Low Ovarian Reserve - What does it really mean?
By Gail F. Whitman-Elia, MD, MPH, HCLD©
Advanced Fertility & Reproductive Endocrinology Institute, LLC
West Columbia, South Carolina
Many centers have come to rely on ovarian reserve testing in order to identify those patients unlikely to
become pregnant prior to initiation of a first IVF treatment cycle. In theory, women unlikely to conceive
can be given the opportunity to avoid the financial disappointment associated with an IVF failure. If a
patient should still choose to use her own oocytes, then appropriate counseling can be given.
Additionally, her treatment schedule can be adjusted in an attempt to optimize the stimulation response
although we currently have no good evidence for the effectiveness of such adjustments.
Establishing a test regimen that defines the best and the worst potential IVF candidates has been a pursuit
of many researchers. Clinical literature is filled with articles addressing this issue. Unfortunately, rather
than helping patients make decisions about their treatment, it appears that pre-treatment ovarian reserve
testing has generated more patient distress than benefit (1). If you personally have had difficulty
understanding what your test results mean you should know that as a professional group IVF practitioners
are also conflicted about what the test results mean and how to appropriately apply them in a given
situation.
What is ovarian reserve?
The goal of any stimulation regimen for IVF is several good quality eggs and a healthy uterine
environment. Ovarian reserve is a theoretical concept. As a practical matter, it refers to the ease at which
an individual’s ovaries can be successfully stimulated with fertility drugs. The single most consistent
variable affecting ovarian reserve is the woman’s age. This is because a woman is born with all the eggs
she will ever have. In most women a majority of the eggs are genetically normal or balanced. However,
there will be some that are genetically abnormal or unbalanced. It appears that the best eggs are ovulated
first. The older a woman is, the fewer genetically balanced eggs she has left to respond to fertility drugs.
This age relationship holds true even in the fertile population. In older women fewer normal embryos are
available for implantation into the uterus. Hence, healthy women over 35 are less fertile than their
younger counterparts. Women 40 and over may have only a 20% live birth rate with IVF treatment using
their own eggs. This is why donor egg therapy has become so popular in this age group.
Unfortunately, there are some young women who respond poorly to attempts at ovarian stimulation.
Perhaps these so called “poor responders” are born with more genetically unbalanced eggs such as in a
Turner’s mosaic syndrome patient or they may have fewer eggs or poor quality eggs because of past
surgical treatment, pelvic infections, cancer treatment, cigarette smoking, ovarian scarring associated with
endometriosis, or unexplained infertility, etc. It is this group of patients that has presented the biggest
challenge to IVF practitioners. Some young woman may have fewer eggs, but are they all of poor quality?
What ovarian reserve tests are commonly used?
There are several clinical markers used to identify the so called “poor responder”. Today the most
commonly used ones in the United States are the basal follicle stimulating hormone (FSH) and the
clomiphene citrate challenge test (CCCT) (2). Measures of inhibin, mullerian inhibiting factor, and a
variety of provocative response tests have been used less frequently (3). More recently, ultrasound has
also been used to anticipate stimulation response (4).
The basal FSH test is a blood test drawn on the second or third day of the menstrual cycle. FSH released
from the pituitary gland stimulates the ovaries to recruit and select eggs so that one will grow and
eventually ovulate. When there are few eggs available the pituitary gland has to send a much stronger
signal so the FSH level will be higher in those circumstances. Most fertility centers have identified an
FSH level above which patients are labeled “poor responders”. Women who fall into the normal range are
believed to be better candidates for IVF. Unfortunately, test results may not be that accurate because it
matters when blood is actually drawn during the menstrual cycle. An estradiol level may be drawn at the
time of the basal FSH to help verify the fact that the patient is having the test drawn on the correct day.
This is because if the estradiol level is elevated, the FSH level will be suppressed. Sometimes women in
early menopause will have elevated day three estradiol levels with suppressed FSH levels giving false
negative results.
The CCCT test was developed as a refinement to the basal FSH test for women 35 years of age or older.
With this test the patient has a basal FSH level drawn on cycle day 3 and another one on day 10,
following the administration of 100 mg clomiphene citrate on cycle days 5 through 9. The test is
interpreted by comparing the basal to stimulated levels of the test results. Those women who demonstrate
an exaggerated FSH release after clomiphene stimulation are said to have failed the test. Some women
with normal basal FSH levels will be identified as poor responders when they are given the CCCT test.
Unfortunately, as more individuals are assigned the “poor responder” label, more normal patients are
inaccurately assigned to the abnormal group.
Ultrasound screening for ovarian volume and antral follicle count is a promising approach. With this
technology patients are assigned to an anticipated ovarian response group based on follicle number.
Clinically, women with very low numbers will have very few eggs at oocyte retrieval. Those patients with
adequate follicle numbers may have a reasonable quantity of oocytes at retrieval despite abnormal pretreatment
blood test results.
What does an abnormal result mean?
A true “poor responder” will have a lower chance of conception and live birth compared to members of
the normal responder group regardless of the age. The problem lies in assigning patients to the wrong
response group on the basis of pre-treatment testing alone.
What do I do if I have an abnormal result?
First, try to establish how important having a child with your own DNA is to you and your partner. Seeing
a mental health provider familiar with assisted reproduction can be helpful. Remember that oocyte donor
therapy is a wonderful option associated with high success rates. You can still have a baby with your
partner’s DNA long as your uterus is receptive.
If you decide that you would like to attempt fertility treatment using your own oocytes despite a lower
chance for success, make sure that your doctor is fully onboard with this approach and that you are
financially and psychologically able to handle the stress of, perhaps, several failed treatment attempts. Get
a second opinion if you have any lingering questions. Be aggressive. Continual pursuit of insemination
cycles is costly and such an approach does not address fertilization issues. A properly planned IVF cycle
can lead to answers and may help a couple with the closure process. And, there will be some patients who
actually take home miracles when given the opportunity for a treatment cycle despite dismal treatment
pre-screening test results.
Conclusion
A young patient with few oocytes may still have one or two eggs capable of resulting in a live-birth.
Ovarian reserve testing identifies patients that have a lower probability of conceiving. Such tests address
averages and not individuals. I will personally never forget one patient who at 33 years of age failed her
clomid challenge test and several IVF stimulation attempts. She subsequently delivered a term infant by
spontaneous conception two years after the delivery of donor egg twins. When making the choice to move
on to donor eggs or adoption be sure that you have explored all available treatment options to your
satisfaction.
References
- Mol et al (2006) Value of ovarian reserve testing before IVF: a clinical decision analysis.
Hum Reprod vol. 21, 1816-1823.
- Scott RT (1996) Evaluation and Treatment of Low Responders. Seminars in
Reproductive Endocrinology, 317-335.
- Kwee et al (2006) The clomiphene citrate challenge test versus the exogenous folliclestimulating
hormone ovarian reserve test as a single test for identification of low
responders and hyperresponders to in vitro fertilization. Fertil Steril vol. 85, 1714-1722.
- Hendriks et al (2007) Ultrasonography as a tool for the prediction of outcome in IVF
patients: a comparative meta-analysis of ovarian volume and antral follicle count. Fert
Steril vol 87, 764-775.
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