Are Microplastics Increasing the Need for Assisted Reproduction?

The prevalence of microplastics throughout our environment has been well reported in recent years, with researchers even finding the tiny particles in the remotest oceans on Earth. One major concern of this pollution is the ability of chemicals used in plastic production to disrupt the normal function of hormones, namely in reproduction and immunity.

In one study of microplastic pollution in Monterey Bay, researchers found that all diving seabirds examined had microparticles in their digestive tracts, and 23% had particles that exhibited the potential for hormone-disrupting effects. Concerningly, this is not a problem restricted to animal life. According to a report from the Endocrine Society and the International Pollutants Elimination Network, human samples consistently show that nearly all people have endocrine-disrupting chemicals (EDCs) in their bodies, which are actively used in plastic production. “EDCs are manmade chemicals that can interfere with the actions of our body’s hormones. Since some can mimic the actions of estrogens and androgens – hormones essential for female and male reproduction – they have the potential to disrupt the normal process of making eggs and sperm,” says Patricia Hunt, regents professor in the School of Molecular Biosciences at Washington State University. “Exposures that occur during development are of even greater concern since they can cause aberrations in the developing reproductive tract of both sexes and affect the germline (the cells that ultimately give rise to eggs and sperm).”

Effects of BPA exposure

Hunt has been focused on the effects of EDCs since 1998, when her research mice were accidentally exposed to one such chemical generally used to harden plastic, bisphenol A (BPA). “Our subsequent studies revealed effects on the earliest stages of oogenesis (the process of making an egg) that occur in the fetal ovary. We also found an effect in males: Perinatal exposure alters the stem cells of the testis (the cells that make continuous sperm production possible), leading to an increase in errors and cell death during spermatogenesis and, ultimately, a decrease in the number of sperm produced,” says Hunt.

Extensive research into the effects of BPA in animals has also revealed a possible association with cancer, cardiovascular disease, aggression, impaired memory and learning, and diabetes. “The effect we described in the mouse on the earliest stages of egg development in the fetal ovary has also been replicated in the rhesus monkey and in C. elegans, the nematode or roundworm. With such a high level of conservation among very diverse species, how could we possibly imagine that we are NOT affected?”

While people can be exposed to BPA via air, dust and water, BPA in food and beverages accounts for the majority of daily human exposure. When plastic food containers are heated, BPA and other chemicals are more likely to leach into the contents, and research shows that when acidic foods are packaged in cans, they have higher levels of BPA. However, according to the US Food and Drug Administration (FDA), there is insufficient evidence to confirm that BPA is unsafe for use in food contact materials. As of the latest assessment conducted in 2014, the FDA considers BPA to be safe at the current levels found in foods. The FDA banned the use of BPA in the production of baby bottles and sippy cups, and infant formula packaging in 2012 and 2013, respectively.

Along with the FDA, the European Food Safety Authority and UK Food Standards Agency also permit the use of BPA in food contact materials and state that the amount of BPA consumed daily is lower than the tolerable daily intake (TDI) of 0.00004 µg per kilogram of body weight (µg/kg/day). The TDI was reduced from 50 to 4 µg/kg/day in 2015, then lowered to the current level in 2021.

In a 2012 study, higher urinary BPA concentrations in women undergoing in vitro fertilization (IVF) were found to be associated with decreased ovarian response, a lower number of fertilized oocytes and decreased blastocyst formation. Another study noted that higher serum BPA was associated with a reduced estradiol response during IVF, which helps thicken the uterine lining to prepare it for implantation.

BPA-Free – A similar story

Concern surrounding BPA led to the production of alternative chemicals such as bisphenol S (BPS). Products made without BPA are typically labeled as “BPA-Free,” but BPS itself has been linked to adverse effects. In 2020, researchers from the University of Guelph found that BPS was more potent than BPA and seemingly hindered heart function within minutes of a single exposure.

In murine studies conducted between 2015 and 2019, BPS exposure was linked to decreased sperm counts, quality, motility and spermatogenesis. In a separate study of female mice, long-term exposure to low doses of BPS was found to cause a reduction in the number of ovarian follicles, decreased ovary volume and cytoskeletal damage in matured oocytes. Researchers from the University of Missouri found that BPS is potentially as harmful as BPA, causing similar morphological defects in the interface of the placenta with maternal endometrium and alterations in the placental content of serotonin and dopamine.

“We have tested several [BPA alternatives] and found that they induce similar effects on the germline in both sexes – as do phthalates,” says Hunt.

Perfluoroalkyl and polyfluoroalkyl substances

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have historically been used in the manufacture of non-stick cookware, stain resistant textiles, electronics, cosmetics, dental floss and food packaging due to their extreme stability, a feature that also makes them a ubiquitously persistent environmental contaminant, despite efforts to phase out the manufacture of the long-chain variety of PFAS chemicals. The Agency for Toxic Substances and Disease Registry say that exposure to high levels of certain PFAS may lead to decreases in infant birth weights, increased risk of high blood pressure or pre-eclampsia in pregnant women and an increased risk of kidney cancer, among other health outcomes. “Many of these consequences potentially relate to recent evidence that some PFAS can act as EDCs,” says Dr. Jacinta Martin, a post-doctoral researcher in the Priority Research Centre for Reproductive Sciences at the University of Newcastle, Australia.

Martin is researching the effects of PFAS on reproduction, “my research focuses on determining the effects of PFAS exposure during key developmental time periods (in utero, during lactation and early childhood) on offspring development.” In her research, she is using a preclinical model to explore how PFAS contamination (reflective of a contamination site in New South Wales, Australia) may influence the developmental trajectory of offspring in terms of their metabolic, behavioral and reproductive outcomes.

Preliminary results from this work have shown that the ability to produce offspring appears to be reduced and attainment of reproductive milestones may also be disrupted. “We have also shown both metabolic and behavior disturbances in animals and are in the process of testing longer term fertility now,” says Martin. 

Fertility trends

Figure 1: Number of IVF cycles by egg and sperm source, 1991-2019. Data taken from Human Fertilisation & Embryology Authority

In 2020, assisted reproductive technologies (ART) contributed to 2% of all infants born in the United States. According to the Human Fertilisation & Embryology Authority, frozen embryo transfers increased by 86% from 2014–2019. The use of donor sperm has also increased by over 4,000 cases from 2006–2019, which could possibly be explained by the finding that sperm counts declined significantly among men from North America, Europe and Australia during 1973–2011, with no evidence of this trend tapering off. A number of studies share findings that exposure to EDCs caused a decrease in semen parameters such as volume, concentration and motility.

The American Center for Disease Control (CDC) defines assisted reproductive technologies (ART) as any fertility-related treatments in which eggs or embryos are manipulated. ARTs, therefore, do not include treatments in which only sperm are handled or procedures in which medicine is taken to stimulate egg production without the intention of having eggs retrieved. The most common type of ART is IVF.

“Currently, many of the ART technologies that exist bypass the obstacles patients have to achieving natural conception. For example, IVF was originally invented for patients who had tubule blockages. In these patients the gametes were unable to physically meet for fertilization. So, to enable these individuals to have children, their gametes were removed and mixed in a dish so that the sperm could find the egg unimpeded and produce an embryo,” explains Martin. Another example of this is intracytoplasmic sperm injection (ICSI), which was invented to allow patients whose sperm were immotile to be combined with an oocyte via injection to make an embryo for transfer.

According to the International Committee Monitoring Assisted Reproductive Technologies (ICMART), there has been a steady increase in ART cycles since 1991, from 140,00 cycles to 1,648,000 cycles in 2019. There are many possible explanations for the increased use of ART, such as public acceptance of same sex couples, later parenthood and increased access to treatment. For example, In 2022, the UK government pledged to remove the requirement for female same-sex couples to self-fund artificial insemination to prove fertility status before accessing IVF services. However, as stated by Martin, “there is significant evidence that EDCs and/or other environmental toxicants, such as PFAS, affect fertility, and these topics are currently being very heavily researched by experts all over the world.”

EDC exposure has already been linked to both male and female fertility issues and as EDCs continue to permeate our environment and our bodies, it is likely that future research will strengthen the associations made between these pollutants and the increasing need for ART. The future is not all bleak though, as the success rates and safety of ART have continued to improve over the past few decades.