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Excess body fat accentuates insulin resistance in patients with PCOS, and obese women with PCOS are more likely than lean women to manifest menstrual irregularities (12). Furthermore, increased body mass index (BMI) is associated with impaired response to standard doses of clomi-phene citrate (18,19). Obesity, independent from hyperinsulinemia, is related to lower oocyte retrieval in IVF and increased total FSH requirements for ovarian stimulation (20, 21).

Weight loss has been found to enhance fertility through improving ovarian function, reducing androgen concentrations, and increasing SHBG. Crosignani et al. studied 33 anovulatory overweight patients with PCOS who were recommended to follow a 1,200 kcal/day diet and increase their physical exercise for a study period of 12 months (22). Twenty-five patients (76%) lost at least 5% of their body weight and 11 patients (33%) had a 10% decrease. Eighteen patients (72% of compliant subjects) resumed regular menstrual cycles, including 15 patients who developed ovulatory cycles during the 12-month study period, and 10 patients (33%) became pregnant within 12 months.

Improved diet and exercise alone, without significant weight loss, may improve ovulation rates. Huber-Buchholz et al. studied the relationship between insulin sensitivity and ovulation in 18 anovulatory obese PCOS women with infertility before and after a 6-month intervention of gradual dietary changes and a moderate exercise regimen (23, 24). Anovulatory subjects who regained ovulation during the study showed an 11% reduction in central fat, a 39% reduction in LH levels and improved insulin sensitivity. This was achieved with moderate lifestyle modification that did not result in significant weight loss.

Whether diet or exercise has a more important role in weight loss in infertile obese PCOS patients is currently being investigated. A recent pilot study by Palombo et al. showed improved fertility in 40 obese PCOS patients with anovulatory infertility who underwent either a structured exercise training program or a hypocaloric high-protein diet (25). After 24 weeks of intervention, improved menstrual cyclicity was seen in both groups. However, the ovulation rate was significantly higher (p < 0.05) in the exercise training group than in the diet group, despite significantly more weight loss in the ovulatory diet group vs. the ovulatory exercise training group (-10.5 vs. -5.6 kg). The authors postulate that the improved ovulation in the exercise group was due to improved waist circumference, which reflects visceral adipose tissue as well as cellular muscle metabolism enhancement, thus improving insulin sensitivity (25). While not statistically significant, there was also a trend toward higher pregnancy rates in the exercise vs. diet group with cumulative pregnancy rates of 35% and 10%, respectively (p = 0.058).

While lifestyle modification can be challenging to achieve and maintain for many patients, it can be effective in restoring fertility in overweight women with PCOS. In obese women, a loss of 5-10% of their body weight can improve or restore reproductive function (22, 26). Diet and exercise are relatively inexpensive compared to other fertility treatments and do not carry an increased risk of multiple gestations. Improvements in mood and self-esteem that may be achieved by weight loss may also improve fertility (27). Because obese women have lower pregnancy rates and higher risks of pregnancy complications, losing weight can help improve outcomes even if fertility treatments are needed

(28). Weight loss is not known to be of benefit for fertility in lean patients with PCOS, and because there are detrimental effects on fertility in patients who are underweight, weight loss should not be recommended in this population (29). Drug therapy is usually warranted in these patients.

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