THE BIOLOGIC CLOCK

The biologic clock refers to the concept of “ovarian reserve”. Ovarian reserve is quite simply the total number of follicles (eggs) left on the ovaries.

A woman has the most eggs she will ever have when she is in her mother’s uterus at about 20 weeks of pregnancy. (i.e. roughly 20 weeks before she is even born). There are approximately a total of seven million immature eggs at this time. The eggs are continuously being lost from that point on, even though there is no menses. This process results, at birth, in a lower number of follicles/eggs in the ovaries. The number of eggs a woman has at birth then is approximately two million. By the time a woman has her first menstrual cycle, on average at age 11-12 years, she has lost approximately 75% more of the total number of eggs she started with. Typically the age of first menstrual period for a woman is about eleven or twelve and at this time there is an estimated 400,000 eggs total in the ovaries. From that point on, every menstrual cycle, if the cycles are regular, the woman produces a group of early eggs referred to as a cohort of antral follicles. This is the number of follicles that have potential to grow and ovulate in any one menstrual cycle. Typically of course, only one from the cohort does grow and ovulate, the rest die off.

There is a certain number in this cohort of antral follicles each month. A woman of young age will have a larger number in the cohort than an older woman. The number of antral follicles in this cohort is relatively stable from month to month and does not fluctuate substantially. However, over a period of several months or a year, the number of follicles in the cohort can be expected to decrease. That is to say that over time, the number of follicles/eggs in the cohort will decrease. This decrease is the “biologic clock”, also referred to as “ovarian aging”. It is inevitable that the number of follciels goes down with time, one cannot change this from happening.

After the age of 35 the rate at which the number of follicles are lost increases. Thus, after the age of 35, on average, a woman will lose eggs faster than she did previously, at a younger age. Ultimately, on average, around the age of 50 there will be no follicles or eggs left in the cohort. This is referred to as menopause.

Assessing the status of any individual female’s ovarian reserve, the number of follicles in the cohort, is relatively easy. There are several tests to assess the cohort size. The most useful tend to be, quite simply, some blood tests early in the menstrual cycle (on day 3, 4, or 5) in addition to a transvaginal ultrasound to count the number of visible follicles present on the ovaries bilaterally. This US is typically done with high-resolution ultrasound. Quite typically also, a female can have all these tests done in the same single office visit This is obviously quite convenient and efficient. The ultrasound perhaps may take on average 5-10 minutes to perform. There are several other blood tests that can be performed depending on the patient’s situation and/or interest in further assessment. The simple basic blood tests include the following: FSH, Estradiol, and Inhibin-B, along with the antral follicle count as determined by transvaginal ultrasound noted above. Other blood tests such as Clomid challenge test, EFORT, GNRH stimulation, etc are more complicated, involved, and time consuming. These other tests tend not to provide substantial additional information that is useful for assessing fertility potential. Thus they need only be done in rare cases, if ever.

Assessing simply the hormonal blood tests noted above without the antral follicle count by vaginal ultrasound, in my opinion, is not acceptable. This does not give the complete picture. This is why the combination of ultrasound and simple blood test, obtained efficiently and effectively in a single visit, is optimal.

This combination of tests allows one to assess the status of ovarian reserve (i.e. where the patient is relative to the biologic clock). If there are low numbers of follicles and/or abnormalities of the blood tests, then of course this has significant implication on that patient’s future fertility potential. This knowledge, of course, may significantly influence how that patient plans her future fertility management. In some cases, of course, we can tell that “time is on your side”. That is to say, if the antral follicle count and blood tests look good, one can reasonably expect that there will not be a dramatic change in these results over a given period of time. As such, this can be very reassuring and helpful to know for the patient or couple. On the other hand, if there is cause for concern with overt or subtle abnormalities of these tests, this may influence how the patient looks at future fertility. Perhaps at minumum, these tests (with physician consultation to describe the results and their implications) may suggest that simple reassessment later would be of significant value.

Ultimately finding out where one is on the spectrum of ovarian reserve, I believe, is of substantial importance for a patient/couple to make decisions about how they will approach child bearing. These tests may provide an indication of how aggressive one should be in pursuing pregnancy and ultimately give information about how to pursue treatment. In the end, of course also, these test results may also go a long way in indicating how successful the various treatment options might be.

Thus, in summary, the simple evaluation is of importance in providing knowledge that provides a rational way for them to discuss childbearing. Ultimately giving the patient/couple an indication of whether treatments need to be pursued, what treatment options are available, and how successful those treatment options might be. Understnading all of this is valuable so that the patient/couple may take control of their future.
Please feel free to contact me via e-mail at pahlering@sherinstitute.com or via phone at (314) 983-9000 if there are further questions. Also, free consultation can be arranged if need be. In addition, our website http://www.haveababy.com/ has a tremendous amount of information and allows people to anonymously query physicians and patients in the SIRM network through the Discussion Board on the website.

Peter M. Ahlering, M.D. Medical Director, SIRM St Louis