WOMEN’S HEALTH |  FRAGILE X PREMUTATION CARRIERS

FXPOI  –  FRAGILE X-ASSOCIATED PREMATURE OVARIAN INSUFFICIENCY

A percentage of women who are carriers for the Fragile X premutation are at risk of developing Fragile X-associated Primary (Premature) Ovarian Insufficiency (FXPOI).
Primary Ovarian Insufficiency (POI) is a condition in which the ovaries stop functioning normally in a woman younger than age 40. Common symptoms of POI include absent or irregular periods and infertility.

Studies show that approximately 1 in 4 women carriers experience FXPOI and overall the average age of menopause is reduced by about 5 years. It is thought that all women with Fragile X premutation status have some decrease in ovarian function. However many women with the Fragile X premutation are able to conceive and family planning options are recommended.

Studies show that women who have POI of unknown cause have about a 1/50 chance of being a carrier of Fragile X, therefore the testing of women experiencing either POI or early menopause-like symptoms is recommended.

RECOMMENDED RESOURCES FOR HEALTH PROFESSIONALS

1. FXPOI – What Do I Need to Know?       WEBINAR, MARCH 2025
   Clinical Associate Professor Amanda Vincent is a leading Australian endocrinologist and menopause specialist, combining clinical practice in menopause with menopause related research, translation and education. Dr Vincent is lead endocrinologist in the Menopause and Menopause Oncology clinics, Monash Health, Clayton and Head of Early Menopause Research, Monash Centre for Health Research and Implementation, Monash University.This webinar focuses on Fragile X-associated Primary Ovarian Insufficiency (FXPOI) and early menopause, covering health considerations and symptom management for women who are Fragile X premutation carriers.  Dr Vincent also discusses the risk factors for FXPOI, and touches on fertility management considerations for young women who may be at risk of fertility issues related to the Fragile X premutation.
   
    
2. FXPOI –  Fragile X And Premature Ovarian Insufficiency – Fact Sheet for health professionals, from Australasian Menopause Society.
   Key Points from the Fact Sheet:
   • Fragile X disorders are due to the expansion of CGG repeats in the FMR1 gene on the X chromosome.
   • The Fragile X premutation (55-200 CGG repeats) affects 1/150-300 women
   • 16-30% of premutation carriers will develop premature ovarian insufficiency (POI). The highest risk and earliest onset of POI is seen in women with 70-100 CGG repeats.
   • There is an overlap between symptoms associated with Fragile X premutation and POI
   • Fragile X screening is recommended for all women diagnosed with spontaneous POI
   • Management of Fragile X POI is similar to other causes of POI
   • Women with the Fragile X premutation should be referred for genetic counselling and Fragile X screening offered to family members. Referral for fertility preservation should be considered for premutation carriers

   The Fact Sheet is available to download from the Australasian Menopause Society website

3.  Guideline on Premature Ovarian Insufficiency  European Society of Human Reproduction and Embryology
4.  FXPOI Guidelines – Consensus of the Fragile X Clinical & Research Consortium

   

REPRODUCTIVE GENETIC CARRIER SCREENING FOR FRAGILE X

Fact Sheet:  Guidance Statement for Females with the Fragile X Premutation  Guidance Statement for FXS PM carriers_13Mar2024
This statement is intended for use by medical practitioners to discuss with their patients, and was produced by Fragile X Association of Australia and Fragile X Alliance, 2024.

Key points from the Guidance Statement:

The Fragile X premutation does not cause Fragile X syndrome.

Females with a Fragile X premutati0n are generally healthy but may have an increased chance of having:

• children with Fragile X syndrome
• fertility problems and/or early menopause

Risk and counselling advice vary with the size of the premutation, and many women will not develop any symptoms or be affected. Information in this statement is mainly derived from studies of families who have a member with the full mutation and so may not apply to women ascertained from population screening who have a member with the  full mutation and so may not apply to women ascertained from population screening.