Diminished Ovarian Reserve

Overview

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Diminished ovarian reserve (DOR) is a condition in which the ovary loses its normal reproductive potential, compromising fertility. The condition may result from disease or injury, but most commonly occurs as a result of normal aging. DOR is present in 10-30% of patients presenting to doctors with infertility; it is a challenge to treat.

Causes

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As women age, their natural fertility potential begins to diminish. This phenomenon is universal and is can be seen even as early as age 30, becoming more pronounced over the next decade. Typically, few women retain normal fertility by the time they enter their mid-40s. Because assisted reproduction does not reverse the changes in the eggs responsible for this decrease in fertility, success rates for patients undergoing IVF parallel the normal decline in natural fertility seen in the population at large. Illness or genetic abnormalities may accelerate this decline. One percent of the population experiences ovarian failure (menopause) earlier than age of 40. This condition is termed premature ovarian failure or premature menopause. Patients with DOR should be screened with a blood test for Fragile X Syndrome, an inherited condition that leads to early ovarian failure, which is also responsible for the most common cause of inherited intellectual disability and autism.

Risk Factors

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Advanced reproductive age, particularly over the age of 40, puts women at risk for DOR. Previous injury to the ovary due to diseases such as endometriosis, pelvic infection, or iatrogenic damage caused by pelvic radiation, chemotherapy or surgery further increases risk.

Symptoms

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Unfortunately, most women exhibit no signs or symptoms of DOR. As the condition progresses over time, women may notice a shortening of the menstrual rhythm (e.g. 28 day cycles reduced to 24 days). Once menopause is imminent, women may notice signs of low estrogen such as hot flashes, trouble sleeping, missed menstrual periods and vaginal dryness.

Diagnosis

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There are multiple ways to assess the functional reserve of the ovary, including blood tests obtained on the second or third day of the menstrual cycle to measure the hormones FSH and Estradiol. FSH levels above a level of 12 mIU/mL are considered mildly elevated; above 15 mIU/mL, abnormal enough to cancel assisted reproduction attempts, since patients in this range will fail to satisfactorily respond to fertility- enhancing medications. Fluctuations in the normal baseline expression of these two hormones indicate declining ovarian reserve. AMH (anti-Mullerian Hormone) is another blood test which correlates well with fertility potential. This hormone generally reflects the number of eggs in the body. It is especially useful when combined with FSH/estradiol blood testing and a transvaginal ultrasound assessment of the number of visible antral follicles. AMH is secreted by pre-antral and early antral follicles, and levels fall months to years before abnormalities in FSH and Estradiol are detectable.

Treatments

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Presently there no treatments exist that can slow down or prevent ovarian aging. Once DOR is identified, treatments are designed to hasten the time to conception, or to cryo-preserve (freeze) eggs or embryos for a patient’s future use. Patients with DOR who are undergoing IVF are typically placed on higher doses of ovarian stimulation regimens in an effort to maximize the number of eggs harvested. However, once the ovary has failed to respond to stimulation, or later fails endocrinologically, donor eggs are recommended to restore a woman’s reproductive potential. By using eggs donated by young women, who are typically in their 20s, women with DOR may conceive and successfully deliver a baby, even long after menopause.

Prognosis

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The prognosis for women with DOR is guarded once the diagnosis is made. Even in the earliest stages DOR reduces pregnancy success and contributes to an increase in miscarriages. The older the patient, the more compromised the clinical picture typically becomes.

Prevention

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There is no way to avoid ovarian aging. The best precaution is to educate patients about reproductive hazards and the risk reproductive aging poses to fertility. Clinical testing designed to assess the ovary’s functional reserve allows for an evaluation of fertility potential. If DOR is suspected, patients should be advised to make plans for reproducing soon, before further compromise occurs.