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Clinical definition

Tests to define

Telomere theory

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Thoughts on Ovarian Reserve

Decreased ovarian reserve is one of the more difficult diagnoses that a patient can have. That is because such patients are much more difficult to help to achieve pregnancy since the normal tools to achieve pregnancy don't work as well. Some patients will likely have at most a few years of potential fertility left, so the situation is urgent. Some may have limited or no fertility left, but the process of finding this out, at times, involves a process of trial and error.

A woman is born with as much as one to two million eggs. Although she will ovulate only three to four hundred of them, the rest will essentially wither away until there are none left. She will then be menopausal. Most of the time, the eggs are in a protected state with a small group of them constantly being released from this protection. Some of these eggs develop small cysts (antral follicles) that are capable of responding to gonadotropin stimulation (primarily FSH). We do not know what causes the ovary to change the status of these eggs, so we refer to the process as a women's biological clock. Those eggs that have left their arrested state will go on and ovulate provided they receive optimal hormonal stimulation. If they don't get this stimulation, they soon undergo an actively defined degeneration (called apoptosis).

Clinical Definition

One way of defining decreased ovarian reserve is when a woman has fewer than 25,000 eggs in her ovaries. Statistically this occurs around age 38. Fertility is still present until around 42 years old and, for most women, therapy to achieve pregnancy is still a reasonable thing to do. Menopause (no eggs) occurs around age 51. However, these numbers are only averages and these events have a distribution around these averages. For example, many women don't experience menopause until well past age 51. Similarly about 10% of all women will have decreased ovarian reserve by age 32. In a practice such as mine, where women are self-selected to come here on the basis of not being able to get pregnant, the incidence of decreased ovarian reserve is even higher.

Women with certain histories need to be especially concerned about their reproductive potential. Of greatest concern is a a family history of early menopause, certain chemotherapies, and pelvic radiation. Also of concern are a history of (significant) pelvic surgery, pelvic infection, severe endometriosis (especially if treated surgically), and smoking (dose and duration related).

Tests for ovarian reserve

Currently, the best method to assess decreased ovarian reserve is a resting antral follicle count since this best correlates with the eggs remaining in a woman's ovaries and her likely response to traditional infertility therapies. Other approaches that are used include a day 3 FSH/estradiol test, a clomid challenge test, a GnRH stimulation test, inhibin measurements and anti-Mullerian hormone (AMH) measurements. When AMH and antrral follicle counts are very low, the diagnosis is certain. A day 3 FSH abnormality is a late finding for this problem. It is important to understand that a normal day FSH levels tells you nothing about your ovarian reserve status (other than the result itself). Sometimes using several approaches is valuable and all results need to be individualized for the patient.

Therapy needs to be aggressive and at minimum should utilize gonadotropins. Although the pregnancy rate with IVF is reduced compared to women of similar age with normal ovarian reserve, the relative benefit of IVF is more important in this situation. The simplified way to think about why there is a reduced pregnancy rate when there are adequate, even if reduced numbers of embryos produced, is that the patient's ovaries are acting older than her chronological age. However, the telomere theory more elegantly explains why this occurs.

The real tragedy with decreased ovarian reserve is when it is not recognized and aggressively treated, sometimes, during years of infertility therapy. Since decreased ovarian reserve can be seen in some women in their twenties, it is important that anyone with a moderately long history of infertility see a physician who is capable of evaluating this problem.