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Premature Ovarian Failure, POF – Causes and Treatments

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Definition of Premature Ovarian Failure

Premature ovarian failure is a term used for the condition when women under age 40 have stopped having periods, and have high FSH levels and low estrogen hormone levels.

About half of young women with spontaneous premature ovarian failure have some eggs and follicles remaining in the ovary. These women can sometimes ovulate (and even get pregnant) after the diagnosis is made. Therefore, some doctors prefer the term “primary ovarian insufficiency”, or POI – as opposed to “failure” which implies a totally menopausal situation.

Diagnosis of Premature Ovarian Failure

  • The diagnosis of POF or POI is made with FSH hormone blood testing, often supplemented with AMH levels and ovarian antral follicle counts.
  • An FSH level above about 30-40 indicates ovarian insufficiency.
  • The serum AMH level is low
  • The antral follicle counts are very low

Causes of Premature Ovarian Failure

There are several known causes for premature ovarian failure.

  • Chromosomal abnormalities
    • 45X (Turner’s syndrome), or a variant of it – often called a “Turner’s mosaic”
  • Damage to the ovaries from surgery, chemotherapy or radiation treatment
  • Premature ovarian failure caused by premutations of the FMR1 gene (gene related to fragile X syndrome) – see below
  • Autoimmune premature ovarian failure – see below

Premature ovarian failure related to premutations of the FMR1 gene

  • Fragile X syndrome is the most common cause of inherited mental retardation.
  • It is a genetic syndrome associated with the expansion of a single trinucleotide gene sequence (CGG) on the X chromosome. This expansion results in a failure to express the FMR1 protein which is required for normal neural development.
    • Normal is 29-31 CGG repeats
    • Premutation has 55-200 CGG repeats
    • Full Mutation has more than 200 CGG repeats
    • Intermediate has 40 – 60 repeats

The premutation situation is the one of importance with regard to premature ovarian failure:

It is estimated that about 20% of women with the FMR1 premutation will have premature ovarian failurePremutation carriers have been identified in 1-7% of women with “sporadic” POI. Sporadic refers to POI not occurring in family clusters.Premutation carriers are found in up to 13% of women with familial premature ovarian failureThe mechanism by which the FMR1 premutation causes impaired ovarian function is unknown.
It is possible that women with this gene variant begin life with a reduced number of eggs in their ovariesOr it could be that the rate of loss over time is increased

Autoimmune causes of premature ovarian failure

Women with POF can have autoimmune dysfunction of other endocrine organs. Therefore, it is prudent to screen for these conditions. The organ associations are:

  • Thyroid disease (most common)
  • Parathyroids
  • Adrenals

Screening of Autoimmune Related Problems of Other Endocrine Organs

  • Thyroid disease – Thyroid function tests and thyroid antibody levels can be checked. Serum calcium, phosphate and protein levels can help evaluate hypoparathyroidism.
  • Adrenal – A morning cortisol level or a corticotropin (ACTH) stimulation test assesses adrenal reserve.
  • Autoimmune Dysfunction – A CBC with differential, sedimentation rate, anti-nuclear antibody and rheumatoid factor can help to assess autoimmune dysfunction.

How Common is Autoimmune Disease in Women with Premature Ovarian Failure?
Laboratory evidence of autoimmune phenomenon is much more prevalent than clinically significant disease.

Studies have shown laboratory evidence of immune problems in about 20% of women with premature ovarian failure.

It is presently unknown as to what the incidence of clinically apparent autoimmune disease will be in these patients over time.

Most commonly found antibodies:

  • Thyroid
  • Lupus-related

Symptoms of Premature Ovarian Failure

  • Periods becoming more irregular and farther apart
  • Hot flashes
  • Night sweats
  • Thinning and drying of the vagina

Treatment of Premature Ovarian Failure

Because this condition is primarily related to the loss of primordial follicles and eggs in the ovaries – there is no treatment that can reverse that process. We do not have a way to make more eggs once they are gone.

Women with well documented premature ovarian failure should be considered for starting on estrogen/progestin replacement therapy if there are no contraindications.

This will provide some protection against osteoporosis by eliminating the severely hypoestrogenic state associated with menopause.

Premature Ovarian Failure and Fertility and Pregnancy: Can I get pregnant with POF?

Regardless of the etiology, there currently is no effective treatment that will be likely to result in a pregnancy (with her own eggs) for premature ovarian failure. Egg donation is a highly successful treatment (see below).

However, some women will spontaneously ovulate on occasion and pregnancy can occur – although it is quite unusual. Those pregnancies that do occur are usually in women on estrogen replacement therapy.

Studies suggest that up to 5-10% of women with POI will eventually get pregnant – on their own, without treatment from a fertility doctor.

Egg Donation with In Vitro Fertilization

Egg donation with in vitro fertilization (IVF) can be a very effective therapy for women with premature ovarian failure that desire pregnancy. In our donor egg program, we have approximately a 75% chance to have a baby with one attempt.

Our egg donation pregnancy success rates


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