The Future of Fertility

The UK Covid vaccine programme is well under way. But as we’ve heard a few times on this show, the SARS-COV2 virus presents a danger until the whole world has been vaccinated. This week, Ghana received its first 600,000 doses of the Oxford/AstraZeneca vaccine. Following India, it is the second country to receive covid vaccines distributed by the scheme COVAX - an organisation working to ensure fair distribution of covid vaccines around the world. Robin Cohen is professor of development studies at the University of Oxford. Katie started by asking Robin about COVAX...

Robin - Well, it was set up primarily by the World Health Organisation. France was also very involved in its initial foundation. And the idea was initially to create a big purchasing block that would be able to negotiate with the big pharmas [pharmaceutical companies] in the case of the companies that are trying to make money out of the vaccines, and with AstraZeneca, who I think as everybody knows is doing it more or less on a freebie basis, or an at cost basis. And the idea was that COVAX would create buying power that would allow a lot of poorer countries and middle income countries access to these vaccines at scale.

Katie - How's it going?

Robin - Well, it's not too bad. Of course, there are two aspects of it. One is that you need the funding to buy the vaccines in the first place. And a number of countries have come to the party in that respect. It's basically [the] World Health Organisation that is brokering COVAX and creating the institutional framework under which it works. So quite a few countries have come, including the UK, to add their money to the COVAX pot. So they bought quite a few vaccines. Not of course, as many as they need. At the moment, they've got roughly about 20 to 30% of the vaccines that they would need to vaccinate a big proportion of the world.

Katie - You've written about richer countries ordering more vaccine doses than are actually needed to immunise their populations. Why is this happening? And what scale are we talking about?

Robin - Well, the scale is really quite enormous. Now let me start by saying, although there are lots of people who've made indignant moral comments about this and said, "why on earth do people need this? Is this a form of vaccine gluttony?". My own view is that basically there was no way in which the procurement agencies could really determine which of the vaccines were safe and effective and gain regulatory approval. So this is not as it were a moral argument at first, but now it is becoming so because it's becoming clearer and clearer that there are many more vaccinations available to rich countries than they could ever possibly use. So just to give you an idea of the magnitude of what we're talking about, if we take collectively Canada, Australia, New Zealand, the EU, the UK, and the US, and put them all together in one bundle, it's well in excess of 1 billion surplus vaccinations, I mean, full vaccinations. So as it were two where two are necessary. So that's an awful lot of vaccinations that are going begging in the medium term. And what we now need to do is ensure that this redistribution is possible, probably through the agency of COVAX.

Katie - Is there another factor to bear in mind here, which is if countries need more than previously thought, for instance, if say someone makes an immune response to the viral vector in a vaccine and therefore dose two can't necessarily be the same type as dose one. Is that something that's important to consider?

Robin - That definitely is important to consider. There are all kinds of issues. There are also production delays, this has been experienced by AstraZeneca in Europe, as we know in mainland Europe. So there are all kinds of contingencies here. But if you take pretty well everything in the round, how many are spoiled, how many might be needed to cover additional variants and so on, there is undoubtedly a very large number remaining that need to be redistributed. And we need to create the mechanisms whereby this happens equitably and fairly.

Katie - What are the logistics of redistributing these vaccines to places that need them?

Robin - Well at the moment, the basic idea is that the countries that are definitely not going to use what they've ordered would be able to divert through donation or through sale. And I suppose there are all kinds of other political issues then come in - do you try to use vaccines to influence your foreign policy outcomes? And we've noticed this happening, particularly in the case of China and Russia, but also in some other cases. So we might, for example, look at the current discussions between the US and Mexico, where the Mexican president is suggesting that the US should send surplus doses to Mexico precisely at the time where they are complex trade negotiations between Canada, the US and Mexico occurring. So there's a very, very complex political structure around the issue of redistribution.

Katie - Would all of the vaccines be suitable for this? Do you think?

Robin - Well, of course it's been argued that not every vaccine can be redistributed because certain of them need a good cold chain. But with a little bit of imagination, it is possible certainly to use all vaccines in most countries. For example, one can create cold, cool ports in airports, international airports in places like Johannesburg or Cape town or Rio de Janeiro, Sao Paolo and redistribute even cool chain, cold chain vaccines at that point.

Superb lyrebird are large songbirds only found in forests in Australia. They’re famous for their incredible ability to mimic sounds - from forest creatures to drills - and they also put on elaborate song and dance displays for potential female mates. Now, scientists have uncovered another sexual song the male lyrebird will sing, which is the one you just heard. It is, they think, an imitation of what’s called a ‘mixed species mobbing flock’ - essentially the alarm calls small birds will make if they see a predator. And it looks like the male birds make these sounds to deter females from running off when they’re trying to mate with them. Eva Higginbotham heard from the University of Wollongong’s Anastasia Dalziell how she made the discovery...

Anastasia - I was recording a very nice male, and the male had just paused in his dawn singing. He'd just taken a break. He was eating some worms. He was quiet and sort of scratching, digging for more food along the ground. And suddenly I saw him stand up straight, and throw his tail over his head, and a female walked into the scene. It was a very exciting moment. And then the odd thing was, he then ran off away from the female, but straight to one of his many display mounds. So these are the circular patches on the forest floor, and she followed him and then I had to follow them. It was really difficult because the forest floor was littered with fallen-over gigantic trees, and hidden things to stumble over. And it was well above my knee in bracken, and it was quite a difficult run. It was really a very intense moment for everyone involved, but I got there and I got to the mound where he was performing his song and dance, to play to the female. She was on the mound with him. It was amazing to see. And then just at the moment that he got on top of her, he switched to this mobbing flock mimicry. It was really clear to see it happen. It was very abrupt. And then of course he was on top of her for about, it was 45 seconds or so, and throughout he was mimicking the mixed species mobbing flock.

Eva - Essentially the male birds, while they're mating, they start doing this amazing mimicry, trying to sound like lots of other upset, small birds that have noticed a predator nearby?

Anastasia - Exactly. So of all the wonderful sounds that the male superb lyrebird can imitate, and does at other times, it's this moment, which you can think, perhaps it's the peak of sexual selection. He's mimicking the buzzy alarm calls. It's absolutely extraordinary.

Eva - Why do you think they're doing this?

Anastasia - This is extremely difficult to interpret, but it wasn't until a bit later when we started to put cameras on male display mounds, so these sort of camera traps, to really film the males during their displays and during their sexual interactions with females, that we started to get a handle on what we think is going on, and noticed that there was another context in which males were switching to the mobbing flock mimicry. And this happens when a female approaches the male on his display mound. And as we'd seen in the other examples, he puts on a big song and dance display to her with his tail over his head and the full lyrebird specific songs. But often these dances don't end in a mating. They end, rather, when the female steps off the mound and seems to go away. And it was the moment the female stepped off, that a male would stop singing his song and dance display, and switch to this mobbing flock mimicry. So now we had two sexual contexts in which the male was producing the mobbing flock mimicry, during copulation itself, and when the female was attempting to leave the male without mating. It was a very strong relationship between female behaviour attempting to leave, and male production of mobbing flock mimicry. So we thought about this and we concluded the best explanation that explains his use of it in both contexts, is that he's attempting to prevent the female from ending the sexual interaction before he's managed to transfer sperm to her, saying something like baby, it's dangerous outside, stay here, safe with me.

Eva - How similar is this mimic of the mobbing flock sound to the real mobbing flock sound? And is it similar enough that the lyrebird females definitely think that this is a real mobbing flock?

Anastasia - We tested the similarity in two different ways. And the first way we did it is we compared the acoustic properties, measured acoustic properties of male mobbing flock mimicry, and then recordings that we've made of actual other species in a mixed species, mobbing flock. And we compare the acoustic parameters and we concluded that they were indeed remarkably similar. And then the second way we tested is by conducting an experiment to test whether birds perceive the similarity between the mimic and the model like we do. So I did a playback experiment by placing a speaker in a forest, and broadcasting the sound of lyrebird mimicry of the mobbing flock, or recordings of real mixed species mobbing flocks. And then we scored how these other members of the forest, other birds responded to those. And we found that as far as their behaviour was concerned, they behaved in the same way, regardless of whether it was a mimicry, or the real mixed species mobbing flock. So it's quite convincing evidence that birds with their very different hearing from ours, also perceive the similarity between the lyrebird mimicry and a real mobbing flock.

Quantifying population growth now and forecasting into the future is an important task - for instance, to know how big a nation’s future workforce will be, how many school places you need etc. So how do scientists actually accomplish this? Brienna Perelli-Harris is an expert on human populations from Southampton University, and spoke to Katie Haylor...

Brienna - Well, demographers tend to use three different types of forecasting methods. The UN uses Bayesian estimation techniques, which takes into account many different previous estimation trends, and when they calculate their forecast they tend to have a lot of uncertainty. So they might have a median-variant, but they do include lots of uncertainty based on what has happened previously. The IHME, which produced a study that was very publicised - it was in the Lancet - over the summer... they tend to make assumptions about contraceptive use and education, but it was rather controversial because many of the assumptions, especially in Africa, didn't really line up with what other demographers were seeing had happened in Africa, because of the stall in fertility in certain regions of Africa.

And then the other way that demographers tend to forecast populations is by estimating how education is going to change over time, because women's education has been one of the most important factors for declining fertility. And this technique also takes into account expert opinion. So these different approaches have been used to forecast global population in general.

Katie - I guess it's important to distinguish between biological fertility, and reproductive choices and agency, isn't it? How does biological fertility stack up as a potential impactor on population change?

Brienna - In general we've seen that the most important factor is age. So as you know, women's reproductive age tends to end around 45-49, and although this has been pushed forward a little bit with assisted reproductive technologies and IVF, it really hasn't pushed that boundary very far; and we see very few births occurring after the age of 45. That is what we take into account most in terms of the biological capacity. And in fact, there have been studies... for example, I did some research in Ukraine, which as you remember was impacted by Chernobyl, and there was a lot of pollution in the environment. And in the early 2000s, I found that only 5% of the population remained childless. This is really due to social norms that have really pushed couples to have children really early, and if you start early, or if a population starts early - around the age of 20 - then childlessness can be very rare, or relatively rare. Although we take into account fecundability on the population level, it's not the main consideration that we demographers use to think what populations are going to do in the future.

Katie - Okay. So what you're saying, is the main biological factor is maternal age. What is the overall biggest factor? Because I would have assumed it's probably finances. Is that true?

Brienna - Yes, and preferences, and... but you're right that economic uncertainty has been one of the most important reasons why certain countries on average have had lower fertility rates. Also, family policies are really important: to what extent couples can balance work, and family, and childcare, and maternity leave. That has also been really important. Also - we talk about gender equality, and to what extent men actually contribute to household labour, as being also really important for these decisions about how many children to have.

We've heard about female fertility, let's turn now to male fertility. Katie Haylor spoke with Bill Colledge, a reproductive physiologist from Cambridge University. Firstly, Katie asked Bill if there's any evidence that the Covid-19 pandemic could be impacting male fertility...

Bill - Well, it's an interesting question. There was a study that was published just a few weeks ago where they were looking at indicators of male fertility, such as sperm numbers and the motility of the sperm, after individuals had a COVID infection. And they found that there was an impairment in the sperm quality even three months after these individuals had got over the initial COVID infection. So that would indicate that if you have a COVID infection it can alter the quality of the sperm. But I would like to reiterate here that you probably would see the same thing with other viral infections as well, such as influenza. There is data to suggest that sperm quality goes down after an influenza, and it's probably more related to the body fighting off a virus in general rather than just COVID. So that's often associated with a high fever and we know that a high fever can impair sperm quality.

Katie - So I guess knowing how long that lasts must be quite a crucial question, right?

Bill - It's a very crucial question. The study only looked after three months, they didn't go any further out than that. So we don't really know how long it would take for the sperm quality to get back to normal. They also didn't relate it to fertility, they were simply looking at sperm numbers and motility. And of course, fertility is a different aspect - is it possible for those individuals to still conceive, even though they have impaired sperm?

Katie - What about stress and anxiety? Catherine mentioned it as some sort of indirect influence. Is there evidence to suggest that stress and anxiety can impact male sperm?

Bill - There is evidence that high stress can alter the male reproductive axes. So if you're under a lot of stress and you have this stress hormone cortisol being produced in the body, that will tend to suppress the reproductive axes, which could lower the amount of testosterone in the body which you need in order to make sperm. So under those conditions you could actually see a reduction in the number of sperm being made - perhaps not so much a change in the quality of the sperm, but just in the quantity.

Katie - Catherine was mentioning the sorts of factors that are understood to influence female fertility outside of the context of the pandemic. Broadly, does that list look the same when we're talking about male fertility?

Bill - It's pretty similar actually. Obesity is a very important contributory factor in male fertility, mainly because individuals that are obese tend to have lower testosterone levels. And as I've said, you need testosterone to get your body to make the sperm, so everyone that has an increase in 9 kilograms has a 10% reduction in fertility. So there's a direct correlation there between body weight and obesity and fertility. There are other factors that also affect male fertility - smoking, I think was mentioned as affecting females, but it will also affect male fertility. There are substances within cigarette smoke that are not very good for sperm production - there are toxic substances like cadmium and lead, and they will certainly interfere with sperm production. And then of course the various toxins that you might find within the environment. Sperm formation is very, very sensitive to these substances, and if you get them in your body it can compromise the sperm formation.

Katie - And what about air pollution? Have there been studies done looking at air pollution and sperm?

Bill - There have been studies done, but as Catherine said, the problem with most of these studies is they tend to just be correlations and they often tend to be done in small groups. The best way to look at this is to look at all of the studies together and to do what is called a meta-analysis to try and put all of the publications into one, and to do the statistics on that to look at whether air pollution can affect male fertility. There has been a meta-analysis done in 2015, and they did show that air pollution does correlate with reduced sperm motility, but it didn't seem to affect overall fertility levels. So again, you've got to be careful talking about a reduction in sperm numbers and how that might affect fertility.

Katie - Now we've heard a number of reports in recent years about sperm quality and quantity being on the decline. Is this the case? What evidence is there to support this? Is it seen across the globe or is this a UK problem?

Bill - So there are several studies over the last 20 years that have clearly indicated a decline in the number of sperm. And again, if you look at all those studies together and you do a meta-analysis, there was a very good meta-analysis done in 1992, and what they found was that indeed there is a reduction in the number of sperm being produced and the amount. So I think in 1940, the average sperm count was 113 million per ml, but by 1990 it had dropped to 66 million per mil. So there has been a significant reduction in the number of sperm. Now this tends to only affect the Western developed countries. Studies have been done in Asia, and they have been done in China. There is some evidence to suggest similar reduction in sperm numbers, but less pronounced. So it does seem to be mainly in the developing Western countries.

Katie - And in just the last sentence, do we actually know why this is happening?

Bill - It's multifactorial, but probably obesity and weight gain will be a big component in this.