Medical management of clomiphene-resistant polycystic ovarian syndrome: an update.

Clomiphene citrate is the traditional first-line treatment for chronic anovulation that characterizes polycystic ovary syndrome (PCOS). A gold standard therapy has always been Clomiphene Citrate (CC). However, 20%-25% of PCOS women fail to ovulate with incremental doses of CC. A good body of evidence suggest that alternatives for PCOS women with CC-resistant anovulation include insulin sensitizers like metformin and pioglitazone. Insulin sensitizers improves pregnancy outcome and ovulation rate by and acts by ameliorating insulin sensitivity and hyperandrogenemia. Metformin is preferred in obese women. Gonadotropins induce ovulation and maintain optimal follicle growth via controlled administration of follicle stimulation hormone. Two regimens are used which includes high and low dose regimen. Low dose regimen is preferred but is associated adverse effects like ovarian hyperstimulation syndrome (OHSS) and increased cost. Extending clomiphene therapy reduces cost and improves pregnancy outcome. Glucocorticoids are preferably used when serum Dehydroepiandrosterone levels are > 200µg/dL. Bromocriptine improves ovulation rate by decreasing prolactin levels. Human Chorionic Gonadotropin restores ovulation but its use is limited during intrauterine insemination. Tamoxifen acts in a similar way as CC but has lesser antiestrogenic effect on the endometrium, cervical mucus, and granulosa cells, hence an added advantage of monofollicular ovulation. Aromatase inhibitors block conversion androstenedione and testosterone to estrogen in ovary and improves ovulation rate. Added advantage includes lesser cost, simple to use, no danger of multiple pregnancies and convenient for patient. Combination of GnRH analogues and Gonadotropins are associated with increased risk of OHSS. D-chiro-inositol, N-Acetylcysteine, melatonin and acarbose are tried with little success.