When I started researching infertility, I kept getting fertility and infertility mixed up. It seems straightforward but there’s an important distinction so let’s get some basic terminology out of the way. Fertility is your ability to conceive a child. And so logically, infertility is your inability to do so. Based on how infertility is measured by the WHO, you’re not considered infertile until you’ve been trying to conceive for at least a year. This is important to note because when you see a headline like “fertility rates are down”, this means people are having fewer kids but not that they can’t have more. I’m focused on infertility.
How big of a problem is this?
From 1990 – 2010, infertility was pretty constant around the world at around 10 – 12% and under 9% in the US. The most recent numbers from the WHO put infertility at nearly 17% globally with the North America clocking in at nearly 20%. Not all of these studies measure infertility in the same way and use various time periods (the first looked at a 5-year span, the WHO looked at both lifetime infertility and the current period).
Combined with the decrease in fertility, we are below the population replacement rate – the rate at which a population stays stable from generation to generation. This has big implications that I won’t get into.
So it seems like something has changed in recent history to cause a rise in infertility. When we look at fertility, things like access to contraception (how many kids were born because of inadequate access?), sex education, and more career emphasis for women would have a big impact on these numbers. But remember infertility is a health condition not a personal choice. So what could that be?
📈 The Measurement Challenge
Infertility is way harder to measure because it’s not a simple population calculation, it requires people opting-in and seeking assistance in many cases. So the data is unreliable at best but I’ll take it directionally to mean infertility hasn’t gotten better with time.
Part of it is how we measure and define infertility, it’s changed from 24 months to 12+ months, making it more common. And having better measurement tools and healthcare available means we are seeing more cases being covered instead of infertile couples just existing silently, untracked.
Why is it so hard to get pregnant?
The statistics of fertility
It’s important to separate what I will call clinical infertility from statistical infertility. I’ve made up these terms for the sake of clarity.
Clinical infertility is a health problem and the one most of us are talking about, whereas statistical infertility is a probability one.
One thing few people talk enough about is how difficult it is to get pregnant. Media and sex ed classes have made it seem like one time is all it takes and BAM pregnant.
A sperm’s journey.
In order for pregnancy to happen, a lot of little things need to go right, each of which have a less-than-100% chance of happening.
First, there need to be enough healthy sperm available from the man. They need to be of high quality and good motility (ability to move). This alone changes the odds to around 20%. From there they must make their way to the egg. Sperm have no intelligence, they just kind of wander around, with some help from the fallopian tubes, to hopefully make it to the egg. Of course the egg itself needs to be released and ready which as we know, is only a 5-day window each month. Then the egg, once fertilized, must successfully implant in the uterus. This is just the first part of the pregnancy saga. When you look at it this way it’s a miracle that it happens consistently at all!
The reality is that even if everything goes right, in a given fertile cycle or window (each month), a young couple only has an 25% chance to successfully conceive. This means even if you tried to conceive 2-3 days during a fertile window, you’d only have a 70-80% chance each year. And this only goes down with age or any number of factors. Just knowing this can help alleviate some of the stress people feel.
⌛ Age’s Role in baby making
As you get older, pregnancy becomes more challenging. A woman has less eggs available and they slowly deteriorate as you age thanks to weaker mitochondria who are responsible for important cellular functions. As a woman’s hormones change she can have issues with her menstrual cycle, making planning harder, and the chances of miscarriage increase.
For men, the effects of aging are less pronounced. As a man gets older, his sperm is lower in quality and motility, however this doesn’t usually happen until their early 40s.
This is what I mean by the statistical odds. To grossly oversimplify it, it’s like rolling a die 50 times and being disappointed because you never got two 6s in a row. The odds of 2 sixes is 1/36, and so getting that in 50 rolls is ~75%. While it’s high, it’s not guaranteed. You could just be unlucky. And my naive math tells me that ~20% of young couples trying for a year straight will still be unsuccessful because of regular math, but this can easily appear as a fertility crisis. This has me thinking – is the 80% success rate due to chance or inherent infertility?
Clearly the stats aren’t as straightforward as we might think at first. I’m still scratching my head about this.
Okay, we got terminology and statistics out of the way. Let’s get down to first principles and build up our own mental model of fertility to understand what it takes to create a baby.
The recipe for making a baby
I’m going to try to get down to first principles. With something as complex as biology, I’m not even sure if first principles apply or are possible, but this is my own personal naive interpretation of them.
There are 3 things necessary right now for creating a baby:
- a sperm
- an egg
- and the uterus (an environment capable of growing the embryo)
These things might change in the future, we might artificially produce an embryo, but those are the key ingredients.
If we break this down into the biological processes required to do these things, we get:
Egg
- Ovaries need to successfully release an egg.
- This means they need to also have eggs available.
Sperm
- Sperm needs to be healthy and available.
- Sperm needs to be able to make its way to the egg to form an embryo.
Uterus
- The embryo needs somewhere to incubate. This is usually the uterus/womb
- The embryo also needs to successfully attach itself.
I’ve intentionally broken these out because each of them represents common failure points that can help us understand infertility better. I could continue to break these down further into what makes these processes possible, but for now we’ll stay at this level.
Looking at it this way, you can see how existing solutions have tried taking some of the different pieces of this equation and attempted to replicate, replace, or remedy it.
- Freezing eggs ensures that eggs are available when they are needed
- Artificial insemination ensures that sperm is available and makes its way to the embryo
- Surrogacy is a way to provide a natural environment to grow an embryo
Fertility Problems
After mapping the process into this super simple framework, we can have an approach for diagnosing problems more effectively thanks to the simple trick of inversion. When one of these things doesn’t exist, we get a problem. If someone is infertile, the cause is one (or a combination) of three things:
- Is there a problem with the eggs?
- Is there a problem with the sperm?
- Is there a problem with the uterus/environment?
From here we might try to understand what the problem is. For example is it the quantity and motility of sperm? Is it the availability of eggs? Each of these have their own root causes.
The easiest way for me to think through root causes is to organize them into two buckets. Across both men and women issues can be categorized as either genetic or acquired.
Genetic factors are things you are born with and much harder to change.
Acquired factors are the result of behaviours and environment.
Genetic
If you are born with specific genetic issues or predispositions, you might have a harder time conceiving. This could be the shape of the uterus, baseline estrogen levels, or ovarian function. For men this includes absence of sperm in semen or low sperm production. These require medical interventions and therapies to treat and aren’t too complex once diagnosed. Studies put estimates around 50% of infertility cases are due to genetic defects.
I won’t spend time talking more about these here, but they are often caused by DNA mutations, inheriting them from our parents, or missing/duplicated chromosomes.
Acquired
The things we hear about most when it comes to infertility and most health problems are acquired factors relating to lifestyle and environment. I would always read things like obesity or stress can lead to lower fertility, it’s hard to draw a clear connection between the two. It seems like the answer is hormones. These chemicals in the body regulate various biological functions and try to keep things stable, which means when they are out of whack, so is the body.
Estrogen is one of the hormones that sits at the root of all female infertility. It’s responsible for:
- regulating the menstrual cycle which ties directly into ovulation
- helps control cervical mucus (helps with fertilization + wayfinding)
- growth of endometrium (growth environment)
- follicle maturation (aids in ovulation)
And if estrogen levels are out of whack, all elements of the process suffer. There are many other hormones relevant for fertility, your luteinizing hormone triggers ovulation, the follicle stimulating hormone makes sure eggs mature, and progesterone helps throughout the pregnancy. These are all tightly interconnected with estrogen – when estrogen levels are too high or too low, there are cascading effects throughout the body. I’m not saying it’s the one thing to fix, but it’s intertwined in a lot of fertility challenges.
Hormone production, like estrogen, is heavily influenced by your lifestyle and environment. It’s impacted by your diet and exercise. It’s impacted by stress. It’s impacted by sleep. If you smoke? Lower estrogen levels.
Men are similarly impacted by their lifestyle and environment. Through a combination of changes in testosterone levels due to sleep, to alcohol impairing sperm motility, and heat exposure impacting spermatogenesis (sperm production). And of course diet directly affects sperm quality because of the nutrients necessary to produce them.
If we understand the role estrogen and testosterone play in fertility and the different elements that impact their levels, it becomes easier to understand how we might start to improve infertility.
❓Unknown factors
In addition to the big offenders (lifestyle and environment), there are more modern inventions that have unclear but potential impacts on fertility. These include birth control pills, microplastics, and even smartphone signals. Research in these areas can appear both conspiratorial and inconclusive, so nothing is decided here.
Trying to make a difference
So what we know is that there are a few ways to slice the problem. Problems can only be with one of the 3 key ingredients, and from there we are looking at genetic defects or impacts from your environment or lifestyle.
As we look to solutions in the next essay, we’ll see how this framework is important to brainstorming.
Am I wrong somewhere? Please let me know as I’m still learning.