Premature Ovarian Aging

Diagnosis of POA

Effective treatment of low ovarian reserveovarian reserve starts with timely diagnosis. Timely diagnosis is crucial because once the OR begins to decline, it continues to decline with time, and we cannot tell how fast POA will progress. At CHR, patients are evaluated based on age-specific hormone values instead of universal cut-off values that are still used at many fertility centers. Use of age-specific values allow us to identify women developing POA at early stages of the condition, when treatment outcomes are much better.

AMH and FSH Tests

Each patient’s ovarian reserve is evaluated by comparing her FSH and AMH levels to the age-specific levels of these hormones, first established by the physicians at CHR:

< 33 Years < 7.0 mlU/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

A diagnosis of POA is reached when age-specific FSHFSH levels are too high and/or age-specific AMHAMH levels are too low. Some colleagues use antral follicle counts (AFCs) to assess OR. At CHR, we do not consider this method to be as reproducible as AMH and FSH levels. However, if AFCs are used to diagnose POA, they should also be age-specific. Without use of age-specific diagnostic levels, it is virtually impossible to identify women with POA, and treatment plans can end up being ineffective because they may not address the basic issue of abnormally low ovarian reserve.

Why POA is so commonly misdiagnosed

"CHR uses age-specific hormone values to accurately evaluate a woman's ovarian reserve status."

POA is likely the most frequently overlooked diagnosis of female infertility. Even good infertility centers fail to identify POA as a cause of infertility because most centers still use universal ovarian reserve parameters, independent of patient age. For example, most centers still consider a follicle stimulating hormone (FSH) level under 10.0 mIU/mL as “normal” at all ages. This makes absolutely no sense since everybody knows that FSH levels increase as women age. An FSH of 9.5 at age 20, therefore, means that the woman has an abnormally high FSH level for her age, which is very different from having the same FSH level of 9.5 at age 45!

The same principle also applies to AMH, which in recent years has become increasingly popular in assessing ovarian reserve. CHR's team was the first to propagate use of age-specific FSH and AMH levels in a number of publications, a routine slowly accepted by colleagues around the world. The figure below demonstrates age-specific FSH and AMH levels, as established at CHR [Modified from Gleicher et al, Reprod Biol Endocrinol 2010;8:64].

AMH-FSH-AGE-Normal graph


The distinction between POA and premature ovarian failure (POF) is of crucial importance: POF, also called primary ovarian insufficiency (POI), is defined by FSH level above 40 mIU/mL (which is a range found in post-menopausal women). Women whose FSH levels are high but still below 40 mIU/mL should be considered to suffer from POA, also called OPOI (occult primary ovarian insufficiency), rather than POF. "Early menopause" or "premature menopause" are also terms used to refer to POF.

Even in the best hands, pregnancy in women with POF is a rare event, unless donor eggs are utilized. CHR does offer experimental treatments to POF patients, but we usually recommend donor eggs as the treatment of choice, although at CHR, it is always the patient who decides which treatment she wants to pursue.

In contrast, POA patients still have an excellent IVF pregnancy chance with use of their own eggs, if given appropriate treatments. As a result of CHR's ongoing research on diminished ovarian reservediminished ovarian reserve and its clinical application, an ever-increasing number of POA patients from all over the world has been seeking treatment at CHR. Today, indeed, no other diagnosis brings as many patients to CHR, which is now considered the "center of last resort" for patients with POA and diminished ovarian reserve.

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Last Updated: November 15, 2014

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