Poor ovarian reserve

Poor ovarian reserve (also known as impaired ovarian reserve, premature ovarian aging or declining ovarian reserve) is a condition of low fertility characterized by 1): low numbers of remaining oocytes in the ovaries or 2) possibly impaired preantral oocyte development or recruitment. Recent research suggests that premature ovarian aging and premature ovarian failure (aka primary ovarian insufficiency) may represent a continuum of premature ovarian senescence.[1] It is usually accompanied by high FSH (follicle stimulating hormone) levels.

Quality of the eggs (oocytes) may also be impaired as a 1989 study by Scott et al. of 758 IVF cycles showed a dramatic decline in implantation rates between high (> 25 mIU/mL) and low day three FSH (<15 mIU/mL) women even though the ages of the women were equivalent between the two groups (mean age 35 years).[2][3] However, other studies show no association with elevated FSH levels and genetic quality of embryos after adjusting for age. The decline in quality was age related, not FSH related as the younger women with high day three FSH levels had higher live birth rates than the older women with high FSH. There was no significant difference in genetic embryo quality between same aged women regardless of FSH levels.[4][5] A 2008 study concluded that diminished reserve did not affect the quality of oocytes and any reduction in quality in diminished reserve women was age related. [6] One expert concluded: in young women with poor reserve when eggs are obtained they have near normal rates of implantation and pregnancy rates, but they are at high risk for IVF cancellation; if eggs are obtained, pregnancy rates are typically better than in older woman with normal reserve. However, if the FSH level is extremely elevated these conclusions are likely not applicable. [7]

Contents

Etiology

  • Natural decline of ovarian reserve due to age[8].
  • Idiopathic.
  • Genetic factors, such as fragile x syndrome. Approximately 20-28% of women with an FMR1 premutation (55-200 CGG repeats) experience fragile x primary ovarian insufficiency (POI) and another 23% experience early menopause (i.e., menopause before the age of forty five).[9]
  • Autoimmune disorders.
  • Adrenal gland impairment.
  • Iatrogenic, e.g., due to radiation, chemotherapy or surgery, such as laserization of the surface of the ovary to treat endometriosis. Excessive laparoscopic ovarian drilling has been reported to cause premature ovarian failure.[10] (The primordial follicles are located in the thin outer one-millimeter layer of the ovary.) [11]

Diagnosis

There is some controversy as the accuracy of the tests used to predict poor ovarian reserve. One systematic review concluded that the accuracy of predicting the occurrence of pregnancy is very limited. When a high threshold is used, to prevent couples from wrongly being refused IVF, only approximately 3% of IVF-indicated cases are identified as having unfavourable prospects in an IVF treatment cycle. Also, the review concluded the use of any ORT (Ovarian Reserve Testing) for outcome prediction cannot be supported. [12] Also Centers for Disease Control and Prevention statistics show that the success rates for IVF with diminished ovarian reserve vary widely between IVF centers.[13]

Follicle stimulating hormone (FSH)

Elevated serum follicle stimulating hormone (FSH) level measured on day three of the menstrual cycle. (First day of period flow is counted as day one. Spotting is not considered start of period.) If a lower value occurs from later testing, the highest value is considered the most predictive. FSH assays can differ somewhat so reference ranges as to what is normal, premenopausal or menopausal should be based on ranges provided by the laboratory doing the testing. Estradiol (E2) should also be measured as women who ovulate early may have elevated E2 levels above 80 pg/mL (due to early follicle recruitment, possibly due to a low serum inhibin B level) which will mask an elevated FSH level and give a false negative result.[14]

High FSH strongly predicts poor IVF response in older women, less so in younger women. One study showed an elevated basal day-three FSH is correlated with diminished ovarian reserve in women aged over 35 years and is associated with poor pregnancy rates after treatment of ovulation induction(6% versus 42%). [15]

The rates for spontaneous pregnancy in older women with elevated FSH levels have not been studied very well and the spontaneous pregnancy success rate, while low, may be underestimated due to non reporting bias, as most infertility clinics will not accept women over the age of forty with FSH levels in the premenopausal range or higher.[citation needed]

A woman can have a normal day-three FSH level yet still respond poorly to ovarian stimulation and hence can be considered to have poor reserve. Thus, another FSH-based test is often used to detect poor ovarian reserve: the clomid challenge test, also known as CCCT(clomiphene citrate challenge test).

Antral follicle count

Transvaginal ultrasonography can be used to determine antral follicle count (AFC). This is an easy-to-perform and noninvasive method (but there may be some discomfort). Several studies show this test to be more accurate than basal FSH testing for older women (< 44 years of age) in predicting IVF outcome.[16] This method of determining ovarian reserve is recommended by Dr. Sherman J. Silber, author and medical director of the Infertility Center of St. Louis.[17]


AFC and Median Fertile Years Remaining[18][19]

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