Beyond Metformin

Well, I am back having spent a very relaxing vacation in Wyoming. If only there were more people in that beautiful state, then I would seriously consider relocating from the Metropolitan DC area. Returning back to DC was like entering a swamp and considering the current state of our elected officials there are more similarities than I really would care to admit...

In any case, as sales of the book on Amazon.com place it only 599,997 book rankings behind Harry Potter, I am taking up where we left off in discussing PCOS. Actually, there are several excellent books dedicated to PCOS and insulin resistance. Just yesterday I printed out info from Amazon.com on the "Insulin Resistance Diet" which many of our patients have found helpful. The book is ranked #300 on Amazon.com...which seems pretty impressive to me...

Moving right along, the problem with Metformin and PCOS is that not all patients will resume ovulation with this drug by itself. In fact, the majority of patients will require additional medications (either Clomid or gonadotropins). I still believe that pretreatment with Metformin makes sense as a higher percentage of women will ovulate with combination therapy compared with clomiphene alone. So here is the next sample question from "100 Questions and Answers about Infertility."



25. I have PCOS and am still not having normal cycles with metformin. What comes next?


Patients who fail to respond to metformin may require ovulation induction with either clomiphene citrate (Clomid) or injectable fertility medications (gonadotropins). Clomid has been an FDA-approved treatment for anovulation since the late 1960s. This anti-estrogen has been used successfully in millions of women with few complications. Clomid binds to estrogen receptors in the brain, causing the pituitary gland to resume normal release of FSH, and thereby inducing follicles to grow and ultimately release an egg. Patients should take the lowest effective dose of Clomid needed to induce ovulation. With increasing doses, the anti-estrogen side effects can reduce fertility by altering the cervical mucus and leading to a thinner endometrial lining. Many physicians initially prescribe a dose of 50 mg of Clomid to be taken on cycle days 5–9. The physician may perform ultrasound monitoring after day 12. Most patients will ovulate around day 17. If no dominant follicle emerges by this day, then an increased dose of 100 mg should be used in the next cycle. A dose of 150 mg is rarely prescribed, because the vast majority of Clomid-responsive patients will ovulate while taking the 50- or 100-mg dose.

Women with PCOS who fail to respond to Clomid can be treated with injectable fertility medications. Gonadotropins (FSH-containing medications) are prepared either using re- combinant DNA technology (Follistim, Gonal-F) or by isolating these hormones from the urine of postmenopausal women (Bravelle, Menopur). By following a very-low-dose protocol (37.5 IU as the starting dose), approximately 90% of patients will achieve a single dominant follicle. If the treatment produces multiple follicles, however, the woman’s risk of multiple pregnancy and ovarian hyperstimulation syndrome (OHSS) may lead to cycle cancellation. Almost all of the high-order multiple pregnancies (e.g., sextuplets) born today result from PCOS patients who took gonadotropins and demonstrated an excessive follicular response.