Owen Gent

WHEN I saw the positive result on my at-home pregnancy test, my mind raced ahead. I imagined how it would feel to hold my child for the first time, what we would call them. I thought of the bedtime stories we would read, pictured family camping holidays at the beach.

I never imagined that, just weeks later, while dancing at a friend’s wedding, a sharp twisting pain would signal that the pregnancy was over.

Like many women who have a miscarriage, I worried I had done something to trigger the loss. Had I exercised too hard? Slept too little? Around the world, studies show that many women experience shame and guilt after losing a pregnancy. One US survey found that 40 per cent of women who had a miscarriage believed it was because of something they did wrong. Though there is no evidence covid-19 increases miscarriage risk, the pandemic only exacerbates these worries. Society can add to the problem. In some countries, the culture of blame is so widespread that losing a pregnancy can land a woman in jail.

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When I looked into the latest research, what I discovered not only challenged ideas that women are somehow responsible for their miscarriages, or experience them because something is wrong, but suggested that, surprisingly, they are usually associated with optimal maternal health. With advances in fertility medicine, we are finally starting to understand what happens in a miscarriage. This progress may offer solace when pregnancies don’t work out and help women struggling to become pregnant. It could even shed light on the role of miscarriage in our evolution.

Until a few decades ago, even medical professionals had little understanding of how often miscarriages occur. The first hint came in 1975, when The Lancet ran a paper titled, “Where have all the conceptions gone?” The authors calculated how many babies you would expect to be born annually to married women in their 20s in England and Wales, and found the true figure was a staggering 78 per cent lower. They proposed the radical idea that most pregnancies are naturally terminated before women know they are pregnant, and that miscarriage is our “principal method of quality control”, but had no way of proving it.

Women who have several miscarriages may actually get pregnant more rapidly than others

John Fedele/Getty Images

Since then, the invention of early pregnancy detection tests – like the pee-on-a-stick test that I did – have confirmed that we do indeed have an exceptionally high rate of pregnancy loss. The pamphlets that come with these tests advise that one in four pregnancies don’t make it past the early stages, but the real figure may be far higher. The latest estimate is that for women in their early 30s, 60 per cent of pregnancies end in miscarriage, mostly in the early stages. This is six times higher than the rate in mice and rabbits and twice that for pigs, sheep and goats. For women in their early 20s, 50 per cent of pregnancies end in miscarriage; in their early 40s, it is 80 per cent.

“For women in their early 30s, 60 per cent of pregnancies end in miscarriage”

Most people have no idea that miscarriages are so common. A survey of 1000 men and women in the US, for example, found that the majority thought they occurred in fewer than 5 per cent of pregnancies. “There is this whole silence and stigma around miscarriage,” says Jade Bilardi at Monash University in Australia. Often, we are oblivious even when our close friends go through them because they typically occur before the 12-week mark when it is considered socially acceptable to announce a pregnancy, she says. “It means that couples often feel very alone and isolated when it happens to them.”

Then there are those haunting feelings that so many women experience in this situation that we did something wrong. This is because stress, diet, exercise, prior birth control use and lifting heavy objects are often incorrectly blamed for miscarriages, says Bilardi. “There tends to be a lot of questioning afterwards, like, ‘Have I been too stressed at work? Did I eat something wrong?’,” she says. “It is common for women to feel shame or guilt or like their body has betrayed them.”

There is evidence that some lifestyle factors like stress, smoking and heavy alcohol consumption do slightly increase the risk of pregnancy loss, as do conditions including endometriosis and thyroid disorders, as well as infectious diseases like the flu. However, most miscarriages are unavoidable because they are caused by chromosomal errors in the embryo, says Shawn Chavez at Oregon Health and Science University. The reason maternal age increases miscarriage risk is due to the rate of chromosomal abnormalities in embryos rising as women get older. Advanced paternal age also slightly increases the rate of chromosomal abnormalities in embryos.

The gatekeeper

Human embryos contain far more chromosomal errors than those of most other mammals. Up to 80 per cent of embryos made through in-vitro fertilisation (IVF) contain at least one chromosomally abnormal cell, and this figure is probably similar for naturally conceived embryos, says Chavez. In comparison, this is true for fewer than 10 per cent of mouse embryos.

Our chromosomes contain all the genes needed to build a functioning human, so embryos with significant abnormalities usually don’t survive. Humans have to be extra fussy because we usually only have one child at a time, says Chavez. “In the case of animals that have litters, maybe they make 10 embryos a month and only eight make it to live birth, but that’s still eight,” she says. “Whereas we typically can only make one embryo per month, so if it isn’t a good one, maybe it’s better to try again next month.”

Until recently, we didn’t know how this vetting system might work, because the ethical and technical challenges of studying early pregnancy made it a “black box”, says Nick Macklon at the London Women’s Clinic in the UK. In the past decade, his research group has started to piece together some of the evidence.

The researchers began by studying what happens when an embryo burrows into the lining of the uterus, called the endometrium, which normally occurs about five days after conception. They couldn’t study this implantation process in pregnant women for risk of harming their pregnancies. So instead, they placed embryos donated by previous IVF patients in a dish on a layer of cells that had been collected from a woman’s endometrium.

When embryos were added, the endometrial cells usually flocked to them and released chemicals designed to promote implantation and growth. But when the embryos had chromosomal abnormalities, the endometrial cells avoided them and stopped secreting pro-implantation chemicals. By depriving them of essential nutrients, the endometrium appears to prevent embryos that are unlikely to survive from attaching to the uterus, says Macklon.

To find out more about this process, Macklon’s team used the liquid that human embryos had been grown in during IVF and flushed it through the uteruses of live mice. Liquid that had sustained embryos that produced successful pregnancies activated 90 genes involved in fostering embryo implantation and growth. In contrast, liquid used with embryos considered unlikely to survive, and so not transferred to a uterus, triggered an extraordinarily strong stress response, activating 544 genes that are thought to work together to drive embryo rejection.

“There’s this idea that human reproduction is inefficient – that’s not true”

Taken together, these findings hint that the endometrium acts as a gatekeeper that waves through the embryos that are most likely to survive while doing everything it can to shut out others, says Macklon. The challenge now is to conduct human studies to confirm this.

One option may be to use an IVF technology called shared motherhood that has recently become available to lesbian couples. It involves one partner incubating an embryo made from her egg and donor sperm in a removable porous capsule inside her uterus for the first 18 hours. The embryo is then transferred into her partner’s uterus to implant and grow into a baby. Researchers could study how different embryos affect gene expression of the endometrium by taking biopsies from women who provided the initial incubating, after the embryos have been safely moved to their partners’ uteruses, says Macklon.

Studies like these could yield critical insights: it is now estimated that about three-quarters of miscarriages occur at the implantation stage. In the past, these early losses probably would have gone unnoticed because they would have looked like a period that was perhaps just slightly heavier or a few days later than normal, says Macklon. Now, early pregnancy tests and the close monitoring of IVF have made us more aware of them.

A developing embryo may send signals that make the uterus more or less receptive

Dr Yorgos Nikas/Science Photo Library

Even if they occur at an early stage, miscarriages are no less distressing, says Bilardi (see “Dealing with loss“). “A lot of people start planning right from the minute they know they’re pregnant: they know their due date, they start planning around that, and start dreaming of becoming a parent,” she says. “When that is taken away, it doesn’t matter how far along you are, it can be a huge source of grief.”

Understanding how the endometrium works as a gatekeeper may also provide an explanation for the small proportion of couples who struggle to have children, says Macklon, either because they can’t get pregnant or they have recurrent miscarriages. He thinks both conditions result from the endometrium sensor being programmed on a slightly wrong setting.

If, for example, the sensor is overly selective, it will block the implantation of all embryos, leading to infertility. In contrast, if it is overly receptive, it will let through embryos with chromosomal abnormalities, potentially resulting in later miscarriage or stillbirth.

If Macklon is correct, this may explain why women who experience recurrent miscarriages paradoxically tend to become pregnant faster than other women. “Recurrent miscarriage is a cruel thing because it makes women feel like serial rejectors of babies,” he says. “When I tell these patients that actually it might be the opposite problem – they’re in fact serial acceptors of babies that nature never intended to make it – they look at themselves differently and often feel an awful lot better.” He says that figuring out why the endometrium sensor is on the wrong setting for these women could lead to new treatments.

Beyond control

Many other factors, including external events beyond a woman’s control, may also influence whether a pregnancy results in a live birth, says Tim Bruckner at the University of California, Irvine. Normally, slightly more male babies are born than female babies. But in the three to five months after traumatic events like the September 11 attacks in New York or the Fukushima Daiichi nuclear disaster in Japan, birth records show that there were fewer male births than usual in affected areas.

Exposure to extremely stressful events in pregnancy may promote the loss of male fetuses because male babies are generally more vulnerable in infancy than female babies. In times of trouble, when this effect is magnified, it may trigger a long-evolved process in a woman’s body to reduce the risk of investing in a male who may not survive, says Bruckner.

There is still a lot we don’t know about the biological mechanisms of the various types of pregnancy loss. But we can surmise that our high miscarriage rate has probably evolved as a way to give us the best chance of having healthy children, says Bruckner. “According to the theory of natural selection, we want to have children that survive infancy and grow up and have children of their own so they can pass on our genes,” he says. “There’s this idea that human reproduction is inefficient because so many pregnancies are lost, but overall it may have led to the preservation of our species.”

As traumatic as my own miscarriage was, it is comforting to learn that it probably wasn’t because of anything I did or anything that was wrong with me. On the contrary, it was most likely due to a random genetic error that I had no control over. Instead of my body failing me, it may have protected me from investing further in a pregnancy that probably wasn’t going to produce a healthy baby.

Bilardi thinks we need more education and public conversation about the true rate and causes of miscarriage so couples aren’t blindsided if it happens to them. “At school, sex education is all about how not to get pregnant. There is nothing to prepare you for what happens if you do want to get pregnant one day,” she says. “It means that when you get to the stage of wanting a family, you often don’t understand how difficult it can be.”

The second time I became pregnant, I felt more prepared for the possibility of something going wrong. I was also very nervous, with every slight abdominal twinge sending me into a panic. But one by one, the nine months ticked by, and I finally delivered my son into the world. Knowing the elaborate vetting process he went through to get here makes me even more appreciative of the fact that, like every other baby, he is truly a miracle.

Dealing with loss

Miscarriages can take a toll on mental health. Research from earlier this year found that one in six women who experience a miscarriage or ectopic pregnancy have symptoms of post-traumatic stress disorder nine months later. One UK study found that 28 per cent of women and 12 per cent of men experience anxiety after losing a pregnancy, which may be due to uncertainty about whether they will eventually be able to have children.

Yet support is lacking. A survey of 300 French women who lost pregnancies found that 78 per cent weren’t given adequate information about the causes of miscarriage and 82 per cent subsequently worried about future pregnancies.

In a study of 22 women in the UK who had miscarriages, one who was sent home without any plans for follow-up care said: “They wouldn’t dream of taking somebody’s appendix out and saying, ‘Bye, we won’t see you again’. ” Similarly, a man surveyed in an Australian study about miscarriage said: “The whole process was really clinical… It was just… ‘Yep that’s it, there’s no heartbeat. Off you go to the next room’. ” No countries offer routine check-ups for couples who have experienced pregnancy loss.

Research suggests that men in particular have a hard time finding a sympathetic ear after a miscarriage. They often feel like they are expected to be the strong, stoic ones and that their grief is less valid than their partner’s.

Lost for words

It can be hard to know what to say to a friend or relative who has a miscarriage, but Jade Bilardi at Monash University in Australia says a simple “sorry about your miscarriage” is better than staying silent for fear of saying something wrong.

She also recommends listening, letting them grieve for as long as they need to, encouraging them to talk to other people who have had miscarriages and offering practical help like dropping off meals.

However, she cautions against offering unhelpful clichés like “It wasn’t meant to be” and unsolicited advice like “it’s because you’ve been working so hard”.

Pregnancy, day by day

A pregnancy lost before 24 weeks is considered a miscarriage by the National Health Service in the UK

DAYS 1-5

MENSTRUATION

The uterus lining (endometrium) is shed because pregnancy didn’t occur in the last menstrual cycle

DAY 6

The endometrium starts regrowing to support pregnancy

DAY 14

OVULATION

The ovary releases an egg into the fallopian tube

CONCEPTION

The egg is fertilised by sperm in the fallopian tube. The resulting embryo begins its journey towards the uterus

DAY 19

IMPLANTATION

The embryo enters the uterus and burrows into the endometrium

DAY 21

Pregnancy detected by blood test

DAY 25

Pregnancy detected by urine test

DAY 29

FIRST MISSED PERIOD

First symptoms like nausea, frequent urination and sore breasts may begin

WEEK 13

Second trimester starts

WEEK 27

Third trimester starts

WEEK 40

Baby delivered

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