AMH & OVARIAN RESERVE
DR SUNDAR NARAYANAN M.D , DLS, D.ART
CONSULTANT ASSISTED REPRODUCTION
& 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
OTHER
FACTORS

BMI (Sedentary life style / high calorie diet)

Ovarian diseases (endometriosis, PID)

Ovarian neoplasm

Pelvic surgery

POF (? genetic / immunological)
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.
(teVelde and Pearson 2002)
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


Doesn’t have any independent role in assessment
of ovarian reserve
Early LH surge and elevation of P4 suggested
sign of poor 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 test 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 after hormonal therapy.

Not altered even after down regulation 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
90
70
AMH
(pmol/L)
75
th
50
40
30
50th
20
25
10
th
10
0
25
30
35
Age (y)
40
45
50
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 given time irrespective
of 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.
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