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Ovarian Reserve and InfertilityDiminished ovarian reserve or function is an important cause of infertility. Women are born with a finite number of eggs, which peak at about 7 million five months into the pregnancy. Only one to two million are present at birth and about 400,000 at puberty. Ovulation will occur approximately 400 times during the reproductive life reaching menopause at about 51 years. Thus, there is a tremendous attrition rate for eggs. This plays a very important part in reproductive potential, that is, the ability to conceive. Diseases such as endometriosis, Turner’s Syndrome, and auto-immune ovarian failure may substantially decrease the reproductive potential. Considering the fact that many couples now delay childbearing into their mid to late 30s, we feel that it is important to have some assessment of ovarian reserve. Age and fertilityWhile a 20 year old woman and a 40 year old woman ovulate the approximate same number of times each year, their monthly pregnancy rate, or fecundity, is much different. This is related to the above. When patients undergo In-Vitro Fertilization, there is an age-related decline in pregnancy rates. The following graph demonstrates the pregnancy rates for all patients in the USA that underwent Assisted Reproductive Technologies (IVF, GIFT, ZIFT) in 1998, as reported by the CDC. Actual delivery rates are a few percentage points below the pregnancy rates.
A woman's age not only affects the chances to conceive from ART, but also affects the risk of miscarriage. Most miscarriages (60 %) are due to numerical fetal chromosome abnormalities. The eggs a woman is born with have only partially completed the division of the chromosomes prior to ovulation. They may be in this suspended state for decades. If the chromosomes fail to completely separate, the resulting egg may have an extra chromosome. When fertilized by a normal sperm, the resultant offspring will have an abnormal chromosome number and likely miscarry. This is consistent with the increased risk of Down's Syndrome (trisomy 21, and extra chromosome 21). The miscarriage rates for patients having ART in 1998 are shown below.
When women undergo egg donation, the dramatic decline in pregnancy rates associated with age is not seen, indicating the effects that age has pregnancy rates and egg quality. Older patients may stimulate less well in IVF and produce fewer total eggs. The may have lower estrogen levels, higher miscarriage rates, and lowers implantation rates. Women in their mid-thirties have been found to have elevated FSH levels, which may be the first sign of declining ovarian reserve. The onset of the decline in reproductive potential is extremely variable. Therefore, ovarian reserve testing can be seen as a qualitative test to estimate where a person is in the process of depleting her ovarian reserve. Tests of Ovarian ReserveThe basic concept of the menstrual cycle helps us to understand the various tests that have been developed to assess ovarian reserve. The pituitary gland secretes follicle stimulating hormone (FSH) which travels through the blood stream to the ovaries to stimulate the growth of follicles that contain eggs. The developing follicle secretes hormones which travel in the bloodstream back to the pituitary gland to decrease the FSH production. This is called negative feedback. Estradiol and inhibin are two hormones involved with this process. In a normal menstrual cycle, the FSH level is lower in the first few days of the cycle and then begins to rise as it stimulates the ovaries. A high FSH level on day 3 of the cycle indicates that the pituitary is attempting to stimulate an ovary that has diminished capacity to respond. This is a problem and a bad prognostic sign.
In summary, the assessment of ovarian reserve helps provide valuable
information about the status of ovarian function. This may help a couple
make a more informed decision concerning treatment options.
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