636 Raymond, Suite 303, Naperville, IL 60563, (312)
440-5055
The
largest number of births ever in the United States
occurred in the post World War II "baby boom"
between 1947 and 1965. Women born during this time
period have reached the age of 35 starting in 1982
and will continue until the end of the century. During
this time period, there is an unprecedented number
of women in their late child bearing years.
In
addition, many women have decided for various reasons
to delay childbearing. This is a significant change
from the patterns of our parents' generation, and
means that more couples will be seeking pregnancy
after the age of 35. Furthermore, these couples also
have a desire to complete their families in a shorter
period of time.
Although there is still some disagreement over the
issue, most fertility experts now agree that fertility
decreases with age. There are several pieces of
evidence that point to this fact. Some of the most
interesting studies involve a religious group known
as the Hutterites. The Hutterites migrated to the
U.S. from Switzerland in the 1870s and now live in
the Dakotas, Montana, and parts of Canada. They are
believers in large families and condemn the use of
any form of contraception. They also marry only within
their own group and since they live in a set geographic
area, are relatively easy to investigate. For these
reasons, they make ideal candidates to study the effects
of aging on reproduction. It was thus found that the
fertility rate (the number of women achieving a pregnancy
per 100 women) is much higher in younger women (twenties)
than in older women (forties). After a pregnancy is
delivered, it is the Hutterites' practice to immediately
attempt to achieve pregnancy again. However, it was
noted that the time between pregnancies became increasingly
longer with increasing age of the women studied. The
average age at the time of the last pregnancy was
40.9.
Other
data also supports the notion that fertility decreases
with age. Compared with younger women, women over
the age of 35 seek evaluation for infertility twice
as often. Some investigators have suggested that this
decline is due to a decreased frequency of intercourse
in "older couples". For this reason, investigators
in France studied the fertility rate amongst women
who were attempting to become pregnant in a donor
insemination program because their own partners had
no sperm. In this way, the frequency of intercourse
did not interfere with calculations of fertility.
As expected, the fertility rate dropped significantly
after the age of 30 and again after the age of 35.
Another similar study suggested that the probability
of having a baby decreased 3.5% per year after the
age of 30.
In addition to the lower chance of becoming pregnant,
as women age they also have a higher chance of losing
the pregnancy (miscarriage). What are the reasons
for this? To explain, it is necessary to discuss some
aspects of genetics.
We
basically all start out when our father's sperm fertilizes
our mother's egg. We therefore have the characteristics
of both our parents. These characteristics are coded
in a special way and are found in the structures known
as chromosomes. In fact, the information found on
these chromosomes contains all the information about
every part of us.
The
sperm and egg each contain 1/2 of the chromosomes
necessary to make a complete human being. In fact,
to describe it in lay terms, the process of making
sperm and eggs is nothing more than the packaging
of different combinations of chromosomes so that they
can be "mixed" together with another egg
or sperm to make different varieties of humans.
Women are born with all the eggs that they will ever
have in their lives (with the chromosomes inside).
Men, on the other hand, make fresh sperm continuously
throughout their whole lives. It takes approximately
90 days for a sperm to be made and to reach maturity.
This is an extremely important difference between
the sexes because, for example, if a 35 year old man
and a 35 year old women attempt to achieve a pregnancy,
they are basically trying to combine a 35 year old
egg with a 3 month old sperm.
The
longer an egg sits around in the ovary, however, the
more likely it is to develop abnormalities in its
chromosomes. If an egg with abnormal chromosomes is
fertilized, then the chances are greater that the
resulting pregnancy will end in miscarriage. In fact,
chromosomal abnormality is the single most common
cause of miscarriage. From many studies, we know that
at least 1/2 of all miscarriages are due to abnormal
chromosomes. A young women (in her 20s), therefore,
has only a 12-15% chance of having a miscarriage each
time she becomes pregnant. A women in her 40s has,
however, a 50% risk of miscarriage.
Not every pregnancy in which the embryo has abnormal
chromosomes will end in a miscarriage. Some will continue
to develop and even result in the birth of a live
baby. These babies, however, can have varying problems,
including birth defects and mental retardation. Down's
syndrome is the most common problem of this type but
there are others. There is a progressive increase
in the risk as age increases. This is all as a result
of aging of the eggs.
Up until recently, it was not known why fertility
decreases with age. One thing was known for sure and
that was that the age of the male partner didn't seem
to matter much. Even men in their 70s still seemed
to be able to produce pregnancies. The Bible carries
stories of men in their 90s fathering children. In
women however, the likelihood a pregnancy after age
45 is an extremely rare event.
The
next question to answer was, why? Research has focused
on two areas: aging of the uterus versus aging of
the eggs. Until recently there was no way to separate
these factors out. However, the technology of egg
donation has enabled to look at these factors separately.
Egg donation is the process whereby eggs from a young
woman can be fertilized and placed into the uterus
of an older woman. If fertility decreases because
an older woman's uterus is less capable of carrying
a pregnancy, then using younger eggs shouldn't produce
very many pregnancies in older women.
What we found, of course, was exactly the opposite.
If you use younger eggs, the rate of achieving pregnancies
in older women is very high. In fact, egg donation
gives the highest rate of pregnancy that is achievable
with any type of fertility treatment! Women in their
forties, fifties, and even sixties can all achieve
very high pregnancy rates with egg donation. This
is excellent proof that fertility decreases with age
due to aging of the eggs and chromosomes. Studies
that have removed eggs from the ovaries of older women
have shown that a large percentage of them have abnormal
chromosomes. So there is probably a continuum of possible
outcomes in chromosomally abnormal eggs. Most probably
won't fertilize, of those that due many will be lost
to miscarriage, the few that remain will end up as
a Down's Syndrome or a related problem.
Every human being is different. Not all women will
develop abnormalities in their eggs chromosomes at
the same age. And if course, even if a women has a
majority of her eggs that contain abnormal chromosomes,
it only takes one to achieve that "normal pregnancy".
The great majority of women will not be able to become
pregnant at age 46. On the other hand, some younger
women can have a more rapid decline in the ability
of their eggs to produce a pregnancy.
The most important test we currently have to determine
a woman's "ovarian reserve",
that is, the capability of her eggs being able to
produce a pregnancy, is a blood test called FSH. FSH
stands for Follicle Stimulating Hormone. FSH is made
in a gland near the brain gland called the pituitary.
It is the KEY hormone responsible for the cyclic development
of eggs every month. As a woman's eggs become less
capable of producing a pregnancy, the levels of FSH
begin to rise. Therefore, as you might expect, FSH
generally increases in women as they get older. Women
who have gone through menopause have very high levels
of FSH (and are incapable of becoming pregnant with
their own eggs). However, young women who have had
an accelerated decline in the quality of their eggs
can also have high FSH levels.
In
order to determine a woman's FSH levels for the purpose
of predicting fertility, the blood should be drawn
on the third day of the menstrual cycle. At my laboratory,
a normal level for FSH on day 3 is less than 10 IU.
Women with levels between 10 and 15 are considered
elevated but have been able to achieve pregnancies
with us. Women with levels over 15, even sporadically,
have an extremely poor chance for pregnancy.
Now
to add little more complexity. Day 3
FSH levels can vary from month to month and can
be affected by such things as estrogen levels. In
other words, a high FSH level one month doesn't necessarily
mean it will be elevated every month. There is evidence
accumulating that, if a woman has levels of FSH that
fluctuate greatly, she may have a better chance of
achieving a pregnancy in a month when her FSH is lower
than in a month when it is very high (though her chance
will probably never be as good as in a woman who never
has high FSH levels).
Unfortunately,
there are no treatments available which can "turn
back the clock" on a woman's ovaries. Many physicians
use fertility medications to try to increase the chance
of pregnancy. For this indication, the idea behind
using fertility medications is to increase the number
of eggs that develop in a given month, thus enhancing
the chance that at least one of them might be able
to be fertilized and develop into a viable pregnancy.
This seems to result in some improvement in results,
but the pregnancy rates are not as good as in younger
women. Also, many women don't respond well to fertility
medications as they get older.
Others
have advocated in-vitro fertilization
(IVF) as a means to achieve pregnancy in such
cases. Unfortunately, the pregnancy rates with IVF
in women over the age 40 are still very low. The most
exciting innovation is the use of preimplantation
genetic diagnosis (PGD) to discover embryos with
an abnormal number of chromosomes so that normal embryos
can by replaced during IVF. Some evidence indicates
that if we are able to replace normal embryos in the
uterus, that the chance for pregnancy may be doubled.
Currently,
the only consistently successful method to improve
pregnancy rates in women with age related infertility
is egg donation. As compared to pregnancy rates of
less than 10% per cycle for women over the age of
forty, egg donation results in pregnancy rates of
over 50% per cycle. In addition, the risks of miscarriage
and Down's Syndrome are dramatically reduced. Thus
the likelihood of "taking home a baby" are
very much higher.
Fertility
decreases with age. This decrease is most likely due
to aging of the eggs and the chromosomes inside them.
The risk of miscarriage and chromosomal abnormalities
in babies also increase with age. The most successful
method for achieving a pregnancy and taking home a
baby at advanced female age is with the use of egg
donation.
