between pollution exposure and IVF outcomes reached similar conclusions to this study. The study showed that increased PM 2.5 exposure in the 3 months prior to egg retrieval was significantly associated with IVF outcome failure. However, the study did not observe an effect of PM 2.5 exposure on IVF outcome in the 1 month and 14 days prior to egg retrieval. This difference may be attributed to the fact that the overall pollution exposure levels in the study area were significantly lower than in the present study. It is noteworthy that the PM 2.5 components were not analyzed in depth, and the possible combined effects of multiple pollutants were not investigated. There is still a paucity of evidence on whether the negative impact of exposure to PM 2.5 and its components on IVF outcomes stems from effects on gametogenic processes or on pregnancy development. In this study, we systematically assessed pollution exposure during the oocyte developmental stage versus the pregnancy stage post embryo transfer by analyzing fresh embryo transfer cycles. The results suggest that poor IVF outcomes may result from the negative effects of exposure to PM 2.5 and its components directly on oocyte development and maturation, with the impact being particularly pronounced the transition from clinical pregnancy to PTB. Notably, BC and OM seem to play stronger effects. Although the specific mechanisms by which PM 2.5 and its components affect oocyte development remain to be elucidated, several potential mechanisms with physiological plausibility exist. The mechanisms of action include induction of oxidative stress, DNA damage, epigenetic DNA modification, and endocrine disrupting effects such as antiestrogen-like and antiandrogen-like activities. − In addition, recent studies have detected ambient black carbon in human follicular fluid and ovarian tissues. A finding that echoes the results of our study and further confirms that developing oocytes may be directly exposed to PM 2.5 and its components. There is still limited research on the association of PM 2.5 and its components with the dynamics of reproductive outcomes in infertile populations, and this study provides new insights into the field. First, multistate regression modeling was used to explore the association between pollution and the dynamic progression of reproductive outcomes, revealing the specific effects of pollution exposure across transitions. In addition, given the difficulty in obtaining data on infertility due to the long duration and high cost of treatment, the data in this study were obtained from professional assisted reproductive facilities in China, with a large sample size and coverage of multiple regions, which significantly improved the reliability and representativeness of the results. The novelty of this study is that it breaks through the limitations of traditional cross-sectional studies by dynamically tracking the infertile population from embryo transfer to pregnancy, and constructing an evidence chain of ‘air pollution exposure - gamete development - pregnancy outcome’ in the same timeline. The large sample cohort not only enhances the extrapolation value of the results, but also provides a methodological paradigm for similar studies, which is of great scientific significance for improving the management of environmental exposure in the field of assisted reproductive. Our study has several limitations. First, exposure assessment was based on gridded estimated TAP data, which may introduce exposure misclassification due to individual mobility and microenvironmental differences. However, such misclassification is likely nondifferential, as residential addresses were similarly assigned across participants, and prior studies suggest that fixed-site estimates correlate well with personal exposure in chronic air pollution studies. Second, outdoor air pollution was estimated based on participants’ home addresses and therefore cannot account for all changes in indoor concentrations. Nonetheless, it has been suggested that air pollution originates primarily from the outdoor environment, therefore, our measurements are broadly consistent with reality. Third, this is a retrospective cohort study and may have some bias, but we have corrected for potential bias by rigorous control of confounders and sensitivity analysis to enhance the robustness of the results. Fourth, the inability of the QGC model to resolve multicollinearity among PM 2.5 components may yield unstable weights, warranting cautious interpretation.

This study used multistate analysis based on retrospective cohort data from a large specialist assisted reproductive hospital to examine the dynamic associations between exposure to PM 2.5 and its components and the progression from infertility to clinical pregnancy and from clinical pregnancy to adverse reproductive outcomes in IVF participants around embryo transfer. Exposure to PM 2.5 and its components in the 3 months prior to embryo transfer was found to be negatively associated with the progression from infertility to clinical pregnancy, and positively associated with the progression from clinical pregnancy to adverse reproductive outcomes, with the effect being most pronounced in the transition from clinical pregnancy to PTB. BC and OM seem to show stronger effects. In addition, the number of high-quality embryos at the cleavage stage mediated the effect. This suggests that early intervention for environmental exposures in infertile patients is expected to improve assisted reproductive success. The role of air pollution in the dynamic transition of reproductive outcomes needs to be further explored in the future to provide a more solid scientific basis for precision medicine policies and interventions.

Environmental pollution has been recognized as one of the greatest modern threats to human health. , Numerous studies have confirmed that environmental pollution is associated with the risk of cardiovascular and cerebrovascular disease morbidity and all-cause mortality, , and it is estimated that environmental pollution is responsible for approximately 9 million deaths per year. In addition, environmental pollution is also strongly associated with reproductive health, with fine particulate matter ≤2.5 μm in diameter (PM 2.5 ) being particularly hazardous. PM 2.5 is a heterogeneous mixture of complex chemical components, mainly including black carbon (BC), organic matter (OM), sulfate ions (SO 4 2– ), nitrate ions (NO 3 – ), ammonium ions (NH 4 + ), etc. A study showed that women living within 200 m of a major road had a 10% increased risk of infertility, with a clear dose-dependent effect. , In addition, for every 10 μg/m 3 increase in PM 2.5 concentration, there is an approximate 10%–20% reduction in fertility. Another study noted a significant association between PM 2.5 exposure within 85 days prior to egg retrieval and an increased risk of preterm birth (PTB) in participants undergoing assisted reproductive technology (ART) treatment (HR: 1.09, 95% CI: 1.02–1.21). Meanwhile, a study found that the rate of pregnancy loss has been on the rise in the U.S. in recent decades, and that women exposed to high levels of air pollution have a significantly increased risk of miscarriage and PTB. In addition, an Australian study found that when PM 2.5 concentrations were in the highest quartile range, the rate of live births was 34% lower compared to the lowest quartile range. However, most studies have focused on the association between PM 2.5 and a single reproductive outcome, overlooking the specificity of pollutants across different transitions, and lack insight into specific mechanisms of action. , PM 2.5 and its components may interfere with the dynamic process from infertility to clinical pregnancy, and clinical pregnancy to pregnancy complications, PTB, and miscarriage, either by impairing pregnancy in in vitro fertilization (IVF) participants or by directly affecting gamete development. In fresh embryo transfer cycles, embryo development, endometrial preparation and pregnancy are on the same timeline and under the same environmental conditions, which avoids freeze–thaw damage, which provides an opportunity for a comprehensive assessment of the environmental impacts at a given point in time. We therefore conducted this study to explore the health effects of PM 2.5 and its components on oocyte development and pregnancy stages by analyzing the dynamics of fresh embryo transfer outcomes, and further tested the potential mediating role of reproductive parameters in the associations.