SUB FERTILITY - FACTS
The one of the area in gynaecology with increasing
One in six couples have difficulty conceiving
Age at which women getting married gradually
Progressive decline in sperm quality
Age 30: 7-15%
Age 31-34: 17-21%
Age 35-39: 17-28%
Age 40: 40-52%
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
Age related decline in female fertility well
Starts at 30,
rapid decline after 37,
virtually zero at 43.
Due to decrease in
(teVelde and Pearson 2002)
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.
BMI (Sedentary life style / high calorie diet)
Ovarian diseases (endometriosis, PID)
POF (? genetic / immunological)
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
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
Spurious fall after hormone therapy.
E2 alone of little value to asses ovarian reserve
Combined E2 and FSH levels – better than E2
E2 of > 80 pg/ml day 3 pre IVF cycle- higher
Early LH surge and elevation of P4 suggested
sign of poor ovarian reserve
Doesn’t have any independent role in assessment
of ovarian reserve
Hetero dimeric protein similar to AMH
Levels > 45 pg/ml – poor response to induction
High false positive rate
Not widely used nowadays.
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.
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)
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
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 no better inference than
Counting the number of primordial follicles on
ovarian biopsy is an attractive concept.
More invasive for a routine clinical screening.
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
Not cycle dependant-can be measured any day
Less cycle to cycle variation than FSH.
Not altered by hormonal therapy.
Not altered even after downregulation with
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
(Visser, et al., 2006)
Increasing age means a decreasing AMH level.
Lower AMH levels at any age predicts a poor
response to ART.
High AMH levels – candidates prone for OHSS.
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
Also a good predictor of response to ovulation
induction both poor as well as excessive response.