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1
AMH
OVARIAN RESERVE
MARKER
DR. JYOTI BHASKAR
DR. SHARDA JAIN
DR. JYOTI AGARWAL
2
AGE WISE INFERTILITY
20-25 2.8% infertile
30-34 10% infertile
35-39 33% infertile
40-45 86% infertile
3
AGE - DECLINE OF OOCYTES
4
MISCARRIAGE RATE
Age 30: 7-
15%
Age 31-34: 17-
21%
Age 35-39: 17-
28%
Age 40: 40-
52%
5
ANEUPLOIDY
10% of eggs are aneuploidic in young
women
30% at the age of 40
50 % at the age of 43
Nearly all the eggs are...
6
(teVelde and Pearson 2002)
OVARIAN RESERVE
Age is an important independent
determinant of
fertitlity and miscarriage
But...
7
OFFER -- OVARIAN RESERVE TEST
Infertile womenInfertile women
Over 30 years of ageOver 30 years of age
with a history ofw...
8
BENEFITS OF ORT IN SUBFERTILE COUPLE
ORT guides in prognosticating outcome inORT guides in prognosticating outcome in
in...
9
Ovarian ReserveOvarian Reserve
10
TESTING FOR OVARIAN RESERVE
Hormone analysis
Ultrasound techniques
Dynamic testing
11
HORMONE ANALYSIS
Follicle Stimulating Hormone (FSH)
Oestradiol
Progesterone
Inhibin B
12
FOLLICLE STIMULATING HORMONE
Usually measured Day 2 or 3 of cycle
Women with > 10 IU/l poor response to
ART
Women aged ...
13
DISADVANTAGE
Variation from month to month
Lab wise variation in values due to
different techniques.
Spurious fall a...
14
SERUM OESTRADIOL
E2 alone of little value to asses
ovarian
reserve
Combined E2 and FSH levels – better
than E2 alone.
E...
15
PROGESTERONE
Doesn’t have any independent role in
assessment of ovarian reserve
Early LH surge and elevation of P4
sugg...
16
INHIBIN B
Hetero dimeric protein similar to AMH
Levels >45 pg/ml – poor response to
induction
High false positive rate
...
17
CLOMIPHENE CHALLENGE TEST
Baseline FSH, LH & E2 followed by CC
100mg/day
from Days 5 to 9
Measure E2, FSH and LH on Day...
18
ANTRAL FOLLICULAR COUNT
Count of total follicles measuring 2 to
5mm in both ovaries on Day 2/3 of
periods.
Can be done ...
19
ANTRAL FOLLICULAR COUNT
NORMAL AFC COUNT – 10-18
POOR RESPONDER - < 7
HYPERRESPONDER - > 20
20
DRAWBACKS OF AFCDRAWBACKS OF AFC
Accurate assessment of AFC requires anAccurate assessment of AFC requires an
experienc...
21
FACTORS AFFECTING AFCFACTORS AFFECTING AFC
Oral contraceptive use (decreases)Oral contraceptive use (decreases)
Polycys...
22
AFC
So far, assessment of antral follicle
count by
ultrasonography, best predicts the
quantitative aspect of ovarian re...
23
ANTI-MULLERIAN HORMONE
24
AMH
AMH is a glycoprotein
Originally known as Mullerian Inhibiting
Substance(MIS)
Appears in females at puberty
Produce...
25
26
AMH is produced by the small growing (primary andAMH is produced by the small growing (primary and
preantral) follicles...
27
The intrafollicular concentrations of AMH
in
normal human antral follicles show a
gradual
reduction as the diameter of ...
28
AMH - unaffected
Not cycle dependant-can be measured
any day
Less cycle to cycle variation than FSH.
Not altered after ...
29
AMH – factors that decrease
Increasing ageIncreasing age
Race and EthinictyRace and Ethinicty
ObesityObesity
Smoking, A...
30
AMH BLOOD LEVEL
High (often PCOS) Over 3.5 ng/ml
Normal Over 1.4 ng/ml
Low Normal Range 0.7 – 1.3 ng/ml
Low 0.3 - 0.6 n...
31
AMH – NORMAL RANGE
32
AMH BLOOD LEVEL
AMH of less than 1.36 ng/ml has a
sensitivity of 75.5% and specificity of
74.8% in prediction of poor r...
33
WE DO HAVE EXCEPTIONS IN REALITY !!!
42 YRS OLD LADY, WITH AMH OF 0.5 ,
SPONTANOUS CONCEPTION---
NOW 28 WEEKS.
NO MISCA...
34
Understanding AMH measurement methods
AMH is measurable in serum
TWO METHODS AVAILABLE ARE
 Diagnostic system Lab ( DS...
35
AMH
Increasing age means a decreasing AMH
level
Lower AMH levels at any given time
irrespective of age predicts a poor
...
36
ADVANTAGE OVER OTHER ORT MARKERS
It is the earliest marker to change with
age
It shows the least intercycle and
intracy...
37
INDIVIDUALISED AMH TAILORED COH
Improves embryo transfer rates, the
incidence of fertilization, pregnancy and
live birt...
38
PROPOSED AMH BASED PROTOCOLS
Low AMH (< 1.4 ng/ml)
Cycle cancellation or poor response
 a. Inform the patient about th...
39
PROPOSED AMH BASED PROTOCOLS
HIGH AMH (> 3.5 ng/ml)
a. Inform about the risk of OHSS
b. Avoid depot GnRHa
c. Low FSH do...
40
CONCLUSION
Anti mullerian hormone (AMH) alone
or best in combination with
antral follicular count (AFC)
is the
BETTER I...
41
ADDRESS
11 Gagan Vihar, Near Karkari
Morh Flyover, Delhi - 51
CONTACT US
9650588339 (Helpline)
011-22414049,22058865
WEBSI...
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AMH OVARIAN RESERVE MARKER Dr Jyoti Bhasker ,Dr. Sharda Jain Dr. Jyoti Agarwal ,

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AMH OVARIAN RESERVE MARKER
AGE WISE INFERTILITY

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AMH OVARIAN RESERVE MARKER Dr Jyoti Bhasker ,Dr. Sharda Jain Dr. Jyoti Agarwal ,

  1. 1. 1 AMH OVARIAN RESERVE MARKER DR. JYOTI BHASKAR DR. SHARDA JAIN DR. JYOTI AGARWAL
  2. 2. 2 AGE WISE INFERTILITY 20-25 2.8% infertile 30-34 10% infertile 35-39 33% infertile 40-45 86% infertile
  3. 3. 3 AGE - DECLINE OF OOCYTES
  4. 4. 4 MISCARRIAGE RATE Age 30: 7- 15% Age 31-34: 17- 21% Age 35-39: 17- 28% Age 40: 40- 52%
  5. 5. 5 ANEUPLOIDY 10% of eggs are aneuploidic in young women 30% at the age of 40 50 % at the age of 43 Nearly all the eggs are aneuploidic at the age of 45
  6. 6. 6 (teVelde and Pearson 2002) OVARIAN RESERVE Age is an important independent determinant of fertitlity and miscarriage But due to considerable individual variation in the age of menopause and age of subfertility. Chronological age ALONE is a POOR indicator of reproductive aging, and thus of the ovarian reserve.
  7. 7. 7 OFFER -- OVARIAN RESERVE TEST Infertile womenInfertile women Over 30 years of ageOver 30 years of age with a history ofwith a history of exposure to a confirmedexposure to a confirmed gonadotoxingonadotoxin i.e., tobacco smoke,i.e., tobacco smoke, chemotherapy, radiation therapy.chemotherapy, radiation therapy. with a strong family history of early menopausewith a strong family history of early menopause oror premature ovarian failure.premature ovarian failure. women who have had extensive ovarianwomen who have had extensive ovarian surgery, i.e., cystectomy and unilateralsurgery, i.e., cystectomy and unilateral oophorectomyoophorectomy
  8. 8. 8 BENEFITS OF ORT IN SUBFERTILE COUPLE ORT guides in prognosticating outcome inORT guides in prognosticating outcome in individual cases byindividual cases by Pre-treatment counsellingPre-treatment counselling Choice of infertility treatmentChoice of infertility treatment Avoidance of ovarian hyperstimulationAvoidance of ovarian hyperstimulation
  9. 9. 9 Ovarian ReserveOvarian Reserve
  10. 10. 10 TESTING FOR OVARIAN RESERVE Hormone analysis Ultrasound techniques Dynamic testing
  11. 11. 11 HORMONE ANALYSIS Follicle Stimulating Hormone (FSH) Oestradiol Progesterone Inhibin B
  12. 12. 12 FOLLICLE STIMULATING HORMONE Usually measured Day 2 or 3 of cycle Women with > 10 IU/l poor response to ART Women aged more than 30 with one value of FSH > 14 IU/l do worse on IVF
  13. 13. 13 DISADVANTAGE Variation from month to month Lab wise variation in values due to different techniques. Spurious fall after hormone therapy.
  14. 14. 14 SERUM OESTRADIOL E2 alone of little value to asses ovarian reserve Combined E2 and FSH levels – better than E2 alone. E2 of > 80 pg/ml day 3 pre IVF cycle- higher cancellation rate
  15. 15. 15 PROGESTERONE Doesn’t have any independent role in assessment of ovarian reserve Early LH surge and elevation of P4 suggested sign of poor ovarian reserve
  16. 16. 16 INHIBIN B Hetero dimeric protein similar to AMH Levels >45 pg/ml – poor response to induction High false positive rate Not widely used nowadays.
  17. 17. 17 CLOMIPHENE CHALLENGE TEST Baseline FSH, LH & E2 followed by CC 100mg/day from Days 5 to 9 Measure E2, FSH and LH on Day 9 to 11 Exaggerated FSH after CC bad prognostic sign Along with other tests like FSH or GNRH agonist stimulation test no better inference than basal values
  18. 18. 18 ANTRAL FOLLICULAR COUNT Count of total follicles measuring 2 to 5mm in both ovaries on Day 2/3 of periods. Can be done in any day of the cycle To be done by Trans Vaginal Ultrasound
  19. 19. 19 ANTRAL FOLLICULAR COUNT NORMAL AFC COUNT – 10-18 POOR RESPONDER - < 7 HYPERRESPONDER - > 20
  20. 20. 20 DRAWBACKS OF AFCDRAWBACKS OF AFC Accurate assessment of AFC requires anAccurate assessment of AFC requires an experienced sonographerexperienced sonographer and can be limited inand can be limited in patients who have had pelvic surgery orpatients who have had pelvic surgery or uterineuterine fibroids and in those who are obesefibroids and in those who are obese Moderate interobserver and intercycleModerate interobserver and intercycle variabilityvariability ofof AFC determinations limits its reproducibility.AFC determinations limits its reproducibility.
  21. 21. 21 FACTORS AFFECTING AFCFACTORS AFFECTING AFC Oral contraceptive use (decreases)Oral contraceptive use (decreases) Polycystic ovary syndrome (PCOS)Polycystic ovary syndrome (PCOS) (increases).(increases).
  22. 22. 22 AFC So far, assessment of antral follicle count by ultrasonography, best predicts the quantitative aspect of ovarian reserve. Most cost effective SINGLE predictor of ovarian reserve -- IS AFC
  23. 23. 23 ANTI-MULLERIAN HORMONE
  24. 24. 24 AMH AMH is a glycoprotein Originally known as Mullerian Inhibiting Substance(MIS) Appears in females at puberty Produced by granulosa cells of pre-antral and small antral follicles of 4-6 mm AMH is not expressed in atretic follicles and theca cells.
  25. 25. 25
  26. 26. 26 AMH is produced by the small growing (primary andAMH is produced by the small growing (primary and preantral) follicles in the postnatal ovary and has two sites ofpreantral) follicles in the postnatal ovary and has two sites of action. It inhibits initialaction. It inhibits initial follicle recruitment (1) and inhibits FSH-dependent growthfollicle recruitment (1) and inhibits FSH-dependent growth and selection of preantral and small antral follicles (2).and selection of preantral and small antral follicles (2). Model of AMH action in the ovary.Model of AMH action in the ovary.
  27. 27. 27 The intrafollicular concentrations of AMH in normal human antral follicles show a gradual reduction as the diameter of the follicle increases, and a sharp decline is observed around 8mm Physiological function- prevent excessive follicle recruitment. Acts as a Gatekeeper
  28. 28. 28 AMH - unaffected Not cycle dependant-can be measured any day Less cycle to cycle variation than FSH. Not altered after down regulation with GNRH agonist. Pregnancy AMH – factors that Increase Polycystic ovaries
  29. 29. 29 AMH – factors that decrease Increasing ageIncreasing age Race and EthinictyRace and Ethinicty ObesityObesity Smoking, Alcohol IntakeSmoking, Alcohol Intake Administration of GonadotropinsAdministration of Gonadotropins Administration of chemotherapy orAdministration of chemotherapy or radiationradiation Surgical removal of one or both ovariesSurgical removal of one or both ovaries Contraceptive PillsContraceptive Pills
  30. 30. 30 AMH BLOOD LEVEL High (often PCOS) Over 3.5 ng/ml Normal Over 1.4 ng/ml Low Normal Range 0.7 – 1.3 ng/ml Low 0.3 - 0.6 ng/ml Very Low Less than 0.3 ng/ml
  31. 31. 31 AMH – NORMAL RANGE
  32. 32. 32 AMH BLOOD LEVEL AMH of less than 1.36 ng/ml has a sensitivity of 75.5% and specificity of 74.8% in prediction of poor response. AMH > 3.5 ng/ml has a sensitivity of 88% and 67% specificity in prediction of hyperstimulation
  33. 33. 33 WE DO HAVE EXCEPTIONS IN REALITY !!! 42 YRS OLD LADY, WITH AMH OF 0.5 , SPONTANOUS CONCEPTION--- NOW 28 WEEKS. NO MISCARRIAGE, NO ANEUPLOIDY THESE CUTOFFS ARE GUIDELINES WHICH HELP IN: 1. COUNSELLING 2. SELECTING THE OPTIMAL PROTOCOL. DECISION HAS TO BE COLLECTIVE – WOMAN’S CHOICE GETS THE PRIORITY
  34. 34. 34 Understanding AMH measurement methods AMH is measurable in serum TWO METHODS AVAILABLE ARE  Diagnostic system Lab ( DSL) (ng/ml)  Immunotech Beckman Coulter ( IBL) assay. ( pmol/l) NEW METHOD : AMH Generation II assay
  35. 35. 35 AMH Increasing age means a decreasing AMH level Lower AMH levels at any given time irrespective of age predicts a poor response to ART. High AMH levels – candidates prone for OHSS.
  36. 36. 36 ADVANTAGE OVER OTHER ORT MARKERS It is the earliest marker to change with age It shows the least intercycle and intracycle variability It can be randomly measured during the cycle It shows no modifications during GnRHa It needs no modification in hypothalamic amenorrhea It is both more convenient and informative than basal FSH
  37. 37. 37 INDIVIDUALISED AMH TAILORED COH Improves embryo transfer rates, the incidence of fertilization, pregnancy and live birth rates. Reduces incidence of adverse outcomes, such as OHSS and failed fertilization
  38. 38. 38 PROPOSED AMH BASED PROTOCOLS Low AMH (< 1.4 ng/ml) Cycle cancellation or poor response  a. Inform the patient about the cycle cancellation or no transfer  b. Low possibility of pregnancy  c. Avoid long suppression  d. Antagonist cycle  e. Use of HMG for stimulation Normal AMH (1.4-3.5 ) Normal Response  a. Standard protocol
  39. 39. 39 PROPOSED AMH BASED PROTOCOLS HIGH AMH (> 3.5 ng/ml) a. Inform about the risk of OHSS b. Avoid depot GnRHa c. Low FSH dose d. Antagonist cycle preferred e. Agonist Trigger f. Blastocyst transfer or Freeze all embryos and transfer later.
  40. 40. 40 CONCLUSION Anti mullerian hormone (AMH) alone or best in combination with antral follicular count (AFC) is the BETTER INDICATOR of ovarian reserve than any other hormonal or sonographic markers available at present.
  41. 41. 41
  42. 42. ADDRESS 11 Gagan Vihar, Near Karkari Morh Flyover, Delhi - 51 CONTACT US 9650588339 (Helpline) 011-22414049,22058865 WEBSITE : www.drshardajain.in www.lifecarecenreivf.com E-MAIL ID Lifecarecentre21@gmail.com info@lifecareivf.com ISO 14001:2004 (EMS) …..Caring hearts, healing hands ISO 9001:2008 ISO 9001:2008 www.globalstemgenn.com , Helpline: 9599044357 www.lifecarecentre.in Helpline:9599044257

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