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Egg Beaters: Checking Your Biological Clock

Despite the long lifespan American women now enjoy, their reproductive lifespan remains unchanged. In most women, a gradual decline in fertility begins in the late 20s and then drops off more sharply around age 35 and then again around 40. Yet fertility in this age group still varies from woman to woman.

That’s one reason why the idea of a test assessing a woman’s ovarian reserve—which depends upon the number and quality of the eggs in the ovaries and how the ovaries respond to certain hormones—is appealing for women seeking fertility treatment, and maybe even for those women who just want a better idea of how fast their biological clock is ticking. A study published in the June 17th issue of the journal Human Reproduction found that ovarian reserve may be determined through an ultrasound, sparking interest in the utility of assessing one’s "reproductive age."

Egg Timers
Though it seems hard to believe, the biological clock begins ticking before female babies are even born. After about 20 weeks in the womb, female fetuses have about seven million eggs, but by the time they’re born, they’re down to about one to two million. Over the next 35 to 40 years, women ovulate 300 to 400 eggs and the rest gradually die on their own until a woman goes into menopause around age 50.

According to the American Society for Reproductive Medicine, a healthy 30-year-old woman has about a 20 percent chance per month of becoming pregnant, while a 40-year-old woman has about a 5 percent chance per month. Although age is the most powerful predictor of fertility, other factors play a role in how quickly one’s ovarian reserve diminishes.

"If you take two 35-year-old women, you have one that may go through this process significantly faster than another 35-year-old." says Fady Sharara, MD, medical director for the Virginia Center for Reproductive Medicine and an associate clinical professor at George Washington University in Washington, DC. "There are some factors that can contribute to this, such as genetic background, smoking, ovarian surgery and exposure to radiation."

Assessing Ovarian Reserve
In order to achieve pregnancy, the follicle-stimulating hormone (FSH) must trigger the development of follicle cells in the ovaries that contain immature eggs. One of these eggs will mature in a process known as ovulation and travel though the fallopian tube to the uterus. If the egg is fertilized by a sperm cell at this time, it may attach itself to the uterine wall and pregnancy may occur.

The more eggs a woman has in her ovaries, and the higher the quality of those eggs, the better her chances of conceiving. In order to assess a woman’s ovarian reserve, there are a number of blood tests that are routinely used in women seeking treatment for infertility. These include the day 3 FSH test, the clomiphene citrate challenge test (CCCT) and the inhibin-B test. Such tests may help determine the appropriate dose of fertility medications, or how well a woman will respond to fertility treatments such as in vitro fertilization (IVF), in which eggs are surgically removed from the ovary and fertilized by a sperm cell outside of the body; fertilized eggs are then place in the uterus.

The FSH test, which is generally considered the standard test, measures the follicle-stimulating hormone. During the first, or follicular, phase of the menstrual cycle, the part of the brain known as the hypothalamus releases a hormone that tells that pituitary gland to release FSH. The hypothalamus and the pituitary gland know whether the follicles have been stimulated because the maturing egg secretes estrogen into the blood stream. If a woman’s FSH level is elevated on the third day of her menstrual cycle, that suggests that her ovarian reserve is reduced because the pituitary gland is having to release an excess amount of the hormone in its effort to stimulate the ovaries.

Physicians caution, however, that FSH test results are not a definitive assessment of fertility. "The FSH test is really only reliable when it’s abnormal, so a reassuring day 3 FSH test does not assure fertility." says Janis Fox, MD, director of egg donation at the Brigham and Women’s Hospital in Boston. That is due, in part, to the fact that the eggs that are responding to FSH might not be of good quality. At the same time, an abnormal, or elevated, test result does not mean a woman won’t be able to conceive. "You can have an elevation in FSH and still be fertile; the younger you are, the less predictive FSH levels are."

The CCCT test may provide additional information in women over the age of 35 with unexplained infertility who have normal FSH test results. This test measures FSH and estrogen levels at day three of a woman’s cycle and again at day 10, after she has taken clomoiphene (Clomid), a medication that induces egg production. If the FSH levels are still high, that may indicate a diminished ovarian reserve.

While not as widely used, the inhibin-B test measures inhibin-B, which is a hormone secreted by certain cells in the ovaries; low levels of this hormone are associated with low pregnancy rates.

The Size of the Eggs
The Human Reproduction study suggests that ovarian volume may reflect the number of follicles remaining in the ovaries, and that this may help determine ovarian reserve and therefore reproductive age. Ovarian volume, which is the size of the ovaries in three dimensions, can be measured with transvaginal ultrasound, a sonogram conducted with a vaginal probe. By analyzing large studies, the researchers found that smaller ovaries and a low number of follicles per ovary correlates with a low ovarian reserve, while larger ovaries and a high number of follicles correlates with a higher ovarian reserve.

Advice to Clock Watchers
Dr. Sharara says that these study findings are good news for all women interested in their fertility to get a sense of their "reproductive age." "If you come in at 35 and you get an ultrasound done, and your ovaries look great, then you may be able to wait, let’s say, a year or so, taking into account what happens to the ovaries as women get older than 35."

"But if you want to wait three, four years, for whatever reason, to have a child, and you do this test and your ovaries don’t look that healthy, you may really want to rearrange your priorities." he continues.

Dr. Fox, however, does not think there is sufficient evidence to justify using the test in the general population, and notes that the quality of the eggs cannot be adequately assessed with the ultrasound. "It’s not a crystal ball: I wouldn’t feel comfortable saying wait another year."

After all, in addition to the difficulty in accurately assessing ovarian reserve, there are factors other than ovarian reserve that can affect fertility, including gynecological conditions such as endometriosis, exposure to sexually transmitted diseases and infertility in a male sexual partner.

"You need to be aware of age." Dr. Fox cautions, "and the biological clock does go off a lot sooner than a lot of women think, but the idea that you can measure and predict the moment when you have to get pregnant is not true."