dr reji's ovarian reserve testing
TRANSCRIPT
Ovarian Reserve Testing
Dr REJI MOHAN,MD,DNBConsultant in OBS GYN & INFERTILITY
Assistant ProfessorGovt Medical College
Kottayam
05/02/2023 [email protected]
Outline
General factsWhat is ovarian reserve
Why measure ovarian reserve
Measures of ovarian reserve
Uses of ovarian
reserve testsSummary
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General Facts
• Women are very different to men with regard to reproductive ageing.
• A woman’s entire lifetime’s supply of eggs is present at birth and it is limited
• Decreasing 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 couple’s reproductive prospects from age 37 onwards but earlier for some women.
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• 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
woman’s 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 11:61–109
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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 eggs† To identify women who have little or no ovarian reserve† To identify women who may be at risk of potential OHSS
† To plan better induction protocols for success and safety of ART
† To counsel women regarding their reproductive potential
• Yates et al HR 2011
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Accurate/Predictive
Highly sensitive Objective Reproducible with low inter
and intra cycle variability Easily measurable Independent of other
factors Cost-effective
Predictors of ovarian performance
The Ideal Ovarian Reserve Screening Method-IDEAL BIOMARKER
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Ovarian Reserve - Tests• Age, Basal FSH (1988), E2 (1995), FSH/LH (1996)• - Inhibin-B (1989)• AMH (Anti Müllerian Hormone)
Static
• Clomifene citrate test (1987)• GnRHa test (1991) (GAST)• Gn stimulation test (1994) (EFORT)
Dynamic
• Ovarian volume• Antral follicle count(functional biomarkers)• Ovarian doppler exam • Ovarian biopsy
Ultrasonography
Newer-genetic –Single nucleiotide
pleomorphisms for fsh receptors,lh receptors
A 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-Müllerian hormone (AMH).
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Age as a biological marker5 months iu : millionsMenopause: 1000450 ovulatory cycles
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Age as a biological marker
Birth rate and age
Nelson et al Hum Reprod update 2013
Miscarrage rate and age
Nelson et al Hum Reprod update 2013
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Biochemical
FSHBasal (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 ‘Normal’FSH values DOR or failure to conceive
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To summarise• Day 3 FSH is an indirect measure of the
size of follicular cohort• Single elevated FSH value has a very
limited reliability• Large inter cycle variability• Wide range of intercycle variables• Simple 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 2–4 of the menstrual cycle but demonstrates some cycle-to-cycle variability.
• However, an elevated value (greater than 60–80 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.
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INHIBIN B• Inhibin 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 test
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AMH Dimeric glycoprotein exclusively produced by the
granulosa cells of preantral (primary and secondary) and small antral follicles. reflects the pool of remaining follicles in the ovary
Also known as Müllerian-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 Level
Very Low Less than 0.3 ng/ml
Low 0.3 - 0.6 ng/ml
Low Normal Range 0.7 - 0.9 ng/ml
Normal Over 1.0 ng/ml
High (often PCOS) Over 3.0 ng/ml
Results 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]
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Ovarian response based on AMH levels
AMH LEVEL ng/ml RESPONSE
> 1.3 NORMAL
>3.5 HYPER RESPONSE
≤1.26 POOR RESPONSE (≤4 oocytes) sensitivity 97%
<0.1 NO RESPONSE
Gnoth et al 2008.
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• AMH when it decreases it is a sign of• follicular reserve exhaustion. • The hormone exhibits a fairly stable expression• throughout the menstrual cycle although minor
fluctuations may be consistent with continuous non-cyclic growth of small follicles
(La Marca et al., 2004).• Therefore, measurements of its concentration are
highly reproducible (cycle to cycle consistency) (Fanchin et al., 2005).
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AMH Other usesAMH in diagnosis(monitor fertility decline)Pretreatment and post treatment levels chemotheapyPrediction of ovarian function after chemotjerapyIncorporated in Guidelines of childhood cancer treatmntResearch on the best protocol of chemotherapyHuman Reprod 2015
Low inter cycle variabilityLack of standardisation
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DYNAMIC TESTS
• Clomifene citrate test (CCCT,1987)• GnRHa test (1991) (GAST)
• Gn stimulation test (EFFORT,1994)(Exogenous Fsh Ovarian Response Tests)
no additional benefit to basal
FSH
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Biophysical• Antral Follicle count• Ovarian volume• Ovarian blood flow
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Antral Follicular Count• Predicts the quantitative aspect of ovarian
reserve• Typically by a TV US 2D scan during early
follicular phase measuring only follicles 9 mm or less in planes calculating the mean diameter
• < 6 predicts poor response• >16 predicts excessive response• Correlates 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 volume• The 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 .
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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 outcomes
• Antimüllerian 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;98:1407–15
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To sum up• AMH 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 disorders
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• ORT allows
pretreatment patient counseling individualization of stimulation
strategy increased cost effectiveness enhanced safety
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Thanks for being with me & God bless you all Thanks To
All my teachersFamily & well wishers
Queries to;[email protected],
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