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Ovarian Reserve Testing
Ovarian Reserve TestingDr REJI MOHAN,MD,DNBConsultant in OBS GYN & INFERTILITYAssistant ProfessorGovt Medical CollegeKottayam
Outline 3/9/[email protected]
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.
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.
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
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
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]
Age as a biological marker
5 months iu : millionsMenopause: 1000450 ovulatory cycles
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
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
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
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.
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
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]
Basal ovarian volume and blood volume
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]
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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