ENVIRONMENT

The testing of pharmaceutical and industrial chemicals should include an evaluation of their impact on fertility and gametes, not just on pregnancy, before they are introduced into the European market, according to ESHRE. This was one of a series of recommendations published by the Society for the first time to highlight ‘serious concerns’ about the impact from environmental factors on reproductive health and declining fertility rates.(1)

Aimed at policy-makers, the document has been drawn up by experts from various fields in response to the well-established link between widespread infertility and exposure to hazards such as climate change, pollutants, hormone-disrupting chemicals, toxic substances, and other related risks. The position statement was formulated following a two-day meeting to review the latest evidence on environmental threats to male and female fertility/reproductive health, and to fetal life.

One of the key lessons learned from the presentations was that harmful substances in what we eat, drink and breathe can have a transgenerational effect, which is why urgent action is needed. Other take-home messages included the need for more human (not just animal) research and that data on the impact of workplace chemicals must be made publicly available so people can take decisions on exposure risk.

The first speaker was Niels Skakkebaek, the co-author of the first landmark study on declining sperm quality.(2) More than three decades on from that research, he described human reproduction as ‘in trouble’, with more children with genital abnormalities and increasing rates of testicular germ cell cancer (TGCC). An important marker of male reproduction, TGCC has reached ‘epidemic’ levels especially among young men, yet ‘no one talks about this’, said Skakkebaek. With new molecular evidence suggesting that TGCC is initiated from germ cells is of fetal origin, Skakkebaek gave support to the theory that environmental exposure in utero to endocrine disrupting chemicals (EDCs) may be contributing to the rise in TGCC, which in turn is linked to lower male fertility rates.

Further effects of pollutants on early human life were highlighted by other speakers. Studies suggest that soot (black carbon) particles can reach the female reproductive system and translocate to fetal organs, even at concentrations below the current annual EU target threshold of 25 µg/m3. Populations exposed to this type of pollution have been found to experience a drop in reproductive capacities. A recent cohort study showed that exposure to black carbon particles in early fetal life is associated with composition/diversity of the childhood intestinal microbiome, and can also affect the endocrine system by disrupting fetal thyroid development.(3)

Many human-made chemicals such as pesticides have not been around as long as black carbon. However, persistent organic pollutants now ‘ubiquitously’ contaminate the environment and biota, said Pauliina Damdimopoulou from Sweden’s Karolinska Institute. The consequence of this is that oocytes are forced to grow in a ‘soup of toxic organic pollutants’ because they cross the placenta, with germlines always exposed.

Damdimopoulou outlined her team’s research based on tissue and blood from Caesarean section patients, which found that women exposed to the highest number of persistent organic pollutants had a lower follicle count in the ovarian cortex. The implication, she said, is that women with the highest chemical exposure will run out of follicles earlier, which undermines their ability to conceive.(4)

More action is needed on these persistent organic pollutants, said Damdimopoulou, so that women can buy whatever they want without risking their health or their baby’s; and more human research is needed too because it is unclear if rodent studies can predict the consequences of lifelong human exposure to chemicals. ‘We need to study women, not rats,’ said Damdimopoulou.

From toxic wild fires to traffic fumes, climate change’s impact on women’s reproductive health is evidenced in numerous studies summarised by Linda Giudice from the US. Heavy metals and fertilisers are among components of wild fire smoke and data demonstrate this pollution can increase the risk of preterm birth. Similarly, the nearer women live to high traffic volume, the greater their odds of preterm birth from 20 to 27 weeks.(5)

Giudice outlined several solutions to this ‘depressing’ situation. Policymakers must ensure sexual/reproductive rights are on the agenda when discussing the climate crisis; individuals can take steps to conserve energy; and countries can retire fossil fuel power plants to cut preterm birth levels associated with sulphur dioxide emissions. She concluded: ‘Health education, safety and human rights of women and girls are jeopardised in the climate change crisis and it’s time to reverse the trend.’

The workplace is a major source of environmental factors which pose harms to reproductive health and fertility in the form of reproductive toxicants including hazardous chemicals. The risks posed by such products are managed by the EU’s regulation on Classification Labelling and Packaging (CLP) and by REACH (Registration, Evaluation, Authorisation and Restriction of chemicals).

However, Karin Hougaard from the National Research Centre for the Working Environment in Denmark said in her presentation that to get a chemical classified is challenging, and that requirements in general for testing are low. Her research shows that almost half the chemicals registered under REACH were not required to be tested for reproductive toxicity (although may have undergone this testing for other reasons). Moreover, occupational legislation focuses on pregnancy, not on early fertility/the unborn child despite the potential threat posed which means the extent of exposure at work and the consequences are not fully known. The good news is that a revision of REACH is expected in late 2023. This review could lead to increased protection in future through prioritisation of reproductive toxicity testing.

The take-home message from the expert meeting was that, while humans cannot avoid all chemical exposure, they can protect themselves from unnecessary contact. There are still many unknowns such as why men and women are affected differently by environmental factors, and the extent to which the workplace affects fertility/reproductive health, which is why data and research in humans are important.

The future may not look entirely bleak given targets to cut carbon dioxide emissions and other measures to clean up the atmosphere. However, the consensus was that policymakers must do better to protect this generation and others to come.


1. See https://www.eshre.eu/Education/Environmental-Seminar
2. Carlsen E, Giwercman A, Keiding N, Skakkebaek NE. Evidence for decreasing quality of semen during past 50 years. BMJ 1992; 305: 609 https://doi.org/10.1136/bmj.305.6854.609
3. Van Pee T, Hogervorst J, Dockx Y, et al. Accumulation of black carbon particles in placenta, cord blood, and Childhood Urine in Association with the Intestinal microbiome diversity and composition in four- to six-year-old children in the ENVIRONAGE birth cohort. Environmental Health Perspectives 2023; 131. https://doi.org/10.1289/EHP11257
4. Björvang RD, Hallberg I, Pikki A, et al. Persistent organic pollutants and the size of ovarian reserve in reproductive-aged women. Environ Res 2022; 208: 112626. doi.org/10.1016/j.envres.2021.112626
5. Bekkar B, Pacheco S, Basu R, DeNicola N. Association of air pollution and heat exposure with preterm birth, low birth weight, and stillbirth in the US: A systematic review. JAMA Netw Open 2020; 3: e208243.
doi.org/10.1001/jamanetworkopen.2020.8243