An understanding of the basics of ovarian cycle and its hormonal control. It provides the reader with the latest evidence about various tests used for assessment of ovarian reserve

1. Ovarian Age and Reproduction:
An Appraisal of diagnostic methods
Dr/ Mahmoud Abdel-Aleem, MD
Assistant Professor Obstetrics and Gynecology
Assiut university.

3. Acknowledgments

4. Ovarian cycle and its control
There is a close synchrony between oocyte and the surrounding
somatic cells within the ovary.

5. Ovarian cycle and its control

6. Ovarian aging
• Females are born with a finite number of follicles
/oocytes.
• Age-dependent:
– Physiologic: 90%
• 40 years: pregnancy becomes difficult.
• 42-43 years: practical end of spontaneous conception.
• 45 years: ultimate loss of reproductive capacity.
– Premature: 10%
• Ovarian insufficiency.

7. • Characteristics of aging ovary
– Decreasing fecundity.
– Decreased oocyte and embryo yield with IVF.
– Increased embryo aneuploidy
– Decreasing embryo quality.
– Decrease IVF results pregnancy rate
“The greatest enemy to IVF specialistsis age” !!!

8. The finite number of oocytes !!!

9. Ovarian aging… A changing paradigm !!
Oocyte Aging
once damaged; no
way???!!!
Aging of ovarian
Environment
once damaged???
Possible beneficial
interventions
Oocyte doesn’t get elder by passage of time but rather has “
suspension in time”. And what gets elderly is the ovarian somatic
cells.
The is the rationale of using some medications to improve ovarian aging

10. HOW CAN WE ASSESS OVARIAN
AGE?
AND SO,

11. Ovarian Reserve
• It describes the woman’s remaining chance of
conception by attempting to quantitate all remaining
follicles. No one can assess.
• Total OR= mathematical ovarian age: all still
unrecruited primordial follicle (non-growing) follicles.
• Functional OR: to quantify growing follicles. So it is a
small component of TOR.

12. • Most tests assess egg quantity rather than egg
quality and these two do not always go hand in
hand.
• No individual test is a perfect marker.

13. OR testing… A changing paradigm !!
Age-
independent
values
Age-Specific
values
So, absolute values of FSH level 10 iu/l or AMH level 1.05 ng/ml
aren’t the ideal way to assess OR.

14. 1- Female age
• Can assess both quantity and quality.

15. Live birth rate/ oocyte collection
at certain age

16. 2- Antral follicle count
• US counting of the follicles measuring 2–10 mm in
mean diameter in the greatest 2-dimensional (2-D)
plane

17. 3- Basal FSH
• FSH should always be interpreted in conjunction with
an E2 result.
– If E2 is > 200pmol/l on Day 2-5,it can suppress FSH and
give false reassurance.

18. • It is an indirect measure of ovarian activity (measure
of a brain hormone).
• Inter-cycle and Intra-cycle variability.
• The ovary remains sensitive to FSH until quite late in
reproductive life so it may only rise once egg number
in the ovary is already very low.

19. 4- Inhibin-B
• The FSH, E2 and
inhibin secretion are
connected by negative
feedback.
• Inhibin B levels don’t
show the expected
gradual accelerated
decline with age.

20. 5- Basal E2
• Day 3 E2 correlates with age.
• Yearly rate of change is
significant only at older ages.
• It doesn’t reflect the number of
antral follicles, but rather their
growth activity during the
follicular phase and so it is is
not alone an accurate marker
of ovarian aging.

21. 6- Anti-Mullerian Hormone
• It is a glycoprotein dimer composed of two 72 kDa monomers.
• It belongs to the Transforming Growth Factor-b (TGF-b) superfamily
and is regulated by a gene located in short arm of chromosome 19.
• Method of measurement:
– A first generation immunoassays
• Immunotech-Beckman Coulter (IOT)
• Diagnostic Systems Laboratory (DSL)
– A second generation immunoassay, the Gen II AMH ELISA,
manufactured by Beckman Coulter.

22. Hot point on pubmed !!!

23. Why unique ?
• It is a direct measure of ovarian function
• Less inter-cycle and Intra-cycle variability.
• Not significantly affected by hormonal medication
• It slowly declines throughout reproductive life as egg
numbers drop even when they remain in large
numbers.

24. Clinical Application
Diagnosis of patients with diminished ovarian reserve.
Screening for polycystic ovary syndrome.
Triaging of patients into or out of cycles of assisted
conception.
Individualisation of controlled ovarian stimulation
protocols in IVF/ICSI.

25. Cut-off points
• Absolute figure: 1.05 ng/mL
• Age-specific values:

28. Anti-Mullerian Hormone
Good news
• AMH is the current best available
tool to assess OR.
• Low AMH cut-points are fairly
specific for poor ovarian response,
but not for pregnancy.
• AMH characterizes the recruitment
state of follicles:
– High AMH= high recruitment.
– Low AMH= low recruitment.
Bad news
• Industry is still developing better kits.
• Further testing as a screening test is
needed.
• AMH isn’t accurate at both advanced
female age and with very low levels (0.4-
0.8).
• Low AMH cut-points isn’t specific for
pregnancy.
• An AMH of 1.05 ng/mL at all ages
differentiates between poorer and better
pregnancy chances.

29. • AMH and AFC correlate well as they both assess the small non growing
follicles.
• Mathematically, FSH and AMH do correlate well:
– AMH 0.5= FSH 12
– AMH 1= FSH 10
• AMH better predicts oocyte yield in IVF than FSH in Young patients
while FSH is more superior in Old patients.
• In predicting response, they don’t correlate as they assess different
cohorts of follicles.

30. AMH in counseling for IVF
GREEN
Above the 25th centile for
younger, fertile women.
80% chance of 6 or
more eggs in IVF.
ORANGE
Between the 25th and 10th
centiles for younger, fertile
women.
50% chance of 6 or
more eggs in IVF.
RED
Below the 10th centile for
younger, fertile women.
20% chance of 6 or
more eggs in IVF.

31. 7- Composite Index in IVF