OVARIAN RESERVE AND INFERTILITY

4.  Women are very different to men with regard to
reproductive ageing.
 A woman’s entire lifetime’s supply of eggs is
present at birth.
 Decreasing ovarian reserve is inevitable with
increasing age, resulting in complete infertility by
age 40-50.
 Decreasing ovarian reserve has a significant
negative effect on a couple’s reproductive
prospects from age 37 onwards but earlier for
some women.
 Ovarian reserve is a measure of how well the
ovaries are still functioning at a certain point in
time.

5.  Ovarian reserve is a term used to
describe the functional potential of the
ovary and reflects the number and
quality of oocytes within it.
 A good test of ovarian reserve 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.

7.  Ovarian reserve is a complex clinical
phenomenon that is influenced by age,
genetics, environmental variable.
 Testing is indicated in :
• 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.

9. Markers of ovarian reserve
1 - Age
2 - Basal serum FSH
3 - Basal serum estradiol
4 - Basal LH/FSH ratio
5 - Basal serum inhibin-B level
6 - Basal serum anti-Müllerian hormone level
7 - Basal ovarian volume
8 - Basal antral follicle count
9 - Ovarian stromal blood flow

11. FSH (Follicle Stimulating Hormone)
- lower is better (Normal <10 iu/L)
› test cycle day 2-4
› fluctuates between cycles when
ovarian reserve poor
AMH (Anti Mullerian Hormone)
› higher is better (normal>5pmol/L)
› less fluctuation between cycles

12. Antral Follicle Count (AFC)
› higher is better
› 5-10 AF’s per ovary –normal reserve
› <3 AF’s per ovary –poor reserve
› >10-15 AF’s per ovary – ‘polycystic’
Menstrual cycle length –
Shortening cycles indicate deteriorating
ovarian reserve.

13. Age and fertility:
In many cases, a woman’s age is the
single most important indicator of
fertility potential. A woman’s fertility
starts decreasing in her late twenties,
and decreases further after age 35.
While a 20 year old woman and a 40
year old woman ovulate the
approximate same number of times
each year, their monthly pregnancy
rate, or fecundity, is much different.

16. FSH
 FSH is the hormone released by the pituitary
gland in the brain to stimulate the ovaries to
produce a dominant follicle (which contains an
egg).
 A “good quality” egg releases certain
substances (e.g. inhibin-B, estrogen) that
suppress the FSH level (negative feedback).
When the egg quality is compromised, these
negative feedback signals are weak and there is
a resultant increase in FSH levels.
 Day 3 FSH is an indirect measure of the size of
the follicle cohort and is regulated by various
factors, including inhibins, activins, estradiol and
follistatins .

18. Antral follicle count measurements
*A normal ovary should have a volume of at least 3
cc with at least 6 – 15 antral follicles.
*Antral follicles are small, fluid filled cysts that are
normally found in the ovaries. The higher the antral
follicle count, the better the fertility potential.
*Small ovaries may indicate compromised fertility
potential, as there may be less follicles - and
therefore less eggs - available within the ovaries.
*The performance of AFC for predicting failure to
achieve pregnancy is poor. This is because while
AFC determines the number of oocytes, a clinically
relevant outcome (pregnancy or live birth)
depends on oocyte quality as well as quantity.

19. Serum estradiol
 Elevated basal estradiol may predict the poor
response even when basal FSH is normal.
The value of cycle day 3 estradiol levels in the
prediction of ovarian reserve is still debatable.
Inhibin-B
 Inhibin-B is mainly produced by the granulosa
cells in growing follicles and offers a more
immediate assessment of ovarian activity than
other serum tests.
 A fall in day 3 inhibin-B levels may predict poor
ovarian reserve before the expected rise in day
3 FSH.

21. Factors affecting Inhibin-B measurements:
• Obesity (decreases)
• PCOS (increases)
• Exogenous FSH administration (increases)
• Oral contraceptive use (decreases).
Anti-Müllerian hormone
 Antimüllerian hormone (AMH) also known as
Müllerian Inhibiting Substance (MIS) is a new
diagnostic marker of ovarian function. The
existence of AMH was first proposed in 1947 by
Professor Alfred Jost.
 This hormone is made in the sertoli cells of the
testes of men.
 It was thought not to exist in women. In recent
years, it has been found in women starting at
puberty.

22. age unit value
Younger than 24
months
ng/mL
pmol/l
15 to 500
100 to 3500
24 months to 12 years ng/mL
pmol/l
7 to 240
50 to 1700
More than 12 years ng/mL
pmol/l
0.7 to 20
5 to 140
In men, inadequate embryonal AMH activity can lead to
the Persistent Müllerian duct syndrome (PMDS), in which a
rudimentary uterus is present and testes are usually undescended.
The AMH gene (AMH) or the gene for its receptor (AMH-RII) are
usually abnormal

23.  Anti-Müllerian hormone (AMH) is produced by
the granulosa cells of the recruited follicles until
they become sensitive to FSH .
 AMH has been identified as a regulator of the
recruitment, preventing the depletion of all
primordial follicle pool at once.
 AMH is a glycoprotein growth factor and a
member of the transforming growth factor
superfamily(TGF-B)with a molecular weight of
140kDa.
 It is primarily produced by the pool of early-
growing follicles, which are believed to serve
as a proxy for the number of primordial follicles
in the ovary

24. AMH is expressed on activation of follicle growth and continues
throughout the pre-antreal stages.
AMH expression declines at approximately 4-mm follicle
diameter with little beyond 8 mm; thus, there is a switch from
AMH to oestradiol production at the time when follicle
selection occurs.

25. Age unit value
Younger than 24 months ng/mL
pmol/l
Less than 5
Less than 35
24 months to 12 years ng/mL
pmol/l
Less than 10
Less than 70
13–45 years ng/mL
pmol/l
1 to 10
7 to 70
More than 45 years ng/mL
pmol/l
Less than 1
Less than 7

26. What is the role of AMH in assessing
ovarian aging and ovarian reserve?
 AMH levels decrease over time even in
“fertile” women who have regular
menstrual cycles.
 AMH levels correlate well with the ovarian
antral follicle count and were the only levels
that decreased longitudinally over time
compared with FSH, estradiol, and inhibin-B
levels.
 With ovarian aging, the first change is a
decrease in AMH levels, followed by a
decline in inhibin-B and finally by an
increase in FSH levels.

27.  AMH levels do not vary significantly during
the menstrual cycle and can therefore be
drawn on any day of the cycle!
 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.

28. What are the factors that influence AMH
levels?
A. Factors that decrease AMH
• Increasing age
• Obesity
• Administration of gonadotropins
• Administration of chemotherapy or
radiation
• Surgical removal of one or both ovaries
B. Factors that increase AMH
• Polycystic Ovarian Syndrome

29. C. Factors that do not influence AMH
• Day of menstrual cycle
• GnRH agonists
• Birth Control Pills
• Pregnancy
What are “normal” and “abnormal” levels of
AMH?
• AMH levels less than 0.2 - 0.5 ng/mL are associated
with increased IVF cycle cancellation rates and
fewer eggs retrieved from the ovaries.
• AMH levels greater than 2.5 ng/mL are associated
with greater number of eggs retrieved and a better
fertility potential.

30.  Recent data suggest that AMH levels may reflect
fertility potential more accurately than
conventional markers like FSH, inhibin-B or estradiol
levels.
 AMH levels may be better indicators of the ultimate
chance that a woman will achieve a pregnancy
than FSH levels.
 A high AMH level (greater than 3.6 ng/mL) may
predict that a woman is at increased risk for
ovarian hyperstimulation syndrome.
› In such women, the dose of medications with IVF can be
reduced to avoid this side effect of fertility treatments.

31.  Women with higher AMH values will tend to have
better response to ovarian stimulation for IVF and
have more eggs retrieved. In general, having more
eggs with IVF gives a higher success rate.
 AMH levels probably do not tell us much
about egg quality, but having more eggs at the IVF
egg retrieval gives more to work with – so more
likely to have at least one high quality embryo
available for transfer back to the uterus.

32. Pre- antral and small antral follicles produce AMH
x6 the density of pre-antral follicles compared
with the normal ovary in PCOS. (Webber et al,
2003)
 High AMH levels in PCOS also due to increased
production by individual follicles (Pellatt et al,
2007)
Some have suggested that asymptomatic
polycystic morphology (PCOM) is not an entity
but a mild variation of normal.

33. A excess LH +insulin
Multiple small follicles
AMH
FSH action
Anovulation progesterone