When a woman's ovaries stop functioning properly before the age of 40, this is known as premature ovarian failure (POF). Among its most relevant genetic causes is the mutation of the FMR1 gene.
This gene produces a protein called FMRP (Fragile X Mental Retardation Protein), whose absence or deficiency is linked to Fragile X syndrome. This syndrome is also one of the most common causes of inherited intellectual disability in males (since this gene is located on the X chromosome). Its impact on female fertility remains little known to the general population. In fact, it is estimated that 20% of women carrying the FMR1 premutation develop POF, compared to only 1% of the general population.

In healthy individuals, the FMR1 gene has fewer than 55 CGG triplet repeats. Therefore, when someone has between 55 and 200 repeats of this triplet, they are considered to have a premutation. This usually does not directly cause Fragile X syndrome, but it can increase the likelihood of having children with the full mutation.
Additionally, women carrying the FMR1 premutation have a significantly higher risk of developing premature ovarian failure, which implies a substantial reduction in ovarian reserve and, in many cases, an early menopause several years before expected.
The mechanism that triggers this ovarian failure is not due to a deficiency of the FMRP protein—as occurs in classic Fragile X syndrome—but rather to toxicity generated by the excess RNA from the premutated gene. This directly affects the development of ovarian follicles, making ovulation difficult and reducing the chances of achieving a natural pregnancy.

In the context of assisted reproduction, women with the FMR1 premutation may have problems responding to hormonal stimulation, so medical professionals will need to adjust these doses more thoroughly to achieve a good result.
For this reason, it is essential to identify whether ovarian failure has a genetic cause in order to design a personalized treatment. In fact, when a young patient presents with ovarian insufficiency without an apparent cause, a genetic analysis of the FMR1 gene is recommended.
In young women carrying the premutation, fertility preservation through egg freezing is a highly recommended option. Often, ovarian function is maintained for a time, but the decline can be faster than usual. Having vitrified oocytes can make a big difference when deciding to pursue motherhood.
Furthermore, if in vitro fertilization is chosen, it is possible to perform preimplantation genetic testing to select embryos with the highest reproductive potential and avoid transmitting the mutation.
Although this genetic alteration is often detected late or overlooked, more and more women, thanks to advances in reproductive genetics, are able to fulfill their desire to become mothers. At IVF-Life, we work every day with the best technology to offer our patients the highest guarantees of success in their treatments.