Anti mullerian hormone
Ovarian ReserveDr. Angelo Smith M.DWHPL
General FactsWomen are very different to men with regard to
reproductive ageing.A womans entire lifetimes 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 couples 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.DefinitionOvarian 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.
5Ovarian Reserve
6Ovarian 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.
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-Mllerian hormone level 7 - Basal ovarian
volume 8 - Basal antral follicle count 9 - Ovarian stromal blood
flow
Measures of Ovarian ReserveFSH (Follicle Stimulating Hormone) -
lower is better (Normal 5pmol/L)less fluctuation between cycles
Antral Follicle Count (AFC)higher is better 5-10 AFs per ovary
normal reserve10-15 AFs per ovary polycystic
Menstrual cycle length Shortening cycles indicate deteriorating
ovarian reserve.
Age and fertility: In many cases, a womans age is the single
most important indicator of fertility potential. A womans 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.
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 .
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. Serum estradiolElevated 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-BInhibin-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.
Factors affecting Inhibin-B measurements: Obesity (decreases)
PCOS (increases) Exogenous FSH administration (increases) Oral
contraceptive use (decreases).
Anti-Mllerian hormoneAntimllerian hormone (AMH) also known as
Mllerian 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.
Reference range in MaleageunitvalueYounger than 24
monthsng/mLpmol/l15 to 500100 to 350024 months to 12
yearsng/mLpmol/l7 to 24050 to 1700More than 12 yearsng/mLpmol/l0.7
to 205 to 140In men, inadequate embryonal AMH activity can lead to
thePersistent Mllerian duct syndrome (PMDS), in which a rudimentary
uterus is present and testes are usuallyundescended. The AMH gene
(AMH) or the gene for its receptor (AMH-RII) are usually abnormal
Anti-Mllerian 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
Amh Production
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.
Age unitvalueYounger than 24 monthsng/mLpmol/lLess than 5Less
than 3524 months to 12 yearsng/mLpmol/lLess than 10Less than 701345
yearsng/mLpmol/l1 to 107 to 70More than 45 yearsng/mLpmol/lLess
than 1Less than 7What 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.
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.
What are the factors that influence AMH levels? 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
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.
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.
AMH levels and pregnancy chances with in vitro
fertilizationWomen with higher AMH values will tend to have better
response toovarian stimulation for IVFand have more eggs retrieved.
In general, havingmore eggs with IVF gives a higher success
rate.AMH levels probably do not tell us much aboutegg 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.
PCOS & AMH Pre- antral and small antral follicles produce
AMHx6 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.
AnovulationA excess LH +insulin
Multiple small follicles
AMH
FSH action
Anovulation progesterone
