Ovarian reserve refers to the residual oocyte - granulosa cell repertoire that at any age is available for procreation. It refers to quantity of eggs.
Age & fertility in women go hand in hand. Women are born with predetermined number of ovarian follicles which subsequently reduce by apoptosis & ovulation till menopause.
The age related decline in fecundity usually starts at the age of 32 years with a dramatic fall after the age of 37 years , when ovaries begin to respond poorly to FSH & LH .As a result body produces more of these hormones in an attempt to " jump start" egg development in the ovaries.
Female fertility has adapted to society's drastic changes. Present day women do not aspire to have children young and instead pursue a good education & career before they settle down. This is almost impossible to do before the age of 30 or later. So more females seek medical advice for subfertility . Women with diminished ovarian reserve have no overt clinical symptoms other than subfertility yet demonstrate subtle changes in baseline hormone levels.
Diminished ovarian reserve is not limited to women of advanced reproductive age , but also encountered in young females as well, seeking help of assisted reproductive techniques.
Ovarian stimulation involves time , money & effort both on the part of patient & physician. Every failed effort leads to tension & frustration to both patient & doctor. So accurate assessment of ovarian response potential before the patient enters ovarian stimulation for assisted reproduction is of pivotal importance.
In recent years several markers of ovarian reserve have been proposed & adopted in clinical practice.
Spectrum of markers for ovarian reserve :
1) STATIC tests
2) DYNAMIC tests
STATIC TESTS are:
i) age : there is a inverse relation between age & fecundity. Rapid fall in fertility after 35 years of age.
ii) FSH: Basal FSH combined with age is better predictor of IVF outcome.Most of ART centres world wide explain poor prognosis when basal FSH value is above 12 IU/l.FSH is not suitable as a diagnostic test to exclude patients , but is used as a screening test for counselling purposes.
iii) FSH : LH ratio : despite a normal basal FSH , an exaggerated FSH:LH ratio points to a deminished ovarian reserve.
iv) E2 : there is enough evidence to suggest that elevated early follicular E2 is associated with poor prognosis even when FSH is in normal range. Early elevation reflects advanced follicular development & early selection of dominant follicle.When E2 level is elevated ( 60 - 80 pg/ml), likelihood of poor response is increased.
v) Inhibin - B: a peptide hormone produced by granulosa cells in the ovary. It is an early indicator of deminished ovarian reserve & its levels are influenced by amount of fat in an individual. Serum baseline levels below 45 pg/ml have been associated with poor ovarian reserve, high IVF cancellation rates & poor pregnancy rates.
vi) AMH: It is produced by granulosa cells of preantral & antral follicles, is only marker that can be assessed in both follicular as well as luteal phase. Because it is produced solely by functional granulosa cells of preantral follicles, it represents both quality & quantity of ovarian follicle pool.Normal range is 1.6-5.0 ng/ml
vii) AFC: it is defined as no. of follicles 10 mm in diameter detected by TVS in follicular phase. It determines the no. of oocytes but not the quality.Low AFC is a sign of ovarian aging. AFC < 4 in both ovaries is highly indicative of poor ovarian reserve & poor outcome in IVF cycle with high cancellation rates.
viii) OVARIAN STROMAL BLOOD FLOW:Ovarian stromal peak systolic velocity by transvaginal pulsed doppler ultrasound in women with normal FSH has been a better predictor for OR compared with age,E2 or FSH:LH ratio. Decreased ovarian stromal blood flow is found in women with low OR
ix) OVARIAN VOLUME: As age advances, ovarian volume decreases due to progressive follicle depletion .Small ovaries are associated with poor ovarian response to superovulation & even high cancellation rate in an IVF cycle. A low ovarian volume < 3 ml has high specificity(80-90%) & widely ranging sensitivity(11-80%).
DYNAMIC TESTS are :
a) CCC test:This test involves the administration of 100 mg clomiphene citrate on days 5-9 & measurement of serum FSH on days 3& 10. A test is said to be abnormal if FSH level is >12 mIU/ml on day 3 &/day 10
b) EFORT: this test involves the measurement of basal FSH& E2 and E2 response 24 hours after administration of 300IU of FSH injection on day 3 of cycle. But it is not a test for prediction of prgnancy in an IVF population
c) GnRH agonist stimulation test:This test evaluates the serum concentration of E2 change from day 2 to day 3 of the cycle after administration of supraphysiological dose of GnRH agonist.A prompt estradiol response to flare effect of GnRH agonist may be associated with better ovarian reserve.
All the tests described so far assess the oocyte quantity and not quality. None of the tests available to us or a combination of tests can predict pregnancy or live birth with accuracy. Chronological age remains the first step in ovarian reserve assessment. Post - primordial, preantral,small follicles are best reflected in AFC & AMH, while larger gonadotrophin sensitive follicles are best represented by FSH.
Ovarian reserve tests have only modest predictive properties. Their accuracy in prediction of pregnancy is limited. A woman cannot be denied on this basis alone and these tests should be used ONLY for screening / counselling purposes. First cycle of IVF still remains the most informative of them all to tell us how a woman will respond to ovarian stimulation