Fragile X-Associated Primary Ovarian Insufficiency | FXPOI

Fragile X-associated primary ovarian insufficiency, one of three known Fragile X-associated disorders caused by changes in the FMR1 gene, is a condition in which the ovaries are not functioning at full capacity in an FMR1 premutation carrier.

Ovaries form part of a woman’s reproductive system. They are like a “nest” that contains all of a woman’s eggs. The eggs are released to the uterus each month midway through a woman’s menstrual cycle, where they wait to be fertilized. If not fertilized, they leave the body in the menstrual period.

Ovaries also produce and release hormones that are important in fertility and for the preparation and maintenance of the eggs. As women age their ovaries slow down in overall function, including their ability to maintain and release eggs. The eggs themselves age and may not be healthy enough for fertilization and development of a baby.

The ovaries in women with FXPOI do not function to full capacity and may resemble ovaries of an older woman, both in the number and quality of available eggs.

Prevalence

About 20% of women who carry a Fragile X premutation over their reproductive life span develop POI, compared with only 1% in the general population.

Evidence shows women with a premutation, on average, experience natural menopause at an earlier age compared to those without a premutation — the mean age of natural menopause being reduced by about five years from the typical age of about 51 years.

Approximately 3% of women who carry the premutation will have menstrual cycle irregularities in their teens or twenties due to FXPOI, and 1% of women who carry the premutation will stop having periods before the age of 18.

About one-third of women with FXPOI, equivalent to 7% of women who carry the premutation, stop having periods at or before age 29.

Not all women with a premutation experience FXPOI. One well-documented risk factor is the premutation repeat size: the highest risk for ovarian dysfunction is for women carrying premutation alleles in the 80-100 CGG repeat range, not the highest alleles of >100 repeats (although these group ranges are not exact).

One study estimated the risk of FXPOI to be 38% in this high-risk group, although more studies are needed to better define high-risk alleles and the reason for this association.

Learn more about the prevalence of the three Fragile X disorders

Signs & Symptoms

Common symptoms of FXPOI (ovarian insufficiency) include absent or irregular cycles, “sub-fertility” or infertility, hot flashes, and premature ovarian failure (POF), which is the complete cessation of menstrual periods before the age of 40. In the wider range of FXPOI symptoms, premature ovarian failure is at the more severe end of the spectrum.

FMR1 premutation carriers can have normal ovarian function, but can still go through early menopause, which is menopause occurring between 40 and 45 years of age (menopause normally occurs between 45 and 55 years old).

Even though women with FXPOI may develop symptoms similar to those of menopause, such as hot flashes and vaginal dryness, FXPOI differs from menopause in some important ways:

Testing

How do you know if you have FXPOI? By definition, all women who have FXPOI have an FMR1 premutation. If you are experiencing FXPOI symptoms and haven’t been tested you should arrange with your physician to have FMR1 genetic testing.

The American Society for Reproductive Medicine and American College of Obstetrics and Gynecology recommend that all women with ovarian insufficiency or elevated FSH (a hormone that reflects ovarian function) levels have FMR1 testing. Any physician or genetic counselor can order testing for Fragile X.

If you can’t find a genetic counselor in your area call us at (800) 688-8765 or visit the National Society of Genetic Counselors.

If you have already been tested and are a confirmed FMR1 premutation carrier, you should alert your physician to the risk of FXPOI in carriers (some physicians might not be aware of this condition).

All female FMR1 carriers should keep a log of their menstrual cycles and note any unusual patterns, missed cycles, abnormally long cycles (more than 35 days), or short cycles (less than 21 days). Also note any other physical changes such as hot flashes, insomnia, vaginal dryness and/or decreased libido, increased anxiety, etc.

If you are concerned that you might have FXPOI, talk to your physician about having your FSH, a hormone that reflects ovarian function, measured. FSH levels increase as you approach menopause or if your ovaries are not functioning properly for your age.

Treatment & Intervention

Many women who are FMR1 premutation carriers can get pregnant. However, all carriers are at risk to have children with FXS so should meet with a genetic counselor to discuss reproductive issues.

Some carriers are initially identified because they have fertility problems and are considering fertility treatment.

If you conceive naturally, you have the option of prenatal testing through amniocentesis or chorionic villus sampling (CVS) to evaluate the genetic status of your pregnancy.

If you do not have normal fertility, you can discuss various assisted reproductive options with your reproductive endocrinologist, including IVF with your own eggs, IVF with eggs donated by a non-carrier, attempting to get pregnant naturally, or adoption.

Learn more about reproductive issues and options

From the fragile x info series

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