Ovarian Reserve Testing
Ovarian Reserve TestingDr REJI MOHAN,MD,DNBConsultant in OBS GYN
& INFERTILITYAssistant ProfessorGovt Medical
CollegeKottayam
Outline 3/9/[email protected]
General Facts
Women are very different to men with regard to reproductive
ageing.A womans entire lifetimes supply of eggs is present at birth
and it is limitedDecreasing ovarian reserve is inevitable with
increasing age, resulting in complete infertility by age
40-50.Decreasing ovarian reserve has a significant negative effect
on a couples reproductive prospects from age 37 onwards but earlier
for some women. 3/9/[email protected]
Folliculogenesis is a complex developmental process involving
cell proliferation and differentiation in response to
gonadotropins.At any time there is a heterogeneous population of
follicles at differentdevelopmental stages within the ovaries.
These stages include resting primordial follicles, preantral and
early antral follicles (0.2-2.0mm) which are in most instances
gonadotropin-independent, small antral follicles (1-5mm) that are
gonadotropin-responsive, and larger antral follicles (> 5mm)
which aregonadotropin-dependent.The human ovary obtains a maximum
of primordial follicles at 5 months of gestational age. Thereafter,
the number decreases in a biexponential fashion until
menopause.
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Testing is indicated in
Before ART esp women above 30Women with a history of exposure to
a confirmed gonadotoxin, i.e., tobacco smoke, chemotherapy,
radiation therapy.Women with a strong family history of early
menopause or premature ovarian failure.Women who have had extensive
ovarian surgery, i.e., cystectomy and unilateral oophorectomy.
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Ovarian reserve The concept of ovarian reserve defines a womans
reproductive potential as a function of the number and quality of
her remaining oocytes in an attempt to predict reproductive
potential
Ovarian Reserve = quantity and quality of the ovarian
follicle/oocyte pool
Wood JW 1989 Fecundity and natural fertility in humans. Oxf Rev
Reprod Biol 11:61109
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Why is prediction of ovarian reserve important in clinical
practice?To identify who have sufficient ovarian reserve to make
IVF using their own eggsTo identify women who have little or no
ovarian reserveTo identify women who may be at risk of potential
OHSSTo plan better induction protocols for success and safety of
ARTTo counsel women regarding their reproductive potential
Yates et al HR 2011 3/9/[email protected]
Accurate/Predictive Highly sensitive Objective Reproducible with
low inter and intra cycle variability Easily measurable Independent
of other factors Cost-effectivePredictors of ovarian performanceThe
Ideal Ovarian Reserve Screening Method-IDEAL BIOMARKER
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Ovarian Reserve - TestsA normal ovarian reserve results in the
development of 8 to 10 follicles and the retrieval of a
corresponding number of healthy oocytes under exogenous
gonadotropin stimulation giving an optimal livebirth rate
(Fasoultotis et al., 2000).
The most promising tests to date include ultrasound assessment
for antral follicle count (AFC) and the biochemical marker, i.e.
the anti-Mllerian hormone (AMH). 3/9/[email protected]
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Age as a biological marker
5 months iu : millionsMenopause: 1000450 ovulatory cycles
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Age as a biological marker
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Birth rate and age
Nelson et al Hum Reprod update 2013
Miscarrage rate and age
Nelson et al Hum Reprod update 2013
BiochemicalFSHBasal (days 2-3) serum FSH levels increase with
aging Indirect biomarker of ovarian reserveInfluenced by Inhibin B
and EstradiolFSH assays are well standardized* but.. High Inter-
and Intra-cycle Variability (Low Reliability)High number of false
negatives ie NormalFSH values DOR or failure to conceive
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To summariseDay 3 FSH is an indirect measure of the size of
follicular cohortSingle elevated FSH value has a very limited
reliabilityLarge inter cycle variabilityWide range of intercycle
variablesSimple to perform but definitely has limitatations
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ESTRADIOL Elevated levels may predict poor response even when
the basal FSH is normal The estradiol level is usually low (less
than 50 pg/mL) on days 24 of the menstrual cycle but demonstrates
some cycle-to-cycle variability. However, an elevated value
(greater than 6080 pg/mL) in the early follicular phase can
indicate reproductive aging and hastened oocyte development..
When interpreted it should be along with basal FSH of the same
cycle.3/9/[email protected]
INHIBIN BInhibin B is a glycoprotein hormone that is secreted
primarily by preantral and antral follicles. The serum
concentration of inhibin B decreases with the age-related decrease
in the number of oocytes. There is significant variability in
inhibin B levels between menstrual cycles. This marker does not
reliably predict a poor response to ovarian stimulation and, thus,
is not a recommended test3/9/[email protected]
AMHDimeric glycoprotein exclusively produced by the granulosa
cells of preantral (primary and secondary) and small antral
follicles. reflects the pool of remaining follicles in the
ovaryAlso known as Mllerian-inhibiting substance (MIS) The first
mention is dated to 1940, A. Jost It is also formed in females in
ovaries from the 36th week of gestation. NOT formed in
FSH-dependent (antral) follicles and also in atretic follicles.
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AMH Blood LevelResults are calculated in ng/mL. To convert to SI
units (International System of Units):The respective converting
factor is [pmol/l] = 7.14 x
[ng/ml]3/9/[email protected]
Ovarian response based on AMH levelsAMH LEVEL ng/mlRESPONSE>
1.3NORMAL>3.5 HYPER RESPONSE1.26 POOR RESPONSE (4 oocytes)
sensitivity 97%16 predicts excessive responseCorrelates with
response to Gns stimulation no of oocytes retrieved and more
recently shown to be a predictor of live birth in IVF cycle.
Mazeela et al 2009
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Basal ovarian volumeThe calculation of ovarian volume requires
ovarian measurements in three planes and the use of the formula for
the volume of an ellipsoid: D1 D2 D3 0.52. Mean ovarian volume, the
average volume calculated for both ovaries from the same
individual, is the value used to assess ovarian reserve. Ovarian
volume correlates with ovarian response to stimulation, it does not
predict failure to conceive When screening for diminished ovarian
reserve with imaging, ovarian volume has limited value compared
with antral follicle count .3/9/[email protected]
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Basal ovarian volume and blood volume
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Combined Ovarian Reserve Tests Because no single assessment of
ovarian reserve has 100% sensitivity and specificity, tests often
are combined in an attempt to improve the prediction of poor
outcomesAntimllerian hormone and antral follicle count are the most
accurate predictors. Because of the heterogeneity of the tests and
cutpoints used in research studies, models of combined ovarian
reserve tests do not significantly improve the ability to predict
poor reproductive outcomes over single ovarian reserve tests
Complicate and increase the expense of screening. Further research
is needed to determine an optimal combination of tests. Fertil
Steril 2012;98:1407153/9/[email protected]
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To sum upAMH is follicle gatekeeper. AMH and AFC are the best
markers of ovarian reserve, age is the best marker for oocyte
quality.
AMH may be used in assessing ferility preservation ,
chemotherapy ovarian surgery. AMH may be used as a biomarker in
diagnosis of endocrine disorders autoimmune
disorders3/9/[email protected]
ORT allowspretreatment patient counseling individualization of
stimulation strategy increased cost effectiveness enhanced
safety3/9/[email protected]
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