Ovarian reserve tests provide an indirect measure of the cohort of recruitable antral follicles present in the FSH window at the beginning of each menstrual cycle..Functional Ovarian Reserve

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2. Ovarian Reserve
Testing & Management

3. Ovarian reserve tests provide an indirect measure of
the cohort of recruitable antral follicles present in the
FSH window at the beginning of each menstrual
cycle..Functional Ovarian Reserve
Fauser and Van Heusden, 1997; McGee and Hsueh, 2000.
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4. Ideal
for
IUI
Stimulation depends on reserve
Ideal
For
IVF
Low reserve:
--Flare / hi dose
Average reserve:
--Antag / mid dose High reserve:
--Luteal / low dose
NOTE: inverse correlation between dose and response across patients
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5. Differentiation is must..
• Good reserve
• Borderline reserve
• Bad functional reserve
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6. • Evaluation of ovarian reserve can identify
patients who may experience
• Poor response or Hyper-response to
exogenous gonadotrophins
• Can aid in the personalization of
treatment to achieve good response and
minimize risks.
AMOGS 2018

7. AMH: Population quantiles with Age
Difficult to predict pace of reproductive decline
Age-specific
quantiles
Age (y)
25 30 35 40 45 50
0
AMH
(pmol/L)
10
25
50
75
90
50
40
30
20
10
70
Ovarian Reserve
150,000
1,000

8. Tests
• ‘Tests’ based on history
• Basal endocrine tests
• Dynamic endocrine tests
• Ultrasound tests
• Invasive tests

9. ‘Tests’ based on history
• Age
• Smoking
• Ethnicity
• Maternal / sibling history
• Menstrual history
• Symptom history
• BMI
• Previous response to OI or IVF

10. Basal endocrine tests
• FSH
• LH- basal, mean, amplitude & response
• FSH:LH ratio
• Estradiol
• Inhibin A and Inhibin B
• Progesterone
• Progesterone:Estradiol ratio
• Anti Mullerian Hormone
• Testosterone
• Vascular endothelial growth factor VEGF
• Insulin like growth factor IGF-1

11. AMOGS 2018 Dr. Dhorepatil
Antral follicle count (AFC), an ultrasound biomarker of follicle
number,
and
The serum anti-Müllerian hormone (AMH),
a hormone biomarker of follicle number have emerged as
preferred methods for assessing ovarian reserve.

12. AMOGS 2018 Dr.Dhorepatil
• Earliest marker to change with age
• The least intercycle variability
• The least intracycle variability
• Randomly measured during the cycle
• No modifications during GnRHa
• No modification in hypothalamic amenorreha
Reliable Marker
Women have limited
Reproductive Lifespan

13. Different cutoff levels
AMOGS 2018 Dr.Dhorepatil

14. AMOGS 2018 Dr.Dhorepatil
Low AMH….0.5 to 0.9ng/ml
Normal Range …0.9 to 3.5ng/ml
High AMH..3.5 to 9.5ng/ml

15. Toner et al,fertil-steril,june13
AMOGS 2018 Dr.Dhorepatil
Factors to be considered additionally
• Age
• AFC, Ov.Volume
• Previous response
• Type of infertility management done
previously

16. Who to be screening
• Age >30
• Long standing Hypothyoid status
• Before 1st IUI OR IVF CYCLE
• Previous ovarian surgery
• Previous chemotherapy/radiotherapy
• Already known high- D 3 FSH
• Not “reassuring” ultrasound image –
Ov. Volume / AFC

17. An approach to Ovulation Induction
for Optimum ovarian responce
• DEMOGRAPHICS AND ANTHROPOMETRICS
Age ,BMI ,Race
cause of infertility
Years of infertility
Previous IVF response -Nutrition and health status
Provide …prognostication & diagnosis
• BIOMARKERS: actual tools to personalize treatment Hormonal biomarkers: FSH .AMH,
inhibin b
Functional biomarkers: antral follicle count(AFC)
Genetic biomarkers: SNP for FSH r, LH-r,E2 r ,
• DYNAMIC TESTS
GnRH agonist stimulation (GAST) ,Clomiphene challenge test

18. Ovarian Response Prediction index (ORPI)
implications for individualised COS
ORPI= AMH (ng/ml) x AFC (2-9 m) and the result was divided by the age (years) of the
patient
Oliveira, et al, reprod biol endocrinol 2012.

19. AMOGS 2018 Dr.Dhorepatil

20. AMH as a predictor of outcome of Quantitative
ovarian reponse OI
• AMH and follicular response..
positive co-relation
• Almost all the studies found a significant co-relation
between AMH and AFC
• AFC and AMH perform with similar power in prediction in
the number of oocytes retrieved

21. AMOGS 2018 Dr.Dhorepatil

22. • Low AMH
AMOGS 2018 Dr.Dhorepatil

24. AMH and DHEA supplementation
• AMH increases in parallel with length of DHEA
supplementation
• This increase is more pronounced in younger POA than older
DOR patients
• Improvement in AMH levels with DHEA supplementation is
highly predictive of pregnancy success
Gleicher et al, Reprod Biomed Online 2010;21:360-365.

25. • For poor response a cutoff of 1.0 ng/mL would have
87% sensitivity and 67% specificity.
• It is therefore clear that AMH has a modest accuracy
for extremes of response to COH; thus, it would not be
feasible to deny treatment based on a low (1.0 ng/mL)
AMH level.
AMOGS 2018 Dr.Dhorepatil

26. • The combination of low AMH levels and poor
ovarian response in the first IVF cycle reflect
unfavorable prognosis and further IVF attempts
or alternate options should be discussed with
couple, like Egg Banking,Egg Donar cycle,Natural
cycle
AMOGS 2018 Dr.Dhorepatil

27. AMOGS 2018

28. Essential Steps
• Diagnosis
• Design of Ovulation stimulation protocol
• Decision of Starting dose of drug
• Maintaining optimum growth of follicles till
the day of HCG
• Decision of trigger.. the drug,day & dose
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29. • The entry of FSH into follicular fluid at
cavitation is believed to provide the induction
stimulus that initiates the process of graafian
follicle growth and development.
• At the cellular level, it is the FSH receptor on
the granulosa cell that is the fundamental
player in this process.
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30. LH and FSH Action on the Follicle
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Capillary network Basement membrane
Theca externa cells
Theca interna cells
Cumulus
Oophorus
cells
Oocyte
Zona pellucida
Granulosa
cells Follicular
antrum
LH receptors
on theca cells
FSH receptors
on granulosa
cells
E2
FSH
LH
A

31. Role of FSH and LH in follicular development and
maturation
• Both FSH and LH are required for promoting follicular
and growth and differentiation…
• FSH stimulates transcription of several genes within the
granulosa cells, leading to the reflection of follicle
differentiation
• FSH..principal stimulator and regulator of antral
follicular growth…
• Adequate amount of LH ..preantral stage..to
stimulate secretion of androgens by thecal cells
which diffiuse in the granulosa to convert into
estrogen through aromatization
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32. Both FSH and LH play critical and
complementary roles
FSH necessary for:
Folliculogenesis
Limited steroidogenesis
LH necessary for:
Estrogen production
‘Healthy’ folliculogenesis
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33. Prerequisites..
• Age
• BMI
• Duration Of Infertility
• Previous h/o induction protocol/response
• Basal USG with blood flow
indices..Ut,Endo,AFC
• Basal Endocrine profile.. FSH, LH, AMH
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34. Key players
• FSH & LH
• Threshold,…Starting dose
• Window..Maintenance dose
• Trigger
• Luteal support
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35. • The goal of folliculogenesis is to produce a single
or multiple dominant follicles from a pool of
growing follicles…
Four major regulatory events :
• Recruitment
• Follicle development
• Selection,
• Surge (maturity)
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36. Choose for ideal Protocols for Ur Pt….
1. CC.
2. clomiphene..step up,extended
3. CC ± FSH or ± HMG.
4. Gn. Standard step-up protocol.
5. Gn. Low dose step-up protocol.
6. Gn. Low dose step-up, step-down
protocol.
7. Adjuvants
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37. Way of stimulation..
• Conventional..Normal responders
• Mild stimulation..poor responders
• Low dose protocol
• Chronic Low dose Protocol..high responders
• Chronic step up AND step down protocol
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38. From “one size fits all” ……..to tailor made COS
Taylor made for perfect individualization
1st step for success: Take the exact measurements
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39. Dose of Gonadotrophins
age PCOS-FSH
hyperrespo
nder
Normal
responder
Poor
responder
<30yrs 75 iu 150iu 225/300
iu
30-35 yrs 75iu 225iu 300/375iu
>35yrs 75/150iu 225/300iu 450/600
iu/egg
donatio

40. Management strategies
• Starting dose criteria
• Change of Urinary to recombinant
gonadotropins (batch to batch consistency)
• Addition of LH at early or mid follicular phase
• Optimization..reducing high LH with wt
reduction, antagonist, antiandrogens,LOD
• Change over from agonist to antagonist for
control of LH..long protocol to short
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41. Starting Dose..key to response?
• How much FSH depends on the threshold of
the pt..individual varies
• This could be stratigies depends on Age, BMI,
AFC, AMH, type of Infertility , Previous
response
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42. Can we predict Starting Dose for the stimulation in IUI or IVF cycle
AGE & AMH,FSH
AGE & AFC,FSH
Dr Dhorepatil 42

43. Strategy for the Initial dose
• IGD Score ( Initial Gonadotrophin Dose)
43Dr Dhorepatil

44. IGD score
score 0 1 2 3 4 5
AGE < 19 20-29 30 to 35 >35
BMI <19 19-22.5 22.6-28.5 28.6-35 >35
AMH >10 3.5-10 0.9-3.4 <0.9
AFC >20 10-20 5-10 3-5 1-2 0-1
Score Rec/Biosimiar Urinary
3 75 150
4-10 150 225
10-14 175 300
15 225 375
44Dr Dhorepatil

45. Case A
• 29yr old, BMI 28,AFC 6,AMH 7.5ng/ml pt.with
tubal patency,no male factor..D2 of the
menses..
• What dose to start for IUI or IVF
• Score..10…dose for IVF-150units
For IUI..75units
45Dr Dhorepatil

46. Our Audit of 200 pts at Ssmile IVF, Pune
2015-16
Pt no IGD score No follicles No Eggs retrived
50 3 15-10 10-15
50 4-10 10-15 8- 10
50 10-14 5-7 4-5
50 > 14 2-3 1-2
Dr Dhorepatil 46

47. Tips… successful ovulation Induction
• You are not doing Ovarian stimulation, but
• You are preparing egg from given ovary to get
pregnancy out of it..
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48. • There is no golden standards, guidelines or
protocol.
• As there is no golden rule, induction of ovulation
depends largely on the doctors experience and
patients merits.
• Think twice before starting induction, and avoid the
routine.
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49. High AMH
• Can high AMH levels be able to predict increased ovarian
response ?
• Women with high AMH have a higher risk of OHSS and can we
use this information to prevent OHSS
• We can develop OHSS free Clinics Strategy
AMOGS 2018 Dr.Dhorepatil

50. AMH and hyper-response

51. Pre-preparation prior to COS when AMH is high
• Life style change
• OCPills
• Metformin
• Mynositol/ D chiroinositol
• PCO drilling
• Predict by no of follicles, oocytes, free fluid, PCV,
ovarian volume and Early prompt action
AMOGS 2018 Dr.Dhorepatil

52. OHSS prevention
The recent implementation of four new modalities:
• The GnRH antagonist protocol,
• GnRH agonist (GnRHa) triggering of ovulation
• Blastocyst transfer
• Embryo/oocyte vitrification,
renders feasible the elimination of OHSS in connection
with ovarian hyperstimulation for IVF treatment.
Reprod Biol Endocrinol.2011 Nov Papanikolaou EG
AMOGS 2018 Dr.Dhorepatil

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Many variables can impact treatment Success
• Patient characteristics
– Age
– Type of infertility
– Psychological stress
• Oocyte / Embryo Competence
• Laboratory Conditions
• Embryo transfer procedure
• Type of stimulation regimen
• Type of gonadotrophin preparation
Keck RBM Online , 2005

54. • Synchronus Follicular growth..small dose to start,early
follicular phase recruitment, small incremental dose
• Critical time of trigger for adequate LH surge
• Appropriate Choice of Injection for stimulation &
trigger
• Right amount of doses
• Avoid Premature LH surge & leutinization
• Constant look for endometrial quality development to
have good functioning endo for implantaion
• Appropriate and right amount of luteal support
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