Many women do not realize that a significant decline in fertility really begins in the early 30’s, not in the late 30’s or early 40’s as many people believe. In fact, for many successful fertility treatments, the biggest predictor of pregnancy outcome is the age of the female partner. The significant impact that age has on fertility is related to both the quality and quantity of a woman’s eggs.
In contrast to healthy men whose sperm cells continuously divide and renew themselves well into later life, healthy women are born with all the eggs that they will ever have. In fact, by the time a female infant is born, still many years away from reproductive potential, the number of eggs in her ovaries has already declined by 80% from their peak numbers. The numbers are even smaller by the time a girl enters puberty and begins to have menstrual cycles.
In addition to this decrease in the number of eggs that women can experience, some women may have poor quality eggs that reduce the likelihood that a given fertility treatment will result in a healthy pregnancy. Ovarian reserve screening is one mechanism by which fertility specialists can partially predict the reproductive potential of a specific patient as well as the potential of her eggs to result in a healthy pregnancy. This information can be used to help couples decide which therapies may be emotionally and financially sound to pursue.
There are essentially 4 different screening tests for ovarian reserve. Three of them are hormonal blood tests, and the third is an ultrasound examination. Follicle stimulating hormone (FSH) is the hormone from the pituitary area in the brain that drives the follicles (or maturing egg sacs) in the ovaries to develop an egg (or oocyte) that is ready to be released (ovulated) and fertilized. How hard a woman’s brain has to work at the beginning of the cycle to get the eggs in the ovaries to respond to the appropriate signals is a reflection of both the number and quality of the eggs that remain in the ovary. This process is reflected by circulating levels of FSH that can be measured, usually on the 3rd day of a woman’s menstrual cycle. We call this test a Day 3 FSH level. In general, FSH levels rise as the egg supply decreases. Elevated levels indicate that response in that patient to a particular treatment may be less likely to result in a healthy pregnancy compared to other patients.
Another type of ovarian reserve testing is the Clomiphene citrate challenge test. This test relies on the same principle that the brain and the ovary communicate with each other through FSH (as modulated by other hormones like inhibin and activin). This test involves measuring the Day 3 FSH and then administering clomiphene citrate (Clomid or Serophene) at a dosage of 2 tablets per day, for days 5-9. The serum FSH levels are then measured again on Day 10. The idea behind this test is to give the ovaries a push in the right direction by stimulating them with the drug before rechecking the FSH. An abnormal result on this screening test may indicate that a woman’s chances of taking home a baby after a specific fertility treatment like IVF may be significantly reduced.
Finally, some investigators are also using antral follicle counts to help determine cycle outcomes. Many fertility treatments rely on stimulating the ovaries to mature more than one fertilizable egg per month. An ultrasound measurement of the antral follicles, or small follicles available to be stimulated that month, may help predict the response of an individual woman to fertility drugs.
The newest and most accurate test available is AMH (antimullerian hormone). AMH is produced by small follicles in the ovary. AMH reflects the pool of active follicles. It can be checked at any point of the menstrual cycle. It can also be checked if someone is on birth control pills. Because AMH does not flucturate as much as FSH it is a more convenient predictor of ovarian reserve.
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It is important to know that low AMH does not mean that it is impossible to get pregnant just low egg count. It does mean that it is harder and that we need to get the ball going because things will not improve over time. AMH is an extremely important test today. It will probably replace all FSH testing in the future for fertility purposes. To some extent it predicts the number and quality of eggs collected with IVF.
Different programs have different approaches to their screening protocols. In general, most women over 35 years of age should be screened before pursuing any type of fertility therapy. Most programs will screen all women regardless of age undergoing therapy with the assisted reproductive technologies like IVF.
However, it is less clear what abnormal values may indicate in women who are younger than 32 years of age. Many times it is valuable to screen women less than 35 if they may be at an increased risk of diminished ovarian reserve (e.g. following surgery for ovarian cysts or removal of endometriosis from the ovary).
Many times when a Day 3 FSH test comes back unexpectedly high, a physician may choose to repeat this test or a patient may request that it be repeated. Despite the relative simplicity of the test, levels may fluctuate or vary considerably in the same woman from month to month and cycle to cycle. Initially fertility specialists thought it made sense to monitor these levels on a regular basis and only perform advanced therapies such as IVF on months when the FSH levels looked normal. Unfortunately, even when using later cycles with normal FSH levels, pregnancy rates were still largely poor in women who had a previously elevated Day 3 FSH level. It now seems clear that a single abnormally high FSH test predicts a markedly reduced chance for healthy pregnancy using a woman’s own eggs, even when the most advanced fertility treatments are utilized. Many of these women may still achieve pregnancy rates of 60-70% using donated eggs or oocytes.
Two areas are worth mentioning when interpreting Day 3 FSH levels. The first is that elevated levels give a woman a reduced chance of conceiving, not no chance. Some women with elevated FSH levels may still conceive using their own eggs, albeit at a reduced rate.
The second area worth mentioning is that ovarian reserve screening is good at predicting bad outcomes, but relatively poor at predicting good outcomes. In other words, a normal Day 3 FSH level will not change the age of your ovaries or eggs. A normal test of ovarian reserve means that you have an average chance of conceiving for your age group. A 44 year old with a day 3 FSH of 4.8 mIU/ml has less than half the chance of conceiving that a 32 year old with an FSH of 4.8 mIU/mL has. She in turn has less chance of conceiving than does a 22 year old with an FSH of 4.8 mIU/mL.
Ovarian reserve testing is good at predicting pregnancy outcomes, and that’s about it. While some women with extremely high levels of FSH may suffer from premature menopause, most women with modestly elevated FSH levels are not perimenopausal. On average, FSH levels begin to rise more than a decade before menopause. Therefore, the time frame from an elevated FSH level to the onset of menopause is very unpredictable. Depending on a woman’s age, the onset of menopause may be anywhere from many months to many years away.
Ovarian reserve screening should be viewed as one more piece of knowledge in your fertility work-up. Just as other hormone levels, a semen analysis, or an x-ray test of the uterus and tubes may help guide your treatment options, ovarian reserve screening is one more piece of information that you and your physician can use to jointly decide what roads may lead to your dreams of creating a healthy family.