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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 - PowerPoint PPT Presentation
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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 recognisedStarts at 30,rapid decline after 37, virtually zero at 43.
Due to decrease in Oocyte quantityOocyte quality
OTHER FACTORS
BMI (Sedentary life style / high calorie diet)
Ovarian diseases (endometriosis, PID)
Ovarian neoplasm
Pelvic surgery
POF (? genetic / immunological)
(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.
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-specificquantiles
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 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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