Association Between Ambient Air Pollution and Pregnancy Rate in Women Who Underwent IVF

S.A. Choe; Y.B. Jun; W.S. Lee; T.K. Yoon; S.Y. Kim


Hum Reprod. 2018;33(6):1071-1078. 

In This Article

Abstract and Introduction


Study Question: Are the concentrations of five criteria air pollutants associated with probabilities of biochemical pregnancy loss and intrauterine pregnancy in women?

Summary Answer: Increased concentrations of ambient particulate matter (PM10), nitrogen dioxide (NO2), carbon monoxide (CO) during controlled ovarian stimulation (COS) and after embryo transfer were associated with a decreased probability of intrauterine pregnancy.

What Is Known Already: Exposure to high ambient air pollution was suggested to be associated with low fertility and high early pregnancy loss in women.

Study Design, Size, Duration: Using a retrospective cohort study design, we analysed 6621 cycles of 4581 patients who underwent one or more fresh IVF cycles at a fertility centre from January 2006 to December 2014, and lived in Seoul at the time of IVF treatment.

Participants/Materials, Setting, Methods: To estimate patients' individual exposure to air pollution, we computed averages of hourly concentrations of five air pollutants including PM10, NO2, CO, sulphur dioxide (SO2) and ozone (O3) measured at 40 regulatory monitoring sites in Seoul for each of the four exposure periods: period 1 (start of COS to oocyte retrieval), period 2 (oocyte retrieval to embryo transfer), period 3 (embryo transfer to hCG test), and period 4 (start of COS to hCG test). Hazard ratios (HRs) from the time-varying Cox-proportional hazards model were used to estimate probabilities of biochemical pregnancy loss and intrauterine pregnancy for an interquartile range (IQR) increase in each air pollutant concentration during each period, after adjusting for individual characteristics. We tested the robustness of the result using generalised linear mixed model, accounting for within-woman correlation.

Main Results and the Role of Chance: Mean age of the women was 35 years. Average BMI was 20.9 kg/m2 and the study population underwent 1.4 IVF cycles on average. Cumulative pregnancy rate in multiple IVF cycles was 51.3% per person. Survival analysis showed that air pollution during periods 1 and 3 was generally associated with IVF outcomes. Increased NO2 (adjusted HR = 0.93, 95% CI: 0.87, 0.99) and CO (0.94, 95% CI: 0.89, 1.00) during period 1 were associated with decreased probability of intrauterine pregnancy. PM10 (0.92, 95% CI: 0.85, 0.99), NO2 (0.93, 95% CI = 0.86, 1.00) and CO (0.93, 95% CI: 0.87, 1.00) levels during period 3 were also inversely associated with intrauterine pregnancy. Both PM10 (1.17, 95% CI: 1.04 1.33) and NO2 (1.18, 95% CI: 1.03, 1.34) during period 3 showed positive associations with biochemical pregnancy loss.

Limitations, Reasons for Caution: The district-specific ambient air pollution treated as an individual exposure may not represent the actual level of each woman's exposure to air pollution. Smoking, working status, parity or gravidity of women, and semen analysis data were not included in the analysis.

Wider Implications of the Findings: This study provided evidence of an association between increased ambient concentrations of PM10, NO2 and CO and reduced probabilities for achieving intrauterine pregnancy using multiple IVF cycle data. Specifically, our results indicated that lower intrauterine pregnancy rates in IVF cycles may be linked to ambient air pollution during COS and the post-transfer period.

Study Funding/Competing Interest(s): This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2013 R1A6A3A04059017, 2016 R1D1A1B03933410 and 2018 R1A2B6004608) and the National Cancer Center of Korea (NCC-1810220-01). The authors report no conflicts of interest.


Air pollution has been suggested to be associated with cardiovascular diseases, respiratory disorders, neuro-psychological conditions, and general mortality (Cohen et al., 2017; Pun et al., 2017; Weaver et al., 2017). These studies mostly focused on five criteria pollutants including particulate matter less than or equal to 10 or 2.5 micrometres in diameter (PM10 and PM2.5, respectively), nitrogen dioxide (NO2), carbon monoxide (CO), sulphur dioxide (SO2) and ozone (O3). Although the specific mechanism is unclear, empirical evidence has shown that exposure to air pollution induces systemic inflammation in the general population and may lead to disease progression in susceptible individuals (WHO, 2013, Hajat et al., 2015; Li et al., 2017).

Conception is a complex process that involves gametogenesis, fertilisation, embryo transport and intrauterine implantation. Reduced fecundity was observed in women who were presumed to be exposed to air pollution that particularly emitted from traffic, although the biological processes involved were not clearly identified (Nieuwenhuijsen et al., 2014; Frutos et al., 2015; Mendola et al., 2017). Passive smoking increased the risk of infertility or subfertility through accelerated follicular loss, increased oocyte aneuploidy, impaired oocyte maturation and poor embryo development (Dechanet et al., 2011; Hyland et al., 2016). A recent report of the Nurses' Health Study II cohort showed exposure to higher concentration of coarse particles was associated with increased risk of infertility (Mahalingaiah et al., 2016). Increased ambient concentrations of PM10, NO2, SO2 and O3 were associated with infertility and a higher risk of miscarriage (Checa Vizcaino et al., 2016).

Epidemiological evidence of exposure to air pollution and obstetric complications or reproductive lifespan suggested potential impacts of air pollution on outcomes of ART. For women who undergo IVF, the probability of pregnancy may decrease with increased air pollution. A few recent studies investigated the associations between air pollution and IVF outcome; however, these were based on a few confounders and/or accounted for a single IVF cycle in each woman, which does not make full use of the data (Missmer et al., 2011; Maity et al., 2014). Analyses including total IVF cycles per woman and adjusting for important risk factors in achieving pregnancy would provide more precise estimations of the association with air pollution (Ehrlich et al., 2012; Kirkegaard et al., 2016). Furthermore, most studies of IVF focused on intrauterine pregnancy, as determined by ultrasonographic examination or live birth (Checa Vizcaino et al., 2016). As women undergoing IVF cycles are almost always tested for serum hCG which can detect pregnancy prior to ultrasonographic examination, biochemical pregnancy loss, presumably associated with impaired early embryonic development or altered endometrial receptivity, can be a useful outcome (Zeadna et al., 2015).

The objective of this study at a fertility centre was to explore the association between ambient concentrations of five criteria air pollutants during each stage of the IVF process and pregnancy outcomes.