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Dr. Gleicher discusses High FSH, its effects on fertility and treatment options.
What is High FSH?
FSH is not the disease, FSH is the symptom, it is a reflection of what the ovary does.
FSH (follicle stimulating hormone) is a hormone released by the pituitary gland which stimulates the growth of follicles and has a role in the maturation of oocytes. The measurement of FSH levels in the blood is one of the most widely used tests to assess a woman's ovarian function and is typically taken on day 2 or 3 of a woman's menstrual cycle. If a woman's FSH levels are above what is expected for her age, then she is considered to have "High FSH".
IVF with High FSH Levels
Success of an In Vitro Fertilization (IVF) cycle depends largely on the patient's ability to produce a good number of high-quality eggs. In attempts to predict the probability of an IVF cycle being successful, experts have developed a number of tools to assess patients' "ovarian reserve." They include blood tests like FSH, and others (like AMH, anti-Müllerian hormone) that can be drawn at any time. Assessing so-called antral follicle counts (AFCs), the number of small follicles at cycle start through vaginal ultrasound, is another popular method of measuring ovarian reserve. High FSH levels, as well as abnormally low AMH and/or AFCs also denote a relatively poor fertility prognosis and low probability of success with IVF.
High FSH and Infertility
Given FSH's role in maturing eggs, you might think that high FSH is a good thing. This, however, is not the case. High FSH, also known as elevated FSH, indicates low ovarian reserve and significantly lower pregnancy chances with In Vitro Fertilization (IVF).
It is important to remember that FSH levels increase, and AMH levels as well as AFCs decline as women age. This means that normal ranges for all of these measurements change. This is often forgotten, even by fertility specialists. At CHR we, however, utilize age-specific FSH levels to determine whether a woman's ovarian reserve is normal or not. Since CHR investigators first reported the use of such age-specific values, their utilization has significantly picked up world-wide.
Interpreting FSH Levels Should Be Age-Specific
A few years ago, CHR's research established age-specific levels of FSH and AMH. Any FSH level means different things if found at different ages. For example, a normal FSH level for a woman at 42 suggests premature ovarian aging (POA) if found in a 32-year old. To really assess a woman's ovarian reserve, and her IVF pregnancy chances, one really needs to look at age-specific AMH and FSH levels. The table below demonstrates age-specific AMH and FSH levels for CHR's patients.
|AGE SPECIFIC BASELINE FSH and AMH LEVELS|
|< 33 Years||< 7.0 mIU/mL||= 2.1 ng/mL|
|33-37 Years||< 7.9 mIU/mL||= 1.7 ng/mL|
|38-40 Years||< 8.4 mIU/mL||= 1.1 ng/mL|
|= 41+ Years||< 8.5 mIU/mL||= 0.5 ng/mL|
Limitations of FSH to Assess Fertility
CHR never withhold IVF from women with elevated FSH
Many fertility centers, unfortunately, still use universal cut-off values for FSH and AMH. When a patient has high FSH or low AMH, they simply refuse treatment, irrespective of patient age and other factors. This approach may ensure higher pregnancy rates at such centers (because they reject women with smaller chances), but it leaves women with elevated FSH and/or low AMH often feeling abandoned. CHR, therefore, does not have such arbitrary cut off values.
FSH is not specific enough
The medical literature suggests that FSH is not as specific as it was thought. Indeed, a number of papers published by CHR's physicians suggest that AMH is actually more specific than FSH in assessing ovarian reserve and pregnancy chances with IVF. Better AMH specificity makes sense because AMH reflects the smaller follicles, which represent a majority of a woman's ovarian reserve. (The figure to the left demonstrates that ranges are narrower for AMH than FSH, suggesting that AMH is more precise in reflecting ovarian reserve.) Given the superiority of AMH, IVF treatment decisions, based on high FSH levels alone, appears outdated.
FSH is only a part of the pictureWhile FSH levels and AMH levels are important in assessing ovarian reserve, both have limitations. Neither FSH nor AMH can, indeed, categorically determine whether a woman can or cannot conceive, unless she has very high FSH levels. AMH can be completely undetectable for a woman to get pregnant with IVF, as over 50 pregnancies so far in women with undetectable AMH at CHR clearly demonstrates. Therefore, placing too much emphasis on high FSH and low AMH can be misleading.
Treatment for FSH Infertility
Our DHEA treatment program for high FSH and diminished ovarian reserve
Yet, perhaps the most important reason for not refusing fertility treatment to women with high FSH levels is this: Even with high FSH, women can conceive, if given proper treatment.
Over the last 5 to 6 years, hundreds of women with diminished ovarian reserve have received high FSH treatment at CHR and ended up conceiving after all, using an IVF protocol specifically developed for women with abnormally poor ovarian reserve. A central component is supplementation with dehydroepiandrosterone (DHEA) prior to IVF. Through extensive research, CHR has been able to demonstrate that DHEA supplementation for at least 6 weeks before start of an IVF cycle can dramatically increase pregnancy chances with IVF in women with high FSH. (Recently, a small-scale clinical trial from Israel also confirmed that DHEA supplementation is an effective treatment for high FSH levels, indicative of diminished ovarian reserve.)
Treating the cause, not the symptom
CHR Publications on POA
- Human Reproduction
The role of androgens in follicle maturation and ovulation induction: friend or foe of infertility treatment?Reproductive Biology and Endocrinology
Towards a better understanding of functional ovarian reserve: AMH (AMHo) and FHS (FHSo) hormone ratios per retrieved oocyte.Journal of Clinical Endocrinology & Metabolism
CHR practically never refuses fertility treatment to women, as long as FSH levels aren't menopausal. To women with very high FSH, our physicians explain relatively low pregnancy chances if they tried with their own eggs (in contrast to the superior pregnancy chances with donor eggs, even in older women). However, if patients, after giving fully informed consent, still wish to "give it a try" before moving on to egg donation, CHR will not withhold IVF treatment solely based on elevated FSH levels.
Most patients come to CHR after having been turned away by other centers, or after having failed multiple IVF cycles elsewhere. We routinely hear that they were told "that their FSH needs to come down before they can try IVF." This is a somewhat silly argument, because high FSH is merely a symptom, and not the disease. For optimal results, one needs to treat the disease, which is the patient's diminished ovarian reserve. This is precisely CHR's approach in treating women with diminished ovarian reserve when placing them on DHEA supplementation. (In this sense, calling DHEA supplementation a "treatment for high FSH levels" is a misnomer.)
With this approach, CHR has been able to achieve impressive IVF pregnancy rates, despite our center's extremely adversely selected patient population with disproportionately large number of women with severely diminished ovarian reserve and high FSH. We suggest you look at our IVF pregnancy rates for the last year in this patient population, and you will be astonished!
Key Facts about High FSH
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Written by Norbert Gleicher, MD
Last Updated: December 31, 2013