AMH & OVARIAN RESERVE

1. AMH & OVARIAN RESERVE DR SUNDAR NARAYANAN M.D , DLS, D.ART CONSULTANT ASSISTED REPRODUCTION & 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 - DECLINE OF 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% 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

7. 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

8. Other factors • BMI (Sedentary life style / high calorie diet) • Ovarian diseases (endometriosis, PID) • Ovarian neoplasm • Pelvic surgery • POF (? genetic / immunological)

9. 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)

10. 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

11. Testing for ovarian reserve • Hormone analysis • Ultrasound techniques • Dynamic testing • Anatomical testing (ovarian biopsy)

12. HORMONE ANALYSIS • Follicle Stimulating 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 • 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. 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. 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. 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-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

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 test no better inference than basal values

21. OVARIAN BIOPSY • Counting the number of primordial follicles on ovarian biopsy is an attractive concept. • More invasive for a routine clinical screening.

22. ANTI-MULLERIAN HORMONE

23. 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

24. 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.

25. 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)

26. Age-specific quantiles 90 70 AMH (pmol/L) 75th 50 40 30 50th 20 25th 10 10 0 25 30 35 40 45 50 Age (y) AMH

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. AMH – NORMAL RANGE

29. 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.

30. 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.

31. THANK YOU