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Dr. Azmi Saleh Abdrbo
FRCOG
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
El-Amal IVF Center
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
El-Amal IVF Center
Ovarian reserve AMH
 D.Diagnosis of PCO ,amenorrhea
 Family planning :ovarian reserve screening
 Ovarian surgery
 Granulosa cell tumors
 Menopause and POI
El-Amal IVF Center
Ovarian reserve
5 months iu : millions
Menopause: 1000
450 ovulatory cycles
El-Amal IVF Center
Ovarian reserve
El-Amal IVF Center
Suppressors
AMH
FOXO3@
PTEN
P27
Naintainers
PDK1
rpS6
Activators
mTORC
Regulation and intiation of follicle growth
Ovarian reserve
Ovarian reserve
El-Amal IVF Center
Regulation and intiation of follicle growth
Ovarian reserve:AMH
AMH
Dimeric glycoprotein
Mural granulosa cells
Paracrine inhibitor
El-Amal IVF Center
Ovarian reserve
El-Amal IVF Center
Ovarian reserve
El-Amal IVF Center
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)
El-Amal IVF Center
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
El-Amal IVF Center
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
El-Amal IVF Center
Anderson 2006m, Nelson 2010 –Hadlow etal 2013
Ovarian reserve:AMH
 AMH peak:
 24.5 years
El-Amal IVF Center
Ovarian reserve
AMH peak 24.5 years
NGF POP:18 MONTH
NGF recrutited :14.5 years
El-Amal IVF Center
Ovarian reserve
El-Amal IVF Center
Ovarian reserve:AMH
AMH in diagnosis
PCO morphology,
Andrgen excess,
Anovulation
PCOS:more than 5ng/ml to 8,4ng/ml,correlated to andrgen
level
AMH correlates TO AFC in PCO
PCO: AMH level and metformin treatment
El-Amal IVF Center
Ovarian reserve:AMH
AMH in diagnosis
PCOS:
AMH may replace AFC in the future
High AMH(8.4ng/ml) may help in diagnosis of PCO in
adolucent since Ultrasound scan may be difficult or not
accurate
May help to plan AMH based protocol for ovulation
induction : clomiphene
El-Amal IVF Center
Ovarian reserve:AMH
AMH in diagnosis amenorrhea
In hypogonadal Hypogonadism :FSL,LH low
AMH is low than normal
Hypergonadal Hypogonadism: AMH undectable
Granulosa cell tumors very heigh levels
Premature ovarian failure AMH may be undectable
El-Amal IVF Center
Ovarian reserve:AMH
AMH in diagnosis
Granulosa cell tumor difficult to diagnose
Ultrasound :Solid cystic mass
Granulosa cell tumors(GCT)AMH : very heigh levels
Granulosa cell tumors require prolonged follow up
Both Inhibin and AMH are sensetive marker for GCT
In J cancer 2015
El-Amal IVF Center
Ovarian reserve:AMH
AMH in diagnosis(monitor fertility decline)
Pretreatment and post treatment levels chemotheapy
Prediction of ovarian function after chemotjerapy
Incorporated in Guidelines of childhood cancer treatmnt
Research on the best protocol of chemotherapy
Human Reprod 2015
El-Amal IVF Center
Ovarian reserve:AMH
Research on the best protocol of chemotherapy
GNRH agonist works well with cyclophosamide based
protocol to avoid ovaruian damage from chemotherapy
Radiotherapy: mointoring of ovarian function
Ovarian surgery : which technique is good?
Uterine artery embolization and AHM level( no significant
effect)
Minim Invasive 2015
El-Amal IVF Center
Ovarian reserve:AMH
AMH in diagnosis(monitor fertility decline)
Ovarian surgery
Endometriosis:effect of endometrioma surgery on AMH
Ovarian function after total hysterectomy Vs supracervical
hysterectomy
J minim Invasive Gynecol 2015
El-Amal IVF Center
Ovarian reserve:AMH
AMH in diagnosis(monitor fertility decline)
Predict ovarian reserve decline in autoimmune diseases
SLE and other autoimmune disorders
Auto immune thyroiditis
Rev Bras Reumatol 2014 J Assist Reprod Genet 2015
El-Amal IVF Center
Ovarian reserve:AMH
AMH in diagnosis(monitor fertility decline)
Treatment of ectopic pregnancy with methotroxate
decreases AMH and AFC
Eur J Obstet Gynecol Reprod Biol 2014
El-Amal IVF Center
Ovarian reserve: AMH
AMH limitations
No international satandard assay
Does not provide direct measurement of primordial follicle
pool
Age and genetics other biomarkers should be taken in
cosideration in the prediction of future fertility
May not be accurate In patient taking OC
Racial variantions
El-Amal IVF Center
Ovarian reserve:AMH
AMH in diagnosis: predictions of menopause Why?
Menopause: End of natural fertlity
Plan career,
Decision on the wish to have childern
Family planning
Fecundability(probability of concieving in low and high
AMH both low fecundability
El-Amal IVF Center
Ovarian reserve:AMH
Predicting remaining reproductive life span(model)
AMH undectable 5 years before final menstrual cycle
Intrpretation in the contex of age,genetics,enviroment
0.2ng/ml median age to menopause 6 ys (gp 40-45ys)
But about 10 ys in age gp 35-39ys
El-Amal IVF Center
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
El-Amal IVF Center
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
El-Amal IVF Center
Birth rate and age
Nelson et al Hum Reprod update 2013
El-Amal IVF Center
Miscarrage rate and age
Nelson et al Hum Reprod update 2013
El-Amal IVF Center
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
El-Amal IVF Center
Ovarian reserve response
predictor
AMH=AFC>FSH>age
Age
 FSH:E2
 Ovarian volume
 AFC
 AMH
 Inhibin
El-Amal IVF Center
Ovarian reserveReponse
prediction
 Age
 FSH
 Ovarian volume
 AFC
 AMH
El-Amal IVF Center
Ovarian reserve
AFC strongly correlated to AMH
AMH combined with AF:increase sensitivity and
specificy
Predict oocyte yield during COS
Identify good prognosis patients for ivf
Response prediction in Ovarian stimulation:OHSS
Predicts poor responders
El-Amal IVF Center
Hadlow et al fertil steril 2013
Ovarian reserve
Why to predict ovarian response
Avoid iatrogenic complication
Ovulation protocol strategy
Agonist protocol VS Antagonist protocol
Flare protocol VS MNC
El-Amal IVF Center
Ovarian reserve:AMH
Why Predict Ovarian response
AFC >=40,AMH>=5.6ng/ml- or 40pmol-antagonist control
agonist triger
AFC 24-40or AMH 2.8-5.6ng/ml or20-40pmol antagonist
control hcg,agonist triger
AFC 10-24,AMH 1--2.8ng or 7-20 pmol Long agonist
control
AFC 2-10,AMH <0.1- 1ng/m1 or -7pmol Flare agonist
El-Amal IVF Center
Nelson S in fertil Steril 2013
Ovarian reserveAMH
Starting
dose
AMH<0.7NG
AMH0.7-2NG
AMH>2.1-4.2ng
AMH>4,2-6.3NG
AMH>6.3NG
El-Amal IVF Center
Ovarian reserveAMH
AMH Vs AFC Ovarian response:Starting Dose
AMH is better in predicting hyporesponse
AFC is better in predicting hyperresponse
El-Amal IVF Center
Improving oocyte quality and
age
 Age=Quality
 Age: Obesity and oocyte quality
 Weight reduction and oocyte quality
Nelson et al Hum Reprod update 2013
El-Amal IVF Center
Avoiding age related decline in
oocyte quality
Oocyte cryopreservation(Social freezing)
Assess embryo quality: aneuploidy screen
DHEA? Testosterone skin batch
Growth hormone?
Vit E Conenzyme Q?
Nelson et al 2013 Hum Reorod Update
El-Amal IVF Center
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
El-Amal IVF Center
Ovarian reserve 2

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Ovarian reserve 2

  • 1. Dr. Azmi Saleh Abdrbo FRCOG El-Amal IVF Center Ovarian reserve
  • 2. 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 El-Amal IVF Center
  • 3. 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 El-Amal IVF Center
  • 4. Ovarian reserve AMH  D.Diagnosis of PCO ,amenorrhea  Family planning :ovarian reserve screening  Ovarian surgery  Granulosa cell tumors  Menopause and POI El-Amal IVF Center
  • 5. Ovarian reserve 5 months iu : millions Menopause: 1000 450 ovulatory cycles El-Amal IVF Center
  • 6. Ovarian reserve El-Amal IVF Center Suppressors AMH FOXO3@ PTEN P27 Naintainers PDK1 rpS6 Activators mTORC Regulation and intiation of follicle growth
  • 7. Ovarian reserve Ovarian reserve El-Amal IVF Center Regulation and intiation of follicle growth
  • 8. Ovarian reserve:AMH AMH Dimeric glycoprotein Mural granulosa cells Paracrine inhibitor El-Amal IVF Center
  • 11. 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) El-Amal IVF Center Anderson 2006m, Nelson 2010 –Hadlow etal 2013
  • 12. 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 El-Amal IVF Center Anderson 2006m, Nelson 2010 –Hadlow etal 2013
  • 13. 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 El-Amal IVF Center Anderson 2006m, Nelson 2010 –Hadlow etal 2013
  • 14. Ovarian reserve:AMH  AMH peak:  24.5 years El-Amal IVF Center
  • 15. Ovarian reserve AMH peak 24.5 years NGF POP:18 MONTH NGF recrutited :14.5 years El-Amal IVF Center
  • 17. Ovarian reserve:AMH AMH in diagnosis PCO morphology, Andrgen excess, Anovulation PCOS:more than 5ng/ml to 8,4ng/ml,correlated to andrgen level AMH correlates TO AFC in PCO PCO: AMH level and metformin treatment El-Amal IVF Center
  • 18. Ovarian reserve:AMH AMH in diagnosis PCOS: AMH may replace AFC in the future High AMH(8.4ng/ml) may help in diagnosis of PCO in adolucent since Ultrasound scan may be difficult or not accurate May help to plan AMH based protocol for ovulation induction : clomiphene El-Amal IVF Center
  • 19. Ovarian reserve:AMH AMH in diagnosis amenorrhea In hypogonadal Hypogonadism :FSL,LH low AMH is low than normal Hypergonadal Hypogonadism: AMH undectable Granulosa cell tumors very heigh levels Premature ovarian failure AMH may be undectable El-Amal IVF Center
  • 20. Ovarian reserve:AMH AMH in diagnosis Granulosa cell tumor difficult to diagnose Ultrasound :Solid cystic mass Granulosa cell tumors(GCT)AMH : very heigh levels Granulosa cell tumors require prolonged follow up Both Inhibin and AMH are sensetive marker for GCT In J cancer 2015 El-Amal IVF Center
  • 21. Ovarian reserve:AMH AMH in diagnosis(monitor fertility decline) Pretreatment and post treatment levels chemotheapy Prediction of ovarian function after chemotjerapy Incorporated in Guidelines of childhood cancer treatmnt Research on the best protocol of chemotherapy Human Reprod 2015 El-Amal IVF Center
  • 22. Ovarian reserve:AMH Research on the best protocol of chemotherapy GNRH agonist works well with cyclophosamide based protocol to avoid ovaruian damage from chemotherapy Radiotherapy: mointoring of ovarian function Ovarian surgery : which technique is good? Uterine artery embolization and AHM level( no significant effect) Minim Invasive 2015 El-Amal IVF Center
  • 23. Ovarian reserve:AMH AMH in diagnosis(monitor fertility decline) Ovarian surgery Endometriosis:effect of endometrioma surgery on AMH Ovarian function after total hysterectomy Vs supracervical hysterectomy J minim Invasive Gynecol 2015 El-Amal IVF Center
  • 24. Ovarian reserve:AMH AMH in diagnosis(monitor fertility decline) Predict ovarian reserve decline in autoimmune diseases SLE and other autoimmune disorders Auto immune thyroiditis Rev Bras Reumatol 2014 J Assist Reprod Genet 2015 El-Amal IVF Center
  • 25. Ovarian reserve:AMH AMH in diagnosis(monitor fertility decline) Treatment of ectopic pregnancy with methotroxate decreases AMH and AFC Eur J Obstet Gynecol Reprod Biol 2014 El-Amal IVF Center
  • 26. Ovarian reserve: AMH AMH limitations No international satandard assay Does not provide direct measurement of primordial follicle pool Age and genetics other biomarkers should be taken in cosideration in the prediction of future fertility May not be accurate In patient taking OC Racial variantions El-Amal IVF Center
  • 27. Ovarian reserve:AMH AMH in diagnosis: predictions of menopause Why? Menopause: End of natural fertlity Plan career, Decision on the wish to have childern Family planning Fecundability(probability of concieving in low and high AMH both low fecundability El-Amal IVF Center
  • 28. Ovarian reserve:AMH Predicting remaining reproductive life span(model) AMH undectable 5 years before final menstrual cycle Intrpretation in the contex of age,genetics,enviroment 0.2ng/ml median age to menopause 6 ys (gp 40-45ys) But about 10 ys in age gp 35-39ys El-Amal IVF Center
  • 29. 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 El-Amal IVF Center
  • 30. 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 El-Amal IVF Center
  • 31. Birth rate and age Nelson et al Hum Reprod update 2013 El-Amal IVF Center
  • 32. Miscarrage rate and age Nelson et al Hum Reprod update 2013 El-Amal IVF Center
  • 33. Oocyte quality and age El-Amal IVF Center
  • 34. Oocyte quality and age  Age=Quality  Age: Obesity and oocyte quality  Weight reduction and oocyte quality Nelson et al Hum Reprod update 2013 El-Amal IVF Center
  • 35. Ovarian reserve response predictor AMH=AFC>FSH>age Age  FSH:E2  Ovarian volume  AFC  AMH  Inhibin El-Amal IVF Center
  • 36. Ovarian reserveReponse prediction  Age  FSH  Ovarian volume  AFC  AMH El-Amal IVF Center
  • 37. Ovarian reserve AFC strongly correlated to AMH AMH combined with AF:increase sensitivity and specificy Predict oocyte yield during COS Identify good prognosis patients for ivf Response prediction in Ovarian stimulation:OHSS Predicts poor responders El-Amal IVF Center Hadlow et al fertil steril 2013
  • 38. Ovarian reserve Why to predict ovarian response Avoid iatrogenic complication Ovulation protocol strategy Agonist protocol VS Antagonist protocol Flare protocol VS MNC El-Amal IVF Center
  • 39. Ovarian reserve:AMH Why Predict Ovarian response AFC >=40,AMH>=5.6ng/ml- or 40pmol-antagonist control agonist triger AFC 24-40or AMH 2.8-5.6ng/ml or20-40pmol antagonist control hcg,agonist triger AFC 10-24,AMH 1--2.8ng or 7-20 pmol Long agonist control AFC 2-10,AMH <0.1- 1ng/m1 or -7pmol Flare agonist El-Amal IVF Center Nelson S in fertil Steril 2013
  • 41. Ovarian reserveAMH AMH Vs AFC Ovarian response:Starting Dose AMH is better in predicting hyporesponse AFC is better in predicting hyperresponse El-Amal IVF Center
  • 42. Improving oocyte quality and age  Age=Quality  Age: Obesity and oocyte quality  Weight reduction and oocyte quality Nelson et al Hum Reprod update 2013 El-Amal IVF Center
  • 43. Avoiding age related decline in oocyte quality Oocyte cryopreservation(Social freezing) Assess embryo quality: aneuploidy screen DHEA? Testosterone skin batch Growth hormone? Vit E Conenzyme Q? Nelson et al 2013 Hum Reorod Update El-Amal IVF Center
  • 44. 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 El-Amal IVF Center