Beginnings

For the past 8 years I have answered questions online at www.inciid.org from patients around the world who were suffering from infertility. Some have been easy while others have been profoundly complex. I have caught my own patients lurking from time to time..."just wanted to see if you would give me the same answer online as you did in person." In the summer of 2005, my beloved father-in-law, Larry Smith, was diagnosed with lung cancer. As a family, we were devastated. Soon after the diagnosis had been made, I attended a conference at Inova Fairfax Hospital on Lung Cancer. Outside the auditorium there was a pharmaceutical company giving away free copies of a book entitled "100 Questions and Answers about Lung Cancer." The book was outstanding and I found it to be very helpful as I tried to negotiate the trials that confronted our family after Larry's diagnosis.

Several months later I contacted the publisher, Jones and Bartlett (no, they don't make wine coolers) to see if they were interested in a 100 Q&A book about infertility and IVF. They responded in a very positive fashion and here we are at the launch of a blog about the book. Of course, it may be that no one will read this except my mother, but she is a pretty good critic so that works for me.

With each post I thought that I would share some insight about how this book came about, and provide a single question (of the 100...). This blog is not meant to be a definitive source of medical information and there are several excellent Infertility Blogs out there... I especially enjoy Dr. Fred Licciardi's (he is an excellent and thoughtful MD).

So here we are:

10. What is ovarian reserve, and how is it tested?
During a woman’s reproductive cycle, each month a single follicle is selected out of a group of potential follicles, reaches maturity, and ovulates a single egg. Many fertility treatments use medications to “rescue” other follicles from that group, so that multiple eggs are released during ovulation as opposed to just a single egg. If physicians could predict which patients would respond well to fertility treatments, then those women with a poor chance of success could defer these treatments and consider other options. Those women who respond well to fertility medications are described as having normal ovarian reserve. Those patients who have a poor response to fertility medications are described as having diminished ovarian reserve.

Ovarian reserve consists of two separate components, both of which determine a woman’s chance of conceiving a child with IVF. The first component is the number of extra follicles that are available to undergo recruitment with treatment using fertility medications. This number depends on several factors, including the woman’s chronological age (as discussed below), previous ovarian surgery, genetics, and exposure to environmental toxins (most notably, tobacco usage). The second component is the actual health of the follicles and the eggs within those follicles. First and foremost, egg quality is determined by a woman’s chronological age. Peak female fertility occurs when a woman is in her twenties and then drops significantly with age, especially following age 35.

This fact has been conclusively demonstrated in many ways but is especially obvious when we look at IVF pregnancy rates. In patients who undergo IVF, studies have shown that around the age of 35 years old a marked decrease occurs in the chance of an embryo implanting successfully. In addition, the miscarriage rate rises with age, especially in those women older than age 40, in whom this rate exceeds 50%. Therefore, the age component of ovarian reserve is essentially immutable. In other words, unless she uses eggs from an egg donor, a woman cannot change her chronological age—and with increasing age, the number of normal eggs inevitably falls sharply. Although it is true that the percentage of normal eggs within an ovary is specific to the individual woman, even the most fertile women possess very few normal eggs after age 40.

The concept of ovarian reserve testing, therefore, represents a means by which the physician attempts to evaluate a woman’s reproductive potential both in terms of the number of follicles that remain and the health of those follicles. There are several ways in which one can assess ovarian reserve. First, the woman’s follicle-stimulating hormone (FSH) level can be measured on day 2 or 3 of a normal menstrual cycle. An estradiol level should be obtained at the same time, because the FSH level can be misleadingly low in women who have a high estrogen level early in the menstrual cycle. Alternatively, ovarian reserve can be assessed by performing a transvaginal ultrasound and counting the antral follicles present. In women with a slightly elevated FSH level, a transvaginal ultrasound may reveal a large number of follicles—somewhat reassuring the patient and her physician that perhaps her ovarian reserve is more normal than might otherwise be expected.

Unfortunately, normal FSH and estradiol levels do not guarantee a normal response to fertility medications. The clomiphene citrate challenge test (CCCT) was initially described as a means to identify those women with normal FSH and estradiol levels on day 3 of the menstrual cycle (day-3 hormones) who may demonstrate a suboptimal response to injectable fertility medications and poor IVF pregnancy rates. In the CCCT, the patient takes 100 mg of clomiphene citrate on cycle days 5 through 9. An FSH level is checked on days 3 and 10. If both of these levels are less than 10 IU/L (international units), then this represents a normal response. If the FSH level is greater than 10 IU/L on day 3 but less than 10 IU/L on day 10, then this represents a borderline situation, but potentially reassuring based on the response of the ovary to stimulation with clomiphene citrate. If the FSH level is normal on day 3 but more than 10 IU/L on day 10, however, the woman is likely to exhibit a suboptimal response to fertility medication, along with high IVF cancellation rates and poor pregnancy rates.

A word of caution is in order regarding ovarian reserve testing, including the CCCT: Virtually all physicians have patients who have successfully delivered a child following an abnormal CCCT. An abnormal CCCT or elevated FSH levels on cycle day 3 do not preclude spontaneous pregnancy and delivery. Nevertheless, the miscarriage rate and the incidence of Down syndrome may be increased in such pregnancies. Patients with diminished ovarian reserve may have successful treatment with the combination of fertility drugs and intra-uterine insemination (IUI), or even with IUI alone. The real benefit of the CCCT is its ability to identify those patients in whom IVF is markedly less likely to be successful, allowing them to focus on other options such as donor-egg IVF, adoption, or less invasive office-based fertility treatments. Overall, ovarian reserve testing represents an important factor when considering various fertility treatments and may be the final arbitrator in selecting the specific treatment plan.