Measurements of Natural Human Fertility, such as Sperm Count, are on the Decline – Or Are They? And Just How Concerned Should We Be?
The seminal environmental book Silent Spring was published sixty years ago this year.
In it, author Rachel Carson argued the case that man-made pollution, especially synthetic pesticides (such as DDT), was destroying the planet’s ecology and would lead to the catastrophic extinction of life on earth.
In case you are unaware of its significance at the time, Silent Spring helped galvanize interest in the environmental movement in the 1960s, which culminated in the banning of DDT and the establishment of the Environmental Protection Agency (EPA) in 1970.
Have we saved the planet?
No, according to Mt. Sinai Medical School epidemiologist Shanna Swan, who maintains we might not yet have saved ourselves from extinction.
In 2017, Swan co-authored a meta-analysis research paper with researchers associated with the Department of Reproductive Health and Research at the World Health Organization in Geneva, Switzerland.
The study, titled Temporal trends in sperm count: a systematic review and meta-regression analysis, makes the bold claim that the total sperm count across the Western world fell 59% between 1973 and 2011.
Swan went on to write a new book outlining the implications of these resulting fertility risks facing the world’s population. Speaking to Axios, Swan is quoted saying: “If you look at the curve on sperm count and project it forward — which is always risky — it reaches zero in 2045. That’s a little concerning, to say the least.”
The work of Swan and her fellow researchers has bolstered arguments by famed environmental champion Erin Brockovich, who writes in the Guardian that we need to limit so-called “reprotoxic” chemicals, including phthalates, PFAS, PCBs, alkylphenol ethoxylate and bisphenol compounds, and organohalogen flame retardants, which may be associated with reproductive issues, including infertility.
But can we accept these assertions at face value?
Are environmental conditions increasing the number of cases of infertility, preterm births (PTB), birth defects (including neurocognitive deficits) as well as maternal and infant mortality worse?
We need to take a closer look.
Use of Assisted Reproductive Technology (ART) Procedures, such as IVF, is on the Rise.
Louise Joy Brown’s 1978 birth in Lancashire, England, was significant.
She was the world’s first so-called “test-tube baby,” conceived in a procedure now known as in vitro fertilization (IVF).
Since that time, IVF has become one of the most widely used Assisted Reproductive Technology (ART) procedures available, giving hope to an estimated 48.5 million couples worldwide that need help conceiving children (assuming they can afford the cost, as we’ll touch on later).
So circling back to our original question… If we assume for argument’s sake that Swan’s assertion that male sperm count fell 59% between 1973 and 2011, what effect would that have on the number of ART procedures? Shouldn’t we see a rapid rise in uptake?
According to the CDC data from 2019, around 2.1% of all infants born in the US were conceived using ART.
On the one hand, that’s a huge number from the perspective of a procedure that was still highly experimental only a few decades ago.
But on the other hand, it means that nearly 98% of births are still being conceived naturally.
We’d have to conclude that even if sperm counts are as diminished in number as Swan and her fellow researchers contend that human reproduction is continuing, at least for the present.
Given Current Trends, is Natural Human Reproduction at Risk? Could We Be at Risk for Extinction?
It’s important to maintain a healthy skepticism when reviewing scientific research and even more so when making predictions about the future.
Indeed, there are studies that question whether it’s possible to accurately correlate sperm count studies from different time periods.
For example, a 1979 study (Male fertility potential in terms of semen quality: a review of the past, a study of the present) questioned whether it was even possible to make a valid comparison between the semen quality data from 1951 with data collected between 1966 – 1977. Why? There are too many inconsistencies in the data sources to make the comparison, according to the paper’s authors, J MacLeod and Y Wang, who believe that the presence of different male cohorts over time could skew the results significantly.
To address these data inconsistency issues, the WHO established a worldwide survey in 1980, known as the WHO Manual for Human Semen Analysis.
The sixth addition of the WHO human semen analysis survey appeared in 2021 (you can download it here), and it indicates that the quantity of human semen produced in male ejaculate has actually stayed constant over the period from 2010 to 2020.
(As a caution, researchers working with the WHO data admit that, unfortunately, the number of research participants remains smaller than ideal and that little to no data was made available from South American or African countries.)
Notably, while researchers didn’t see significant changes in sperm counts over the period, they did find that men suffering from subfertility have more health issues than normal men, including higher risks of cardiovascular disease, hospitalization, diabetes, and autoimmune diseases.
Given the latest WHO research, we may not be experiencing the rapid drop in human semen that would lead to a collapse of the human race.
However, more studies are needed to understand what changes may be happening and to what degree environmental factors might be altering semen quality as well as female reproductive organs.
Has Current Laboratory Research Identified Potential Causes of Human Infertility?
For any couple seeking to start a family, a diagnosis pointing to potential infertility issues can be a heartbreaking prognosis.
What are the possible causes?
Researchers are looking at many factors, including exposure to air pollution.
· Effect of Cigarettes on Male Fertility
Exposure to air pollution (including smoking and secondhand smoke) isn’t healthy for anyone but may be even more important for those seeking to conceive a healthy child. A 2017 meta-analysis of 5,865 participants found that smoking is associated with reduced sperm count and motility, and it’s worse for heavy smokers. (The study also reports that, worldwide, approximately 37% of men of reproductive age smoke cigarettes.
· Decreased Male Sperm Count in Areas of High Air Pollution and Ozone Concentrations
Several recent papers seek to draw a correlation between air quality and reproductive and neonatal health. A 2019 study attempts to correlate air pollution (in eastern Sicily, Italy) with decreased sperm counts. Men living near industrial facilities had lower sperm counts compared to those living further away; however, no change was found in sperm concentration or motility. A 2019 Polish study found a decreased percentage of sperm with normal morphology among men exposed to higher levels of ozone in the atmosphere. Similar findings of decreased semen quality among men living in areas of high ambient ozone pollution in Beijing were reported by Chinese researchers.
· The Reproductive Risk of Exposure to Particulate Dust, Seasonal Air Pollution, and Silica Nanoparticles (SiNPs)
Researchers are also investigating the impact of dust and nanoparticles on reproductive health. A 2020 study found exposure to Asian dust storms blown into western Iran is associated with reduced semen quality. Czech researchers found reduced semen quality among young men exposed to seasonal air pollution. A 2022 meta-analysis also suggests that high levels of air pollution exposure appear to have a negative effect on semen quality. And finally, silica nanoparticles in air pollution could trigger unwanted changes in spermatocyte cells.
· Investigation of the Effect of Superfund Sites on Reproductive Health
Here in Texas, the Houston area alone has more than 20 EPA superfund sites, e.g. locations identified by the Federal government as needing special cleanup and long-term mitigation. The region’s preterm birth rate is 1.6% higher than the national average, so researchers, led by Dr. Kjersti Aagaard, professor of obstetrics and gynecology at Baylor and Texas Children’s Hospital, are currently investigating the impact on reproductive health for those living close to Superfund sites.
Some superfund sites associated with the mining or petrochemical industry are responsible for exposure to heavy metals. A recent study indicates that exposure to cadmium can lead to significant changes in mice spermatozoa, which in turn could “affect fertility in the exposed individual as well as their offspring, through paternal inheritance.”
· Gene–Disease Relationships (GDRs) and Multigenerational Health Effects
Scientists are gaining new insight into the mechanisms of disease caused by changes to our genes, some of which appear to cause multigenerational health effects in children or even grandchildren. One recent example is from the University of Bristol, which started studying a cohort of 14,000 pregnant women and their offspring in 1991. The so-called “Children of the 90s” study has uncovered some surprising connections, including the relationship between smoking as a parent and the incidence of obesity in the parent’s grandchildren.
A recent paper published in Human Reproduction Update points out that approximately 4% of infertile men have a genetic cause for their infertility, with 60 – 70% unexplained. The researchers theorize that wider use of next-generation sequencing (NGS) technologies could help identify more genetic causes of infertility.
· “Forever” Chemicals and Heavy Metals that Potentially Affect the Endocrine System
Researchers are concerned about chemical exposures that can mimic human hormones; potentially disrupting the human endocrine system, including causing problems with fertility. A 2016 meta-analysis of the evidence linking prenatal and postnatal exposure to endocrine-disrupting chemicals came up short in finding a clear-cut, direct causal link with reproductive health issues, including cryptorchidism, hypospadias, low sperm count, and testicular cancer. Researchers believe more study is needed, particularly since the effects of chemical exposures could take significant time before they are detectable.
A separate study published in 2020 attempted to determine if there is a causal link between exposure to PFAS chemicals and reproductive health issues. PFAS is a class of synthetic compounds of which Teflon is the most commonly known variety. Researchers felt stymied because nearly every patient they could study had already been exposed to detectable amounts of PFAS chemicals in their bloodstream, thus, there is no natural control group to make comparisons with.
Other so-called “forever chemicals” that can potentially disrupt the endocrine system (and hence fertility) include phthalates, bisphenol A (BPA), or bisphenol E and S (which are BPA analogues). A new Spanish study published this month contends that “exposure to environmental chemicals, such as bisphenol A, and maternal stress has been shown to negatively influence pubertal development and gonadotropic function in adulthood to these chemicals.” The wider issue that concerns researchers is the impact of chemically induced changes to puberty and male testes could have on adult reproductive function and fertility.
· Increased Age of Couples Seeking to Conceive
Western industrialized society has changed in recent decades, with couples delaying marriage and/or seeking to start a family. But with more couples waiting longer to conceive, there is an increased risk of complications due to increased age. Increasing age not only affects sperm count and quality, it also reduces the ovarian oocyte (egg) quality and quantity. This change can also affect the success of IVF procedures for older women seeking to get pregnant.
As a result, age demographics can have a big effect on population growth. In Texas, for example, there is currently a baby boom underway, which demographers associate with the relatively young population migrating into the state.
· Rising Incidence of Obesity Worldwide
Obesity can also be a cause of male infertility. According to a recently published paper in Metabolites, the prevalence of obesity has increased to around 20% worldwide. Researchers are concerned that obesity can lead to increased inflammation and difficulties with insulin signaling – possibly due to issues related to sirtuins (the signaling proteins which help regulate metabolism) – which in turn may have a detrimental effect on testicular function. Another study published in the International Journal of Molecular Science asks the same question: Obesity and Male Reproduction: Do Sirtuins Play a Role?
· Oxidative Stress and the Negative Effects of Poor Nutrition
Oxidative Stress (OS) may be another cause of infertility – possibly due to environmental exposures, illness, or poor diet, e.g. one lacking in antioxidants.
But first, what is oxidative stress?
The body creates oxygen-based compounds (known as Reactive oxygen species or ROS) during normal mitochondrial oxidative metabolism as well as in response to exposure to xenobiotics, cytokines, or bacterial infections. Normally, the body can mount a strong enough antioxidant defense, but if it becomes overwhelmed, cellular damage can result, known as oxidative stress. A 2008 paper points out that about half of all infertile men show signs of oxidative stress. Another paper dating from that time suggests that women showing signs of oxidative stress may have pregnancy complications, including infertility and early pregnancy loss.
· Neonatal Risk Due to Covid Infections
What about the Covid-19 virus? What effect does it have on fertility and pregnancy?
Unfortunately, one of the first major international studies on Covid and pregnancy, published in JAMA Pediatrics in April 2021, found that “COVID-19 in pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications…”
This was followed up in August 2021 with another study that looked at 870,000 women who gave birth between March 2020 and February 2021. Women with Covid were 22 more likely to have a premature birth, 14 more times likely to require intubation, and 15 times more likely to die compared to pregnant women without a Covid diagnosis.
Fortunately, Covid vaccines are approved for pregnant women, and a study in the New England Journal of Medicine finds no increased risk for miscarriage. Given the potential risks of contracting Covid during pregnancy, the choice to get vaccinated seems wise.
However, there is widespread mistrust among many members of the public. Some public officials, such as Florida Gov. Ron DeSantis (R), suggest that a covid vaccine could cause infertility. However, a study at Boston University indicates this is not the case: a Covid vaccine “does not impair fertility in either partner,” but a male Covid infection might be associated with a short-term decline in fertility.
Current Fertility Lab Treatment Options
We’ve talked about potential causes of infertility, but what treatments are currently available?
Broadly speaking, there are several categories of assisted reproductive technology (ART), including:
· In Vitro Fertilization (IVF)
The sperm and egg are fertilized outside the body then returned to the uterus.
· Intrauterine Insemination
This approach implants sperm directly in the uterus, an approach associated with single mothers using donor sperm from a sperm bank but can also be used if the male sperm doesn’t naturally travel to the egg, due to low mobility or other issues.
· Intrafallopian Transfer
Rather than fertilize an egg in the laboratory, this procedure performs the egg and sperm fertilization inside the woman’s fallopian tube.
· Intracytoplasmic Sperm Injection (ICSI)
For males with low sperm count, an individual healthy sperm can be collected and injected into an egg using a small needle.
· Cryopreservation
Sperm, eggs, and associated reproductive tissue can be preserved for IVF at a later date. Couples may elect to “save” younger eggs and sperm for use when they are older and more likely to have complications. Eggs and sperm can also be “banked” prior to treatments such as cancer chemotherapy or radiation, which might affect fertilty.
To learn more about fertility interventions, see this recent study: Evaluating interventions and adjuncts to optimize pregnancy outcomes in subfertile women: an overview review.
Will Artificial Conception Become the Norm? If so, what are the Implications for Society?
While it’s difficult to predict what changes will occur in fertility in the coming decades, one thing is pretty certain: the cost of fertility laboratory treatment options is expensive and will likely stay that way.
What are the implications of this?
If researchers such as Swan are correct and the quantity and quality of male sperm will drop precipitously in the coming years, the cost of sending an increasing number of couples to get fertility treatments will be quite prohibitive.
Currently, it’s estimated that one fertility treatment (e.g. a single IVF cycle, including ovarian stimulation, egg retrieval, and embryo transfer) can cost prospective US parents between $15,000 and $30,000.
Who will pay for it? The government? The medical insurance companies? Or is it an out-of-pocket expense for couples?
Already the cost of fertility treatment is prohibitive for many in poor and low income countries.
Long-term this could have some profound implications:
- The government or insurance companies could decide who gets fertility treatment. (To some extent, this is already true in the US)
- For those who can’t afford it but need it, there will be fewer babies – and the result could lead to economic decline due to de-population.
- On the other hand, providing free fertility treatment could be very expensive.
There is certainly a lot to think about.
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