Observed Effects on Very Early Pregnancy Linked to Ambient PM2.5 Exposure in China among Women Undergoing In Vitro Fertilization-Embryo Transfer

doi:10.1021/envhealth.4c00107

. 2024 Oct 21;2(12):918-928.

doi: 10.1021/envhealth.4c00107. eCollection 2024 Dec 20.

Observed Effects on Very Early Pregnancy Linked to Ambient PM_2.5 Exposure in China among Women Undergoing In Vitro Fertilization-Embryo Transfer

Changxin Lan^{1

2}, Yichun Guan³, Haining Luo⁴, Xiaoling Ma⁵, Yihua Yang⁶, Hongchu Bao⁷, Cuifang Hao⁸, Xiaojin He⁹, Han Zhang^{1

2}, Ning Gao^{1

2}, Weinan Lin^{1

2}, Mengyuan Ren^{1

2}, Tianxiang Wu^{1

2}, Chao Wang^{10

11}, Xiaoqing Ni^{10

11}, Chunyan Shen³, Jianrui Zhang³, Junfang Ma⁴, Rui Zhang⁵, Yin Bi⁶, Lili Zhuang⁷, Ruichao Miao⁸, Ziyi Song¹², Tong An¹², Zhengteng Liu⁷, Bo Pan¹³, Mingliang Fang¹⁴, Jing Liu¹⁵, Zhipeng Bai¹⁶, Fangang Meng¹⁷, Yuanchen Chen¹⁸, Xiaoxia Lu¹⁹, Yuming Guo²⁰, Yunxia Cao^{10

11}, Qun Lu^{12

21}, Bin Wang^{1

2

19}

Affiliations

¹ Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China.
² Institute of Reproductive and Child Health, Key Laboratory of Reproductive Health, National Health and Family Planning Commission of the People's Republic of China, Beijing 100191, China.
³ Department of Reproductive Medicine, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, China.
⁴ Reproductive Medicine Center, Tianjin Central Hospital of Gynecology Obstetrics, Maternity Hospital of Nankai University, Tianjin 300052, China.
⁵ The First Hospital of Lanzhou University, the First Clinical Medical School of Lanzhou University, Lanzhou 730000, China.
⁶ Guangxi Reproductive Medical Center, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
⁷ Reproductive Medicine Centre, Yuhuangding Hospital of Yantai, Affiliated Hospital of Qingdao University, Yantai 264000, China.
⁸ Qingdao Women and Children's Hospital, Affiliated Hospital of Qingdao University, Qingdao 266555, China.
⁹ Reproductive Medicine Center, Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
¹⁰ Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
¹¹ Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, Hefei 230022, China.
¹² Medical Center for Human Reproduction, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
¹³ Yunnan Provincial Key Lab of Soil Carbon Sequestration and Pollution Control, Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China.
¹⁴ Department of Environmental Science and Engineering, Fudan University, Shanghai, 200433, China.
¹⁵ MOE Key Laboratory of Environmental Remediation and Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China.
¹⁶ State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China.
¹⁷ Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
¹⁸ Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, PR China.
¹⁹ Laboratory for Earth Surface Processes, College of Urban and Environmental Science, Peking University, Beijing, 100871, China.
²⁰ Climate, Air Quality Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria 3004, Australia.
²¹ Center of Reproductive Medicine, Peking University People's Hospital, Beijing 100044, China.

PMID: 39722841
PMCID: PMC11667290
DOI: 10.1021/envhealth.4c00107

Observed Effects on Very Early Pregnancy Linked to Ambient PM_2.5 Exposure in China among Women Undergoing In Vitro Fertilization-Embryo Transfer

Changxin Lan et al. Environ Health (Wash). 2024.

. 2024 Oct 21;2(12):918-928.

doi: 10.1021/envhealth.4c00107. eCollection 2024 Dec 20.

Authors

Affiliations

¹ Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China.
² Institute of Reproductive and Child Health, Key Laboratory of Reproductive Health, National Health and Family Planning Commission of the People's Republic of China, Beijing 100191, China.
³ Department of Reproductive Medicine, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, China.
⁴ Reproductive Medicine Center, Tianjin Central Hospital of Gynecology Obstetrics, Maternity Hospital of Nankai University, Tianjin 300052, China.
⁵ The First Hospital of Lanzhou University, the First Clinical Medical School of Lanzhou University, Lanzhou 730000, China.
⁶ Guangxi Reproductive Medical Center, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
⁷ Reproductive Medicine Centre, Yuhuangding Hospital of Yantai, Affiliated Hospital of Qingdao University, Yantai 264000, China.
⁸ Qingdao Women and Children's Hospital, Affiliated Hospital of Qingdao University, Qingdao 266555, China.
⁹ Reproductive Medicine Center, Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
¹⁰ Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
¹¹ Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, Hefei 230022, China.
¹² Medical Center for Human Reproduction, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
¹³ Yunnan Provincial Key Lab of Soil Carbon Sequestration and Pollution Control, Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China.
¹⁴ Department of Environmental Science and Engineering, Fudan University, Shanghai, 200433, China.
¹⁵ MOE Key Laboratory of Environmental Remediation and Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China.
¹⁶ State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China.
¹⁷ Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
¹⁸ Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, PR China.
¹⁹ Laboratory for Earth Surface Processes, College of Urban and Environmental Science, Peking University, Beijing, 100871, China.
²⁰ Climate, Air Quality Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria 3004, Australia.
²¹ Center of Reproductive Medicine, Peking University People's Hospital, Beijing 100044, China.

PMID: 39722841
PMCID: PMC11667290
DOI: 10.1021/envhealth.4c00107

Abstract

The adverse effect of ambient PM_2.5 exposure on very early pregnancy (VEP) remains controversial among epidemiological studies but is supported by toxicological evidence. We adopted a multicenter retrospective cohort of 141,040 cycles to evaluate the effect of PM_2.5 exposure on the VEP using the in vitro fertilization and embryo transfer platform and high-resolution PM_2.5 data in China. We first investigated the association between PM_2.5 exposure 1 week before and 1 week after the embryo transfer date and VEP. The average PM_2.5 concentrations of the 2 weeks were approximately 47 μg/m³. The pooled results revealed a negative association between women's accumulated PM_2.5 exposure during the 2 weeks near the day of embryo transfer and success odds of VEP with the relative risk of 0.999 (95% CI: 0.997-0.999) at each increase of 10 μg/m³. The women with the fresh cycle or one transplanted embryo were considered as a vulnerable population. Furthermore, seven periods for the fresh cycle and five periods for the frozen cycle from 85 days before oocyte retrieval to the day of gestational sac detection by ultrasound detection were defined. For these exposure periods, no association between the average PM_2.5 exposure and VEP risk was identified. Our study provided large-scale population evidence for the association between PM_2.5 exposure near embryo transfer day and VEP and identified vulnerable populations among women undergoing in vitro fertilization-embryo transfer.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

**Figure 1**
Basic survey information. (A) Geographical distribution of the included patients; (B and C) number of cycles over year and month, respectively; (D) average PM_2.5 concentration during the survey period (2012–2021). The national PM_2.5 data of 1-km resolution during 2012–2021 from the open database of Tracking Air Pollution in China (http://tapdata.org.cn/).

**Figure 2**
Pooled associations of PM_2.5 exposure in various exposure period or day with the success odds of biochemical pregnancy and clinical pregnancy. The results are presented as relative risk for every 10 μg/m³ of PM_2.5 increase. (A) The time points and periods for assigning PM_2.5 exposure of patients. The embryo transplant day is denoted as D0, while the average PM_2.5 concentrations in the 6th to the 1st days before the embryo transplant day to the transplant day are denoted as D6_B to D1_B, and from the 1st to the 6th day after the embryo transplant day for each patient are denoted as D1_A to D6_A, of which the total period was 13 days. The average PM_2.5 concentrations during the periods from the 6th, 5th, ..., and 1st days to the embryo transplant day and from the embryo transplant day to the 1st, 2nd, ..., and 6th days are denoted as P6_B, P5_B, ..., P1_B, and P1_A, P2_A, ..., and P6_A, respectively. The period from D6_B to D6_A is denoted as P13. Two very early pregnancy includes (B and C) biochemical pregnancy and (D and E) clinical pregnancy. The related associations based on the exposure assessments of the average period and daily time are depicted in left and right panels, respectively. Red point indicates statistical significance with P value <0.05.

**Figure 3**
Interaction effects between PM_2.5 exposure and the clinical factors on the success odds of biochemical pregnancy (BP) and clinical pregnancy (CP). The results are presented as relative risk for every 10 μg/m³ of PM_2.5 increase. (A) Pooled associations of PM_2.5 exposure with the CP and BP stratified by age, type of embryo transfer, number of transferred embryos, and infertility causes of ovulation disorder, tubal factor, diminished ovarian reserve, and endometriosis among the women undergoing *in vitro* fertilization and embryo transfer; (B and C) interaction effect between PM_2.5 and type of embryo for BP and CP in Tianjin Center, respectively; (D and E) interaction effect between PM_2.5 and number of transferred embryos for BP and CP in Henan Center, respectively. P value for the statistical testing of the interaction effect.

**Figure 4**
Pooled associations between PM_2.5 exposure and the two very early pregnancies of biochemical pregnancy (BP) and clinical pregnancy (CP). The results are presented as relative risk for every 10 μg/m³ of PM_2.5 increase. The periods for assigning PM_2.5 exposure were separately defined for the fresh cycle with seven periods (A) and the frozen cycle with five periods (B). Two very early pregnancies were investigated, including BP (C) and CP (D) in fresh cycles, and BP (E) and CP (F) in frozen cycles.

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References

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[1] Skakkebæk N. E.; Lindahl-Jacobsen R.; Levine H.; Andersson A. M.; Jorgensen N.; Main K. M.; Lidegaard O.; Priskorn L.; Holmboe S. A.; Bräuner E. V.; Almstrup K.; Franca L. R.; Znaor A.; Kortenkamp A.; Hart R. J.; Juul A. Environmental Factors in Declining Human Fertility. Nat. Rev. Endocrinol 2022, 18 (3), 139–157. 10.1038/s41574-021-00598-8. - DOI - PubMed

[2] Skakkebæk N. E.; Lindahl-Jacobsen R.; Levine H.; Andersson A. M.; Jorgensen N.; Main K. M.; Lidegaard O.; Priskorn L.; Holmboe S. A.; Bräuner E. V.; Almstrup K.; Franca L. R.; Znaor A.; Kortenkamp A.; Hart R. J.; Juul A. Environmental Factors in Declining Human Fertility. Nat. Rev. Endocrinol 2022, 18 (3), 139–157. 10.1038/s41574-021-00598-8. - DOI - PubMed

[3] Inhorn M. C.; Patrizio P. Infertility Around The Globe: New Thinking on Gender, Reproductive Technologies and Global Movements in the 21st Century. Hum Reprod Update 2015, 21 (4), 411–26. 10.1093/humupd/dmv016. - DOI - PubMed

[4] Inhorn M. C.; Patrizio P. Infertility Around The Globe: New Thinking on Gender, Reproductive Technologies and Global Movements in the 21st Century. Hum Reprod Update 2015, 21 (4), 411–26. 10.1093/humupd/dmv016. - DOI - PubMed

[5] Nieuwenhuijsen M. J.; Basagana X.; Dadvand P.; Martinez D.; Cirach M.; Beelen R.; Jacquemin B. Air Pollution and Human Fertility Rates. Environ. Int. 2014, 70, 9–14. 10.1016/j.envint.2014.05.005. - DOI - PubMed

[6] Nieuwenhuijsen M. J.; Basagana X.; Dadvand P.; Martinez D.; Cirach M.; Beelen R.; Jacquemin B. Air Pollution and Human Fertility Rates. Environ. Int. 2014, 70, 9–14. 10.1016/j.envint.2014.05.005. - DOI - PubMed

[7] Slama R.; Bottagisi S.; Solansky I.; Lepeule J.; Giorgis-Allemand L.; Sram R. Short-term Impact of Atmospheric Pollution on Fecundability. Epidemiology 2013, 24 (6), 871–9. 10.1097/EDE.0b013e3182a702c5. - DOI - PubMed

[8] Slama R.; Bottagisi S.; Solansky I.; Lepeule J.; Giorgis-Allemand L.; Sram R. Short-term Impact of Atmospheric Pollution on Fecundability. Epidemiology 2013, 24 (6), 871–9. 10.1097/EDE.0b013e3182a702c5. - DOI - PubMed

[9] Zhang Y.; Wang J.; Chen L.; Yang H.; Zhang B.; Wang Q.; Hu L.; Zhang N.; Vedal S.; Xue F.; Bai Z. Ambient PM2.5 and Cclinically Recognized Early Pregnancy Loss: A Case-control Study With Spatiotemporal Exposure Predictions. Environ. Int. 2019, 126, 422–429. 10.1016/j.envint.2019.02.062. - DOI - PubMed

[10] Zhang Y.; Wang J.; Chen L.; Yang H.; Zhang B.; Wang Q.; Hu L.; Zhang N.; Vedal S.; Xue F.; Bai Z. Ambient PM2.5 and Cclinically Recognized Early Pregnancy Loss: A Case-control Study With Spatiotemporal Exposure Predictions. Environ. Int. 2019, 126, 422–429. 10.1016/j.envint.2019.02.062. - DOI - PubMed

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Observed Effects on Very Early Pregnancy Linked to Ambient PM_2.5 Exposure in China among Women Undergoing In Vitro Fertilization-Embryo Transfer

Affiliations

Observed Effects on Very Early Pregnancy Linked to Ambient PM_2.5 Exposure in China among Women Undergoing In Vitro Fertilization-Embryo Transfer

Authors

Affiliations

Abstract

Conflict of interest statement

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Abstract

Conflict of interest statement

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