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Success rates
for many infertility treatments, particularly for
IVF, appear increasingly to be age dependent.
The ovary seems to be the key. Over time, the
number of egg-producing follicles in the ovary goes
down. This change varies strikingly from one
individual to the next. The current trend in
infertility treatment is to determine which women
are already experiencing biologic aging of ovaries
and their eggs. Diminished ovarian reserve is
the depletion of the total number of eggs and the
loss of quality of those that remain. Lab
tests can help identify the couples who have a
lower chance of success with regular IVF or
ovulation induction, and who might need to consider
other options. Assessing diminished ovarian
reserve can also help identify those patients at
higher risk for miscarriage, since miscarriage
rates increase with age.
USING AGE AS A
GUIDELINE
As a woman ages,
her ovaries age and she eventually loses the
ability to have a normal ovulation. At birth,
the human female has the maximum number of
eggs. The number declines until the supply is
exhausted at menopause. With fewer eggs, the
ovaries respond less well to signals from the
pituitary gland in the brain, which regulates the
hormones of the menstrual cycle. So ovulation
problems become more common in women in their
thirties and forties.
Findings from
studies on insemination with donor sperm show a
direct association between the age of the woman and
the ability to become pregnant. Pregnancy
rates for women of apparently normal fertility who
receive artificial insemination with donor sperm
are highest for women under 30 and drop for women
over 35.
Shortening of
menstrual cycles may also signal diminished ovarian
reserve. It is not a good sign for a woman's
fertility if cycles that were once 27 to 28 days
shorten to 23 or 24 days. It is thought that
with age the eggs become a bit deaf to hormonal
signals from the pituitary gland. As a
result, the pituitary gland starts sending signals
earlier, which causes faster egg development and
shorter cycles.
An interesting
twist is that chronological age does not always
equal biological age. The fertility problems
of some women in their 30s are similar to those of
other women in their 40s. Two women with
apparently normal cycles can have very different
levels of ovarian reserves. The process
starts earlier for some, and such differences are
not apparent from how youthful or healthy a woman
looks.
BLOOD TESTS TO MEASURE
OVARIAN RESERVE
Fortunately,
accurate tests now exist that can predict quite
successfully the aging of the ovaries. What's
more, the tests are simple and relatively
inexpensive. Diminished ovarian reserve was
originally thought to be a problem only in women
over 40, but it is now understood be an issue for
some women in their 30s. For these women, the
success rates with most infertility treatments are
going to be lower. Most programs these days
require women over 40, or, in some cases, women in
their 30s to have lab studies done to try to assess
levels of ovarian reserve.
So-called day 3
studies involve measuring FSH and estrogen
levels (estradiol level) on the third day of the
menstrual cycle. A blood test on day 3 of the
menstrual cycle is taken in order to measure the
level of follicle stimulating hormone (FSH), which
is one of the gonadotropic hormones produced by the
pituitary gland. FSH, together with LH,
controls estrogen production from the ovaries.
Estradiol, which is also measured, is the
main estrogen produced by the ovaries in the
process of ovulation.
A result that shows
an elevated FSH means the pituitary gland is
sending a frenzy of signals to the ovaries to get
them to function, but that the ovaries in turn are
not responding well. A normal FSH but high
estrogen level on day 3 is also no promising.
This paradoxical finding suggests that the
estrogen level is too high early in the cycle,
which in turn suppresses the FSH. It is
generally agreed that FSH levels of higher than 12
mIU/mL on day 3 or estrogen level s of higher than
50 to 60 pg/mL indicate at least some evidence of
diminished ovarian reserve.
Another test for
diminished ovarian reserve is the clomiphene
challenge test. Some experts believe
that it may predict even more precisely which women
have low ovarian reserves. It is relatively
new and is not used by all programs. A blood
test to measure the level of FSH is done on day 3,
then the patient is given clomiphene for five days,
then on day 10 the FSH level is measured
again. A number of studies have shown that an
elevated FSH level on day 3 or on day 10 of this
clomiphene-challenge-test cycle indicates
diminished ovarian reserve.
CAREFUL USE OF
RESOURCES
Ultimately, test to
assess ovarian reserve cannot identify which
couples will and which will not get pregnant.
But these tests can help couples make informed
choices and can help steer those with significantly
diminished ovarian reserves to the most
cost-effective options, such as donor egg
IVF.
The research on
donor egg IVF has helped clarify that the decline
of fertility with age is largely due to the
ovary. Pregnancy rates have been consistently
high for this type of IVF, where women in their
forties have successful pregnancies that come from
eggs donated by young, healthy women in their
20s. In donor egg IVF, the husband's sperm
are used to fertilize eggs from a donor; the early
embryos that result are then transferred to the
wife's uterus. Donor egg IVF is being used in
many cases for women in their 40s, who otherwise
have a low chance of achieving a pregnancy with
IVF.
The expense of
infertility treatment is relative. For
couples who succeed, the cost of this care is part
of a substantial investment in parenthood.
For those who fail, it is money spent for no
gain. Everyone undertaking IVF would like to
know what the chances of success are. Day 3
studies and tests such as the clomiphene challenge
test are not a crystal ball, but they may help
guide the planning of infertility
treatment.
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