The Silent Assault of AIR POLLUTION ON HUMAN FERTILITY

The Imperative of Air Filtration in Enhancing IAQ for Reproductive Health and Assisted Reproductive Facilities

By Dr. Iyad Al-Attar, Global Correspondent, Technology and Innovation, IFN

As part of his visit to the International Federation of Fertility Societies (IFFS) conference in Tokyo, Japan, Dr. Iyad Al-Attar, the global correspondent for technology and innovations at International Filtration News, conducted insightful interviews with many experts from the IFFS. Dr. Al-Attar focuses on the growing concern about the ever-degrading Indoor Air Quality (IAQ) concern and its potential correlation with human infertility worldwide. Experts shared their perspectives on the factors contributing to the global decline of human fertility and the increased need for Assisted Reproduction Technologies (ART).

Arriving at Tokyo Airport to attend the International Federation of Fertility Societies (IFFS) conference brought to mind the story of Louise Joy Brown, the world’s first In Vitro Fertilization (IVF) baby born in the UK in 1978. Just five years later, Japan celebrated its first successful IVF baby as well. Known as a leader in IVF and Assisted Reproductive Technologies (ART), Japan has made significant strides in addressing its declining birth rates. Since 2022, the Japanese government has expanded public insurance coverage for ART and male infertility treatments, making these options more financially accessible to patients. This proactive approach has clearly contributed to the increase in the number of ART cycles. Japan boasts a strong network of ART facilities, with hundreds of registered clinics and hospitals involved in treatment. The Japan Society of Obstetrics and Gynecology (JSOG) has been at the forefront of monitoring and reporting advancements in ART since 1986, highlighting a long-standing commitment to the field. The IFFS, being a global organization, represents national fertility societies that aim to stimulate research, disseminate educational information, and promote superior clinical care in all aspects of reproductive and fertility medicine worldwide. Today, Japan boasts an impressively high utilization rate of ART, with a notable percentage of births resulting from IVF. In fact, in 2021, one in every 11.6 babies born in Japan was conceived through IVF. It’s no surprise that the IFFS conference continues to return to Japan – this is a place where the seemingly impossible becomes a reality.

Connecting Air Quality and Reproductive Health

Listening to the first lecture at the conference inspired me to think of what it takes for a family to plan and conceive a healthy baby. Potential parents meticulously plan every step on the journey to parenthood, from diet to lifestyle. But have we ever considered the air we breathe within our home, workplace, or even the sterile environment of an IVF lab? When does building a healthy lifestyle begin to include exposure to filtered air free from particulates, gases, and bioaerosols? Declining global human fertility rates are a growing concern, prompting extensive research into contributing factors. While genetic predispositions and lifestyle choices play a role, emerging scientific evidence increasingly implicates environmental exposures, particularly those related to IAQ.

Humans spend a significant portion (up to 90%) of their time indoors, making IAQ a critical parameter of public health and well-being1. Inhaling up to 13,000 liters daily makes even low concentra- tions of inhaled pollutants a considerable health risk2. Ultimately, the air we breathe in enclosed spaces is a critical determinant of our overall health and, alarmingly, our reproductive capabilities. A blend of invisible pollutants, from everyday household dust particles and chemicals to industrial emissions trapped indoors, can act as endocrine-disrupting chemicals (EDCs)3. These insidious substances interfere with our delicate hormonal balance, potentially impacting fertility in both men and women and posing unique risks within the sensitive environment of laboratories4,5.

The IFFS consensus document (https://doi.org/10.1093/humupd/ dmad028) highlights infertility as a widespread and burdensome disease that demands greater recognition, prevention efforts, and equitable access to care. Research has strongly advocated for viewing the desire to build a family as a human right, emphasizing the need for integrated policies that address both population trends and individual reproductive health needs6. The call to action emphasizes increasing awareness, promoting human rights in reproductive choices, and improving access to quality, affordable fertility care, particularly in low- and middle-income countries.

Strategies to mitigate risks, enhance reproductive health, and reduce pregnancy complications are necessary for planning and conceiving a healthy baby6. Addressing the impacts of various indoor air pollutants on human fertility requires an understanding of the implications for endocrine system performance associated with indoor environments. Air quality and filtration technologies are essential for meeting the specific needs of IVF laboratories7.

From a public health perspective, research on IAQ advanced during the COVID-19 pandemic, establishing a framework for healthcare professionals to manage pregnant women [8]. Yet the work needs to advance further to understand and remedy the global issue of infertility, which now underscores the nexus between environmental factors and human reproductive health9

Urban Environments and Fertility

Cities typically suffer from higher concentrations of outdoor air pollution stemming from vehicular emissions, industrial activities, and construction, which readily infiltrate indoor spaces. Furthermore, urban areas feature a higher density of multi-family housing, where shared ventilation systems and proximity to external pollutant sources can exacerbate indoor air issues. City dwellers often spend a substantial amount of time indoors, making air quality a predominant determinant of their health.

There is increasing evidence that improved IAQ and advanced air filtration technologies can protect and enhance fertility, particularly in urban environments, where unique pollution challenges exacerbate their impact on human wellbeing10. Also, a strong association exists between exposure to poor IAQ and the increased prevalence of ART facilities, including IVF laboratories, in urban areas11. Exposure to mixtures of particulate matter, volatile organic compounds (VOCs), biological agents, combustion byproducts, and EDCs correlates with adverse reproductive outcomes in both men and women12.

Complicating the matter, extreme climate conditions play a critical role in impacting how buildings operate within harsh environmental conditions such as sandstorms, wildfires, and excessive air pollution. Also, air quality strategies appear insufficient in addressing the growing issue of air pollution resulting from emissions from power generation (34%), transportation (16%), and industries (11%)13. In urban settings where outdoor pollution readily infiltrates indoor spaces, these conditions deteriorate the ambient conditions for human occupants. Consequently, the role of fit-for-purpose air filtration systems, including High-Efficiency Particulate Air (HEPA) filters and gas phase filters, becomes imperative for mitigating the adverse health consequences of airborne pollutants. Research links increasing exposure to air pollutants to a significant impact on gamete quality, embryo development, and overall fertility rates14.

Mitigating urban IAQ requires a multifaceted approach, considering the chemical and biological interactions among indoor pollutants are complex and vary widely. Also, varying levels of exposure influence building design, preplanned architecture, and activities within the indoor space. Researchers are just beginning to gain a fundamental understanding of the actual impact of pollutants and their byproducts, presenting a significant challenge for effectively mitigating indoor air quality.

Complicating Matters

The accumulation and synergistic toxicity of pollutants in indoor environments, which function as dynamic chemical reactors, must be considered. Various indoor sources, such as building materials, furnishings, and cleaning products, can emit VOC compounds throughout their lifespan. The cumulative exposure to air pollutants, including primary emissions and secondary reaction products, even at low concentrations, can result in a toxic burden on health. Thus, an innovative, comprehensive, multi-pollutant filtration strategy is necessary to capture not only primary particulate and gaseous pollutants but also their precursors and byproducts of indoor chemical reactions.

Humidity influences the proliferation of biological contaminants and the emission of chemical pollutants. Maintaining appropriate humidity levels is crucial for effective IAQ management15. High humidity levels (above 60-70%) create an ideal environment for biological pollutants such as mold, mildew, dust mites, bacteria, and certain viruses to thrive. Excessive moisture can also increase the emission of VOCs from building materials and contribute to the formation of new irritants, such as sulfuric aerosols, when water vapor interacts with other airborne compounds.

Conversely, low humidity levels (below 30-40%) can enhance the spread of airborne germs and cause dryness and irritation in the respiratory tract, potentially worsening symptoms for individuals with asthma or other respiratory conditions. Effective humidity control, achieved through proper ventilation, air conditioning, dehumidifiers or humidifiers, is thus a crucial preventative measure that complements air filtration by addressing the sources of both biological and chemical contaminants. Environmental control systems must manage temperature, humidity, and air purification to achieve optimal IAQ.

The ART of Fertility

A growing body of epidemiological evidence establishes a strong and concerning association between exposure to air pollution and elevated rates of infertility and adverse pregnancy outcomes16 Research indicates that both maternal and paternal exposure to ambient air pollution can have a detrimental effect on human embryo development, even during ART cycles, such as IVF17. These factors suggest that the impact of air pollution extends beyond natural conception, influencing the success of advanced fertility treatments. Furthermore, a systematic review and meta-analysis revealed that more than one in seven pregnant women exposed to indoor air pollution experienced at least one adverse pregnancy outcome: underdeveloped growth for gestational age18. This research highlights the pervasive nature of influence that air pollution has on not only the ability to conceive but also the healthy progression of pregnancy.

To mitigate the detrimental effects of air pollution on reproductive health, researchers have focused on four key pathways consistently identified across various pollutant types: oxidative stress, inflammation, DNA damage, and hormonal disruption.

• Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to detoxify them. Air pollutants, particularly particulate matter and heavy metals, induce the excessive generation of ROS, leading to cellular damage, mitochondrial dysfunction, and programmed cell death (apoptosis) in sensitive reproductive cells, such as oocytes and spermatozoa. This cellular damage compromises their viability and function, directly impacting fertility.

• Inflammation is caused when pollutants trigger systemic or localized inflammatory responses in reproductive tissues, such as the endometrium – the inner lining of the uterus. This inflammatory environment can be detrimental to processes like embryo implantation, making the uterine lining less receptive. Chronic inflammation can also contribute to broader reproductive disorders and increase the chance of early pregnancy loss.

• DNA damage is a direct consequence of exposure to various air pollutants, including particulate matter, VOCs, and heavy metals. This damage can manifest as direct breaks in the DNA strands or fragmentation, affecting the genetic integrity of sperm and oocytes and leading to impaired gamete quality, reduced embryo viability, and potentially even epigenetic changes that can be passed on to future offspring, influencing their longterm health.

• Hormonal disruption is caused by endocrine-disrupting chemicals, such as VOCs, which can block the natural reproductive hormones of the body, including estrogen, progesterone, and testosterone. Any hormonal imbalance can impact the control cycles which produce eggs and sperm. Hormonal disruption can lead to reduced sperm count and egg production in menstrual cycles.

Hormonal disruption involves pollutants mimicking, blocking, or altering the synthesis and function of natural hormones essential for reproduction. Many EDCs, including phthalates and some VOCs, directly interfere with the endocrine system, affecting the production and regulation of hormones like estrogen, progesterone, testosterone, FSH, and LH. This disruption can impair gamete production, reduce ovarian reserve, cause menstrual cycle irregularities, and negatively impact sperm quality and count, thereby significantly hindering fertility. The sensitivity of developing tissues to endocrine signals during critical periods (fetal development, infancy, childhood) means that even low-level exposures can have profound and lasting effects on reproductive potential.

The evidence overwhelmingly indicates that airborne pollutants are a significant contributor to hormonal disruption. From fine particulate matter to gaseous pollutants, PAHs, phthalates, and heavy metals, these environmental contaminants interfere with the intricate balance of the endocrine system through various mechanisms.

The pervasive nature and widespread exposure to these pollutants underscores the broad implications for public health, contributing to rising infertility rates and adverse pregnancy outcomes. There is a growing public health challenge that re- quires implementing stringent air quality regulations, conducting continuous monitoring, and conducting further research to fully elucidate the complex interplay between air pollution and endocrine health19. Mitigating airborne pollution is not merely about improving respiratory health; it is a crucial step towards safeguarding global health and well-being.

IVF Imperative: Pristine Air for Precious Beginnings

In the quest for parenthood, the air one breathes is an often-overlooked factor and is a silent threat to human fertility and the delicate process of IVF. It has never been more imperative to incorporate sustainable and efficient air filtration

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For couples undergoing IVF treatments, it is essential to inform them that air quality has a direct impact on the viability of gametes and embryos. IVF laboratories require high levels of air purity to mimic the ideal conditions that should be operating within the human body. Poor air quality can compromise gamete health, harming eggs and sperm and impacting their ability to fertilize. Embryos are particularly vulnerable to airborne contaminants, which can disrupt their development and reduce implantation rates. VOCs have been linked to embryotoxicity and increased miscarriage risks. Maintaining optimal air quality through advanced filtration technologies is essential for improving IVF outcomes and ensuring a safe, conducive environment for embryo development.

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Although several studies have established the profound impact of air pollutants on human health systems, the actions to achieve the highest level of optimal air quality in homes, schools, and the workplace are somewhat limited compared to the rising risks of human infertility. By prioritizing optimal air quality indoors and sustainable, efficient air filtration, we can create healthier indoor environments that safeguard natural reproductive potential and enhance success for couples embarking on an IVF journey.

The power of clean air is one of the most significant advancements in our advanced healthcare systems. A sense of urgency is emerging in the IFFS community to apply this clean-air mindset to other indoor environments so that we avoid surrendering our health, well-being, and even reproductive future to the silent assault of air pollution.

Dr. Al-Attar is IFN’s Global Correspondent, Technology and Innovation, with insight as a mechanical engineer and an independent air filtration consultant. He is a Visiting Academic Fellow in the School of Aerospace, Transport, and Manufacturing at Cranfield University, consulting for air quality and filter performance relevant to land-based gas turbines. His expertise is on the design/performance of high-efficiency filters for HVAC and land-based gas turbine applications, focusing on chemical and physical characterization of airborne pollutants. Dr. AlAttar is also the strategic director, instructor, and advisory board member of the Waterloo Filtration Institute. In 2020, Eurovent Middle East appointed Dr. Al-Attar as the first associated consultant for air filtration, as well as an Indoor Air Quality (IAQ) patron for EUROVENT.

Bart CJM Fauser, MD, PhD, FRCOG

Supporting global family-building strategies is the key current focus area of the International Federation of Fertility Societies (IFFS), where I currently act as the scientific director. This means, in practical terms, creating awareness among politicians, policymakers, international organizations (such as the EU and WHO), journalists, health insurance companies, employers, and young people about the need to facilitate those who desire to have children. We believe that family planning education in high schools should not only involve spreading knowledge to prevent unwanted pregnancies but also strategies to improve the chances of building a family if desired.

Employers should understand that next to career planning, family planning should also represent a vital activity to motivate young (female) employees. It should be recognized that the decision to have or not have children is not for women only. Men should take more responsibility in establishing a family and engage in more household activities thereafter.

Increasingly robust scientific evidence suggests a distinct role of environmental changes and pollution on the reproductive health of both males and females. Studies in males focused on declining sperm quality, whereas preliminary studies in women suggest detrimental effects on puberty, impaired fertility, and premature menopause. Access to fertility care should also be evaluated in the context of a rapid decline in global fertility rates. Increasingly, countries are extending funding for IVF treatment. However, in most countries, patients have to pay out of pocket for treatment. Conse- quently, access to care varies significantly in different countries, with one out of 10 children born due to IVF in some countries like Denmark and Japan, whereas this represents way less than 1% of all children in other countries like Mexico. As recently stated by the World Health Organization (WHO), approximately one in every six couples requires medical assistance to achieve their dream of having children. Hence, around 15% of the population can be diagnosed with infertility. However, this is not well established and may vary in different parts of the globe. An increased prevalence of infertility is often mentioned, although solid scientific evidence to support such a statement is not available.

About Bart CJM Fauser, MD, PhD, FRCOG. Professor Em. of Reproductive Medicine, University of Utrecht, The Netherlands, Scientific Director International Federation of Fertility Societies (IFFS), Consultant, Executive Board Member

Gian Carlo Di Renzo

Nutrition plays a major role in the healthy pregnancy and development of the fetus. In addition, nutrition can expose humans to a wide range of potentially hazardous environmental constituents, such as organic pollutants and heavy metals, from marine or agricultural food products during processing, production, and packaging. Humans are constantly exposed to these constituents through air, water, soil, food and domestic products.

During pregnancy, the rate of cellular division and differentiation is higher; exposure to any of these environmental toxicants can lead to developmental defects as they cross the placental barrier. In some cases, these contaminants can also harm subsequent generations, as they can affect the reproductive cells of the fetus. Pregnant women are considered a vulnerable population to food contaminant exposure and require a proper dietary chart and conscious food choices. The placenta acts as a barrier between the fetus and the mother, also helping to deliver nutrients, clear waste, and protect against noxious compounds. Many pollutants can cross the placenta and accumulate in the fetal region, exposing the fetus to these compounds at a higher level than the mother.

The International Federation of Gynecology and Obstetrics is raising awareness to minimize toxin exposures as it is linked to the declining well-being of both fetus and mother. Dietary recommendations are required to balance the risks and benefits of contaminants exposure and nutrient absorption. Food is a source of both essential nutrients and environmental toxicants. Here, we have researched the possible toxicants in the food industry and their influence on the in-utero development of the fetus, along with the importance of dietary interventions and the need to balance a healthy diet to mitigate the harms.

Cumulative exposure to environmental toxicants can influence the mother’s prenatal environment, affect fetal development, and have long-term effects on the health of the offspring. Reproductive health professionals witness firsthand the increasing numbers of health problems facing their patients, and preventing exposure to toxic chemicals can reduce the burden on women, children, and families around the world. These recommendations have been approved by the General Assembly of FIGO in 2015: Advocate for policies to prevent exposure to toxic environmental chemicals. Work to ensure a healthy food system for all. Make ecological health part of health care. Be a champion of environmental justice.

About Gian Carlo Di Renzo. Di Renzo GC, editor. Environment, climate and human reproduction, Volume 89. Best Practice & Research Clinical Obstetrics & Gynaecology. London: Elsevier, 2023

Di Renzo GC, Conry JA, Blake J, DeFrancesco MS, DeNicola N, Martin JN Jr, McCue

KA, Richmond D, Shah A, Sutton P, Woodruff TJ, van der Poel SZ, Giudice LC. International Federation of Gynecology and Obstetrics opinion on reproductive health impacts of exposure to toxic environmental chemicals. Int J Gynaecol Obstet. 2015 Dec; 131:219-25. PMID: 26433469.