Decreased ovarian reserve indicates that there is a significant
reduction in the amount of eggs that are able to mature in the
ovaries. A "significant" reduction in ovarian reserve
can be defined as one which results in a reduced fertility rate.
Woman with a regular menstrual cycle still have some residual
number of eggs that will mature. One important question is "what
test results for ovarian reserve suggest a reduction in fertility?"
Tests available to determine ovarian reserve include
- * the cycle day 3 FSH concentration,
- * the cycle day 3 estradiol concentration, and
- * the clomiphene citrate challenge test.
The "cycle day 3 FSH" blood levels can be drawn anytime
of the day on cycle day 2, 3 or 4, with the first day of a full
flow being cycle day 1. Research suggests that the difference
in FSH concentration between cycle day 2, 3, and 4 is small so
that the patient can have a sample drawn on the most convenient
of these days. The study demonstrating this used only a small
number of women (20 women under 40 years of age) and reports a
less than 20% coefficient of variation between FSH values determined
for the same women over the course of these days. A second study
from another infertility center confirmed these findings.
Multiple reports since 1989 have correlated the cycle day 3 FSH
concentration to pregnancy rates (usually at the time of In Vitro
Fertilization). IVF success (pregnancy rate) is reported to be
independently associated with both the woman's age and the cycle
day 3 FSH concentration. In other words, both are important. The
early classic studies from the Jones Institute in Norfolk, Virginia
revealed a 17% success rate per IVF cycle (very high at that time)
when the cycle day 3 FSH concentration was less than 15 IU/L,
9% when 15-25 IU/L and 4% when greater than 25 IU/L. Generally,
a cycle day 3 FSH level of less than 15 IU/L (using the Leeco
assay, see next paragraph) is considered reassuring.
The cycle day 3 FSH concentration depends on the assay used to
determine its value. In the USA there are several different assays
with 2 different assay systems in common use (Leeco and Becton
Dickenson). These assays use different standard solutions for
the test, and therefore give different results for the same samples.
When compared head to head in one preliminary report, the Leeco
assay yielded values 2.4-2.5 fold higher than the Becton Dickenson
assay at three different points (concentrations) along the standard
curve in the range expected for reproductive age women. Therefore,
a value of 25 IU/L on the Leeco assay correlates roughly to 10
IU/L on the Becton Dickenson assay. This has led to confusion
and occasionally misinterpretation of results. The system used
in the early studies on cycle day 3 FSH concentrations is the
Leeco assay and has a normal range of 5-20 IU/L. The Becton Dickenson
assay has a normal range of 1.5-6.3 IU/L.
Recently (1995), the "cycle day 3 estradiol" concentration
was reported to predict the pregnancy rate at IVF. As with most
hormonal assays, knowledge of the assay used is critical since
the available estradiol assays are varied and appear to give different
values for the same samples. The physician must become familiar
with the assay that (s)he uses to establish clinically relevant
cutoff values. The report introducing estradiol as a useful parameter
in assessing ovarian reserve (from one of the most successful
IVF centers in the USA) found no pregnancies in women undergoing
IVF if the "estradiol concentration on their assay was greater
than 75 pg/ml" or if "the FSH was greater than 17 IU/L
and the estradiol was greater than 45 pg/ml" in 600 IVF cycles.
Since the estradiol assay used in this study was established in
their own hospital the comparison to other assays may show significant
differences. Once standard data within a lab system is established
the estradiol level may be a predictable and valuable parameter
helping to predict fertility treatment outcome and ovarian reserve.
The clomiphene citrate challenge test uses this fertility medication
(100 mg per day for cycle day 5 to 9) to provoke an ovarian response.
The test usually involves checking hormone levels (such as FSH,
estradiol, progesterone) on cycle day 3 and again on cycle day
10. Most often, the FSH response to the clomiphene citrate is
used to determine ovarian reserve. In several reports from a diverse
number of infertility centers, an abnormal FSH concentration on
cycle day 3 or 10 heralds a poor success in ovarian response to
fertility medication and lower fertility rates. The FSH concentrations
that should be used for cutoff values are not well standardized,
with some large groups using 10 IU/L on the Becton Dickenson assay
(equivalent to roughly 25 IU/L on the Leeco assay). Progesterone
has also been proposed as another predictive variable in the clomiphene
citrate challenge test. One report on this challenge test demonstrated
no pregnancies in women whose progesterone concentration was greater
than 1.1 ng/ml on cycle day 10 compared to a 19% pregnancy rate
if the progesterone concentration was less than 0.9 ng/ml on this
day. It seems that these findings remain to be confirmed and standardization
must still be established for this test to gain widespread acceptance.
A decreased ovarian reserve suggests a poor prognosis in terms
of fertility. If a woman with a decreased reserve is very committed
to persuing fertility using her own eggs, a frank discussion with
an experienced infertility specialist should focus on the likelihood
of success given the findings from her ovarian reserve evaluation.
Age and the reason for the ovarian dysfunction should be considered.
Donor egg programs are becoming increasingly available and are
an alternative that some women might want to consider if their
own ovarian reserve is very low. The fertility rate is roughly
predicted by the donor's age, and the recipient carries the pregnancy
from the time of embryo transfer (prior to implantation). An experienced
donor egg program will most likely have the type of support and
counseling often found helpful in this situation.
The in vitro maturation of immature eggs, that is the possibility
of harvesting immature eggs from the ovaries and maturing these
eggs to the point of becoming fertilization capable in culture
(in vitro) has been the subject of a great deal of recent discussion
and research. Although there have been a few pregnancies that
have carried to term with this technique (in 1997 I believe there
have been only 3 liveborn deliveries from this technique in the
world literature), the technique is still in its infancy. Once
the "bugs have been worked out" of this technique, the
in vitro culturing of immature eggs will most likely revolutionize
IVF. It is possible that at that stage, infertility specialists
will also be able to select the few best eggs from thousands of
eggs matured in culture from ovaries with decreased ovarian reserve
and improve the fertility of these couples.
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