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Day 3 FSH Testing - Follicle Stimulating Hormone

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Day 3 FSH Testing - Follicle Stimulating Hormone

Testing for egg quality: Ovarian reserve

 

Background

It would be nice to have a reliable test to determine how good the eggs are in an individual woman at a point in time - as well as how many she still has remaining. We have some screening tests, however, they are far from perfect. 

This page will focus on day 3 FSH and estradiol testing. The  ovarian reserve page has more overview information on egg quality issues, as well as other screening tests. Antral follicle counts and response of the ovaries to stimulation with injectable gonadotropins are other variables that affect the overall chance for conception markedly when we attempt in vitro fertilization.

There are several ways that we try to predict "egg quality" as well as trying to estimate chances for conception with various forms of treatment. Female age is an important variable. However, a woman can be 45 with exceptionally good quality eggs and still be fertile, or, she can be 25 with very poor quality eggs and be infertile. These are extreme examples, the main point is that egg quality on the average tends to decline slowly starting in the early 30's, then more significantly in the late 30s and much more dramatically in the early 40s. However, egg quality in an individual woman can be average for her age, better than average, or worse than average.

It would be nice to have a reliable test to determine how good the eggs are in an individual woman at a point in time. We do have some screening tests, however, they are far from perfect.

These tests are often referred to as tests of ovarian reserve. In other words, does the woman have a good reserve of high quality eggs remaining in her ovaries?

 

Day 3 follicle stimulating hormone: FSH

Follicle stimulating hormone (FSH) is one of the most important hormones involved in the natural menstrual cycle as well as in pharmacological (drug-induced) stimulation of the ovaries. It is the main hormone involved in producing mature eggs.

FSH is the same hormone that is contained in the injectable gonadotropins which are used to produce multiple eggs for infertility treatment.

When a women goes into menopause she is essentially running out of eggs in her ovaries. The brain senses that there is a low estrogen environment and more FSH is released from the pituitary gland in an attempt to stimulate the ovaries enough to produce a good follicle and estrogen

You can think of it like stepping on the gas pedal in the car to get going. The FSH is the gas, and the pituitary gland releases FSH to get a follicle "going" at the beginning of every menstrual cycle. If there are less follicles left (and perhaps lower quality follicles) the "gas" has to be increased to get a follicle to start developing. In a menopausal woman, the gas pedal is on the floor for the rest of her life - even though there are no follicles (or eggs) left that are capable of developing, the woman's body never gives up trying and FSH levels are permanently elevated.

Women in menopause usually have FSH levels that are above 40 mIU/ml. As women approach menopause their baseline FSH levels (day 3 of their cycle) will tend to gradually increase over the years. When they run out of follicles capable of responding, their FSH will be quite high (over 30-40 mIU/ml) and they will stop having menstrual periods.

By measuring a baseline FSH on day 3 of the cycle (we do it on either day 2, 3, or 4), we can often get an indication that the women is closer to menopause and has relatively less "ovarian reserve". Another way of saying this is that if the baseline FSH is elevated the ovarian reserve (how many eggs are left) and probably also the egg quality is reduced. In other words, it usually reflects a compromise of both quantity and quality.

There are some practical problems associated with this test:

1. The cut off values used to say that egg quality is good, ok, or poor is very laboratory dependent. What this means is that a given level of, for example, 12 in one laboratory may reflect good ovarian reserve and egg quality - whereas the same level in another laboratory using a different assay may reflect poor ovarian reserve, poor egg quality, and low live birth rates with IVF. See below for more on interpretation of results.

2. While an abnormal result (high baseline FSH) tends to be very predictive of poor egg quality, a normal result does not necessarily mean that the egg quality is good. There are a significant number of women with normal baseline FSH values that do have poor egg quality that is not being reflected in their FSH value.

This is particularly true for women in their 40s. An infertile 44 year old woman with a normal FSH (for example 6) still has a very low probability of conceiving and delivering with in vitro fertilization - or with any other fertility treatment. The fact that she is 44 greatly diminishes her chances - even if her FSH is normal. This is why IVF programs have age cutoffs. The oldest women accepted by IVF programs varies somewhat - most programs have a cutoff somewhere between age 42-45. Infertile women older than this will rarely be successful using their own eggs. However, women in their 40s are excellent candidates for in vitro fertilization with donor eggs.

 

Interpretation of day 3 FSH levels

In our center we are currently using a DPC assay run on an Immulite machine. We consider normal for this assay to be under 8. As levels go above 8.0 we often see a reduction in response as illustrated in the table below. If your levels were run with a different assay, you can not compare the results to those shown here with any confidence at all! For example, with some assays, a level of 14 is normal...

Day 3 FSH level

Interpretation (DPC Immulite only)

Less than 6

Excellent. Very reassuring level.

6-8

Normal. Expect a good response to stimulation.

8 -10

Fair.  Response is between completely normal and somewhat reduced (response varies widely). Overall, a somewhat reduced live birth rate.

10 - 12

Lower ovarian reserve. Usually show a reduced response to stimulation and some reduction in egg and embryo quality with IVF. Reduced live birth rates.

12 - 17

Generally show a more marked reduction in response to stimulation and usually a further reduction in egg and embryo quality with IVF. Low live birth rates.

Over 17

"No go" level in our center. Very poor (or no)  response to stimulation. No live births. "No go" levels must be individualized for the particular lab assay and IVF center.

 

Some caveats about day 3 FSH testing

In general, your ovarian reserve and your egg quality is a s bad as your worst FSH. If you have an FSH of 15 in one cycle and have it repeated in another cycle and get a 7 - the situation is not improving. Some women do "bounce around" with FSH levels in the normal to abnormal range - but they will generally respond and have chances for pregnancy more like those women who are consistently at their higher FSH level.

Waiting for a menstrual cycle with a lower FSH level and then stimulating quickly for IVF is probably of no benefit at all.

Young (e.g. under 35) women with elevated FSH levels stimulate better and have a higher pregnancy potential than "older" women.

Day 3 estradiol

A blood estradiol level on day 3 (we do it on any day between days 2 and 4) of the menstrual cycle is a way to potentially discover some of those women with a normal day 3 FSH that may in fact have decreased egg quality. What we would like to see on day three is a low FSH level in conjunction with a low estradiol level. If the FSH is normal but the estradiol level is elevated, the elevated estradiol may be artificially suppressing the FSH level in to the normal range.

The idea of using day 3 estradiol levels as an adjunct in evaluating egg quality is relatively new. Clearly defined cutoff values for normal and abnormal are not well defined and are also lab-dependent. I like to see the day 3 estradiol less than about 80. In our experience, levels of 80-100 are borderline, and over 100 is abnormal. We like to repeat any borderline results in another cycle.

There is not much data that suggests that an elevated day 3 estradiol is a problem in itself. The problem is more so that it is potentially "masking" the detection of the poor ovarian reserve by suppressing an FSH level that would otherwise be elevated.

 

Clomiphene challenge test

A clomiphene challenge test is a dynamic type of test that can discover some cases of poor ovarian reserve that are still showing a normal day 3 FSH.

This test is done by:

1. Obtaining a day 3 FSH and estradiol

2. The woman takes two tablets of clomiphene (100 mg) on days 5-9 of the cycle

3. Repeat an FSH level on day 10 of the cycle

The normal test would show a low FSH on day 3, a low estradiol on day 3 and also a low FSH on day 10.

Cut off values for the day 3 and the day 10 FSH values are very lab dependent and must be determined by experience with the laboratory being used. In other words, only your infertility specialist can interpret your results.

 

In vitro fertilization

This is a treatment for infertility, but at the same time it can give much useful information about egg and embryo quality. By careful examination of the eggs and embryos during the in vitro incubation process we can sometimes get clues about why pregnancy has not occurred previously.

For example, the oocytes may demonstrate poor morphology, or may have problems with maturation, or with fertilization, proper cleavage, etc..

Treatment options for women with elevated FSH and reduced ovarian reserve

Lupron "flare" protocol for ovarian stimulation in low responders

In vitro fertilization with assisted hatching

In vitro fertilization with coculture

In vitro fertilization with donor eggs

 

 

 

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