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Dr. Azmi Saleh AbdrboFRCOG
El-Amal IVF Center
Ovarian reserve
Ovarian reserve
Population of nongrowing follicle wthin ovary: acyclic ovarian activity(primordial follicles)
Population of small gorwing follicles responsive to FSH
(Ovulatory potential) Quantity and quality of primordial follicle
at a given age. Indirect measure of future fertility,onset of
menopause
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Ovarian reserve
Ovarian reserve
Plan fertility preservation Fertility outcome Response to ovarian stimulation Predict pregnancy rate Monitor fertility decline Fertility after chemotherapy and cancer
treatment
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Ovarian reserve AMH
D.Diagnosis of PCO ,amenorrhea Family planning :ovarian reserve screening Ovarian surgery Granulosa cell tumors Menopause and POI
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Ovarian reserve
5 months iu : millionsMenopause: 1000450 ovulatory cycles
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Ovarian reserve
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SuppressorsAMHFOXO3@PTENP27
NaintainersPDK1rpS6
ActivatorsmTORC
Regulation and intiation of follicle growth
Ovarian reserve
Ovarian reserve
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Regulation and intiation of follicle growth
Ovarian reserve:AMH
AMHDimeric glycoproteinMural granulosa cellsParacrine inhibitor
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Ovarian reserve
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Ovarian reserve
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AMH variability AMH: glycoprotein secreted by Granulosa
cells in small gowoing follicle up to 8mm Older studies: stable at any point in
menstrual cycle Recent studies: minor varation in level(no
change)
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Anderson 2006m, Nelson 2010 –Hadlow etal 2013
AMH variability
Marker of preantral and smal antral follicle up to 8mm Reflect primordial follicle pool
size(indiectly) AMH: suppressed during pregnancy and
prolonged GNrHa , O C
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Anderson 2006m, Nelson 2010 –Hadlow etal 2013
Ovarian reserve
AMH: suppressed during pregnancy and prolonged GNrHa , O C
AMH may not retain its accuracy as predictor of ovarian reseve in OC users
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Anderson 2006m, Nelson 2010 –Hadlow etal 2013
Ovarian reserve:AMH
AMH peak: 24.5 years
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Ovarian reserve
AMH peak 24.5 yearsNGF POP:18 MONTHNGF recrutited :14.5 years
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Ovarian reserve
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Ovarian reserve:AMH
AMH in diagnosisPCO morphology, Andrgen excess,AnovulationPCOS:more than 5ng/ml to 8,4ng/ml,correlated to andrgen levelAMH correlates TO AFC in PCOPCO: AMH level and metformin treatment
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Ovarian reserve:AMH
AMH in diagnosisPCOS:
AMH may replace AFC in the futureHigh AMH(8.4ng/ml) may help in diagnosis of PCO in adolucent since Ultrasound scan may be difficult or not accurateMay help to plan AMH based protocol for ovulation induction : clomiphene
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Ovarian reserve:AMH
AMH in diagnosis amenorrheaIn hypogonadal Hypogonadism :FSL,LH lowAMH is low than normalHypergonadal Hypogonadism: AMH undectableGranulosa cell tumors very heigh levelsPremature ovarian failure AMH may be undectable
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Ovarian reserve:AMH
AMH in diagnosis Granulosa cell tumor difficult to diagnoseUltrasound :Solid cystic massGranulosa cell tumors(GCT)AMH : very heigh levelsGranulosa cell tumors require prolonged follow upBoth Inhibin and AMH are sensetive marker for GCTIn J cancer 2015
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Ovarian reserve:AMH
AMH 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 chemotherapy
Human Reprod 2015
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Ovarian reserve:AMH
Research on the best protocol of chemotherapyGNRH agonist works well with cyclophosamide based protocol to avoid ovaruian damage from chemotherapy Radiotherapy: mointoring of ovarian functionOvarian surgery : which technique is good?Uterine artery embolization and AHM level( no significant effect)Minim Invasive 2015
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Ovarian reserve:AMH
AMH in diagnosis(monitor fertility decline)Ovarian surgery
Endometriosis:effect of endometrioma surgery on AMHOvarian function after total hysterectomy Vs supracervical hysterectomyJ minim Invasive Gynecol 2015
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Ovarian reserve:AMH
AMH in diagnosis(monitor fertility decline)Predict ovarian reserve decline in autoimmune diseasesSLE and other autoimmune disordersAuto immune thyroiditis
Rev Bras Reumatol 2014 J Assist Reprod Genet 2015
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Ovarian reserve:AMH
AMH in diagnosis(monitor fertility decline)
Treatment of ectopic pregnancy with methotroxate decreases AMH and AFCEur J Obstet Gynecol Reprod Biol 2014
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Ovarian reserve: AMH
AMH limitationsNo international satandard assayDoes not provide direct measurement of primordial follicle poolAge and genetics other biomarkers should be taken in cosideration in the prediction of future fertilityMay not be accurate In patient taking OCRacial variantions
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Ovarian reserve:AMH
AMH in diagnosis: predictions of menopause Why?Menopause: End of natural fertlityPlan career,Decision on the wish to have childernFamily planning Fecundability(probability of concieving in low and high AMH both low fecundability
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Ovarian reserve:AMHPredicting remaining reproductive life
span(model)AMH undectable 5 years before final menstrual cycleIntrpretation in the contex of age,genetics,enviroment0.2ng/ml median age to menopause 6 ys (gp 40-45ys)But about 10 ys in age gp 35-39ys
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Ivf outcome and AMH
Low AMH<0.47ng/ml is associated with poor prognosis for IVF outcome
AMH>2ng good outcome
Lehmann et al J Assist Reprod Genet 2014
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Oocyte quality and age
Age=Quality Ovarian reserve test=Quantity Age: Miscarriage rate Age: Obesity and oocyte quality Weight reduction and oocyte quality
Nelson et al Hum Reprod update 2013
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Birth rate and age
Nelson et al Hum Reprod update 2013
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Miscarrage rate and age
Nelson et al Hum Reprod update 2013
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Oocyte quality and age
El-Amal IVF Center
Oocyte quality and age
Age=Quality Age: Obesity and oocyte quality Weight reduction and oocyte quality
Nelson et al Hum Reprod update 2013
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Ovarian reserve response predictor
AMH=AFC>FSH>age Age FSH:E2 Ovarian volume AFC AMH Inhibin
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Ovarian reserveReponse
prediction
Age FSH Ovarian volume AFC AMH
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Ovarian reserveAFC strongly correlated to AMHAMH combined with AF:increase sensitivity and specificyPredict oocyte yield during COSIdentify good prognosis patients for ivfResponse prediction in Ovarian stimulation:OHSSPredicts poor responders
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Hadlow et al fertil steril 2013
Ovarian reserve
Why to predict ovarian responseAvoid iatrogenic complicationOvulation protocol strategyAgonist protocol VS Antagonist protocolFlare protocol VS MNC
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Ovarian reserve:AMH
Why Predict Ovarian responseAFC >=40,AMH>=5.6ng/ml- or 40pmol-antagonist control agonist trigerAFC 24-40or AMH 2.8-5.6ng/ml or20-40pmol antagonist control hcg,agonist trigerAFC 10-24,AMH 1--2.8ng or 7-20 pmol Long agonist controlAFC 2-10,AMH <0.1- 1ng/m1 or -7pmol Flare agonist
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Nelson S in fertil Steril 2013
Ovarian reserveAMH
Startingdose
AMH<0.7NG
AMH0.7-2NG
AMH>2.1-4.2ng
AMH>4,2-6.3NG
AMH>6.3NG
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Ovarian reserveAMH
AMH Vs AFC Ovarian response:Starting DoseAMH is better in predicting hyporesponseAFC is better in predicting hyperresponse
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Reprod Biomed online2013
Improving oocyte quality and age
Age=Quality Age: Obesity and oocyte quality Weight reduction and oocyte quality
Nelson et al Hum Reprod update 2013
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Avoiding age related decline in oocyte quality
Oocyte cryopreservation(Social freezing)Assess embryo quality: aneuploidy screenDHEA? Testosterone skin batchGrowth hormone?Vit E Conenzyme Q?
Nelson et al 2013 Hum Reorod Update
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conclusion
AMH is follicle gatekeeper. AMH and AFC are the best markers of ovarian reserve, age is the best marker for oocyte quality. Maximizing oocyte yield for all patient is no longer an appropriate stimulation strategy. ORT allows pretreatment patient counseling, individualization of stimulation strategy, increased cost effectiveness, enhanced safety. 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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