Anti-Mullerian Hormone1 Testing of Ovarian Reserve

What is the official name of the AMH gene? The official name of this gene is anti-Mullerian hormone. AMH is the gene's official symbol. The AMH gene is also known by other names, listed below. Read more about gene names and symbols on the About page. What is the normal function of the AMH gene? The AMH gene provides instructions for making a protein that is involved in male sex differentiation. During development of male fetuses, the AMH protein is produced and released (secreted) by cells of the testes. The secreted protein attaches (binds) to its receptor, which is found on the surface of Mllerian duct cells. The Mllerian duct, found in both male and female fetuses, is the precursor to the female reproductive organs. Binding of the AMH protein to its receptor induces self-destruction (apoptosis) of the Mllerian duct cells. As a result, the Mllerian duct breaks down (regresses) in males. In females, who do not produce the AMH protein during fetal development, the Mllerian duct becomes the uterus and fallopian tubes. How are changes in the AMH gene related to health conditions? persistent Mllerian duct syndrome - caused by mutations in the AMH gene Persistent Mllerian duct syndrome type 1, a disorder of sexual development that affects males, is caused by mutations in the AMH gene. Males with this condition have female reproductive organs in addition to normal male reproductive organs. At least 38 mutations in the AMH gene have been identified in people with persistent Mllerian duct syndrome type 1. Most mutations change single protein building blocks (amino acids) in the AMH protein. Other mutations result in a premature stop signal that leads to an abnormally short protein. Still other mutations delete regions of DNA from the AMH gene, which changes the instructions for the protein. The mutated AMH protein cannot be released from the cells of the testes or cannot bind to the receptor on the Mllerian duct cells. As a result, the Mllerian duct cells never receive the signal for apoptosis. The Mllerian duct persists and becomes a uterus and fallopian tubes. Because the AMH protein is not involved in the formation of male reproductive organs, affected males also have male reproductive organs. Where is the AMH gene located? Cytogenetic Location: 19p13.3 Molecular Location on chromosome 19: base pairs 2,249,112 to 2,252,071 The AMH gene is located on the short (p) arm of chromosome 19 at position 13.3. More precisely, the AMH gene is located from base pair 2,249,112 to base pair 2,252,071 on chromosome 19. See How do geneticists indicate the location of a gene? in the Handbook. Where can I find additional information about AMH? You and your healthcare professional may find the following resources about AMH helpful. Educational resources - Information pages (2 links) You may also be interested in these resources, which are designed for genetics professionals and researchers. PubMed - Recent literature OMIM - Genetic disorder catalog Research Resources - Tools for researchers (4 links) What other names do people use for the AMH gene or gene products? anti-Muellerian hormone MIF MIS

Page author Richard Sherbahn MD

Related Pages Ovarian Reserve Problems Antral Follicle Counts Day 3 FSH Test Age and Fertility IVF Ovarian Stimulation IVF costs In vitro fertilization IVF Insemination IUI IVF Success Rates Egg Donation Donor Egg Success Rates

What is AMH?
AMH, or anti-mullerian hormone is a substance produced by granulosa cells in ovarian follicles. It is first made in primary follicles that advance from the primordial follicle stage. At these stages follicles are microscopic and can not be seen by ultrasound. AMH production is highest in preantral and small antral stages (less than 4mm diameter) of development. Production decreases and then stops as follicles grow. There is almost no AMH made in follicles over 8mm.

muellerian-inhibiting factor muellerian-inhibiting substance Mullerian inhibiting factor Mullerian inhibiting substance See How are genetic conditions and genes named? in the Handbook. Where can I find general information about genes? The Handbook provides basic information about genetics in clear language. What is DNA? What is a gene? How do genes direct the production of proteins? How can gene mutations affect health and development? These links provide additional genetics resources that may be useful. Genetics education Human Genome Project Resources for Genetic Researchers

Therefore, the levels are

AMH and fertility How can AMH hormone levels be a fertility test?
Since AMH is produced only in small ovarian follicles, blood levels of this substance have been used to attempt to measure the size of the pool of growing follicles in women. Research shows that the size of the pool of growing follicles is heavily influenced by the size of the pool of remaining primordial follicles (microscopic follicles in "deep sleep"). Therefore, AMH blood levels are thought to reflect the size of the remaining egg supply - or "ovarian reserve".

With increasing female age, the size of their pool of remaining microscopic follicles decreases. Likewise, their blood AMH levels and the number of ovarian antral follicles visible on ultrasound also decreases. Women with many small follicles, such as those with polycystic ovaries have high AMH hormone values and women that have few remaining follicles and those that are close to menopause have low anti-mullerian hormone levels.

AMH levels and pregnancy chances with in vitro fertilization

Women with higher AMH values will tend to have better response to ovarian stimulation for IVF and

have more eggs retrieved. In general, having more eggs with IVF gives a higher success rate. We do not have a lot of data yet on what to tell couples going through IVF about their AMH results and chances for conception. However, the table below shows ranges for AMH levels and some information about interpretation. AMH levels probably do not reflect egg quality, but having more eggs at the IVF egg retrieval gives us more to work with - so we are more likely to have at least one high quality embryo available for transfer back to the uterus.

What is a normal AMH level? Interpretation of anti-mullerian hormone levels and chances for conception
There are some problems involved with interpretation of AMH hormone levels. Because the test has not been in routine use for many years, the levels considered to be "normal" are not yet clarified and agreed on by the experts. Also, not all current commercial assays give equivalent results. The table below has AMH interpretation guidelines from the fertility literature and our own experience. Do not get carried away with the cutoff values shown here. For example, the difference between a 0.6 and a 0.7 ng/ml test result puts a woman in a "different box" in this table - but there is very little real difference in fertility potential.

In reality, it is a continuum - and not something that categorizes well. Interpretation High (often PCOS) Normal Low Normal Range Low Very Low AMH Blood Level Over 3.0 ng/ml Over 1.0 ng/ml 0.7 - 0.9 ng/ml 0.3 - 0.6 ng/ml Less than 0.3 ng/ml

More will be learned regarding anti-mullerian hormone levels and outcomes as we continue to use the AMH fertility test and study the relationship between AMH hormone values and fertility, ovarian responsiveness, chances for IVF success, etc.

Ovarian reserve testing methods

Anti mullerian hormone is one potential test of ovarian reserve. There are other tests that are currently used for evaluation of the remaining egg supply. None of the tests are perfect, and fertility specialists will often use a combination of tests to try to get a better estimate of the size of the remaining egg supply. Note: Anti mullerian hormone has also been referred to (mostly in the past) as "mullerian inhibiting substance", or MIS.

Learn more about ovarian reserve: Overview of ovarian reserve testing Antral follicle counts and ovarian response to stimulation Day 3 FSH testing Egg quantity and quality and ovarian reserve

Treatment options for women with reduced ovarian reserve:

Lupron "flare" protocol for ovarian stimulation in low responders In vitro fertilization with assisted hatching In vitro fertilization with donor eggs

Ovarian reserve fertility tests evaluation of egg quantity and quality

Page author Richard Sherbahn MD

Female age is a very important consideration when estimating the probability for conception because it is a strong determinant of egg quality. A 45 year old can have good quality eggs (for her age) and still be fertile, although this is rare At the other extreme, a 25 year old can have very poor quality eggs and be infertile These are extreme examples. The point is that egg quantity and quality declines in the mid 30s - and faster in the late 30's and early 40s.

Ovarian Reserve Tests Day 3 FSH testing AMH hormone testing Antral follicle counts Related Pages Egg quantity and quality In vitro fertilization, IVF IVF stimulation protocols IVF success rates IVF costs Egg donation Donor egg success rates

Egg quantity and quality in a 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 many eggs remain and how good the eggs are in an individual woman at a point in time. We have some screening tests but they are not perfect. These tests are often referred to as tests of "ovarian reserve" We are testing the supply (or reserve) of eggs remaining in the ovaries

Do ovarian reserve tests check egg quantity, quality, or both?

Ovarian reserve testing can tell us quite a lot about the remaining quantity of eggs a woman has, but it tells us little about the quality of those eggs. Age is the best "test" that we have at this time for egg quality

Egg quality and quantity and effect on success with fertility treatment Testing fertility potential in women in the general population

Day 3 FSH (follicle stimulating hormone) and estradiol (E2) test

By measuring a baseline FSH on day 3 of the cycle, we sometimes get an indication that the women is closer to menopause and has relatively less "ovarian reserve". In other words, if the day 3 FSH is elevated the egg quantity is reduced.

More about day 3 FSH and estradiol testing More about premature menopause

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 discussed on the day 3 FSH page.

Response of the ovaries to ovarian stimulation with injectable gonadotropins (FSH)

This is not really a "test" that we do to help us determine egg quantity and quality - it is part of a treatment for infertility. However, the response of the ovaries when the woman takes injectable FSH for stimulation is often very predictive of the egg quantity - and therefore, also the relative chances for success with infertility treatment. Response to stimulation and antral follicle counts are important predictors of outcome, and are discussed in detail elsewhere.

Anti-Mullerian hormone levels, AMH

Blood levels of the hormone AMH are often used by fertility specialists as part of the evaluation of ovarian reserve.

Provocative tests of ovarian reserve

We can also challenge the ovaries with drugs (hormones) and assess whether they have responded appropriately in order to distinguish women with good ovarian reserve from women with diminished reserve. For example, the exogenous FSH ovarian reserve test involves giving an FSH injection on day 3 of the cycle and testing both the baseline FSH and baseline and 24 hour post-injection estradiol to see if a normal response has resulted. If the estradiol response is poor, ovarian reserve and egg quantity are also likely to be poor. The woman is also less likely to be a "normal responder" to gonadotropin stimulation.

In vitro fertilization
This is a treatment for infertility, but at the same time it can give us much useful information about egg andembryo quality. By careful examination of the eggs and embryos during the in vitro incubation process we sometimes get clues about why pregnancy has not occurred previously. For example, the eggs may demonstrate poor morphology, or may have problems with maturation, or with fertilization, proper cleavage, etc.

Treatment options for women with reduced ovarian reserve:

In vitro fertilization

Lupron "flare" protocol for ovarian stimulation in low responders In vitro fertilization with assisted hatching In vitro fertilization with donor eggs

Antral Follicle Counts, Resting Follicles and Ovarian Reserve Testing egg supply and predicting response to ovarian stimulation
Page author Richard Sherbahn MD

Related Pages Day 3 FSH Ovarian reserve, antral blood test follicles and egg supply AMH blood test Women are born with all the eggs they will ever have. Eggs are lost Age and constantly until menopause, when fertility none remain. "Ovarian reserve" Egg quantity refers to the reserve of the ovaries and quality (remaining egg supply) to be able to In vitro make babies. fertilization We want a test that shows how IVF success many eggs a woman has at a point rates in time - as well as telling us about IVF pricing the quality of the eggs. plans Antral follicle counts by ultrasound IVF are one of the best ovarian reserve stimulation tests that we currently have protocols available. IVF with donor eggs

IVF success rate by antral Number of eggs retrieved at count IVF by antral count 2007-2010 data from our 2007-2010 data from our program program Age under 35 years old Age under 35 years old Details on antrals and IVF outcomes for other age groups is below

What Are Antral Follicles?

Antral follicles are small follicles (about 2-8 mm in diameter) that we can see - and measure and count - with ultrasound. Antral follicles are also referred to as resting follicles. Vaginal ultrasound is the best way to accurately assess and count these small structures. In my opinion, the antral follicle counts (along with female age) are by far the best tool that we currently have

for estimating ovarian reserve, the expected response to ovarian stimulating drugs, and the chance for successful pregnancy with in vitro fertilization. Presumably, the number of antral follicles visible on ultrasound is indicative of the relative number of microscopic (and sound asleep) primordial follicles remaining in the ovary. Each primordial follicle contains an immature egg that can potentially develop in the future. When there are only a few antral follicles visible, there are far fewer eggs remaining as compared to when there are more antrals. As women age, they have less eggs (primordial follicles) remaining and they have fewer antral follicles. Antral follicle counts are a good predictor of the number of mature follicles that we will be able to stimulate in the woman's ovaries when we give injectable FSH medications that are used for in vitro fertilization. The number of eggs retrieved correlates with IVF success rates. 1. When there are an average (or high) number of antral follicles, we tend to get a "good" response with many mature follicles. We tend to get a good number of eggs at retrieval in these cases. Pregnancy rates are higher than average. When there are few antral follicles, we tend to get a poor response with few mature follicles. Cancellation of an IVF cycle is much
2.

more common when there is a low antral count. Pregnancy rates are lower overall in this group. The reduction in success rates is more pronounced in women over 35 years old. 3. When the number of antral follicles is intermediate, the response is not as predictable. In most cases the response is intermediate. However, we could also have either a low or a good response when the antral counts are intermediate. Pregnancy rates are pretty good overall in this group. More on egg quantity and quality issues and ovarian reserve High ovarian volume and high antral follicle

counts Ultrasound image of an ovary at the beginning of a menstrual cycle. No medications being given. The ovary is outlined in blue. There are numerous antral follicles visible - marked with red. 16 are seen in this image. Ovary had a total of 35 antrals (only 1 plane is shown). This is a polycystic ovary, with a high

antral count and high volume (ovary = 37 by 19.5mm) This woman had irregular periods and was a "high responder" to injectable FSH drugs. Normal ovarian volume and "normal" antral follicle counts

Ultrasound image of an ovary early in the menstrual cycle. No medications being given. The ovary is outlined in blue. 9 antral follicles are seen - marked with red. The ovary has normal volume (cursors measuring ovary = 30 by 18mm). Expect a normal response to injectable FSH.

Low ovarian volume and low antral follicle

counts An ovary is outlined in blue and is small (low volume) with only 1 antral Her other ovary had only 2 antrals She had regular periods and a normal day 3 FSH test Attempts to stimulate her "sleepy" ovaries for IVF were not successful

How many antral follicles is "good"?

There is not a perfect answer to this question. Unfortunately, we do not live in a perfect world, and some ovaries have not yet read up on antral follicle counts to know how they are supposed to respond to stimulation. Antral follicle counts can also be somewhat "observer-dependent". This means that if we had several different trained ultrasonographers do an antral count on a woman, they would not all get exactly the same result. Therefore, what we decide

looks like 6 antral follicles, at another clinic might have been read as 4 or 8, etc.

From our own observations and experience, here are some general guidelines:
Total number Expected response to injectable of stimulating drugs and chances antral for IVF success follicles
Extremely low count, very poor (or no) response to stimulation. Less Cycle cancellation is likely. than 4 Should consider not attempting IVF at all. Low count, we are concerned about a possible/probable poor response to the stimulation drugs. Likely to need high doses of FSH product to stimulate ovaries adequately. 4-6 Higher than average rate of IVF cycle cancellation. Lower than average pregnancy rates for those cases that make it to egg retrieval. Reduced count Higher than average rate of IVF cycle 7-10 cancellation. Moderately reduced chances for pregnancy success as a group. 11-15 Intermediate count

Response to drug stimulation is sometimes low, but usually adequate. Slightly increased risk for IVF cycle cancellation. Pregnancy rates as a group are slightly reduced compared to the "best" group. Normal (good) antral count, should have an excellent response to ovarian stimulation. Likely to respond well to low doses of 16-30 FSH drugs. Very low risk for IVF cycle cancellation. Some risk for ovarian overstimulation. Verry good pregnancy success rates overall. High count, watch for polycystic ovary type of ovarian response. Likely to have a high response to low Over 30 doses of FSH product. Higher risk for overstimulation and ovarian hyperstimulation syndrome. Very good pregnancy rate overall.

Correlation of antral counts and IVF outcomes As shown below, there is a strong association between antral numbers and: Ovarian response to stimulating medications Chances for IVF success Risk of having a cancelled cycle

In the charts below:

Live birth success rates shown by green columns Rate of cycle cancellation before egg retrieval shown by yellow columns Average number of eggs retrieved shown by red text

Antrals and IVF Success - Female age under 35

IVF live birth rates are reduced with low antral follicle counts Women with low antral counts give fewer eggs and have higher cycle cancellation rates The average antral follicle count in women under age 35 age was 28

Antrals and IVF Success - Women of ages 35-37

Women 35 to 37 years old have somewhat lower success than the under 35 group Higher rates of cycle cancellation are also seen The average antral follicle count at age 35-37 was 21 Antrals and IVF Success - Female age 38-40 years

The average antral follicle count at age 38 to 40 was 15

Antrals and IVF Success - Female age 41-42

Women age 41 to 42 have substantially lower success rates Having more than 22 antrals was best The average count at this age was only 13 The above data is from our IVF program at the Advanced Fertility Center of Chicago Risk for cycle cancellation according to the antral count As seen in the above charts, the chance of "cancellation" when attempting in vitro fertilization is higher with low antral follicle counts. IVF attempts are sometimes "cancelled" when the ovaries respond very poorly to stimulation meds. This is because success rates are very low when less than 3 mature follicles are present on ultrasound.

More about IVF cycle cancellation

Response to stimulation with gonadotropins (FSH drugs)

The level of response of the ovaries when the woman takes injectable FSH for stimulation is often predictive of the egg quantity and quality - and therefore, also the relative chances for success with infertility treatment. The level of response that we will get from ovarian stimulating drugs can be estimated in advance with antral follicle counts (see above table). There are no absolute and accepted cutoffs for defining "low", "normal", or "high-responders". However, here are some guidelines. Low responder: When stimulated aggressively with injectable FSH will develop less than 5 mature follicles - often requiring high doses of the medications Some women will only develop 1 or 2 mature follicles - even on high drug doses These women might not be good candidates for IVF using their own eggs and could possibly need IVF with donor eggs

"Normal" or "average" responder:

When stimulated aggressively with injectable FSH will develop 5-8 mature follicles as well as several smaller ones

High responder: When stimulated with injectables can develop about 8 or more mature follicles as well as many small and medium-sized follicles These women usually respond briskly to lower doses of medications They are at higher risk for ovarian hyperstimulation syndrome

In vitro fertilization is a treatment for infertility and is not done as a "test", but it does give us some information about egg and embryo quality. Careful examination of the eggs and embryos during the in vitro incubation process in the laboratory can give us clues about "egg quality" For example, eggs may demonstrate poor morphology, may have problems with maturation, or with fertilization, proper cleavage, or blastocyst formation, etc.

Day 3 FSH Fertility Testing of Ovarian Reserve - Follicle Stimulating Hormone Test
Page author Richard Sherbahn MD Background on Ovarian Reserve Testing We would like to have a reliable test to determine how many eggs a woman has remaining and how good they are at any point in time There are screening tests for "ovarian reserve" as fertility doctors call it. Is there still a good reserve of eggs remaining in the ovaries? This page is about day 3 FSH and estradiol testing

See ovarian reserve for more on egg quantity and quality issues and other ovarian reserve tests.

Related Pages Female Age and Fertility Ovarian Reserve Problems Antral Follicle Counts AMH Test of Ovarian Reserve Stimulation of Low Responders Premature Ovarian Failure In Vitro Fertilization, IVF Our IVF Success Rates IVF Using Donor Eggs Our Donor Egg Success Rates

Antral follicle counts and response of the ovaries to stimulation with injectable gonadotropins are other variables that affect the overall chance for conception when we attempt IVF - in vitro fertilization. Female age is a very important variable. However, a woman can be 42 and still have some good quality eggs (and still be fertile), or she can be 25 with poor quality eggs and be infertile, although this is rare. In general, egg quantity and quality tends to decline slowly starting in the early 30's, and then much faster in the late 30s and early 40s.

What does FSH hormone do?

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

What produces FSH hormone?

Both FSH and LH hormone are produced by the pituitary gland at the base of the brain. When a women goes into menopause she is running out of eggs in her ovaries. The brain senses that there is a low estrogen environment - and signals the pituitary

to make more FSH hormone. More FSH is released from the pituitary in an attempt to stimulate the ovaries to produce a good follicle and estrogen hormone. 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 amount of "gas" has to be increased to get a follicle 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. The woman's body never gives up trying - FSH levels are permanently elevated. Women in menopause have high FSH hormone levels - 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 high and they stop having periods. If this happens in a woman under age 40, we call it premature ovarian failure or primary ovarian insufficiency

Why do we measure the FSH level on day 3?

By measuring a woman's baseline FSH on day 3 of the cycle (we do it on day 2, 3, or 4), we get an indication as to whether she has normal "ovarian reserve". We are looking at how hard her body needs to "step on the gas" early in the menstrual cycle to get a follicle growing. Therefore, if the baseline FSH is elevated the ovarian reserve (how many eggs are left) is reduced (sometimes the egg quality is also reduced).

Some practical problems with the day 3 FSH test:

1. The cut off values used to say that egg quantity is good, OK, or poor is laboratory dependent. For example, and FSH of 11 in one laboratory may reflect good ovarian reserve whereas a level of 11 in another lab using a different assay may indicate diminished ovarian reserve. See below for more. While an abnormal result (high baseline FSH) tends to be very predictive of low egg quantity, a normal result does not necessarily mean that the egg quantity is good. There are a significant number of women with normal FSH values that have a reduced egg supply. The lower egg supply is not being reflected in their FSH value. This is why doing antral follicle counts and AMH levels can be useful. By doing multiple ovarian reserve tests, we are more likely to find an ovarian reserve problem if there is one.
2.

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 a baby 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 44 will very rarely be successful using their own eggs. However, these women are excellent candidates for in vitro fertilization with donor eggs.

Interpreting day 3 FSH blood test results - what are normal FSH levels?
In our fertility center we currently use an assay made by DPC that is run on an Immulite machine. We consider normal FSH level to be anything less than 9. As levels go above 9 we often see a reduction in response to ovarian stimulating drugs as described in the table below. If your FSH levels were run using a different assay, you can not compare your results to those shown below with confidence. For example, with some assays an FSH of 12 is normal. Day 3 FSH FSH interpretation for DPC Immulite assay

level
Less Normal FSH level. Expect a good than 9 response to ovarian stimulation. Fair. Response is between normal and somewhat reduced (response varies 9 - 11 widely). Overall, a slightly reduced live birth rate. Reduced ovarian reserve. Expect a reduced response to stimulation and 11- 15 some reduction in embryo quality with IVF. Reduced live birth rates on the average. Expect a more marked reduction in response to stimulation and usually a 15 - 20 further reduction in embryo quality. Low live birth rates. Antral follicle count is an important variable. Over 20 This is pretty much a "no go" level in our center. Very poor (or no) response to stimulation. "No go" levels should be individualized for the particular lab assay and IVF center.

More issues regarding day 3 FSH testing

In general, your ovarian reserve is as bad as your worst FSH. If you have an FSH of 15 in one cycle and then a a 7 in another cycle - the situation is not improving. Some women "bounce around" with FSH levels in the normal to abnormal range. However, they tend to respond and have chances for

pregnancy as predicted by their highest FSH level. Waiting for a menstrual cycle with a lower FSH level and then stimulating right away for IVF is not of any proven benefit. Young women (under 35) with elevated FSH levels tend to stimulate better and have a much higher IVF success potential than "older" women. The better egg quality in the younger women can compensate for the quantity problem. More about egg quality, egg quantity and fertility problems

Day 3 estradiol testing

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 quantity and quality. What we want 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 will often be artificially "suppressing" the FSH level down to the normal range. The idea of using day 3 estradiol levels as an adjunct in evaluating egg quantity and quality is relatively recent. Clearly defined cutoff values for normal are not well established. We like to see the day 3 estradiol less than about 80. We repeat

borderline or abnormal results in another menstrual cycle to try to get a "true" FSH. There is some evidence that an elevated day 3 estradiol indicates a problem with ovarian reserve. This is sometimes the case, but often the issue is just that the elevated estrogen level is "masking" the potential for detecting low reserve by suppressing FSH into the normal range.

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. Take 2 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 Clomid challenge test result is a low FSH on day 3, a low estradiol on day 3 and a low FSH on day 10. Cut off values for the day 3 and the day 10 FSH values are assay dependent and must be determined by experience with the lab being used.

In vitro fertilization - IVF

In vitro fertilization is a treatment for infertility, not a test. However, the IVF cycle details can give useful

information about egg and embryo quality. By careful examination of the eggs and embryos during in vitro culture we can get clues about why pregnancy has not occurred previously. For example, the eggs may demonstrate poor morphology, may have problems with maturation, with fertilization, or with 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 donor eggs

Egg quality & quantity & the relationship to fertility, infertility and IVF success
Page author Richard Sherbahn MD

Female age is important in considering the probability for pregnancy because it is very much related to egg quality, which in turn is crucial in determining embryo quality.

Related Pages Egg number IVF success Embryo quality In vitro fertilization Egg quantity, also IVF stimulation referred to as ovarian reserve, overview is the number of eggs a IVF success woman has remaining for the rates future Donor egg In general, egg quantity is success rates also closely related to age, but it can vary dramatically at IVF costs Come here for any age IVF Tests of ovarian Egg Testing reserve are done by fertility specialists to estimate the Testing for egg remaining egg supply supply Antral follicle counts on Antral follicle ultrasound, day 3 FSH testing, counts and AMH levels are the best AMH blood tests of ovarian reserve testing Day 3 FSH The number of eggs blood testing obtained with IVF has a strong influence on the chance for success

Can we test eggs for quality?

We can test egg supply with ovarian reserve testing (mentioned above) but we do not have a test for egg quality. At this time, the best test of egg quality is female age Chromosomal abnormalities in eggs increase significantly with aging Poor egg quality is often related to chromosomal abnormalities - aneuploidy

Patients often say: "My eggs are fine, I don't think I need testing for that." When asked how they know the eggs are fine, the most common answers are; "Because I get my period every month" "Because my gynecologist said my eggs are fine"

However, the gynecologist did not do any tests of ovarian reserve, so the patient got information based on an assumption and not based on data. Or, maybe the patient and the gynecologist did not communicate well and there was a misunderstanding about the "egg issue". A 45 year old can have some good quality eggs and still be fertile, although this is rare At the other extreme, a 25 year old can have poor quality eggs and be infertile (also rare)

These are extreme examples. The point is that egg quantity and quality declines significantly as women age. IVF success rates and age

When does ovarian reserve and fertility begin to decrease?

The decline in fertility potential in women usually begins in the early 30s and accelerates in the mid to late 30's. Egg quantity and quality in an individual woman can be average for her age, better than average, or worse than average. When couples try to get pregnant on their own (yes, fertility doctors approve of having a sex life and getting pregnant without our help) a limiting factor will sometimes be egg quality. She may have regular monthly menstrual cycles and have sex on the perfect day for the sperm and egg to have a date. But if the egg she ovulates is poor quality (a red dot in the figure below) then it will either: 1. Not fertilize 2. Fertilize, but not develop properly to become capable of implanting in the uterus 3. Implant - but then not be "healthy and normal" enough to be able to continue proper fetal development - resulting in a miscarriage.

When we do ovarian stimulation and intrauterine insemination or in vitro fertilization procedures, the issues are similar. With these treatments there also can be an issue of egg quantity as well as egg quality If only a few eggs develop in response to the ovarian stimulating drugs, we have a lower chance of success because of a reduced supply (quantity) issue. There could be an egg quality issue as well. Number of eggs obtained and success rates with IVF

The drawings and discussion below are to help illustrate issues about the relationship between egg quantity, egg quality, age and fertility potential.
Dots are eggs Green dots are eggs that are "good" enough to fertilize, develop normally into a quality embryo and result in a healthy baby being born. Red dots are eggs that are not "good" enough to fertilize, develop into a quality embryo and jump through all of the hoops in order to become a healthy baby.

A sample from an ovary of a woman of advanced "reproductive age" - for example age 42

Few eggs and a low percentage of quality eggs

This represents a sample from an ovary of a young woman - for example, age 28 Many eggs and a high percentage of quality eggs For example, if we are doing IVF on 2 women as represented above with the "dots": One is 42 with low ovarian reserve, the other is 28 with good ovarian reserve We give the ovarian stimulating drugs to both women

The 42 year old has a low remaining number of eggs - and therefore has a low response to the drugs - and we get 4 dots (eggs) The 28 year old has a lot of eggs remaining - and therefore has a high response to the drugs - and we get 14 dots (eggs) Even more importantly, we need green dots instead of red dots to have a baby The response of the ovaries to the drugs is random - green dots (good eggs) are not more likely to respond compared to red dots (poor quality eggs)

If we (randomly - with our eyes closed) dip a soup ladle into the (42 year old) ovary (upper one) and get 4 dots - are any of them green? It is likely that they would all be red - which would result in a failed IVF cycle. If we dip a ladle into the soup of dots from the ovary with good reserve (lower one) and get 14 dots - are any of them green? It is likely that at least some would be green - which would then be expected to result in good embryo quality, a successful IVF cycle and a live birth. Perhaps there would also be some frozen embryos that could be used later to have more children. Quite often, the reason IVF fails is as simple as "we didn't get a green dot"

The point is not that a 42 year old should not try IVF and a 28 year old should. This is just to illustrate issues related to egg supply, egg quality, resulting embryo quality and chances for success with IVF and other fertility treatments. Testing fertility potential in the general population (not infertility patients)

Treatment options for women with reduced ovarian reserve:

In vitro fertilization Lupron "flare" protocol for ovarian stimulation in low responders In vitro fertilization with assisted hatching In vitro fertilization with donor eggs