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Premature Ovarian Failure

Definition
Premature ovarian failure is defined as the cessation of menstrual periods before the age of 40. It occurs in 1 in 1,000 women between the ages of 15 and 29 and 1 in 100 women between the ages of 30 and 39. The average age of onset is 27 years. A family history of POF is found in about 4% of the women experiencing the condition. Premature Ovarian Failure may occur abruptly over one to two months or gradually over several years. Some women may experience symptoms of menopause such as hot flashes, no menses, and vaginal dryness. Usually, if a woman has POF, she begins to have irregular periods which will eventually stop. Either her cycle day 3 FSH or her estrogen levels may be elevated. In most cases of POF, no cause is ever identified. Pelvic surgery, chemotherapy and radiation therapy can cause POF, as can uncommonly severe pelvic inflammatory disease. Premature ovarian failure is a difficult and disturbing diagnosis for most women.

Causes
Premature ovarian failure may be caused by factors occurring prior to birth or after the onset of puberty. Factors occurring prior to birth may be related to defects in the ovary, oocyte, or ovarian follicle. These defects usually occur as a result of a chromosomal abnormality in the fetus, as seen in several inherited disorders, one of which is Turner's syndrome.

Factors that result in ovarian failure after puberty or in the late 20's and early 30's may be associated with specific disorders, such as ovaries that are resistant to the hormones necessary for ovulation and menses. A biopsy of these abnormal ovaries will show follicles that do not respond normally to the hormones FSH and LH.

A rare syndrome is associated with a defect in the enzyme 17 hydroxylase, which affects the formation of hormones necessary for ovulation and also results in premature ovarian failure.

Destruction of eggs from radiation of the ovaries occurs during cancer therapy and results in permanent loss of menstrual periods. Several anti tumor drugs, such as cyclophosphamide, are also associated with ovarian failure.

Diagnosis/Evaluation Recommended:

  • Complete history and physical examination
  • Chromosome study (karyotype)
  • Complete blood count with additional studies as determined
  • Thyroid studies
  • Parathyroid studies
  • Ovarian antibodies test (if available)
  • Serum LH and FSH and estradiol values in the follicular phase of the cycle (at least two samples should be performed to rule out intermittent ovarian failure and to confirm the diagnosis)
  • Possible ovarian biopsy

Treatment
Unfortunately, there is no proven method of stimulating the ovaries if POF is diagnosed. However, when the diagnosis of premature ovarian failure is made, therapeutic regimens are considered.

  • If you have untreated hypothyroidism, your physician will place you on thyroid medication.
  • If associated autoimmune problems are found, steroid therapy may be used for some individuals.
  • A short course of estrogen replacement therapy may lower the FSH to an acceptable value before attempting ovulation induction with human menopausal gonadotropins. Administration of high dose human menopausal gonadotropins (Gonal F™, Follistim™, Repronex™) after priming with estrogen/progestogen replacement therapy has resulted in pregnancy in a small number of cases.

With the new in vitro fertilization technologies using donor eggs, pregnancy has been achieved in women with premature ovarian failure who until recently had no hope for conception. Donor oocyte IVF is performed with an egg from an anonymous or a designated donor (friend, relative) and is fertilized with the sperm of the ovarian-failure patient's partner or donor. The resulting embryo is placed back into the patient's uterus after appropriate priming with estrogen and progesterone.

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