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FSH as a marker of egg stores and IVF success
Title: IVF performance of women who have fluctuating early follicular FSH levels
Author: A. Lass, et al.
Address: Cambridge, England
Source: Journal of Assisted Reproduction and Genetics 17:566-573 (November) 2000
Summary: In order to have a successful in vitro fertilization (IVF) treatment, it is of great importance that the ovary responds to gonadotropin stimulation and thus develop several follicles. Especially in older women, failure to respond to gonadotropin stimulation is common. Because researchers believe it would be clinically and economically beneficial to predict a poor response prior to treatment, they conducted this study to determine if women who have early follicular follicle stimulating hormone (FSH) levels >12 mIU/ml have reduced response to follicular stimulation for IVF in a following month, despite normal FSH levels. Subjects were 303 women > 38years old and/or who had previously had a poor response to superovulation for IVF. Blood samples were collected on day 2 of menstruation before beginning treatment and were tested for FSH, luteinizing hormone (LH) and estradiol (E2). In 38.6% of these women, FSH levels were >12 mIU/ml. Of these, 66 gave a further 130 blood samples for FSH measurement in the following months. Sixty percent of the tests showed raised FSH value >12 mIU/ml. Thirty women whose repeat FSH levels were less than 12mIU/ml underwent 41 IVF cycles. Sixty-three other women, older than 38 and/or who had a poor response to superovulation previously and whose FSH levels were less than 12 mIU/ml, made up the control group. There were no differences in the responses to superovulation and delivery rates between the two groups. Researchers concluded that women whose early follicular phase FSH levels were raised >12 mIU/ml had an increased risk (>50%) that in subsequent cycles levels would remain raised. They also found it was not possible to predict which individuals would have favorable FSH levels. If the cycle day 2 FSH level returns to a "normal" level of less than 12 mIU/ml, women >40 years had substantial cycle cancellation rates (43%). However, those patients who achieved the stage of embryo transfer had a good chance of conceiving, regardless of their age.
Comment: Success with in vitro fertilization therapy is directly correlated with the capacity to induce more than one follicle to preovulatory development. The capacity of the ovary to respond to gonadotropin stimulation is directly proportional to egg stores, and egg stores to age. It is of paramount clinical and economic importance to predict patients that will not respond well to stimulation, both to design the most effective stimulation protocol and to counsel about the chances of success. As egg stores dwindle FSH increases to compensate for the loss in order to protect normal ovulation as long as possible. Several methods, including early follicular phase FSH, estradiol, inhibin and the clomiphene challenge test, have all been proposed to access egg stores. Some believe that if the FSH level is ever elevated that the chances are markedly reduced for IVF pregnancies. Others believe that if stimulation is postponed until a cycle in which the FSH level is lower, that success is improved. It seems reasonable to both repeat FSH level and not start stimulation unless the level is under 12. We have found that women with an FSH level above 8 have significantly lower response to stimulation. In our practice, pregnancy after IVF with a day 2-3 FSH over 10 have been rare, however, there have been a substantial number of women who have conceived spontaneously with elevated FSH levels. An occasional spontaneous pregnancy has occurred with an FSH level over 20. I suggest that an estradiol level be drawn in addition to the FSH level. When the estradiol is over 50pg/mIU, FSH secretion has started to fall and the FSH measurement may not be as valid. I have not found that the clomiphene challenge (solely used as a test) or inhibin levels to have a particular advantage over the day 2-3 estradiol/ FSH determination.