It would be optimal to be able to accurately assess oocyte quality prior to performing IVF in order to estimate the prognosis. Because the ultimate assessment is achieved by direct microscopic examination of the oocyte and embryo, we are left with indirect means of assessment before oocyte retrieval is actually performed.
Early follicular phase FSH and estradiol levels
Scott et. al. showed in 1989 that women with early follicular phase serum FSH levels over 25 mIU/ml (in the assay performed at that time) did not conceive with IVF despite the fact that oocytes may have been retrieved and embryos transferred. The initial study included FSH levels drawn on cycle day 3. It was subsequently shown that there is no significant difference in levels drawn on cycle days 2, 3, or 4. This finding is independent of the woman's age, and appears to be more predictive of outcome than age alone. Elevated estradiol levels at this time of the cycle also appear to be related to poor IVF outcome.
Clomiphene challenge test
In 1987, Navot, et. al. reported the use of a clomiphene citrate challenge test (CCCT) to assess "ovarian reserve", a term which is now commonly used to refer to the processes of follicular depletion and diminished oocyte quality. After drawing blood samples for FSH and estradiol levels on cycle day 3, the patient is given 100 mg clomiphene citrate on cycle days 5-9, followed by FSH and estradiol determinations on cycle day 10. Typically, a normal result is considered to be a baseline FSH level under 10 to 12 mIU/ml and a cycle day 10 level no higher than 10 to 12 mIU/ml, and preferably lower than 10 mIU/ml. The estradiol level would be expected to be significantly elevated by day 10, but the normal range is debated. In fact, at least one author has suggested that the day 10 estradiol level is of no prognostic value. Women with an abnormal CCCT, regardless of age, can be expected to have a higher chance of cycle cancellation, a lower number of oocytes retrieved, and a lower pregnancy rate than women with a normal CCCT.
An abnormal CCCT is suggested to be a result of decreased follicular inhibin production. Inhibin is a glycoprotein produced by the follicle, which specifically inhibits the pituitary release of FSH. As inhibin production falls, possibly as a result of chronological age or "ovarian age", there is less inhibition of FSH release in the follicular phase, resulting in higher day 10 FSH levels during the CCCT.
Measurement of Inhibin
Because an elevated early follicular phase FSH and an abnormal CCCT are both felt to be a reflection of declining inhibin levels related to poor ovarian reserve, attempts have been made to find a relationship between serum inhibin levels and IVF success. This could provide a more direct prognostic assessment of ovarian reserve.
In the normal menstrual cycle, inhibin B levels are highest in the early to mid follicular phase and decrease in the late follicular phase. Several studies have shown higher levels of inhibin to be associated with a greater number of oocytes retrieved and a higher chance of pregnancy. Hofman, et. al. reported in 1998 that women with normal CCCT results had higher inhibin levels on both cycle days 3 and 10 as compared to women with poor CCCT results. Seifer, et. al. showed that women with an inhibin level of >45 pg/ml had a decreased response to gonadotropin stimulation, a lower number of oocytes retrieved, a higher cancellation rate, and a lower pregnancy rate. In contrast to these findings, Corson et. al. found in 1999 that serum inhibin levels did not correlate with CCCT results or the chance of pregnancy with IVF. Similar findings were reported by Creus, et. al. in 2000, who found cycle day 3 FSH levels to be more predictive of IVF success than inhibin levels.
Ultrasound evaluation of the ovaries
In 1997, Tomas, et. al. attempted to assess ovarian reserve by ultrasound measurement of ovarian volume and number of small follicles present. They found a correlation between the number of small follicles and the number of oocytes ultimately retrieved. Lass, et. al. reported an association between ovarian volume and ovarian reserve. The following year, Chang, et. al. showed a correlation between the number of small follicles on cycle day 1 and the number of oocytes retrieved as well as the pregnancy rate. Syrop, et. al., in 2000, also showed a relationship between ovarian volume and IVF outcome. This was confirmed by Sharara, Lim, and McClamrock.
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