FEMALE fertility is often said to “fall off a cliff” after 35, but there is growing recognition that this idea overlooks much of what we now know about how and when women become pregnant.
In terms of milestones, turning 35 years old may seem unremarkable. Unless, that is, you’re a woman who hopes to get pregnant – in which case it can loom large.
For decades, the age has been seen as a watershed moment for female fertility. Before 35, the theory often goes, most women will have little trouble conceiving, but that point, fertility falls off a cliff. For those who do become pregnant later, there even are particular medical terms, including “geriatric pregnancy” and “advanced maternal age”, used to drive the point home.
But the reality is more nuanced, say experts. It’s true that more women in their late 30s will experience difficulties conceiving – and, in some cases, face more risks in pregnancy and delivery itself – than women in their late 20s or early 30s. However, the decline is a continuum, not a cliff, and it looks different from one woman to the next.
“From 35 years onwards, the rate of decline speeds up, in egg quality and quantity,” says Lorraine Kasaven, an obstetrician-gynaecologist and clinical research fellow at Imperial College London with a special interest in fertility. “The rate of decline, however, will vary from individual to individual.”
Infertility – clinically defined as not being able to get pregnant spontaneously after a year of trying – becomes more likely the older that prospective parents get. One of the largest studies on the topic, for example, found that, of 2,820 Danish women who had intercourse at least twice a week, 84% of those aged 25-29, 88% of those aged 30-34, and 73% of those aged 35-40 conceived within 12 menstrual cycles.
Of course, not being able to get pregnant in that time frame doesn’t mean never being able to. Another study found that, of women in their late 30s who hadn’t conceived after a year of trying, more than half still got pregnant naturally after two more years if their partner was younger; if their partner was 40, 43% did.
For those who go on to use assisted reproductive technologies (ART), there is still more hope. According to the most recent data, for example, in 2020 for example, 40.6% of all egg retrievals for 35- to 37-year-old female patients in the US led to live births. That’s lower than the average of 54.1% for under-35s. But the decline holds steady until the 38- to 40-year age range, when it hits 26.9%. For patients over 40, it drops to 9.3%.
Of course, this is the success rate per egg retrieval. Patients who persist with multiple cycles have still higher chances. One study of more than 150,000 women, for example, found that, in women less than 40 years old, using their own eggs, there was a 68% chance of having a live birth with six cycles of in vitro fertilisation. For women aged 40 to 42, the success rate of six cycles was less than half that. (While it is worth noting that the data lumps together all women under 40, the median age of the participants was 35).
These numbers point to a decline happening sometime in the late 30s. They also show, however, that the majority of women in their late 30s will conceive naturally within a year. And they underscore that the real watershed moment may be 40, not 35.
“The most women have difficulties in getting pregnant when they’re over 40, even though they go into menopause at an average age of 51.7,” says Anja Bisgaard Pinborg, head of the fertility department at Copenhagen’s Rigshospitalet and clinical medicine professor at the University of Copenhagen.
The ‘real’ 35: 38? Or 40?
One recent academic review, for example, looked at how likely it was that women who were defined as infertile could conceive spontaneously, without medical assistance, after a year. At 35 years old, these women had a 29% chance. That rate remained steady until age 38, after which it fell more quickly. At 39, 25% of women were successful; at 40, 22%; at 41, 18%; and at 42, 15%.
But even that change needs to be interpreted with caution, points out Spencer McClelland, an obstetrician-gynaecologist at the Denver Health Hospital, US, who has criticised his field’s focus on the age 35. “There is a statistically significant change in the rate of decline at 38. But is it clinically relevant? Maybe not,” he says. “Is 29% at 35 that different from 22% at 40? Probably most people would not find much difference in those numbers. So from either a woman’s or doctor’s perspective, it means we shouldn’t react differently to a 35-year-old vs 40-year-old when counselling about fertility.”
The 18th Century parish studies aren’t the only source of the focus on 35. Another is the risk-benefit calculation of amniocentesis, McClelland says. In the 1970s, as he has written before, the only way to genetically test a foetus was by amniocentesis – which involves using a needle to draw amniotic fluid and, at the time, was normally done to determine the likelihood of Down syndrome. The procedure comes with a risk of miscarriage. At what age was the risk of an amniocentesis-induced miscarriage outweighed, mathematically, by the chance of Down syndrome? Around age 35.
Yet even that risk-benefit calculation is now outdated, he points out. Today, there is about a one in 500 chance of miscarriage due to amniocentesis, compared to one in 200 in the 1970s. That would mean the calculation would be in favour of doing the procedure at a younger age – 32.5 – than in the 1970s. It’s something of an “absurdity”, he points out, that improvements in amniocentesis safety mean that the age at which we define pregnancy-related risk is younger – not older.
Why conceiving becomes harder
Why does conceiving become more difficult at all? For ovulating women, a lot of it, specialists say, has to do with two factors: egg quantity, and quality. While female babies are born with all the eggs they’re ever going to have – about two million – by puberty, that’s already about 600,000. The ovarian reserve continues to decline into adulthood.
“As we get older, women have less eggs, and the quality of the eggs also declines,” Kasaven says. “So, it does become harder to naturally conceive, and even when you go for fertility treatment, overall success rates may be less, compared to if you were to do it when you’re younger.”
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Egg quality is important, too. As we age, we have a higher proportion of abnormal eggs left.
That’s part of why fertility, in and of itself, is just one dimension to consider.
Another risk is miscarriage. “The other thing that that happens in the late 30s is that the chromosomes in the X (chromosome) are getting more unstable – that’s why there’s an increased risk of chromosomal aberrations, such as Down syndrome. So, many of the pregnancies will end up in a miscarriage,” says Pinborg.
One very large study of more than 1.2 million pregnancies, for example, found that the risk of miscarriage was around 10% for women aged 20-24, but started to rise more steeply close to the age of 35, when it was over 20%. By age 42, more than half of intended pregnancies – nearly 55% – were lost.
Birth defects and stillbirth also become more common as we age, but generally closer to 40, not 35. One study of 1.2 million births registered in Norway from 1967 to 1998 looked at the average age of the parents, for example, and found that birth defects became markedly more common when the parents’ mean age was 40-44 (with a mean age of 38 for the mother and 45 for the father), while infant mortality rose around 35-39 (with a mean age of 34.5 for the mother and almost 39 for the father). “While the 40–44 parental age category had an increased risk relative to the benchmark group, it was vastly exceeded by the risk for the 45–49 parental age category,” the researchers write.
But younger wasn’t always better: couples with an average age of between 20 and 24, for example (where the mean age of the mother was 21), had the same infant mortality risk as those aged 40-44 (with the mother’s mean age of 38).
Even age-associated risks, however, are complicated. Egg quality is also impacted by factors like smoking, alcohol consumption, and obesity, for example.
Other risks commonly associated with “advanced maternal age” are nuanced, too. It’s common, for example, to hear that the risk of pre-eclampsia is higher after age 40. But one authoritative study which looked at more than 25,000 pregnancies over 10 years found that, after taking other risk factors into account, like whether mothers smoked, age alone did not increase the risk of pre-eclampsia.
The same study also found that other commonly discussed risks, such as that of an emergency caesarean-section or placenta previa, increased from the age of 40 or 45 – not 35. One exception was the risk of gestational diabetes, which increased from age 30 onwards.
Men matter, too
Meanwhile, the focus on female fertility alone can distract from the fact that male age matters, too. The study of European couples found that while a father’s age had no bearing on the likelihood of conceiving if he was 35 or under, that changed in the late 30s. “Among 35-year-old women, the proportion of couples failing to conceive within 12 cycles increases from 18% if the male partner is 35 years old to 28% if the male partner is 40,” the researchers write. After two years, that fell to 9% and 16%, respectively.
There also is a higher risk of miscarriage if the father is over 40.
Sperm quality declines with age, research has found, including in terms of sperm count, motility, and the percentage of normal sperm. While sperm regenerates every two to three months, unlike eggs, the decline in quality may stem from some similar reasons – including DNA damage, environmental toxins, and hormone-related declines.
So for couples, or women, approaching their mid- or late 30s or 40s, what is the takeaway?
One aspect to note, say specialists, is that in IVF, using younger eggs, such as frozen or donor eggs, mitigates much of the effect of the mother’s age on live-birth success rates as she gets older.
This is why many who work in the field recommend that, if a woman wants to preserve her fertility and can afford the process, it can be a good idea to freeze her eggs. But every patient also has to weigh the costs and benefits, notes Kasaven.
“If you’re freezing too young, like in your 20s, it’s probably not cost-effective,” she says, given that many younger women will go on to naturally conceive. Studies trying to determine the most cost-effective age, on average, for a woman to freeze her eggs have found it is around 35 years old.
Particularly when she sees a patient who wants to be a parent but who has been waiting for the right partner, Pinborg says she starts with a simple question.
“When a single woman comes in, I start by saying, ‘How do you see your life? Do you absolutely see yourself with a child?’ Or do you say, ‘Okay, if I get a child it’s fine with me, or if I don’t, it’s fine?’,” she says. “If she says, ‘I can’t see myself in life without a child, it has always been my dream’ – then I say, ‘You need to think about it before you’re 40. You need to use donor semen when you’re 37, 38.’
“There are so many ways of making a family today.”
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