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Managing infertility in PCOS – lifestyle modifications, clomiphene, letrozole, gonadotropins and IVF.

A cornerstone of managing PCOS is lifestyle modifications. In many women, losing as little as 10% of body weight and maintaining the weight loss can restore normal menstrual patterns. However, weight loss can be challenging for many obese women with PCOS. Other treatments, such as progestogens or birth control pills, are aimed at restoring regular periods and reducing the risks of developing abnormal uterine lining. Some birth control pills and medications such as spironolactone and flutamine, which suppress androgens, are used to reduce cosmetic effects of increased androgens (acne and increased body hair).

The treatment of infertility for overweight women should include lifestyle modifications in weight, physical activity and diet. These factors have general health benefits, and may result in a spontaneous return to normal ovulation, and/or better response to medications used to induce ovulation. Pre-pregnancy improvements in these factors will also optimize pregnancy progress and outcome.

Clomiphene citrate has been used for many years and remains one of the principal medications to date. In recent years, letrozole has become an alternative, and in fact, a well-conducted clinical trial has just reported better live birth and ovulation rates with letrozole. While insulin-sensitizing agents such as metformin have been popular, two well-conducted clinical trials have failed to demonstrate increased pregnancy success among patients taking metformin and clomiphene, when compared with patients taking clomiphene citrate alone. However, some women with PCOS who are older and have increased abdominal obesity, or those with evidence of insulin resistance may benefit from the additional use of metformin.

Before letrozole has become a treatment option, the next step for those who have failed to respond to clomiphene is gonadotropin treatment (see below) or a surgical procedure called laparoscopic “ovarian drilling”. The procedure requires general anesthetics and involves passing a laparoscope – a thin tube containing an optic device attached to a camera for display on a monitor — through the abdominal wall to directly visualize the pelvic structures, including the ovaries — to facilitate “drilling” holes superficially on the surface of each ovary. Despite its claims to be as effective as gonadotropin treatment, the dose chosen to define clomiphene failure is not uniform and the procedure is not without its drawbacks. This procedure should be considered only in women with PCOS who have failed to respond to adequate doses of clomiphene or letrozole and when there is a concurrent reason for laparoscopy.

Depending on age, duration of infertility, and other factors, appropriate uses of gonadotropins or IVF are effective options if the above fail. While gonadotropin therapy effectively increases ovulation and pregnancy rates, drawbacks include resources required for hormone and ultrasound monitoring, cost, multiple pregnancy risk, and the potential for ovarian hyperstimulation. IVF is indicated for women with PCOS who fail gonadotropin therapy or who have other indications for IVF treatment.