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Premature Ovarian Failure (POF)

The term Primary Ovarian Insufficiency (POI) replaces the old terminology of Premature Ovarian Failure (POF). It affects approximately 1% of women. It occurs when the ovaries become depleted of eggs and stop functioning normally before age 40. When this happens, the woman’s estrogen level decreases drastically and her menstrual cycles become irregular or completely stop. Ovarian failure can cause bone loss (osteoporosis) and a variety of menopausal symptoms including hot flashes, vaginal dryness, night sweats, difficulty sleeping and irritability.
The life cycle of the human ovary.

By mid-gestation in fetal life, the human ovary possess 7 million potential eggs. No new eggs are produced after that. As a matter of fact, about 85% of these eggs are lost before birth, so that at birth, the number of remaining eggs is estimated to be 1 million.

After birth, the number of eggs in the ovary continues to gradually decrease, so that by puberty only 200,000 eggs remain.

In a typical menstrual cycle, multiple eggs are recruited, but only 1 egg is released and the remaining eggs are lost. As a woman gets older, the proportion of poor quality eggs remaining in the ovary increases, resulting in increased infertility especially after age 35.

In the span of a woman’s reproductive life only 400 eggs are released (ovulations). The remaining ones are lost and never participate in the process of ovulation.

What causes POI?
  • Medical treatments such as chemotherapy and radiation therapy.
  • Genetic causes such as:
    • Turner’s syndrome in which a woman has only one normal X chromosome and an altered second X chromosome.
    • Fragile X syndrome in which the X chromosomes are fragile and break.
  • Autoimmune disorders affecting the ovaries, thyroid or adrenal glands.
  • Ovarian surgery for benign diseases such as severe and recurrent endometriosis or recurrent ovarian cysts.
  • POI occurs more frequently when there is family history premature ovarian insufficiency.
  • Cigarette smoke, chemicals, pesticides and viruses might hasten ovarian failure.
In 50% of women affected by POI, the exact cause may be never known.
How is POI diagnosed?
  • Careful review of the medical history.
  • Hormone testing for Follicle Stimulating Hormone (FSH), Estrogen and Antimullerian Hormone (AMH). These tests should be repeated a second time to confirm the diagnosis.
  • Ultrasound to count the number of eggs remaining in the ovary (Antral follicle Count or AFC).
  • Genetic testing including chromosomal analysis and Fragile X mutation.
Can POI be treated?

For women with POI who want to conceive there are no proven options to permanently restore ovarian function resulting in successful birth of a genetically related offspring. At present time only 10% of women with POI may conceive with their own eggs.

In most cases of premature ovarian insufficiency, the only reliable strategy to achieve pregnancy is the use of donor eggs

Recently several publications have demonstrated successful differentiation of stem cells to egg-like cells in the laboratory utilizing stem cell (MSC) technology. The hope is that in the future ovarian rejuvenation with stem cells may be utilized to restore ovarian function and fertility.

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