Ovarian reserve refers to the reproductive potential left within a woman's two ovaries based on number and quality of eggs. Diminished ovarian reserve is the loss of normal reproductive potential in the ovaries due to a lower count or quality of the remaining eggs

1. Dr. Laxmi Shrikhande
MD; FICOG ;FICMU
• Director-Shrikhande Fertility Clinic, Nagpur
• President Menopause Society, Nagpur
• National Corresponding Editor-The Journal of Obstetrics & Gynecology of India
• Senior Vice President FOGSI 2012
• Vice Chairperson ICOG
• Governing Council member ICOG 2012-2017
• Governing Council Member ISAR 2014-2019
• Governing Council Member IAGE for 3 terms
• Patron-Vidarbha Chapter ISOPARB
• Chairperson-HIV/AIDS Committee, FOGSI (2007-09)
• Received Best Committee Award of FOGSI
• Received Bharat excellence Award for women’s health
• President Nagpur OB/GY Society 2005-06
• Associate member of RCOG
• Member of European Society of Human Reproduction
• Visited 96 FOGSI Societies as invited faculty
• Delivered 3 orations
• Publications-Thirteen National & seven International
• Presented Papers in FIGO, AICOG, SAFOG, AICC-RCOG conferences
• Conducted adolescent health programme for more than 15,000 adolescent girls

2. Markers of Ovarian reserve
Dr Laxmi Shrikhande
Chief Consultant | Shrikhande fertility Clinic
Nagpur [Maharashtra] INDIA

3. What do we mean by ovarian reserve?
• term used to describe
• the functional potential of the ovary and
• reflects the number and quality of
oocytes within it

4. In ideal test
• should be predictive of conception (with or
without treatment) and
• should indicate how long current levels of
ovarian activity can be maintained before
ovarian ageing sets in

5. Ovarian reserve tests

6. Age
• Single most important factor
• At no cost
• Both quality and quantity

7. Natural Decline of Oocytes with Age

8. Decline in 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

9. Ovarian Reserve

10. Why we need markers of ovarian reserve ?
• Age of onset of decline in ovarian reserve is highly
variable
• Hence, the need for a marker to predict ovarian
reserve and fertility potential
• To identify young women with diminished ovarian
reserve
• To identify women with adequate OR even at the
age where natural fertility is lost (41 yrs)

11. 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
• Variations within and between menstrual cycle
• Lab wise variation in values due to different
techniques.
• Spurious fall after hormone therapy.

12. Basal FSH
• Meta analysis of 37 studies
• Diversity in methodology and definition of poor
response
• Finding of high FSH don’t exclude her from IVF
treatment

13. Serum Oestradiol
• E2 alone of little value to asses ovarian reserve
• Combined E2 and FSH levels – better than E2
alone.
• E2 of < 20 pg/ml and > 80 pg/ml - higher
cancellation rate

14. FSH : LH ratio
• Can be used as an additional predictor for decreased
OR
• High ratio on D3 is associated with an inferior
outcome in IVF cycle
• Ratio is an early indicator of ovarian ageing
• No clinical use as OR marker

15. Inhibin B
• Hetero dimeric protein similar to AMH
• Levels > 45 pg/ml – poor response to
induction
• High false positive rate
• Not widely used nowadays.

16. AMH
• AMH is a glycoprotein
• Appears in females at puberty
• Produced by granulosa cells of pre-antral and small
antral follicles
• Reflects the growing pool of follicles in the ovary and
indirectly the entire pool of remaining eggs – the
“ovarian reserve”

17. Role of AMH
• Plays a role in the initial recruitment and
selection of the dominant follicle.
17

18. Poor
responder
Normal
responder
Hyper
responder
AMH helps define patient subgroups
<1ng 2-3.5ng >3.5ng
▪Highly correlates with ovarian response-
▪97%sensitivity in predicting poor response
▪98%accuracy in predicting normal response
Current Opin Obstet Gynae 2010 Jan
Hum Reprod Update 2010 Mar-Apr 16(2)
Fertil Steril 2010 Feb 93(3)

19. Individualised treatment plan
• Reduction of both excessive response and
cancellation of cycle
• Reduced risk of OHSS
• Increased pregnancy and live birth rates
• Cost reduction

20. Women who are overweight have 65% lower
AMH levels than thin women, indicating that
obesity may be associated with decreased
ovarian reserve and/or with ovarian dysfunction.
Obesity and AMH

21. AMH-benefits over other markers
• most sensitive predictor of ovarian response to
COH
• 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.
• No inter observer variation as in AFC

22. AMH assay
• 2 assays-apply diff antibodies
• 1.DSL-Diagnostic Systems Laboratory
• 2. IOT-immunotech
• AMH levels are 40 % higher in IOT assay as
compared to DSL assay
• No international standard yet developed

23. AMH assay
• With the merger of both the companies in 2010
under Beckman Coulter led to the introduction of a
single new 2 step sandwich type enzymatic ,
microplate assay (the AMH gen II assay)
• AMH gen II assay is calibrated to the old IOT
standards and are thus comparable to IOT assay
• It has 2 fold greater sensitivity than the IOT assay

24. Pico AMH assay
• Has different calibration than Gen II assay
• Enhanced sensitivity over Gen II-enables
measurement of very low AMH concentrations
• Suitable for clinical use
• Need further studies in diff centres regarding its
stability

25. AMH – test
• Optimal storage and handling conditions
• Urgent need to prepare international reference
preparation to make test results comparable
• Until then we need to be careful in translating AMH
cut off values from studies to our clinical practice

26. AMH and its Interpretation
Ovarian Fertility
Potential
Pmol/L ng/ml
Optimal Fertility 28.6 to 48.5 4.0 to 6.8
Satisfactory Fertility 15.7 to 28.6 2.2 to 4.0
Low Fertility 2.2 to 15.7 0.3 to 2.2
Very low/ undetected 0.0 to 2.2 < 0.3
26

28. Role of AMH in women with cancer
• As it is secreted from granulosa cells AMH assay can
aid in diagnosis and follow up of ovarian granulosa
cell tumors
• Sensitivity ranges form 76-93 % for diagnosis of GCT
• Postop it can help as a marker for the efficacy of
surgery and for disease recurrence

29. Role of AMH in cancer survivour
• AMH assay before and after cancer treatment may
be useful to those women who are concerned about
fertility potential
• Levels usually drop during chemotherapy with
certain amount of recovery 2-6 months there after
• The main goal of AMH assay in young cancer
survivor would be to predict the long term
reproductive outcome

30. AMH-the best OR
• Best currently available marker in terms of sensitivity
and specificity as compared to AFC, FSH, E2 and
inhibin B

31. Clomiphene citrate challenge test CCCT
• Baseline FSH on D3
• CC 100 mg D5-9
• D10 FSH > 10 mIU/ml diminished OR
• Additional cost
• Pt compliance affect
• Absence of standardized abnormal test definitions
• Not an eligible OR test

32. Gonadotropin analog stimulation test GAST
• Leuprolide acetate SC 1mg
• Estradiol level on D2/3
• Increase of FSH and LH values twice the baseline
value or fall of estradiol
• Not eligible test
• Wide variety of analog doses,administration timing,
non standardization of threshhold values of
hormones tested

33. Exogenous FSH ovarian reserve test (EFORT)
▪ Baseline E2 and FSH
▪ Administer 300 IU FSH
▪ Recheck E 2 – 24 hours later : an increase in
E2 >30 pg/ ml
▪ Of no proven benefit
Fanchin et al 1994

34. 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

35. Antral follicular count
• Count of total follicles measuring 2 to
5mm in both ovaries on Day 2/3 of
periods.
• Inter observer variation is a limitation.
• cycle to cycle variability

36. AFC
• 2 D real time TVS by 7 MHz transducer is adequate
• Manual counting on stored 3 D images

38. Ovarian volume
• D1xD2xD3x0.52
• Cut off 3.0 MI
• 3 D better than 2 D
• Inter observer variation
• Stand alone- not eligible

39. Ovarian Doppler
• Trans-vaginal pulse Doppler can assess ovarian
blood flow
• Some suggestion that high vascularity in early
follicular phase good prognostic sign
• Not of clinical value at present because of
different flow derived predictors

40. • women over 30 years of age
• women with a history of exposure to a confirmed
gonadotoxin, i.e., tobacco smoke, chemotherapy,
radiation therapy.
• women with a strong family history of early menopause
or premature ovarian failure.
• women who have had extensive ovarian surgery, i.e.,
cystectomy and unilateral oophorectomy.
Whom to subject for marker tests ?

41. Clinical application of OR test
• In general the average age at first child is 30 yrs
• Accurate OR testing will motivate some women to
start family early or go for oocyte frezing
• Alternatively it can reassure some women about
delaying childbirth
• Helps in individualisation of treatment plan-expectant
to ART

42. But we want
a baby !
Ovarian reserve markers helps
Helps counsel the patient in advance so that patients can
make an appropriate and informed choice.
Individualize expectation of oocyte yield
Cost of drug regimens
Discomfort to the patient expected
Risk of complications
Chances of disappointment

43. summary
• ORTs till date have modest predictive value for
pregnancy outcome as this is dependent on many
more factors apart from OR
• ORTs are indicative of ovarian reserve status in both
the quantitative and qualitative sense
• ORTs at best should be considered as screening
tests and not as diagnostic tests
• Treatment should not be denied based on these
tests to assumed ovarian aged woman

44. 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.

45. My World of
sharing happiness!
Shrikhande Fertility Clinic
Ph- 91 8805577600
shrikhandedrlaxmi@gmail.com