Reproductive aging affects women more than men. A woman’s eggs are formed when she is only a fetus and by the time she is born 50-75% of the eggs have already died. At the time of the first period, a woman has only 10-20% of the eggs she had at birth. A woman uses about 500-1000 eggs per month. When the eggs are all gone, she is considered to be in menopause and sterile (about age 51).The loss of fertility occurs about ten years before the loss of menstrual periods and menopause.
These statistics then are the backdrop for discussions about fertility rates and whether to delay conception or to start infertility evaluation and treatment. We can achieve success even into the early 40’s, but as a woman ages, the success rates drop and the costs to achieve a baby go up (at least in general).
The mechanism for reproductive aging is genetic. The eggs formed before the woman was born. So as the woman ages, the eggs released have been sitting in the ovary for longer and longer periods of time. Scientists believe that the spindle apparatus in the eggs, which lines up the chromosomes for duplication and division (meiosis) becomes broken leading to more eggs with unequal separation of chromosomes. The unequal chromosomes (aneuploidy) then lead to abnormal embryos and infertility or miscarriage.
The 3 key tests for ovarian reserve are: AFC (Antral Follicle Count), AMH (Anti-mullerian Hormone) and FSH. The relationship of these tests are indicated in the graphic above. AFC and AMH measure egg numbers while FSH might be thought of as a quality measure. However, quality and quantity are related and each of these tests measures both factors. The tests become abnormal at different times, thus we usually measure all of them to ensure a complete picture of fertility potential.
In the late 1980’s and early 1990’s, researchers began to investigate if an elevated FSH level in a younger woman would predict diminished fertility since older women near and after menopause are infertile and they have high FSH levels. Essentially, all studies have shown this relationship even though some researchers differ in their interpretation of the predictive value of FSH.
- FSH values vary from menstrual cycle to menstrual cycle.
- Several studies suggest that the pregnancy rate does not vary but rather can be predicted from the highest value not the lowest or current value.
- The FSH level varies depending on the laboratory that performs the test. Each infertility center should establish their own cutoff values for normal, borderline (decreased pregnancy rates) and abnormal (no pregnancy expected).
The CCT is very similar to a test for diabetes call the glucose tolerance test or GTT. The GTT is also a hormone stress test which measures the baseline blood glucose level before having the patient drink a bottle of sugar water (glucola) and then retest the blood glucose two hours later. If the two hour post-glucola blood level of glucose is high then the patient has diabetes. Please note that if the patient is menopausal or diabetic then the FSH or Glucose respectively will be high at any time of the day or night and no stress test is necessary.
We sometimes perform a CCT rather than a baseline test only. In our experience, about 37% of all abnormal test results come from the day 10 FSH level obtained with the CCT. This fact means that had we only looked at the baseline FSH, then we would have incorrectly assumed that the FSH levels were normal. When we have very strongly normal AFC and AMH levels then the CCT does not had much information and we waive the test.
Here is a video presentation about reproductive aging and the CCT: