Clomid Challenge Test

The clomid challenge test is an evaluation of female pituitary hormone levels. This test utilizes the fertility medication Clomid (clomiphene citrate) to increase the accuracy of finding women with decreased ovarian reserve. The clomid challenge test is also known as the clomid challenge, the clomiphene challenge test, the clomiphene citrate challenge or simply CCCT.

Clomid challenge test background

As a physician, I would like to be able to predict those women who will be able to achieve pregnancy with current treatments and those who won’t. There are many factors that can be used to predict a woman’s chances of conceiving. For example, the higher a woman’s age, the lower her chances for achieving pregnancy — regardless of the treatment. This is true even for women who had normal fertility when they were younger.

The term used to describe a woman’s chance for conceiving is ovarian reserve. Ovarian reserve can be described as normal or poor. The tests used to predict ovarian reserve have limitations. For example, a test that shows poor ovarian reserve is very predictive for women who won’t get pregnant. On the other hand, if a test shows normal ovarian reserve, it does not mean that she will definitely get pregnant. This is a very important concept. A test that shows normal ovarian reserve hasn’t really helped you predict your chances. A test that shows poor ovarian reserve predicts a very poor chance for getting pregnant.

Understanding the Clomid Challenge Test

The clomid challenge test looks primarily at a hormone called FSH (Follicle Stimulating Hormone) at two different time points. FSH is normally produced by the pituitary gland and stimulates the ovaries to develop follicles (the small cysts which contain eggs). As the follicles develop, they produce hormones such as estradiol and inhibin-B that flow through the blood back to the pituitary gland and regulate the FSH production. This is known as a negative feedback loop.

In the picture above, the red line represents FSH levels that were obtained every day during a clomid challenge test. A small increase in FSH levels are seen during the time that the woman is taking the clomid. This increased FSH level stimulates the ovaries, the ovaries produce suppressing hormones and the FSH levels decline. By day 10 of the clomid challenge test, the FSH levels should be suppressed down to the normal range as shown in the picture.

If either the Day 3 FSH level or the Day 10 FSH level in a clomid challenge test is elevated, it is considered abnormal. A high FSH level is a sign of poor ovarian reserve. This is true if either the first or second FSH level is elevated. There are several reasons why the FSH level may be elevated in a clomid challenge test.

Let’s take the example of a woman who has had surgery to remove both of her ovaries. She obviously is unable to achieve pregnancy. If a clomid challenge test was performed, she would have very high FSH levels.

Another example is a 70 year old woman who went through menopause at age 50. Again, this woman has no chance to become pregnant (without egg donation!) even though she still has her ovaries. A clomid challenge test on this woman will also show high FSH levels.

Finally, let’s take two more examples. This time, let’s look at women with infertility for over a year. One woman is 25 years old and one woman is 42 years old.

The twenty five year woman who has an abnormal clomid challenge test is currently thought to have a decreased number of eggs remaining in the ovaries. Since women have all of the eggs they are ever going to have before they are born, women who have less eggs may have been born with a lower number or they may have lost eggs more rapidly than is considered normal. Most eggs are lost through a continual process of degeneration. The rate of degeneration may be faster in some women for unknown reasons. Other factors can affect the number of eggs. Smoking, for example, is often associated with an abnormal clomid challenge test and is thought to damage or destroy eggs. If a woman has had surgery on her ovaries, this can reduce the number of eggs as well.

The 42 year old woman with an abnormal clomid challenge test most likely has two problems: a decrease in the number of eggs in the ovaries and a problem with the “quality” of the eggs that are remaining. The decrease in the number of eggs may be completely normal for her age and a normal rate of egg degeneration. The egg quality decline is also a function of age. These women are highly unlikely to achieve pregnancy with their own eggs.

Interpretation of the Clomid Challenge Test

There is one concept that must be stressed above all else. A normal clomid challenge test tells you nothing. It does NOT prove that your ovaries are working well. It simply fails to prove otherwise. The clomid challenge test is not a sensitive enough test to identify every woman with decreased ovarian reserve. Some women with very poor egg quality are going to be missed. So, if you are 42 years old and your clomid challenge test is normal, it does NOT mean you have the fertility of a twenty year old!!On the other hand, an abnormal clomid challenge test has specific predictive value. These predictions are very accurate and have been confirmed by a number of different studies from a large number of investigators. It is well documented that women with an abnormal clomid challenge test:

Respond poorly to injectable fertility drugs (gonadotropins)
Have higher cancellation rates in IVF
Have fewer eggs retrieved in IVF
Have much lower pregnancy rates in IVF and IUI
Have higher miscarriage rates
Increased risk for chromosomally abnormal embryos

Difficulties in interpreting the clomid challenge test

The FSH hormone that is measured in a clomid challenge test, is not static. It is part protein and part sugar molecule. The sugar portion changes during the course of the menstrual cycle and throughout a woman’s life. Because of this variability, not all assays measure FSH the same way. In fact, if you sent the same blood specimen to three different laboratories for analysis of the FSH level, you will likely get three different numbers back. It is therefore, critically important that each laboratory that runs this test knows the levels at which ovarian function is reduced.

For example, an FSH level of 10 in one lab might be 20 in another lab. The normal values listed by commercial laboratories are not the normals for trying to assess fertility. If your doctor does not know the normal levels for his lab, you should go to a doctor who does.

Protocol for the clomid challenge test

Here is how the clomid challenge test (CCCT) is performed.

Call the office with the first day of your full flow period. (Day 1). When you call, be prepared to schedule an appointment for either Day 2 or 3 and Day 10 or 11.
Day 2 or 3-Come to the office for your blood test and a transvaginal ultrasound.
On Day 5, start taking the clomiphene citrate tablets. Each pill contains 50 mg. You will take two pills each day (a total of 100 mg) for 5 days.
Day 10 or 11- Come to the office for your final blood test (FSH only).
That’s it! You’re done. Finish any other tests and consult with Dr. Morris to discuss the results.

Clomid Challenge Test