"A question some women face: when to freeze their eggs." This was the start of a news piece I heard on NPR as I drove to work this morning. It caught my attention and I realized we haven't spent much time on this blog exploring the tests used to help achieve pregnancy.
The premise of "ovarian reserve" testing is rather straightforward: they are supposed to help a woman concerned about fertility decide whether she should freeze her eggs for future use or if she can wait to conceive because time is still on her side.
Unlike sperm, which are produced continually over a man's reproductive lifetime, the number of eggs in the female ovaries peaks during fetal development, declines over time, and do not regenerate. Thus, female fertility declines with each year of life. Tests of ovarian reserve are supposed to reflect the number and quality of remaining eggs, a key element in reproductive potential. Ovarian reserve tests include both blood tests and ultrasound tests. This post will focus on the blood tests.
With normal ovarian function, the developing eggs in the ovary secrete hormones which keep the concentration of follicle-stimulating hormone (FSH) in its normal range during the first few days of the menstrual cycle. When the number of developing eggs is decreased, the concentration of FSH is increased. Thus, measuring FSH on day 3 of the menstrual cycle is a test of ovarian reserve and higher values are associated with lower fertility.
Estradiol is released from developing eggs during the first few days of the menstrual cycle. Estradiol concentrations are usually low during days 2-4 but increase thereafter. A high value at this time suggests poor ovarian reserve.
Anti-Müllerian hormone (AMH) is produced by the granulosa cells of eggs and so its concentration reflects the size of the ovarian pool of eggs. As the number of eggs declines, so too does AMH. But while the concentration of AMH predicts the quantity of eggs, it does not predict their quality.
Inhibin B is another hormone released by eggs and so it is similar to AMH in evaluating the number of eggs in the ovary. Because inhibin B helps to regulate FSH concentrations, a low inhibin B is associated with a high FSH. Unlike AMH, inhibin B shows a lot of variation across menstrual cycles so it's not a recommended test of ovarian reserve.
Clomiphene Citrate Challenge Test
Clomiphene is a selective estrogen receptor modulator that causes the pituitary gland to release the hormones needed to stimulate ovulation. This test is performed by measuring FSH on cycle day 3 (before giving Clomiphene) and again on day 10 (after giving Clomiphene, daily, on days 5-9). In women with normal ovarian reserve, the rising inhibin B and estradiol concentrations produced from the developing eggs would suppress FSH. However, in women with decreased ovarian reserve, FSH is elevated on day 10 due to the lower concentrations of inhibin B and estradiol.
Not surprisingly, no single test is adequate to evaluate a woman's ovarian reserve. To address that, it is not unusual for doctors to perform several of these tests in an effort to provide a more definitive answer. Unfortunately, there is still no universally agreed upon definition of "decreased ovarian reserve" and evidence of decreased reserve (biochemical or otherwise) does not correlate very well with the inability to conceive.
So while there is a very strong desire to have definitive tests to predict a woman's fertility potential in an effort to help her decide if she can wait to conceive or take action such as harvesting and freezing eggs for future use, such answers are not yet available from lab tests alone.