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
(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
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
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
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
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
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
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
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
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
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
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
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
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.
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
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
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
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
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
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
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
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
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
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
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
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
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
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.
