AMH & OVARIAN RESERVE
DR SUNDAR NARAYANAN M.D , DLS,
D.ART
REPRODUCTIVE ENDOCRINOLOGIST &
GYNEC ENDOSCOPIC SURGEON
SUB FERTILITY - FACTS
 The one of the area in gynaecology with increasing
demand
 One in six couples have difficulty conceiving
 Age at which women getting married gradually
increasing
 Progressive decline in sperm quality
AGE WISE FERTILITY
 20-25 2.8% infertile
 30-34 10% infertile
 35-39 33% infertile
 40-45 86% infertile
AGE - DECLINE OF OOCYTES
MISCARRIAGE RATE
Age 30: 7-15%
Age 31-34: 17-21%
Age 35-39: 17-28%
Age 40: 40-52%
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
OVARIAN RESERVE
 Age related decline in female fertility well
recognised
Starts at 30,
rapid decline after 37,
virtually zero at 43.
 Due to decrease in
Oocyte quantity
Oocyte quality
(teVelde and Pearson 2002)
OVARIAN RESEVE
 There is considerable individual variation in the
age of menopause and, subsequently, also in the
age of subfertility. Hence, chronological age alone
is a poor indicator of reproductive aging, and
thus of the ovarian reserve.
OTHER FACTORS
 BMI (Sedentary life style / high calorie diet)
 Ovarian diseases (endometriosis, PID)
 Ovarian neoplasm
 Pelvic surgery
 POF (? genetic / immunological)
OVARIAN RESERVE
 Criteria used to assess ovarian function and to
subject sub fertile patients for ovarian
stimulation are still a matter of much debate
 Various biochemical and ultrasonographic
markers are used to investigate the ovarian
reserve in candidates for ART
TESTING FOR OVARIAN
RESERVE
 Hormone analysis
 Ultrasound techniques
 Dynamic testing
 Anatomical testing (ovarian biopsy)
HORMONE ANALYSIS
 Follicle Stimulating Hormone (FSH)
 Oestradiol
 Progesterone
 Inhibin B
FOLLICLE STIMULATING
HORMONE (FSH)
 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
 Variation from month to month
 Lab wise variation in values due to different
techniques.
 Spurious fall after hormone therapy.
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
PROGESTERONE
 Early LH surge and elevation of P4 suggested
sign of poor ovarian reserve
 Doesn’t have any independent role in assessment
of ovarian reserve
INHIBIN B
 Hetero dimeric protein similar to AMH
 Levels > 45 pg/ml – poor response to induction
 High false positive rate
 Not widely used nowadays.
ANTRAL FOLLICULAR COUNT
 Count of total follicles measuring 2 to 5mm in
both ovaries on Day 2/3 of periods.
 Some correlation with ovarian response but only
at low threshold
 If AFC < 5- significantly worse outcome.
 Inter observer variation is a limitation.
AFC
 So far, assessment of the number of antral
follicles by ultrasonography, the antral follicle
count (AFC), best predicts the quantitative
aspect of ovarian reserve
(Scheffer, et al., 2003)
OVARIAN DOPPLER
 Trans-vaginal pulse Doppler can assess
ovarian blood flow
 Some suggestion that high vascularity in
late follicular phase good prognostic sign
 No clinical value at present
CLOMOPHENE 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 no better inference than
basal values
OVARIAN BIOPSY
 Counting the number of primordial follicles on
ovarian biopsy is an attractive concept.
 More invasive for a routine clinical screening.
ANTI-MULLERIAN HORMONE
AMH
 AMH is a glycoprotein
 Appears in females at puberty
 Produced by granulosa cells of pre-antral and
small antral follicles
 Physiological function- prevent excessive follicle
recruitment
AMH
 Not cycle dependant-can be measured any day
 Less cycle to cycle variation than FSH.
 Not altered by hormonal therapy.
 Not altered even after downregulation with
GNRH agonist.
AMH
 Therefore, a serum marker that reflects the
number of follicles that have made the transition
from the primordial pool into the growing follicle
pool, and that is not controlled by gonadotropins,
would benefit both patients and clinicians. In
recent years, accumulated data indicate that
anti-Müllerian hormone (AMH) may fulfill this
role.
(Visser, et al., 2006)
AMH
Age-specific
quantiles
Age (y)
25 30 35 40 45 50
0
AMH
(pmol/L)
10
25th
50th
75th
90
50
40
30
20
10
70
AMH BLOOD LEVEL
 High (often PCOS) Over 3.0 ng/ml
 Normal Over 1.0 ng/ml
 Low Normal Range 0.7 - 0.9 ng/ml
 Low 0.3 - 0.6 ng/ml
 Very Low Less than 0.3 ng/ml
AMH – NORMAL RANGE
AMH
 Increasing age means a decreasing AMH level.
 Lower AMH levels at any age predicts a poor
response to ART.
 High AMH levels – candidates prone for OHSS.
CONCLUSION
 Anti mullerian hormone(AMH) alone or better in
combination with antral follicular count (AFC) is a
better indicator of ovarian reserve than any other
hormonal or sonographic markers available at
present.
 Also a good predictor of response to ovulation
induction both poor as well as excessive response.
THANK YOU

Amh and ovarian reserve

  • 1.
    AMH & OVARIANRESERVE DR SUNDAR NARAYANAN M.D , DLS, D.ART REPRODUCTIVE ENDOCRINOLOGIST & GYNEC ENDOSCOPIC SURGEON
  • 2.
    SUB FERTILITY -FACTS  The one of the area in gynaecology with increasing demand  One in six couples have difficulty conceiving  Age at which women getting married gradually increasing  Progressive decline in sperm quality
  • 3.
    AGE WISE FERTILITY 20-25 2.8% infertile  30-34 10% infertile  35-39 33% infertile  40-45 86% infertile
  • 4.
    AGE - DECLINEOF OOCYTES
  • 5.
    MISCARRIAGE RATE Age 30:7-15% Age 31-34: 17-21% Age 35-39: 17-28% Age 40: 40-52%
  • 6.
    ANEUPLOIDY  10% ofeggs 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
  • 7.
    OVARIAN RESERVE  Agerelated decline in female fertility well recognised Starts at 30, rapid decline after 37, virtually zero at 43.  Due to decrease in Oocyte quantity Oocyte quality
  • 8.
    (teVelde and Pearson2002) OVARIAN RESEVE  There is considerable individual variation in the age of menopause and, subsequently, also in the age of subfertility. Hence, chronological age alone is a poor indicator of reproductive aging, and thus of the ovarian reserve.
  • 9.
    OTHER FACTORS  BMI(Sedentary life style / high calorie diet)  Ovarian diseases (endometriosis, PID)  Ovarian neoplasm  Pelvic surgery  POF (? genetic / immunological)
  • 10.
    OVARIAN RESERVE  Criteriaused to assess ovarian function and to subject sub fertile patients for ovarian stimulation are still a matter of much debate  Various biochemical and ultrasonographic markers are used to investigate the ovarian reserve in candidates for ART
  • 11.
    TESTING FOR OVARIAN RESERVE Hormone analysis  Ultrasound techniques  Dynamic testing  Anatomical testing (ovarian biopsy)
  • 12.
    HORMONE ANALYSIS  FollicleStimulating Hormone (FSH)  Oestradiol  Progesterone  Inhibin B
  • 13.
    FOLLICLE STIMULATING HORMONE (FSH) 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  Variation from month to month  Lab wise variation in values due to different techniques.  Spurious fall after hormone therapy.
  • 14.
    SERUM OESTRADIOL  E2alone 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.
    PROGESTERONE  Early LHsurge and elevation of P4 suggested sign of poor ovarian reserve  Doesn’t have any independent role in assessment of ovarian reserve
  • 16.
    INHIBIN B  Heterodimeric protein similar to AMH  Levels > 45 pg/ml – poor response to induction  High false positive rate  Not widely used nowadays.
  • 17.
    ANTRAL FOLLICULAR COUNT Count of total follicles measuring 2 to 5mm in both ovaries on Day 2/3 of periods.  Some correlation with ovarian response but only at low threshold  If AFC < 5- significantly worse outcome.  Inter observer variation is a limitation.
  • 18.
    AFC  So far,assessment of the number of antral follicles by ultrasonography, the antral follicle count (AFC), best predicts the quantitative aspect of ovarian reserve (Scheffer, et al., 2003)
  • 19.
    OVARIAN DOPPLER  Trans-vaginalpulse Doppler can assess ovarian blood flow  Some suggestion that high vascularity in late follicular phase good prognostic sign  No clinical value at present
  • 20.
    CLOMOPHENE 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 no better inference than basal values
  • 21.
    OVARIAN BIOPSY  Countingthe number of primordial follicles on ovarian biopsy is an attractive concept.  More invasive for a routine clinical screening.
  • 22.
  • 23.
    AMH  AMH isa glycoprotein  Appears in females at puberty  Produced by granulosa cells of pre-antral and small antral follicles  Physiological function- prevent excessive follicle recruitment
  • 24.
    AMH  Not cycledependant-can be measured any day  Less cycle to cycle variation than FSH.  Not altered by hormonal therapy.  Not altered even after downregulation with GNRH agonist.
  • 25.
    AMH  Therefore, aserum marker that reflects the number of follicles that have made the transition from the primordial pool into the growing follicle pool, and that is not controlled by gonadotropins, would benefit both patients and clinicians. In recent years, accumulated data indicate that anti-Müllerian hormone (AMH) may fulfill this role. (Visser, et al., 2006)
  • 26.
    AMH Age-specific quantiles Age (y) 25 3035 40 45 50 0 AMH (pmol/L) 10 25th 50th 75th 90 50 40 30 20 10 70
  • 27.
    AMH BLOOD LEVEL High (often PCOS) Over 3.0 ng/ml  Normal Over 1.0 ng/ml  Low Normal Range 0.7 - 0.9 ng/ml  Low 0.3 - 0.6 ng/ml  Very Low Less than 0.3 ng/ml
  • 28.
  • 29.
    AMH  Increasing agemeans a decreasing AMH level.  Lower AMH levels at any age predicts a poor response to ART.  High AMH levels – candidates prone for OHSS.
  • 30.
    CONCLUSION  Anti mullerianhormone(AMH) alone or better in combination with antral follicular count (AFC) is a better indicator of ovarian reserve than any other hormonal or sonographic markers available at present.  Also a good predictor of response to ovulation induction both poor as well as excessive response.
  • 31.