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Dr. Azmi Saleh Abdrbo FRCOG El-Amal IVF Center Ovarian reserve

Ovarian reserve 2

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Dr. Azmi Saleh AbdrboFRCOGEl-Amal IVF CenterOvarian reserve

Ovarian reservePopulation 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 El-Amal IVF Center

Ovarian reserve

Ovarian reservePlan fertility preservationFertility outcomeResponse to ovarian stimulationPredict pregnancy rateMonitor fertility declineFertility after chemotherapy and cancer treatmentEl-Amal IVF Center

Ovarian reserve AMHD.Diagnosis of PCO ,amenorrheaFamily planning :ovarian reserve screeningOvarian surgery Granulosa cell tumorsMenopause and POIEl-Amal IVF Center

Ovarian reserve5 months iu : millionsMenopause: 1000450 ovulatory cycles

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Ovarian reserve

El-Amal IVF [email protected]ORCRegulation and intiation of follicle growth

Ovarian reserve

Ovarian reserve

El-Amal IVF Center

Regulation and intiation of follicle growth

Ovarian reserve:AMHAMHDimeric glycoproteinMural granulosa cellsParacrine inhibitor

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Ovarian reserve

El-Amal IVF Center

Ovarian reserve

El-Amal IVF Center

AMH variabilityAMH: glycoprotein secreted by Granulosa cells in small gowoing follicle up to 8mmOlder studies: stable at any point in menstrual cycleRecent studies: minor varation in level(no change)

El-Amal IVF CenterAnderson 2006m, Nelson 2010 Hadlow etal 2013

AMH variability

Marker of preantral and smal antral follicle up to 8mmReflect primordial follicle pool size(indiectly)AMH: suppressed during pregnancy and prolonged GNrHa , O C

El-Amal IVF CenterAnderson 2006m, Nelson 2010 Hadlow etal 2013

Ovarian reserve

AMH: suppressed during pregnancy and prolonged GNrHa , O CAMH may not retain its accuracy as predictor of ovarian reseve in OC users

El-Amal IVF CenterAnderson 2006m, Nelson 2010 Hadlow etal 2013

Ovarian reserve:AMHAMH 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:AMHAMH 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:AMHAMH 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 : clomipheneEl-Amal IVF Center

Ovarian reserve:AMHAMH 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 undectableEl-Amal IVF Center

Ovarian reserve:AMHAMH 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:AMHAMH 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 2015El-Amal IVF Center

Ovarian reserve:AMHAMH in diagnosis(monitor fertility decline)Ovarian surgery

Endometriosis:effect of endometrioma surgery on AMHOvarian function after total hysterectomy Vs supracervical hysterectomyJ minim Invasive Gynecol 2015El-Amal IVF Center

Ovarian reserve:AMHAMH 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 2015El-Amal IVF Center

Ovarian reserve:AMHAMH in diagnosis(monitor fertility decline)

Treatment of ectopic pregnancy with methotroxate decreases AMH and AFCEur J Obstet Gynecol Reprod Biol 2014El-Amal IVF Center

Ovarian reserve: AMHAMH 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 variantionsEl-Amal IVF Center

Ovarian reserve:AMHAMH 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 fecundabilityEl-Amal IVF Center

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 AMHLow AMH2ng good outcome

Lehmann et al J Assist Reprod Genet 2014El-Amal IVF Center

Oocyte quality and ageAge=QualityOvarian reserve test=QuantityAge: Miscarriage rateAge: Obesity and oocyte qualityWeight reduction and oocyte qualityNelson et al Hum Reprod update 2013El-Amal IVF Center

Birth rate and age

Nelson et al Hum Reprod update 2013El-Amal IVF Center

Miscarrage rate and age

Nelson et al Hum Reprod update 2013El-Amal IVF Center

Oocyte quality and age

El-Amal IVF Center

Oocyte quality and ageAge=QualityAge: Obesity and oocyte qualityWeight reduction and oocyte quality

Nelson et al Hum Reprod update 2013El-Amal IVF Center

Ovarian reserve response predictor AMH=AFC>FSH>age AgeFSH:E2Ovarian volumeAFCAMHInhibin

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Ovarian reserveReponse prediction

AgeFSHOvarian volumeAFCAMH

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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

El-Amal IVF CenterHadlow et al fertil steril 2013

Ovarian reserveWhy to predict ovarian responseAvoid iatrogenic complicationOvulation protocol strategyAgonist protocol VS Antagonist protocolFlare protocol VS MNC

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Ovarian reserve:AMHWhy 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 4,2-6.3NGAMH>6.3NG

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Ovarian reserveAMHAMH Vs AFC Ovarian response:Starting DoseAMH is better in predicting hyporesponseAFC is better in predicting hyperresponse

El-Amal IVF CenterReprod Biomed online2013

Improving oocyte quality and ageAge=QualityAge: Obesity and oocyte qualityWeight reduction and oocyte quality

Nelson et al Hum Reprod update 2013El-Amal IVF Center

Avoiding age related decline in oocyte qualityOocyte cryopreservation(Social freezing)Assess embryo quality: aneuploidy screenDHEA? Testosterone skin batchGrowth hormone?Vit E Conenzyme Q?

Nelson et al 2013 Hum Reorod UpdateEl-Amal IVF Center

conclusionAMH 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 disordersEl-Amal IVF Center