July 6, 2010

Ovarian Reserve

“Ovarian Reserve” is a term referred by many infertility specialists to describe the size, quality and developmental potential of the eggs remaining in the ovary. As a woman age’s ovarian reserve diminishes and the chance of a chromosomal abnormal egg and thus the potential for miscarriage increases. As a result, older women are less likely to become pregnant and are progressively more likely should they become pregnant to have a miscarriage. Approximately 13% of women under age 35 desiring pregnancy will have difficulty having a baby and a similar percentage of those pregnant will have a miscarriage. While 25% of women age 35-39 will have difficulty conceiving, by the age of 40, 34% of women attempting pregnancy will have difficulty and approximately 26% of those over age 40 who are pregnant will have a miscarriage. In some women, ovarian reserve and fertility decreases earlier than expected. Predisposing factors include smoking, endometriosis involving the ovary, ovarian surgery, chemotherapy, and radiation. Some women may have a genetic predisposition, suggested by their mother’s or their sister’s early menopause or related to being a carrier for Fragile X. In most women, no cause for diminished ovarian reserve can be identified. Alterations in menstrual cycle length may be one of the earliest indicators of reproductive aging, but most women with decreased reserve have no change in their menstrual pattern.

The simplest and most common “ovarian reserve” test is determination of a hormone made in the pituitary gland called follicle stimulating hormone (FSH) which is as the name suggests a hormone that is secreted to induce the ovary to make a follicle leading to a mature (ready to be fertilized) egg. The concentration of FSH in the serum obtained by venopuncture is ideally obtained on the 2nd, 3rd, or 4th day following the onset of menstrual flow. In most laboratories, FSH values greater than 10-15 IU/L are thought suggestive of diminished ovarian reserve. The serum estradiol concentration, obtained concurrently with FSH is also important since elevated levels (>75-80 pg/mL) may lower FSH concentrations below values that would otherwise suggest diminished ovarian reserve. Many fertility physicians use the clomiphene citrate challenge test (CCCT) as a method to assess ovarian reserve by measuring the serum FSH level again on cycle day 10 after taking 100 mg/day of clomiphene citrate (Clomid, Serophene) on cycle days 5-9. An abnormally elevated cycle day 2-4 FSH or estradiol concentration or stimulated (cycle day 10) FSH level (>10-15 IU/L) suggests diminished ovarian reserve. Other proposed but less well established hormonal indicators of decreased ovarian reserve include a low serum anti-mullerian hormone or inhibin B level, and a poor estradiol response to stimulation with FSH medications or gonadotropin-releasing hormone (GnRH) agonist stimulation. Ultrasonic indicators of diminished ovarian reserve obtained by a vaginal probe ultrasound examination include a decreased ovarian volume or antral follicle count, and reduced ovarian vascularity (blood flow).

Ovarian reserve testing has some value for predicting ovarian response to fertility treatments (ovarian stimulation) and may help in planning therapy (ovulation induction for IUI or IVF). However, the accuracy of these tests is limited especially in women under age 40. An abnormal test result may suggest decreased probability of success, but does not absolutely predict failure. Ovarian reserve testing does provide important information, but age and previous fertility or response to gonadotropin therapy (FSH, LH, hMG stimulation) have greater relevance and predictive value. Women with mildly abnormal results may have a lower fertility potential but they are not sterile. Therefore like all test results they should be interpreted, explained, and applied with caution, sensitivity and compassion.

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Joseph A. Hill, III, M.D.

Joseph A. Hill, III, M.D. Board-Certified in Reproductive Endocrinology and Infertility