Randomized controlled trial of preconception interventions in infertile women with polycystic ovary syndrome

Context: Lifestyle modification is recommended in women with polycystic ovary syndrome (PCOS) prior to conception but there are few randomized trials to support its implementation or benefit. Objective: This study aimed to determine the relative efficacy of preconception intervention on reproductive and metabolic abnormalities in overweight/obese women with PCOS. Design, Setting, and Participants: This was a randomized controlled trial of preconception and infertility treatment at Academic Health Centers in women with infertility due to PCOS, age 18-40 y and body mass index 27-42 kg/m2. Intervention: Women were randomly assigned to receive either 16 weeks of 1) continuous oral contraceptive pills (OCPs) (ethinyl estradiol 20 mcg/1mgnorethindrone acetate) ("OCP"); 2) lifestyle modification consisting of caloric restriction with meal replacements, weight loss medication (either sibutramine, or orlistat),andincreasedphysicalactivitytopromotea7%weightloss ("Lifestyle");or3)combinedtreatment with bothOCPandlifestyle modification ("Combined"). After preconception intervention,womenunderwent standardized ovulation induction with clomiphene citrate and timed intercourse for four cycles. Pregnancies were followed with trimester visits until delivery. Main Outcome Measures: Weight, ovulation, and live birth were measured. Results: Weconsented 216 and randomly assigned 149women(Lifestyle: n=50; OCP: n=49; Combined: n-50).WeachievedsignificantweightlosswithbothLifestyle(meanweightloss,-6.2%;95%confidence interval (CI),-7.4-5.0; and Combined (mean weight loss-6.4%; 95% CI,-7.6-5.2) compared with baselineandOCP(bothP<.001). Therewasasignificant increase in the prevalence of metabolicsyndrome at the end of preconception treatment compared with baseline within OCP (odds ratio [OR, 2.47; 95% CI, 1.42-4.27) whereas no change in metabolic syndrome was detected in the Lifestyle (OR, 1.18; 95% CI, 0.63-2.19) or Combined (OR, 0.72; 95% CI, 0.44-1.17) groups. Cumulative ovulation rates were superior after weight loss: OCP, 46%; Lifestyle, 60%; and Combined,67%(P<.05). Live birth rates were OCP, 12%; Lifestyle, 26%; and Combined, 24% (P=.13). Conclusions: A preconception weight loss intervention eliminates the adverse metabolic oral contraceptive effects and, compared with oral contraceptive pretreatment, leads to higher ovulation rates.