HomeHealthPremature ovarian failure: A cause of infertility

Premature ovarian failure: A cause of infertility

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Oladapo Ashiru

Premature ovarian failure is the extreme state of complete primordial follicle depletion. It is an irreversible situation characterised by amenorrhea, permanent infertility, and elevated menopausal gonadotropin levels. At present, no proven method can determine that a woman has no primordial follicles remaining in the ovary, so, in effect, this term is merely a concept that cannot be proven. For this reason, the authors prefer not to use the word premature ovarian failure (POF).

  • Management of primary ovarian insufficiency.
  • Discuss the test results on a special visit (not by phone).
  • The diagnosis of POI/POF can be particularly traumatic for young women.
  • Use of appropriate terminology is essential (use of POI or insufficiency is preferred instead of premature menopause or early menopause).
  • Explain the nature of the disease and advise the patient of sources of information and support.
  • Counsel

 The ovary is a reproductive organ and a source of essential hormones that help maintain healthy bones. Adequate replacement of these missing hormones, a healthy lifestyle, and a diet rich in calcium are imperative.

 POI/POF is not menopause. Spontaneous ovarian activity and pregnancies are possible.

Allow the patient enough time to accept the diagnosis. Family planning decisions are after the patient has had some time to come to terms with her condition.

 No proven therapies exist to restore fertility; experimental treatment should be performed only under a review board-approved research protocol.

 Currently available options to resolve infertility include the change of family building plans, such as adoption, ovum donation, or embryo donation.

 Hormone therapy (HT)

 All women with POI/POF should receive cyclical HT with estrogens and progestins to relieve estrogen deficiency symptoms and maintain bone density.

 A few women may need HT even before amenorrhea develops to alleviate menopausal symptoms.

Estrogens

 Transdermal or oral estrogens can be used. Control studies have not established the appropriate dose for young women with ovarian failure. According to the authors, clinical judgment, administer doses twice as high as the recommended dose for HT for postmenopausal women (transdermal estradiol 100-150 mcg instead of 50 mcg daily, conjugated equine estrogens [CEE] 1.25 mg instead of 0.625 mg daily or oral estradiol 2-4 mg instead of 1 mg daily). Such doses usually achieve adequate estrogen level of the vaginal epithelium in young women with POI/POF and help maintain age-appropriate bone density.

The estrogens can be administered continuously or cyclically (21 days on, seven days off). Because no controlled studies compare the efficacy and safety of one method over another, the choice of therapy should come after consideration of the patient’s preference and physician’s experience.

Estrogen therapy (ET) does not prevent ovulation and conception in these patients; in fact, it may improve the chance of pregnancy by theoretically lowering the LH level to the normal range and preventing premature luteinisation of the remaining follicles. Patients should be informed that they must obtain a quick pregnancy test if menstrual bleeding fails to appear when expected.

 Oral contraceptives provide more sex steroids than is required for replacement, and the authors advise against this approach. Furthermore, oral contraceptives may not help prevent pregnancy in women with POI due to the elevated gonadotropin levels.

Progestins should be administered cyclically, 10-14 days each month, to prevent endometrial hyperplasia that unopposed estrogen may cause. Young women with POI/POF have a 5-10% chance of spontaneous pregnancy (unlike postmenopausal women). If an expected withdrawal bleeding is missing, a pregnancy test should be performed, and a pregnancy diagnosis should not be delayed.

 The recommended regimens include medroxyprogesterone 10 mg for 10-12 days each month or micronised progesterone 200 mg daily for 10-12 days each month.

Androgens

Women with ovarian failure have lower levels of free testosterone compared with ordinarily ovulating age-matched controls, but only 13 per cent have levels below the lower limit of normal. Androgen replacement is used for persistent fatigue, low libido, and poor well-being despite adequate estrogen replacement and when depression has been ruled out or adequately treated. It should be performed with high caution and for relatively short periods until more data are available.

Available medications include oral methyltestosterone 1.25-2.5 mg/d, injectable testosterone esters 50 mg every six weeks intramuscularly, and subcutaneous testosterone pellet implants 50 mg every 3-6 months.

 Restoration of fertility

No intervention has been proven to increase the ovulation rate or restore fertility in patients with POI/POF.

Gonadotropin therapy carries a theoretical risk of exacerbating autoimmune POI.

 The use of prednisone or dexamethasone to restore ovarian function in suspected autoimmune ovarian failure is not indicated clinically.

The use of these agents carries a risk of osteonecrosis. Their use in patients with POI should be confined to studies approved by an institutional review board.

The use of unproven treatments to restore fertility should be avoided because they can interfere with the development of spontaneous pregnancy.

Patients with POI/POF can have a successful pregnancy with a donor egg. A decision to proceed with such a procedure should be made after a fair discussion of different options. The age of the patient is of less importance than the age of the egg donor.

Other possibilities may include embryo adoption, adoption, or change of life plans.

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