Success Factors

Age: There is no doubt that age is the single most important factor in determining your chance of achieving a successful conception through IVF. As the oocyte (egg) ages, it undergoes changes that render it less and less fertile as a woman advances through her 30's and 40's. As a woman's age advances, her chance of conceiving through IVF decreases. Furthermore, her risk of early pregnancy loss increases during this same time period, mainly related to the increasing frequency of chromosomal abnormalities within the oocyte and thus the developing embryo. Preimplantation genetic diagnosis (PGD) is a promising procedure designed to help identify genetically problematic embryos prior transfer back to the uterus. PGD may help to reduce the risk of early pregnancy loss related to the chromosomal abnormalities (aneuploidy) frequently found in embryos produced from aging oocytes.

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FSH Levels: Day 3 follicle-stimulating hormone (FSH) levels are also critically important in evaluating your potential for successful conception in an assisted reproductive technology program. This blood test is typically drawn on the third day of a woman's menstrual cycle. Day 3 FSH levels have been shown to be an incredibly accurate predictor of IVF success, independent of age. Essentially, an elevated Day 3 FSH value indicates a very poor prognosis for conception through IVF, and a high risk of pregnancy loss should the rare conception occur. Unfortunately, if you ever exhibit an elevated FSH value, having a normal value at a later time does not favorably change this prognosis. Every IVF program establishes a "threshold" FSH value unique to their laboratory, above which pregnancies are very rarely conceived despite great effort and repeated IVF attempts. At RMA, we have determined that an FSH value of 15 or higher predicts that IVF will be of no value in helping to achieve pregnancy. FSH values over 14.5 have produced only rare pregnancies in our program. Prior to initiation of any IVF cycle, Day 3 FSH values are evaluated. Many factors can artificially depress FSH values, but only diminished ovarian fertility reserve can cause an elevated FSH level. Ovum donation is generally recommended as the most potentially successful treatment option in the setting of elevated FSH levels, especially when associated with age beyond 35.

Ovarian Fertility Reserve: The clomiphene citrate challenge test can also be used to determine the extent of your ovarian fertility reserve. This test was designed to "unmask" undiagnosed cases of diminished ovarian reserve when Day 3 FSH values are apparently normal - the equivalent of a "stress test" for the ovaries. During the CCCT, a Day 3 FSH value is assessed. If normal, 100 mg/day of clomiphene citrate (Clomid, Serophene) is administered from days 5-9 of your menstrual cycle. An FSH level is then assessed on Day 10. If either the Day 3 or Day 10 FSH value is elevated, the test is considered abnormal and predicts a poor prognosis for IVF outcome.

The Effects of Age on Fertility

Aging is a normal, inescapable process. As we age, various components of our bodies develop limited function or cease to function altogether. Changes in our reproductive processes are some of the more subtle changes that take place. However, as societal changes have resulted in many women delaying childbearing, these nearly silent changes can have a huge impact on a woman's life. The scientific community had recognized for quite some time that a woman's reproductive potential declines with age. Unfortunately, there are few, if any, outward signs of decline in reproductive potential for most women. A woman may continue to have regular cycles until she nearly reaches menopause, but her chance of conception starts to decline at a much younger age (Figure 1), generally around 30 years old. This results in a situation where nearly 1/3 of the couples with the woman 35 or older will have problems with fertility. It has been estimated that only 10-30% of women over 40 are able to become pregnant on their own. In addition, a woman's chance of miscarriage also increases with age.

Figure 1: The chance of conceiving a pregnancy that results in a child starts to decrease in the 30's and is markedly diminished in the 40's.

Figure 2: The chance of miscarriage increases with age.

The probable reason for the decrease in chance of conception and the increase in miscarriage with age is the increased number of abnormal oocytes (eggs) that are present (Figure 3).

Figure 3: The percentage of eggs in infertility patients that have abnormal chromosomes increases with age.

Evaluation of Ovarian Reserve

Ovarian reserve is the term that we use to describe where a woman's ovaries are in the aging process. Age is an important determinant of ovarian reserve. As we have previously discussed, the chances of conception clearly decrease with age. However, not all women of the same age have the same reproductive potential. The further evaluation of ovarian reserve is accomplished by tests that measure important components of the reproductive system.

The standard screening test is the measurement of the hormones FSH (Follicle Stimulating Hormone), LH (Luteinizing Hormone) and Estradiol on cycle day 2, 3, or 4. (Day one of your cycle is the first full day of full menstrual flow). The FSH level is the most important of the three tests, with the measurement of LH and estradiol modifying how we look at the FSH level. It has been clearly demonstrated that there are subtle rises in the FSH level as a woman ages, and that women with abnormal FSH levels can have considerable difficulty conceiving using their own oocyte.

Another test that can be incorporated into the evaluation of ovarian reserve is the Clomiphene Citrate Challenge Test (CCCT). In this test, the cycle day 3 labs are followed by 5 days of the ovulation induction agent clomiphene citrate (Clomid, Serophene). On cycle day 10, the FSH and estradiol are re-drawn. We expect the FSH level to be in a certain range, due to the feedback from the follicle (s) developing under the stimulation by the clomiphene citrate. If the FSH is not in the correct range, the test is abnormal and the live birth rate for these patients is extremely poor. This test picks up another 30% of the patients with abnormal ovarian reserve.

A simple test of ovarian reserve that can be employed is the Basal Follicle Count. Early in the cycle, the small follicles that can be seen with ultrasound are counted. A low number of follicles can predict the increased likelihood of a poor response to therapy and decreased chance of live birth. Very high numbers of small follicles suggests a tendency to over respond to hormonal stimulation.

It is important to understand that none of these tests individually are absolute when test results are normal or equivocal. (A markedly elevated FSH level, indicating a loss of reproductive potential, is as close to certainty as we get.) However, they can be part of a picture, combined with the patient's age and response to previous treatment that gives the physician a pretty good idea where the patient's ovarian function stands.