|Premature ovarian failure and infertility|
Premature Ovarian Failure: Background and definitions
Premature Ovarian Failure is a disorder affecting the ability of a woman’s ovaries to function correctly. Premature ovarian failure (POF) affects approximately 1% of the female population. POF, also known as primary ovarian insufficiency, is characterized by absence of menstrual bleeding, low estrogen levels, and possible onset of autoimmune diseases in women younger than 40 years.
The word “failure” does not accurately reflect the true nature of this disease. The disorder is not permanent in all women. Remission of the disease is possible. In fact, up to 5% of women with POF may conceive without any specific fertility treatment. Thus, the preferred term now is ovarian insufficiency.
However, premature ovarian failure is a cause of infertility . Often, women with infertility and absence of menstrual cycles will be mistakenly diagnosed with an ovulation problem and referred to a fertility specialist for ovulation drugs. Ovulation drugs are ineffective in women with premature ovarian failure however.
Premature ovarian failure is NOT premature menopause
Menopause is defined as the “permanent cessation of menses; termination of menstrual life.” It generally occurs around the age of 50. Premature ovarian failure is NOT premature menopause. Around 50% of women affected still experience unpredictable and intermittent ovarian function for many years. For this reason, some women can still become pregnant even after being diagnosed.
When treating POF, hormone therapy is essentially replacing the hormones the body would normally make on its own. When treating menopause, elevated ovarian hormone levels are extended, not replaced.
Understanding premature ovarian failure
Two Forms forms of ovarian insufficiency
Primary ovarian insufficiency is when the ovary fails to respond to the hormone signals sent from other parts of the body like the hypothalamus and pituitary glands. This is the form that is commonly referred to as premature ovarian failure.
Secondary ovarian insufficiency is when the problem lies directly in the hypothalamus and pituitary glands. These parts of the central nervous system fail to stimulate the ovaries and subsequent ovarian function. Secondary ovarian insufficiency is not considered to be premature ovarian failure. Most fertility experts think of these as ovulatory problems.
Causes of premature ovarian failure
Follicle depletion due to chromosome abnormality
All eggs in the ovaries are surrounded by supporting cells known as granulosae cells. As an egg begins to mature in the ovary, the granulosae cells produce a small amount of fluid. The term “follicle” refers to the small cyst that contains the egg, fluid and supporting cells. A woman has all of the follicles (and therefore eggs) she is ever going to have in her life before she is born. All during her life, the number of follicles is decreasing due to an ongoing process of degeneration.
Follicle depletion results in the lack of eggs in the ovary due to either an inadequate supply at birth or follicle atresia (degeneration). One example of follicle atresia occurs in fetuses with only a single X chromosome (normal females should have two X chromosomes). When these fetuses are born, they are referred to as having Turner’s Syndrome. Women with Turner’s Syndrome initially develop normal ovaries with a normal amount of immature eggs before birth, but accelerated follicle degeneration leads to ovarian insufficiency at an early age. Some women with Turner’s syndrome will never have periods. Others with a milder version may start to have periods as a teenager and then stop after a few months or years.
Follicle dysfunction means that while apparently healthy eggs remain in the ovaries, they fail to function for properly. The table below lists examples of causes of follicle dysfunction.
It is suggested that approximately 6% of women with spontaneous POF have mutations in the FMR1 gene . This is the gene mutation responsible for fragile X syndrome -the most common cause of hereditary mental retardation. The risk of a woman having this mutation is higher if she has a family history of premature ovarian failure. Around 14% of women with a family history of POF will have an FMR1 mutation as compared with 2% of women who have no family history of POF. To prevent these genetic reoccurrences, it is important to research the family medical history.
There are other mutations that have been found in families with POF. There are likely others that have not been discovered. While each mutation individually is found in only a small percentage of POF patients, when taken together, they may be responsible for 25-30% of all cases of POF.
Problems with the immune system
Autoimmune disease is a problem that occurs when the body fails to recognize its own parts as itself. Consequently, the body starts attacking its own cells and tissues.
Some of the diseases associated with autoimmune POF:
Symptoms of POF
AmenorrheaAmenorrhea is the absence of a normal menstrual period
Estrogen DeficiencyWomen with POF experience some symptoms of menopause including hot flashes, night sweats, sleep disturbance, and vaginal dryness. Other symptoms may include mood swings, energy loss, low sex drive, painful sex, and bladder control problems.
Women with low estrogen levels from POF appear also to be at an increased risk for developing osteoporosis (bone thinning which can lead to fracture) and heart disease.
InfertilityAs mentioned before, women who have this disease have a significantly lower chance of getting pregnant compared to women without this disease. However, remissions and spontaneous pregnancies can occur.
Other symptomsOther signs of POF should be taken into consideration as well. Another symptom present for some women is dry eye syndrome. POF patients have been shown to have an increased incidence of ocular surface disease as compared to normal women.
Treatment of premature ovarian failure
Unfortunately, there has not been a treatment developed to improve ovarian function and increase the pregnancy rate in POF patients. Doctors and scientists have not developed a way to create new eggs or to make existing eggs work better. Yet, there are hormone replacement therapies available to treat the symptoms that results from low estrogen levels.
Spontaneous pregnancies can and do occur, although not commonly. There has been no medication, hormone or other treatment that results in pregnancy occurring more often than it does without any treatment at all. This is a very important point! Several well done studies have confirmed that treatment of women with POF does not result in a higher pregnancy rate than no treatment at all.
The only therapy that significantly improves the likelihood of a pregnancy in a woman with POF is egg donation. Egg donation is a form of in vitro fertilization in which eggs are removed from an “egg donor”, fertilized and then placed into the hormonally prepared uterus of the woman with POF. Since she is not using her own eggs, the chance for pregnancy using egg donation in a woman with POF is very high. The underlying cause of the POF does not impact on the very high success of this technique.
Estrogen ReplacementFor estrogen replacement, most women do well using a transdermal patch. Oral estrogen therapy can be given to women who prefer this route. Typically, about twice as much estrogen is needed compared to post menopausal women to alleviate symptoms.
Oral contraceptives or birth control as hormone replacement therapy contain twice as much steroid hormone that is required to alleviate symptoms of POF. Nonetheless, many younger women prefer to use oral contraceptives since it does not carry the same “stigma” as other types of hormone replacement, which is usually used by older, menopausal women.
Some women have fears of about estrogen therapy; however, remaining deficient at such a young age most likely poses a greater health risk than replacing the hormones normally supplied by the body.
Because low estrogen levels causes a decrease in bone density possibly leading to osteoporosis, women should have1200-1500mg of calcium in their diet everyday. An adequate intake of Vitamin D is also important. Supplements should be taken if the need is not met.
To improve bone mass and muscle strength, POF patients are encouraged to perform weight-bearing exercise for 30 minutes at least 3 times a week. Participation in outdoor sports is recommended.
Despite the fact that this disease occurs only in roughly 1% of women, young women who develop Premature Ovarian Failure have unique needs that require special care. Egg donation is still considered the best option for infertility in women with POF. However, this disease can still result in spontaneous pregnancy. In this way, this condition is not early menopause and should not be treated as such. Women with POF/POI should be educated on the nature of their disease and the current research efforts. It is important to be aware of the condition and the options for future treatments.
|Last Updated ( Wednesday, 22 February 2012 )|