16 Jul Diminished Ovarian Reserve
Jan is a 37 year old female who has never been pregnant and has been trying to conceive for eight months. She presented to her general obstetrician gynecologist who, as part of her testing, ordered blood testing to look at ovarian reserve. Jan was advised that her test results showed that her ovarian reserve was diminished, and her physician referred her to a reproductive endocrinology and infertility specialist. When Jan tried to research this topic on the internet, she was overwhelmed by the amount of information on “diminished ovarian reserve” and “high FSH” and felt very anxious about her chances to have a baby.
What is diminished ovarian reserve?
Ovarian reserve is a woman’s fertility potential, and measurements of it are intended to describe the size and quality of the remaining pool of eggs. Diminished ovarian reserve is associated with depletion in the number of eggs and worsening of egg quality.
At birth, women have approximately one million eggs. By puberty, that number decreases to around 300,000. Select eggs are ovulated (or “released”) each month, but the majority of remaining eggs undergo atresia. Atresia is a process whereby oocytes degenerate and are no longer viable. This process occurs in all women, regardless of whether a woman takes oral contraceptive pills or is pregnant. This underlies the concept of the “biological clock.” It is known that the number and quality of eggs declines with a woman’s age, but that fertility may vary significantly between women of the same age. Women begin to lose ovarian reserve before they stop having regular periods.
How is ovarian reserve measured?
No ovarian reserve test reliably predicts the possibility of becoming pregnant and no single test is 100% accurate. As a result, ovarian reserve tests should be interpreted carefully.
An abnormal ovarian reserve test may indicate that the ovarian aging process has begun. Ovarian reserve tests do predict a woman’s response to hormonal stimulation. Women with diminished ovarian reserve have a lower chance of becoming pregnant during hormonally stimulated cycles compared women of the same age who have normal ovarian reserve testing.
Ovarian reserve testing includes both biochemical (blood laboratory) and ultrasound measurements of the size of the ovarian egg pool. Biochemical tests most commonly used include FSH, estradiol, and antimullerian hormone (AMH), or tests such as a Clomiphene citrate challenge test. Ultrasound measures of ovarian reserve include antral follicle count (AFC).
- FSH- This hormone is made by the pituitary gland in the brain. The concentration is measured on day two or three of the menstrual cycle. This is the simplest and most widely utilized measure of ovarian reserve. The abnormal range may vary with the levels validated for any particular assay, but typically levels >10 mIU/mL are consistent with diminished ovarian reserve. Elevated FSH levels predict the response of a patient’s ovaries to hormonal stimulation, but are less able to predict the likelihood for successful pregnancy. Of note, many women with diminished ovarian reserve will have normal FSH levels on day three, so a normal day 3 FSH does not confirm normal ovarian reserve.
- Estradiol – This hormone is made by the ovaries and is also collected day two or three of the menstrual cycle. It provides additional information in the interpretation of FSH results. An elevated estradiol level (typically >60-80 pg/mL) can suppress FSH and thus also be predictive of diminished ovarian reserve. When both FSH and Estradiol are elevated, ovarian response to stimulation is likely to be poor.
- Clomiphene Citrate Challenge test- This test measures FSH and Estradiol after stimulation with Clomiphene. This test is used less commonly than other tests.
- AMH – This hormone is produced by the granulosa cells of small follicles in the ovaries, and levels correlate directly with ovarian reserve (the higher the ovarian reserve, the higher the AMH levels). Follicles are small, fluid filled pockets in the ovary, each of which contains an egg. AMH can be measured any day of a patient’s menstrual cycle and does not vary between menstrual cycles. Low AMH levels predict a poor ovarian response to hormonal stimulation but are not as accurate in predicting pregnancy.
- AFC – This is a transvaginal ultrasound measurement of the total number of antral follicles measuring 2-10mm in both ovaries and produces a useful measure of ovarian reserve. AFC measurements correlate well with response to hormonal stimulation. Ongoing studies are attempting to establish normative levels of AFC based upon a patient’s age.
How do I know if my ovarian reserve is diminished?
The only way to know your ovarian reserve is diminished is to have ovarian reserve testing. A woman with diminished ovarian reserve may have regular, normal menstrual cycles. However, due to hormonal changes that occur with diminished ovarian reserve, some women may begin to have shorter menstrual cycles.
What are risk factors for diminished ovarian reserve?
As described above, the aging process is the largest risk factor for diminished ovarian reserve. The decline in the pool of eggs starts to accelerate in a woman’s mid- to late-thirties. Ovarian surgery and smoking are other risks for diminished ovarian reserve.
Can anything be done to improve ovarian reserve?
In the case of Jan, what are her best treatment options?
Assuming the rest of the evaluation for Jan and her partner is normal (normal hysterosalpingogram and normal semen analysis), Jan should be counseled regarding her treatment options and likelihood for success. A basic approach to many infertility treatments includes providing hormonal stimulation to increase the number of eggs a patient ovulates each month, either as part of an intrauterine insemination (IUI) cycle or in vitro fertilization (IVF) cycle.
For further information or to schedule an appointment, please call our Reproductive Medicine Clinic at (414) 805-7370.