EFFECTS OF DECREASED HYPERINSULINEMIA ON THE OVULATORY RESPONSE TO CLOMIPHENE

Virginia Commonwealth University, Richmond VA

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Abstract

A trial to determine if taking metformin along with clomiphene will increase the number of women who ovulate in response to clomiphene. The objective of this study is to test the hypothesis that patients with the problem of not ovulating due to polycystic ovary syndrome (PCOS), who are resistant to clomiphene, will have an improved ovulatory response to clomiphene with the correction of the amount of insulin in the blood. Failure to ovulate is estimated to cause 40% of female infertility, with the vast majority of cases due to PCOS. Clomiphene remains the primary therapy to induce ovulation. Yet, 25% of patients on clomiphene don't ovulate. Other inexpensive alternatives have small responses and a more expensive therapy has some undesirable side effects. Evidence supports the role of excess insulin in the blood in causing PCOS and failure to ovulate. It is hoped that reducing the serum insulin levels in clomiphene resistant patients will improve their ovulatory response to clomiphene. This will be a double blind , placebo controlled study of clomiphene resistant women that assesses the ovulatory and hormonal responses to clomiphene treatments after chronic administration of either metformin or placebo. There will be 60 women in the study who will be randomly placed in the metformin group or the placebo group. These women will all have failed to ovulate on clomiphene at the 100mg dose as part of their treatment for not ovulating. An overnight fast is required for the first visit to the CRC. Subjects will be given a glucose drink and several blood tests will be done. Then women will be assigned to groups 1 or 2 and will be given medication to be taken three times a day for seven weeks. During the seven weeks, the subjects will return to have blood tested for ovulation every ten days. If ovulation occurs during the seven weeks, the subject has completed the study. If the subject does not ovulate during the seven weeks, clomiphene at the 50mg dose will be given for five days each month. Blood will be tested during that time for ovulation. After taking each round of clomiphene, an ultrasound will be done of the ovaries. If there is still no ovulation, the clomiphene dose will be raised and will continue to be raised until ovulation occurs. Then, if the subject successfully ovulates, the same dose will be continued for six cycles or until conception. If no ovulation occurs, the study medication will be revealed. Those who were taking metformin will be finished with the study. After six weeks of no medications, those who were in the placebo group will then take metformin for several weeks and will follow the same regimen that the first group followed.