Like a Virgin (25 page)

These are the easy obstacles. Humans may have a bigger problem.

A woman, even at peak fertility, needs sperm in order to make a baby. But fertile
Homo sapiens
males may not be with us indefinitely. The male Y chromosome appears to be hurtling down the
evolutionary road towards what, some scientists predict, will be extinction. Our age as a species may be a factor in the future of reproduction as well.

The loss of the Y chromosome would certainly put humans in a complicated position. Over the past three decades, since the birth of Louise Joy Brown, technologies have emerged from the realm of
science fiction into the reality of our hospitals and homes to make reproduction possible where it had previously not been. But can science get round the problems that come with getting older?

Age gradually yet surely strips women of the key factors in being fertile – for instance, having good quality eggs, ovaries that function so that ovulation happens
frequently (and efficiently),
and a healthy womb. Medically speaking, thirty-five is the age at which a woman is branded as an ‘older mother’ in maternity wards,
where even conventional childbirth becomes necessarily more medicalized. Decline seems to begin from the age of thirty, becomes more obvious between ages thirty-five and forty and increases quite
dramatically after that. After thirty-five years of age, even if an egg does become fertilized, the ability of the embryo to implant in the womb decreases by around three percent each year. From
the mid-thirties onwards, women are faced with six threats: declining fertility, miscarriage, genetic defects that accumulate with age, high blood pressure (which if unmanaged is very dangerous),
stillbirth, and, rarely, death of the mother. Forty-one doesn’t sound old, but it officially marks the point at which fertility stops and sterility begins. By forty-five years of age, there
are only one hundred pregnancies for every thousand women having unprotected sex. Even IVF does not escape the age-effect. While a thirty-year-old will have about a thirty percent chance of
becoming pregnant with this method, a forty-four-year-old faces a sliver of a chance: about 0.8 percent.

Yet, within the space of the past few decades, more and more women have chosen to have their first child later in life. In 1970, 11,704 American women had their first child between the ages of
thirty-five and thirty-nine; by 1986 that number had jumped to 44,427, and by 1997 to 88,501. Twenty percent of women give birth to a first child when they are over the age of thirty-five. The
birth rate for women aged forty to forty-five has risen thirty-two percent since 1999, and for women aged forty-five to forty-nine it has more than doubled. In 2008, seventy-one British women aged
fifty or older gave birth for the first time. Many of these women were only able to become pregnant with medical intervention.

A similar story has, of course, unfolded in the US. The
number of childbirths among women over forty almost trebled between 1989 and 2009, from 9336 to 26,976, and the
numbers of first births is even more staggering. In 1970, little more than 2400 women had their first-born child between the ages of forty and forty-four. By 1986, the figure had risen to 4419. In
1997, more than 15,550 women in this cohort gave birth to a first child.

In social terms, having babies later in life is no bad thing. Being able to choose when we have children is now possible because we have access to effective contraceptives, and about half of the
rise in the age at first birth is attributed to a rising level of education. Women with higher levels of education are more likely to postpone having a first child, and so as more women have
finished university or gone on to pursue postgraduate education, or have attained economic independence, the age of first childbirth has gone up. In 2006, fifty-eight percent of all UK higher
education qualifications were awarded to women – just thirty years after the fight to gain admission of women to male-only colleges still lingering at Oxford and Cambridge. It may come as no
surprise, however, that if you look at UK birth data, the map of births late in life follows the contours of social class. There is a higher average rate of forty-something mothers in the wealthier
south of England compared to the poorer north, a pattern that can even be seen on a city level, between inner London and the relatively cheaper outer boroughs. Late motherhood is as much a marker
of the better-off middle classes as a designer handbag. Infertility treatments do not come cheap.

In order to allow women to have children late in life, we have to use medical intervention. That’s because, any time between the
ages of forty and
sixty, most usually around age fifty-two, the majority of women will stop menstruating. After this happens, becoming pregnant naturally is extremely rare – close to zero percent after age
forty-five, even if a woman pumps herself full of hormones to keep her ovaries functioning as they did earlier in life.

As we have seen, a female embryo’s ovaries contain all of the eggs a woman will have in her life. These eggs, immature as they are at this stage, number between four million and seven
million. But by the time a bouncing baby girl is born, she will already only have half as many. During puberty, around age thirteen, she will have on average 400,000 eggs remaining to cover her
lifetime of fertility. If you do the maths quickly, you’ll realize that should be enough to have one egg every month for thirty thousand years. As it happens, only four hundred to five
hundred of this multitude of eggs are released in cycles of ovulation; the rest are unrelentingly destroyed – either literally imploding or dying from neglect if they aren’t in the
right chemical environment. The majority of eggs never actually mature to the point where they can be fertilized.

Starting from the age of thirty-five, a woman’s eggs start committing suicide at an accelerated speed. So while at the age of thirty-eight a woman may have around twenty-five thousand
eggs, by the time she is forty-five she will have closer to five thousand; by her early fifties, she will have only a few hundred left. So regardless of whether a woman becomes pregnant or uses an
oral contraceptive, such as the pill, that stops her eggs from being released, a woman’s supply of eggs is doomed to extinction by then. Importantly, those eggs that linger in the ovaries,
taking their time to die, will stop doing what they are supposed to.

By and large, as we get older, the machinery in most of our cells simply doesn’t work as well; eggs are not the only cells in a woman’s body that go wrong with age, but they tend to
be
particularly affected by the process. This is because of the way in which egg cells develop. Unlike other cells, some of the eggs in a female foetus may have to wait for
fifty years before they are triggered to mature, in readiness for fertilization. While they wait, the chromosomes they contain are lined up in a relatively orderly fashion on what is called a
spindle
, a structure that forms when a cell is dividing to create two (or four) new cells. The spindle helps guide chromosomes into newly created cells, so that their distribution is equal.
Of course, having too many or too few chromosomes can be disastrous for health, so eggs and sperm must only ever contain twenty-three chromosomes or face serious repercussions. While the
egg’s chromosomes sit on this spindle, waiting for half a century for their chance, the DNA they carry may well be degrading. The spindle itself may also become damaged, meaning that the
chromosomes are not divvied up as neatly as they should be when the egg finally divides. This is partly because, with age, there is also a decline in the levels of certain proteins, called
cohesins
, that normally hold chromosomes together by entrapping them in a ring – something that’s essential for chromosomes to split evenly when a cell divides. This is one of
the reasons why older women are more likely to produce abnormal eggs, which increase the risk of infertility, miscarriage, and birth defects, including the chances of having a baby with Down
syndrome.

Down syndrome babies have three full or partial copies (called a
trisomy)
of chromosome 21, rather than the usual two. Though approximately twenty-five percent of all spontaneous
abortions in the first trimester carry chromosome 21 trisomies, the chromosome error alone obviously does not terminate the pregnancy. Indeed, one in every seven hundred babies is born with
chromosome 21 trisomy, and it remains the leading cause of learning difficulties and developmental delays in humans. Women with Down syndrome are sometimes able to
reproduce.
Most men with chromosome 21 trisomy are sterile from birth. Although the exact causes are not known, this infertility may be caused by hormonal deficits, changes to the shape of the gonads, or
problems generating sperm.

Other chromosome trisomies are likely to have devastating effects too. For instance, embryos that have one copy or three copies of chromosomes 1 or 19 end up being miscarried before a woman even
thinks to perform a pregnancy test. Similarly, in nearly all recorded cases of girls who carry XXX instead of XX in their sex chromosome, the extra X has come from the mother, not the father, and
those mothers were usually older than average. Most XXX girls are of normal weight, height, mental function, and fertility, but they tend to experience a very early menopause, around the age of
thirty. Somewhat like taking a too-high dose of a medicine, an extra chromosome translates into a too-high dose of certain genes, and abnormally high dosages are ultimately detrimental to a
child’s health. In this case, the more X chromosomes a girl carries, the more severe her symptoms will be. That’s not to say that sperm cannot carry this chromosomal corruption,
however. There is a significant increase in rogue X chromosomes found in the sperm of older men. A son who carries an extra X chromosome will suffer from Klinefelter syndrome, and will likely have
difficulty producing sperm, to some extent; generally, he will be sterile. The condition affects one in a thousand men.

The eggs may be damaged by the environment of the ovaries themselves, which are no longer a safe haven as a woman ages. For example, oxygen levels, pH balance (whether acidic or basic), and
hormone concentrations are in flux, and each of these in turn can make it more difficult for the eggs to separate the chromosomes from each other normally in pairs. If the chromosomes stay together
rather than splitting apart, then one of the two new cells will have two of the same
chromosomes and the other will have none. As the number of eggs ripening in each cycle
drops in the run-up to the menopause, there is an increase in chromosomal abnormalities within the eggs. In fact, in IVF programmes the vast majority of eggs that come from women who are
thirty-seven years or older have too many or too few chromosomes, as well as mutations in their DNA and in the machinery that controls the way in which this DNA is expressed. For example, ageing
eggs are more prone to producing
hydatidiform moles
, the grossly distorted embryos that result when genes that are normally silent and locked become active, even without the proper
imprinting that tells the DNA what to do. When this happens, the renegade DNA behaves as if it has come from the father rather than the mother, so that the embryo is effectively working with two
sets of paternal genes. All that can come out of this combination is a mass of tissue inside the womb that, as of now, can never develop into a baby.

An ageing woman’s eggs no longer mature in readiness for fertilization, as younger, healthy eggs normally would, when they are exposed to follicle-stimulating hormone, or FSH. As the
menopause approaches, the ovaries stop responding to FSH (they also stop producing oestrogen and progesterone, as we saw earlier). In response, the body produces more and more FSH – ticking
and tocking louder and louder. The interactions between the hypothalamus, the pituitary gland, and the ovary change as well. The seamless orchestration of hormones necessary for successful
fertilization and pregnancy transforms into a cacophony. But it is the eggs and their corrupt chromosomes that are most at fault. When an older woman is implanted with young eggs – even just
the cytoplasm, that cellular soup inside an egg minus its DNA – they become pregnant, despite all of the other changes going on in the body. In fact, older women actually stand a better
chance of becoming pregnant with donated
young eggs than younger women do of conceiving naturally.