Ovarian Reserve Screening –
An integral part of the initial infertility evaluation
It is known that a woman’s decline in her fertility occurs long before menopause, even though her menses may be regular, and continues to have ovulatory cycles. Fertility peaks when a woman is in her late teens and her twenties, and begins to decline at age 30. It drops more rapidly after age 37 and even faster with every year after age 40. By age of 45, the chance of pregnancy and live birth is very low.
The age related decline in fertility is based on the biological fact that women are born with a limited number of eggs. Since no new eggs are formed throughout a woman’s life, the number of eggs steadily declines over time until they are all depleted at menopause. Most of a woman’s eggs are lost even before she has her first menstrual period. Surprisingly, this loss is unaffected by the use of birth control pills or lack of menstrual periods.
A decline in a woman’s fertility It is not only a problem of quantity of eggs, but also a problem of quality. Over time, the quality of the remaining eggs deteriorates. This is the primary cause of the age related decline in a woman’s fecundity. The fact that the age-related decrease in fertility is due primarily defective oocyte quality also explains why a woman’s advancing age is linked to increased risks of chromosomal abnormality in newborns and an increased risk of spontaneous miscarriage.
The Ovarian Reserve
The term “ovarian reserve” refers to a woman’s current supply of eggs, and is closely associated with her reproductive potential. As a woman ages, her supply of eggs gradually declines over time until the eggs are depleted at menopause. Age is the single most important predictor a woman’s reproductive potential, but age alone has limited predictive value. Although we expect the ovary to age in a certain way, biological aging of the ovaries can occur independently of chronological age. Two women at the same age can have vastly different possibilities of conceiving on any given month. These differences are particularly wide in the 36-41 year old age group. That is why screening for ovarian reserve is a fundamental part of the initial infertility evaluation.
Ovarian volume and antral follicle count
Antral follicles, also referred to as resting follicles, are small follicles (about 2-8 mm in diameter) that we can accurately count and measure with a transvaginal ultrasound. The antral follicle count (AFC) is the number of antral follicles, generally in both ovaries taken together if not else specified. It is presumed that the number of antral follicles visible on ultrasound is indicative of the relative number of microscopic primordial follicles (containing immature eggs) remaining in the ovary.
The antral follicle count (in conjunction with female age) is one of the best tools that we currently have for estimating ovarian reserve, for predicting the response to ovarian stimulation with medications, and for predicting the chances of pregnancy after in-vitro fertilization.
Small ovaries on ultrasound may indicate compromised fertility potential, since the size of the ovaries has been shown to correlate with ovarian function and response to treatment.
In our clinic, we use the information from antral follicle count and the ovarian volume to select the protocol and dose for ovarian stimulation medications at the beginning of an IVF cycle.
The Follicle Stimulating Hormone (FSH) level
The simplest and most commonly used test to assess the ovarian reserve is obtaining a serum follicle stimulating hormone (FSH) level measured on day three of the menstrual cycle. (First day of full menstrual flow is counted as day one. Spotting is not considered start of period.)
The FSH is produced by the pituitary gland in the brain that stimulates the growth and recruitment of the ovarian follicles (containing eggs). An elevated FSH level is an indirect indicator of compromised egg quantity and quality.
Cycle day 3 is chosen because at this time the estrogen (estradiol) level is expected to be low, a critical feature, since an elevated estradiol will artificially decrease an FSH level and give us a false sense of security about the ovarian reserve. Thus, any determination of FSH needs to include the corresponding estradiol (E2) level to indicate that the FSH level was drawn, when the estrogen level was low.
In a woman with infrequent menstruation, an FSH level and estrogen level could be measured at any time and is valid if the estrogen level is low.
Generally, normal FSH levels are below 10 mIU/mL and values between 10-14 mIU/mL are considered borderline. An elevated FSH level correlates consistently with poor prognosis even for IVF success, regardless of age. In the Palmetto Fertility Laboratory, an FSH greater than 14 mIU/m l is considered highly abnormal, and live birth rates would be very low.
One problem with measuring FSH levels is that not everyone with a diminished ovarian reserve will have an abnormally elevated FSH level. An elevated FSH level indicates “diminished ovarian reserve” and correlates consistently with a poor prognosis even for IVF success, regardless of age. However, a normal level does not signify that everything is okay. When the FSH is normal, age continue to be an important predictor of a woman’s reproductive potential.
Another problem is that when FSH levels are measured repeatedly, they can vary significantly from cycle‐to‐cycle. For example, a patient with an abnormally high FSH level one month may have a normal FSH level in a subsequent cycle. The ovarian reserve has to be significantly compromised for the FSH levels to be persistently elevated. For a while we thought that it might be possible to wait for a month with a better level and improve the odds that a given cycle would work. Unfortunately we learned that the intermittent high FSH is as bad a prognostic sign in months where the FSH is normal as in months where it is high. It is the highest FSH level that is the best predictor of a woman’s reproductive potential.
The Clomiphene Citrate Challenge Test (CCCT)
The clomiphene citrate challenge test (CCCT) is a more sensitive test of ovarian reserve. This test involves the measurement of a cycle day 3 FSH and estradiol, and stimulated cycle day 10 FSH after treatment with clomiphene citrate (100mg/day, cycle days 5-9). An elevated FSH on cycle day 10 has the same meaning as an elevated day 3. Once again, a normal CCCT does not necessarily mean that the ovarian reserve is normal. When the CCCT is normal, age continue to be an important predictor of a woman’s reproductive potential. In our practice we use the CCCT to screen women with previous surgery of the ovaries, and women older than 35 because the incidence of diminished ovarian reserve begins to increase more rapidly at that time.
Ovarian reserve tests are generally reliable but certainly not infallible. An abnormal test does not preclude the possibility of pregnancy. Therefore, some women with abnormal ovarian reserve testing conceive naturally.
An abnormal test simply indicates that a successful pregnancy is less likely and this information is used in counseling patients regarding their reproductive potential. Except perhaps when grossly abnormal, test results are not used to deny treatment but only to obtain prognostic information that can help guide the choice of treatment and best use of available resources.