leads many women to ask probing questions about their own
fertility. These questions vary in their specifics, but in a general
sense can be boiled down to the desire to know how much time
a woman has left to start a family.
To help address this question, our research is focusing on
the factors that determine how many eggs are stored in the
ovaries and the relationship between that number and the
length of the fertile window. We have even taken this basic
question a step further by using specially modified mouse models
to investigate the possibility that fertility can be prolonged by
increasing the number of available eggs.
At present a crystal ball allowing us to peer into our future
fertility does not exist. Most people are familiar with the concept
that fertility declines with age. Even so, many are lulled into a
false sense of security by frequent reports of celebrities in their
forties conceiving and bearing children with apparent ease.
Some women are taken by surprise upon discovering that
conceiving and having a healthy child may be challenging or
perhaps impossible for them in their late thirties. Many believe
that fertility treatments will enable them to have a child, no
matter what their age.However, it is not always so straightforward. If no eggs are
left in the ovary, then no amount of IVF will produce a baby.
Even if eggs remain in the ovary, their quality may be insuffi-
cient to support a healthy pregnancy. In these cases, a short-
fall in the egg supply chain means the demand for motherhood
cannot be easily accommodated. Clearly, the decision to delay
childbearing is not without its risks.
Being able to precisely predict future fertility would obviously
be of enormous benefit to women, enabling them to better plan
their futures and make informed reproductive choices. However,
predicting future fertility is challenging. This is because repro-
ductive lifespan is intimately linked to the quantity and quality of
eggs stored in a female’s ovaries, and egg quantity and quality are
influenced by a plethora of genetic and environmental factors.
A baby girl is born with a finite number of eggs stored in
her ovaries, which we call the ovarian reserve, and it is not
possible to make new eggs after birth. The implications of this
biological limitation are twofold:- the ovaries must be endowed with enough healthy eggs at
birth to sustain fertility for a sufficient period of time to
allow for reproduction; and- an egg ovulated by a women in her forties was actually made
before she was even born and has been sitting dormant in her
ovaries ever since.
Over time, for reasons we only partially understand, the eggs
lose quality, which we define as their capacity to generate a
healthy baby following fertilisation. Additionally, the quan-
tity of available eggs gradually decreases with each passing year,
through natural cell death or ovulation.
Consequently, when the supply is used up, or only low-
quality eggs remain, pregnancy may no longer be possible. Under
these circumstances, the only option for pregnancy is to “borrow”
an egg from a younger woman.
We know that the number of eggs established in the ovaries
at birth combined with the rate at which that number declines
throughout life impacts greatly on the duration of fertility.
However, both of these factors vary considerably between indi-
viduals because the initial number of eggs found in the ovary at
birth and the subsequent rate of depletion are influenced by
many things.
One of the known variables involves the massive loss of eggs
that occurs as part of normal ovarian development. It surprises
many women to learn that, for largely unknown reasons, approx-
imately two-thirds of the eggs made in the developing foetal
ovary are destroyed before birth, never having the chance to
develop further and ovulate. Differences in the rate of egg loss
during this time likely contributes to the vastly different number
of eggs found in individuals at birth, and is likely to be pre de-
termined to some degree by genetics.
Furthermore, the rate of loss before and after birth can be
influenced by a plethora of external factors. Exposure to ciga-
rette smoke and other environmental toxicants, as well as anti-
cancer treatments, all hasten depletion of the ovarian reserve.
However, determining to what extent an individual’s egg supply
may be depleted by these factors is not yet possible.
On the other hand, claims that women in their forties can
conceive easily if they maintain a healthy lifestyle should be
regarded with caution. While a healthy lifestyle is important for
a healthy pregnancy, there is currently scant evidence that
healthy eating and fitness will slow the natural loss of eggs,
improve the quality of an old egg or prolong fertility beyond its
natural duration.
The nuances of the relationship between egg number and
length of the fertile lifespan are unclear. At this point there is
no formula that can be applied to enable us to say to a woman:
“You have xnumber of eggs, which means you have ytime left
to start a family”. Moreover, we cannot accurately measure the
number of eggs that a woman has without removing her ovaries.
Available ovarian reserve tests, such as serum levels of anti-
Mullerian hormone, may provide reassurance about a woman’s
current ovarian reserve and fertility status, but such tests cannot
- an egg ovulated by a women in her forties was actually made
18 | JAN/FEB 2016
... elimination of PUMA prevents
the natural loss of eggs in the
developing embryo, and
consequently females are born with
twice as many eggs as normal.