FXPOI, or fragile X-associated primary ovarian insufficiency, is one of three known Fragile X-associated Disorders (FXD) ^[1]. All the FXD are caused by changes in the FMR1 Gene ^[2].

What Is FXPOI?

FXPOI is a condition in which the ovaries are not functioning at full capacity in an FMR1 premutation carrier. Common symptoms of FXPOI include absent or irregular periods, symptoms of menopause such as hot flashes, etc, early menopause and infertility. ^[3]

What Do Ovaries Do?

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.

How Does FXPOI Differ From Early Menopause?

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:

• Women with FXPOI can still get pregnant in some cases because their ovaries may occasionally function to release viable eggs. Women who have completed menopause cannot get pregnant because their ovaries no longer release eggs.
• Women with FXPOI can experience a return of menstrual periods. Women who have completed menopause will not have menstrual periods again.
• 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 45-55)

 What Is POF and How Does It Differ From FXPOI?

POF stands for “premature ovarian failure,” which is the complete cessation of menstrual periods before the age of 40. The range of FXPOI symptoms includes POF, which is at the more severe end of the spectrum. FXPOI also includes other symptoms of ovarian insufficiency including irregular cycles, “sub-fertility” or infertility, hot flashes, etc. All of these encompass a wider range of symptoms than POF alone.

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 ^[4] you should arrange with your physician to have FMR1 genetic testing.

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.

How Common Is FXPOI?

FXPOI occurs in about 20-25 percent of adult female FMR1 premutation carriers. It has also been reported in teenagers who are carriers, though it is less common in that population.

Can Women With an FMR1 Premutation Get Pregnant?

Many women who are FMR1 premutation carriers can get pregnant. However, all carriers are at risk to have children with fragile X syndrome ^[5] so should meet with a genetic counselor to discuss reproductive issues ^[6].

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

If you have normal fertility, you can try to conceive naturally or look into Reproductive Options ^[6] such as pre-implantation genetic diagnosis (PGD). PGD is an assisted reproductive technique offered by a limited number of laboratories in the country, which involves testing a fertilized egg in the laboratory and then implanting only unaffected eggs into a woman through in vitro fertilization (IVF).

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.

How Can You Find Out If You Are an FMR1 Premutation Carrier?

Any physician or genetic counselor can order Testing ^[4]. If you can’t find a genetic counselor in your area call the NFXF at (800) 688-8765 or visit the National Society of Genetic Counselors ^[7] website and click on the “Find a counselor” link.

The American Society for Reproductive Medicine (ASRM) and American College of Obstetrics and Gynecology (ACOG) recommend that all women with ovarian insufficiency or elevated FSH levels have FMR1 testing.

About 2 percent (1/50) of women with ovarian insufficiency are found to have an FMR1 premutation, as do about 7 percent (1/15) of those with a personal and family history of ovarian insufficiency.