Fragile X-Associated Primary Ovarian Insufficiency (FXPOI): Research Activities and Scientific Advances

Institute Activities and Advances

Through its intramural and extramural organizational units, the NICHD supports and conducts a broad range of research on Fragile X-associated disorders, including FXPOI. Short descriptions of some of this research are included below.

Understanding FXPOI

NICHD researchers in the Unit on Integrative Reproductive Medicine, in the Division of Intramural Research Program in Reproductive and Adult Endocrinology, are working to understand the causes of female infertility. A main focus is the natural history of reproductive health and fertility difficulties in girls and women with FMR1 premutations.

The unit is developing a registry of women with known or suspected FMR1 premutations. The registry will allow researchers to follow participants over time and study possible effects on reproductive health. The registry will also allow researchers to track development of common medical conditions—such as thyroid disease, psychiatric disorders, hypertension, and neurological disorders—to see if women with an FMR1 premutation have increased health risks.

In addition, there currently are no health or reproductive screening guidelines for women who carry a premutation, nor are there guidelines for the genetic counseling of these women. The registry, and the research it will allow for, soon will enable guidelines to be established1. For details, visit

Researchers supported by the Fertility and Infertility (FI) Branch are studying women with diminished ovarian reserve, including those who have an FMR1 premutation. These women have regular menstrual periods but lower levels of luteinizing hormone, which stimulates the release of eggs from the ovaries. Although fewer than 45 repeats in the FMR1 gene is considered normal, preliminary data show that fewer than one-fifth of women with diminished ovarian reserve have 35 to 44 repeats in the FMR1 gene. Researchers are examining this "high-normal" number of repeats and their effects (if any) on ovarian reserve.2

The Effects of FMR1 Premutations in Children and Adults

Research supported by the Intellectual and Developmental Disabilities Branch (IDDB) is exploring the neurodevelopmental and neurodegenerative effects of the FMR1 premutation in children and adults. Researchers are investigating the relationship between the premutation and cognitive and social deficits in boys, and between the premutation and age-related changes in adults age 40 and older.3

Better Diagnostics and Screening Tools for Fragile X and Premutations

Several NICHD-supported research groups are seeking ways to better diagnose and screen for Fragile X mutations and premutations. One potential screening method would test a small drop of blood on a paper card to detect Fragile X syndrome in newborns.4

Other Activities and Advances

NIH Research Plan on Fragile X Syndrome and Associated Disorders

  • In 2009, the NIH developed a research plan to advance the understanding of Fragile X syndrome and its associated conditions: NIH Research Plan on Fragile X Syndrome and Associated Disorders. The plan puts forward goals to guide future research, setting research priorities for each of the conditions. A major priority is to investigate the biological processes underlying all three disorders and how to better diagnose and treat them. Other priorities are studying the prevalence of the gene variations in the population and how the three conditions affect families.

  • The NICHD's IDDB funds three Fragile X Syndrome Research Centers. The centers are geared toward stimulating multidisciplinary, multi-institutional research and translating basic research findings into clinical practice.

  • The Reproductive Medicine Network (RMN), funded through the NICHD's FI Branch, carries out large, multicenter clinical trials of diagnostic and therapeutic interventions for infertility and reproductive diseases and disorders. The Network's structure allows investigators to test hypotheses in large numbers of patients who are enrolled in common protocols at multiple centers. This method produces answers more rapidly than working through individual sites. The Network allows external investigators with secured funding to gain access to RMN data and samples on a case-by-case basis, following an external scientific review of the proposed research's relevance to the RMN mission and its scientific significance.


  1. Trans-NIH Fragile X Research Coordinating Group and Scientific Working Groups. (2008). National Institutes of Health Research Plan on Fragile X syndrome and associated disorders. Retrieved September 12, 2012, from (PDF - 440 KB).
  2. Pastore, L. M. (n.d.). FMR1 CGG repeats in primary ovarian insufficiency women vs. 2 comparison groups. Retrieved September 11, 2012, from
  3. Hagerman, R .J. (n.d.). Genotype-phenotype relationships in Fragile X families. Retrieved September 11, 2012, from
  4. Latham, G. J. (n.d.). Enabling use of blood spot cards for accurate high-throughput fragile X screening. Retrieved September 11, 2012, from
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