Fertility Crisis: why IVF isn't working

If you want to have kids, then you need to know about this chart. It shows the number of follicles that a woman has. Follicles usually contain eggs and start from a peak of over a million before she's even been born, to just a few hundred by her late 40s. This, and a drop in egg quality, means it's harder for women to get pregnant from their mid-30s — which is a problem, as across the rich world people are trying to start families later, and one in six couples now struggle to get pregnant.

Age-related infertility is one of the biggest challenges for the fertility sector today.

So, what's the answer? Freezing your eggs may seem like a good way to delay having children. Can women really take fertility into their own hands via egg freezing?

> "We're a little afraid that people who freeze at an unknown entity, at a new lab, might come back in 10 years and their success isn't what they thought it would be."

Or could jaw-dropping scientific advances do away with the need for human ovaries altogether?

> "It has this potential to actually be able to create entirely new egg cells for people that don't otherwise have fertility options right now."


Deborah is going through in vitro fertilization, or IVF.

> "Find my stuff... I like my subcutaneous injection pens..."


She struggled to get pregnant in the past and is now trying for her third child.

> "I think my age really played into wanting to do more IVF. I'm 37, and I kind of saw this as like my last window to possibly be able to go in and create a few more embryos."



For each cycle, she injects herself with hormones to stimulate her ovaries to produce as many mature eggs as possible. These are then extracted and fertilized in the lab — by mixing them with sperm or injecting sperm directly into the egg.

It’s physically and emotionally challenging.

> "I'm not good with the hormone side effects. I end up getting really moody and really sad. Personally, I find it to be a very unpleasant experience."



Despite the live reality of IVF, the market for assisted reproductive technology is booming. It’s estimated to be worth around $20 billion — and counting.

Here in the U.S., it's a very high-margin sector. You see a lot of private equity money going into the sector because of that. They also like it because it's relatively lightly regulated compared to other parts of medicine.

Demand is growing — and there is a lot of unfulfilled demand out there. Ergo, there's a lot to sell.

Much of this demand is coming from people who, like Deborah and her partner, are trying to conceive later in life — when they're up against their biological clock.

The trouble is, IVF is an imperfect technology for age-related infertility. Although success rates have improved dramatically in the past 30 years, on average, in Britain, 38-year-old women still have less than a 20% chance of having a baby after one embryo transfer. And progress across the board has largely stalled.

> "I would say it's a sector that, despite all the froth and excitement, is actually pretty stuck at the moment."




To understand why, we need to go back to the 1970s, when this remarkable footage of the first IVF baby shocked the world.

> "Okay, this is in pretty good condition..."



The first IVF baby was Louise Brown. She was the daughter of Lesley Brown, who had blocked fallopian tubes.

IVF was first invented to help women with mechanical reasons for infertility. It wasn't designed to improve ovarian reserve. It wasn't designed to improve egg quality. And it still can do neither of those things.

In a sense, we're using the wrong tool to address the infertility crisis.

So, if IVF can't beat the biological clock — then what can?

One solution that seems to be everywhere in the media is egg freezing.

> "Egg freezing, egg freezing, egg freezing..."



You're sort of stopping the clock on as many eggs as you can — and then coming back to them later.

M was in her late 20s when she started looking into fertility preservation.

> "I had essentially been single for a while, and I had heard about egg freezing. I thought I would start saving towards it."



This doesn't come cheap.

In America, a woman can spend $30,000 to $40,000 on two cycles of freezing and storage. In the UK, where M lives, costs are lower — but it still took years of saving before she could go ahead.

> "I wanted to give my future self — my older self — my younger eggs."



She’s far from alone in taking this step.

In Britain, the annual number of egg freezing cycles carried out with the intention of use by patients increased tenfold between 2009 and 2019. While it fell slightly during the pandemic, it rose sharply in 2021.

But this still represents a tiny number of women relative to the UK population.

There’s been more growth in America — thanks in part to employers subsidizing treatment.

> "You see quite a lot of growth for two reasons really: partly more types of employers who are making this part of their benefit package, and partly just awareness."



Slowly but surely, the evidence around its relative effectiveness is becoming more solid.

In a good lab, around 90% of eggs can survive freezing and thawing. And it's clearer how many eggs a woman needs to freeze for a chance of getting pregnant.

According to the largest U.S. study on this so far, 70% of women who first froze their eggs when they were under 38 and then thawed at least 20 of them went on to have a baby. But even then, success is never guaranteed.

As well as trying for a baby, Deborah and her husband Jake run a website, Fertility IQ, which helps people navigate the fertility market — including egg freezing.

> "So, our egg freezing course is probably our most popular course. We've seen a dramatic change in the demographics of the people that come to take the course. The trend is for people to come younger..."



But they fear the increased demand and profitability of egg freezing means some clinics are overselling the chance of success.

> "The quality of the clinic, in many ways, is going to determine the odds that it works. There are so many startups now in the space, but the reality of what's going on behind the scenes in that lab is really unknown. And so we're a little afraid that people who freeze at an unknown entity, at a new lab, might come back in 10 years and have a really terrible surprise — that their success isn't what they thought it would be."



When M froze her eggs, she was surprised how little information was available.

> "The doctors don't tell you: look, if you go into egg retrieval, you might not get the numbers that you want."



And when her first retrieval didn’t go as well as she hoped, she was devastated.

> "I thought, I'm too young to have what I thought was a failed attempt. I thought, I'm gonna have to do this another two times — and where am I gonna get that money from? I don't want to have to inject... do this whole process again."



Medically, it's the same as going through an IVF cycle — except for the last bit: fertilizing the egg and then placing it in your womb. It’s a physically taxing thing to go through.

M did eventually freeze her eggs successfully. But some researchers have started to wonder if there’s a better way of doing things — perhaps by taking ovaries out of the baby-making equation altogether.


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This is Dr. Hayashi Katsuhiko. Seven years ago, he made headlines by announcing he'd grown egg cells — or oocytes — from mice in the lab, without needing an ovary at all.

> "When I saw the first result of oocyte production in culture, we were so excited."



Hayashi and his team used a technique called in vitro gametogenesis — or IVG — to make the eggs. The Japanese team took skin cells from a mouse's tail, and using a cocktail of chemicals, nudged them into becoming pluripotent stem cells — a special type of cell that can develop into many different types of tissue.

These stem cells were then further nudged into becoming oocytes, which were fertilized to create baby mice. Perfecting the process took 10 years.

> "The first time I got the baby from such an impediment oocyte was just... amazing. Just amazing."



Dr. Hayashi's team then took this one step further — by growing egg cells using stem cells from male mice, creating, in effect, mice with two dads.


Their work has caught the attention of Silicon Valley entrepreneurs who are excited about the possibilities of this new tech.

> "I myself am gay, and something I’m very personally interested in — in terms of how it could allow people like me to be able to have biological children with their partners."



Matt Krisiloff, who is a founding member of OpenAI, is so invested in the promise of IVG that he set up a company, Conception, to try to develop Dr. Hayashi's work into humans.

> "It has this potential to actually be able to create entirely new egg cells for people that don't otherwise have fertility options right now. So, think: women in their 40s or 50s, potentially same-sex couples, or say, cancer patients as well that have had their eggs wiped out by chemotherapy."



> "If you look at the spikiness, is it irregular? Yes. But it's actually not a problem."



Matt says his team hopes to produce proof-of-concept human eggs within a year — and that this could be just the beginning.

> "If you can really take a skin or blood sample and turn these into eggs, that could be a lot better than the traditional IVF experience, which requires hormone injections and a surgical procedure to take out the eggs. Honestly, I can even imagine a scenario down the line where mainstream people may want to have this technology as the way they have children — just in the sense that it could allow for much more genetic screening for disease purposes."



But there are many safety concerns to address before eggs grown in a lab via IVG could be used in fertility treatment.

> "The longer embryos remain in the dish outside a woman’s body, the more tiny, minute changes there are to that embryo — which do not mimic the natural process. In IVF, there's a protracted period of out-of-body manipulation, and I think all of that generates concerns about safety and the viability of those cells."



The lab-grown eggs have so far also had a very low success rate for producing baby mice.

But even if IVG is never safe enough to be used in humans as fertility treatment, it could still help move the dial in research into how to make babies.

> "If nothing else, what you're doing is creating a readily available stock of eggs for people to do research on and understand the basic science of human reproduction — which is currently so difficult to do, in part because not that many women donate their eggs just to research. And so it enables research that, up until now, has been very difficult."



Not content with growing eggs in a lab, Dr. Hayashi is now researching ways to stop a woman's biological clock altogether — using a protein that occurs naturally in cells called cohesin.

> "People believe that the decrease of the cohesin is one of the reasons why aged people cannot get a baby."



The idea is that if you can understand why immature eggs age, then can you stop some aging? Could you potentially give women a pill that would freeze her ovarian reserve in her 20s, so that at some point, when she wanted to become pregnant, the eggs in her ovaries at that point would not be 40-year-old eggs — but would in fact be 25-year-old eggs?

Despite the promise of this research, it will be a very long time before this is anywhere near a reality.

Just trying to beat the biological clock, there is at least the hope that perhaps future generations will be making babies in entirely new ways — and later in life.