The Iranian Journal of Obstetrics, Gynecology and Infertility

The Iranian Journal of Obstetrics, Gynecology and Infertility

Association between Lead and Infertility Risk: A Systematic Review of Existing Evidence

Document Type : Review Article

Authors
Sepehr Khoshbaf Khiabanian 1
Ghazaleh Eslamian 2
Bentolhosna Dehghan Nayeri 1
Aref Adeli Mosabbeb 1
Fatemeh Habibollahi 1
Kiana Hasibi 1
1 M.Sc. Student of Food Science and Technology, Student Research Committee, School of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2 Assistant Professor, Department of Cellular and Molecular Nutrition, School of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
10.22038/ijogi.2026.93567.6640
Abstract
Introduction: Infertility is a major public health challenge, and growing evidence highlights the role of environmental factors—particularly heavy metals—in reproductive disorders. Lead, as a ubiquitous environmental pollutant, can affect male and female fertility even at low exposure levels through mechanisms such as oxidative stress, hormonal disruption, and DNA damage in germ cells. This systematic review aimed to summarize the existing evidence on the association between lead exposure and infertility.
Methods: The observational studies—including case–control, cross-sectional, and longitudinal designs—along with analyses based on national datasets and some studies employing a dietary assessment approach, which had assessed the association between lead exposure and infertility, semen quality, or spontaneous abortion, were systematically searched and evaluated. The search was conducted in PubMed, Scopus, Web of Science, SID, Magiran, and ISC, covering articles published up to June 2025 with no initial time restriction, and limited to Persian and English languages. In total, 18 eligible studies were included in the qualitative synthesis.
Results: In men, lead exposure—especially in seminal fluid and with co-exposure to other metals—was relatively consistently associated (i.e., repeatedly showing the same direction of effect in most studies) with reduced semen quality and increased sperm DNA damage. In women, the findings were more heterogeneous. Some studies associated higher blood lead or cumulative dietary lead exposure with infertility or spontaneous abortion, while non-significant results were reported at lower exposure levels. These associations were more pronounced in susceptible subgroups: older age, higher BMI, multi-metal exposure, and micronutrient deficiencies.
Conclusion: Lead exposure may adversely affect reproductive health in both sexes; however, the evidence regarding the direction and reproducibility of associations is more consistent in men than in women. Longitudinal studies with multi-matrix exposure assessment and mixture-based analyses are needed to define risk thresholds.
Keywords
Heavy Metals
Lead
Reproductive Health
Semen Quality
Spontaneous Abortion
Subjects
1.     Carson SA, Kallen AN. Diagnosis and management of infertility: a review. Jama 2021; 326(1):65-76.
2.     Feng J, Wu Q, Liang Y, Liang Y, Bin Q. Epidemiological characteristics of infertility, 1990–2021, and 15-year forecasts: an analysis based on the global burden of disease study 2021. Reproductive health 2025; 22(1):26.
3.     Direkvand Moghadam A, Delpisheh A, Sayehmiri K. The prevalence of infertility in Iran, a systematic review. The Iranian journal of obstetrics, gynecology and infertility 2013; 16(81):1-7.
4.     Cox CM, Thoma ME, Tchangalova N, Mburu G, Bornstein MJ, Johnson CL, et al. Infertility prevalence and the methods of estimation from 1990 to 2021: a systematic review and meta-analysis. Human Reproduction Open 2022; 2022(4):hoac051.
5.     World Health Organization. Infertility prevalence estimates, 1990–2021. World Health Organization; 2023.
6.     Abangah G, Rashidian T, Nasirkandy MP, Azami M. A meta-analysis of the prevalence and etiology of infertility in Iran. International journal of fertility & sterility 2023; 17(3):160-73.
7.     Brugo-Olmedo S, Chillik C, Kopelman S. Definition and causes of infertility. Reproductive biomedicine online 2001; 2(1):173-85.
8.     Manouchehri A, Shokri S, Pirhadi M, Karimi M, Abbaszadeh S, Mirzaei G, et al. The effects of toxic heavy metals lead, cadmium and copper on the epidemiology of male and female infertility. JBRA assisted reproduction 2022; 26(4):627-30.
9.     Hosseini B, Eslamian G. Association of dietary factors with male and female infertility: review of current evidence. Thrita 2014; 3(3):e20953.
10.  Mosabbeb AA, Eslamian G, Habibollahi F, Hasibi K, Khoshbaf Khiabanian S, Dehghan Nayeri B. A systematic review on the effects of monosodium glutamate on quantity, concentration, morphology, and motility of sperm in male rats. The Iranian Journal of Obstetrics, Gynecology and Infertility 2024; 27(7):67-81.
11.  Mitra S, Chakraborty AJ, Tareq AM, Emran TB, Nainu F, Khusro A, et al. Impact of heavy metals on the environment and human health: Novel therapeutic insights to counter the toxicity. Journal of King Saud University-Science 2022; 34(3):101865.
12.  Angon PB, Islam MS, Das A, Anjum N, Poudel A, Suchi SA. Sources, effects and present perspectives of heavy metals contamination: Soil, plants and human food chain. Heliyon 2024; 10(7).
13.  Yu C, You Q, Bai X, Mu F. Association between heavy metal exposure and pregnancy loss: evidence from NHANES 2011–2016. Reproductive Biology and Endocrinology 2025; 23(1):87.
14.  Liu D, Shi Q, Liu C, Sun Q, Zeng X. Effects of endocrine-disrupting heavy metals on human health. Toxics 2023; 11(4):322.
15.  Lei HL, Wei HJ, Ho HY, Liao KW, Chien LC. Relationship between risk factors for infertility in women and lead, cadmium, and arsenic blood levels: a cross-sectional study from Taiwan. BMC Public Health 2015; 15(1):1220.
16.  Bellas J, Vázquez E, Beiras R. Toxicity of Hg, Cu, Cd, and Cr on early developmental stages of Ciona intestinalis (Chordata, Ascidiacea) with potential application in marine water quality assessment. Water Research 2001; 35(12):2905-12.
17.  Chang SH, Cheng BH, Lee SL, Chuang HY, Yang CY, Sung FC, et al. Low blood lead concentration in association with infertility in women. Environmental research 2006; 101(3):380-6.
18.  Bhardwaj JK, Paliwal A, Saraf P. Effects of heavy metals on reproduction owing to infertility. Journal of Biochemical and Molecular Toxicology 2021; 35(8):e22823.
19.  Collin MS, Venkatraman SK, Vijayakumar N, Kanimozhi V, Arbaaz SM, Stacey RS, et al. Bioaccumulation of lead (Pb) and its effects on human: A review. Journal of Hazardous Materials Advances 2022; 7:100094.
20.  Kumar S, Islam R, Akash PB, Khan MH, Proshad R, Karmoker J, et al. Lead (Pb) contamination in agricultural products and human health risk assessment in Bangladesh. Water, Air, & Soil Pollution 2022; 233(7):257.
21.  Alawadhi N, Abass K, Khaled R, Osaili TM, Semerjian L. Heavy metals in spices and herbs from worldwide markets: A systematic review and health risk assessment. Environmental Pollution 2024; 362:124999.
22.  Briffa J, Sinagra E, Blundell R. Heavy metal pollution in the environment and their toxicological effects on humans. Heliyon 2020; 6(9).
23.  Assi MA, Hezmee MN, Haron AW, Sabri MY, Rajion MA. The detrimental effects of lead on human and animal health. Vet World 2016; 9(6):660-71.
24.  Abedi AS, Nasseri E, Esfarjani F, Mohammadi-Nasrabadi F, Hashemi Moosavi M, Hoseini H. A systematic review and meta-analysis of lead and cadmium concentrations in cow milk in Iran and human health risk assessment. Environmental Science and Pollution Research 2020; 27(10):10147-59.
25.  Yeganeh M, Shahbazi K, Cheraghi M, sadat Hasheminasab K, Marzi M, Beheshti M. Risk assessment of dietary exposure to cadmium and lead through wheat and rice consumption in Iran. Ecotoxicology and Environmental Safety 2026; 309:119582.
26.  Aromataris E. Furthering the science of evidence synthesis with a mix of methods. JBI Evidence Synthesis 2020; 18(10):2106-7.
27.  Faikoğlu R, Savan K, Utku Ç, Takar N, Zebitay AG. Significance of maternal plasma lead level in early pregnancy loss. Journal of Environmental Science and Health Part A 2006; 41(3):501-6.
28.  Ahmed H, El-Desouky AI, Rashed LA. Role of antioxidants, environmental exposure to lead and cadmium in spontaneous abortion. Egypt J Occup Med 2007; 31(2):217-36.
29.  Telišman S, Čolak B, Pizent A, Jurasović J, Cvitković P. Reproductive toxicity of low-level lead exposure in men. Environmental research 2007; 105(2):256-66.
30.  Attalla SM, Eldakroory SA, Mosad SM, Goda HE. A comparative study of lead, cadmium, zinc and selenium concentration in pregnant and aborted woman. Mansoura Journal of Forensic Medicine and Clinical Toxicology 2009; 17(2):27-41.
31.  Vigeh M, Yokoyama K, Kitamura F, Afshinrokh M, Beygi A, Niroomanesh S. Early pregnancy blood lead and spontaneous abortion. Women & health 2010; 50(8):756-66.
32.  Pant N, Kumar G, Upadhyay AD, Gupta YK, Chaturvedi PK. Correlation between lead and cadmium concentration and semen quality. Andrologia 2015; 47(8):887-91.
33.  Zafar A, Eqani SA, Bostan N, Cincinelli A, Tahir F, Shah ST, et al. Toxic metals signature in the human seminal plasma of Pakistani population and their potential role in male infertility. Environmental geochemistry and health 2015; 37(3):515-27.
34.  Zhou Y, Fu XM, He DL, Zou XM, Wu CQ, Guo WZ, et al. Evaluation of urinary metal concentrations and sperm DNA damage in infertile men from an infertility clinic. Environmental Toxicology and Pharmacology 2016; 45:68-73.
35.  Sukhn C, Awwad J, Ghantous A, Zaatari G. Associations of semen quality with non-essential heavy metals in blood and seminal fluid: data from the Environment and Male Infertility (EMI) study in Lebanon. Journal of assisted reproduction and genetics 2018; 35(9):1691-701.
36.  Lee S, Min JY, Min KB. Female infertility associated with blood lead and cadmium levels. International journal of environmental research and public health 2020; 17(5):1794.
37.  Wijesekara GU, Fernando DM, Wijeratne S. The effects of Pb on sperm parameters and sperm DNA fragmentation of men investigated for infertility. Journal of basic and clinical physiology and pharmacology 2020; 31(4):20190239.
38.  Tousizadeh S, Mohammadi-Moghadam F, Sadeghi R, Ahmadi A, Shakeri K. Investigation of the levels of essential and non-essential metals in women with and without abortion history: A study based on the Persian population of the Shahrekord cohort. Chemosphere 2023; 329:138434.
39.  Lin J, Lin X, Qiu J, You X, Xu J. Association between heavy metals exposure and infertility among American women aged 20–44 years: A cross-sectional analysis from 2013 to 2018 NHANES data. Frontiers in public health 2023; 11:1122183.
40.  Suomi J, Tuominen P. Cumulative risk assessment of the dietary heavy metal and aluminum exposure of Finnish adults. Environmental Monitoring and Assessment 2023; 195(7):809.
41.  McClam M, Liu J, Fan Y, Zhan T, Zhang Q, Porter DE, et al. Associations between exposure to cadmium, lead, mercury and mixtures and women’s infertility and long-term amenorrhea. Archives of Public Health 2023; 81(1):161.
42.  He Y, Su X, Niu Z, Zhang B, Mu H, Wang L, et al. Association Between Mixed Metal Exposures and Female Infertility: A Large Cross-sectional Study. International Journal of Environmental Research 2025; 19(3):103.
The Iranian Journal of Obstetrics, Gynecology and Infertility
Volume 29, Issue 3
May 2026
Pages 94-110