Randomized Controlled Trial of Preconception Interventions in Infertile Women With Polycystic Ovary Syndrome

J Clin Endocrinol Metab. 2015 Nov;100(11):4048-58. doi: 10.1210/jc.2015-2778. Epub 2015 Sep 24.


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/m(2).

Intervention: Women were randomly assigned to receive either 16 weeks of 1) continuous oral contraceptive pills (OCPs) (ethinyl estradiol 20 mcg/1 mg norethindrone acetate) ("OCP"); 2) lifestyle modification consisting of caloric restriction with meal replacements, weight loss medication (either sibutramine, or orlistat), and increased physical activity to promote a 7% weight loss ("Lifestyle"); or 3) combined treatment with both OCP and lifestyle modification ("Combined"). After preconception intervention, women underwent 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: We consented 216 and randomly assigned 149 women (Lifestyle: n = 50; OCP: n = 49; Combined: n = 50). We achieved significant weight loss with both Lifestyle (mean weight loss, -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 baseline and OCP (both P < .001). There was a significant increase in the prevalence of metabolic syndrome 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.

Trial registration: ClinicalTrials.gov NCT00704912.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-Obesity Agents / therapeutic use
  • Behavior Therapy
  • Birth Rate
  • Body Mass Index
  • Clomiphene / pharmacology
  • Combined Modality Therapy
  • Diet, Reducing
  • Drug Resistance
  • Female
  • Fertility Agents, Female / pharmacology
  • Humans
  • Infertility, Female / etiology
  • Infertility, Female / prevention & control
  • Infertility, Female / therapy*
  • Life Style
  • Metabolic Syndrome / complications*
  • Metabolic Syndrome / epidemiology
  • Motor Activity
  • Obesity / complications
  • Obesity / diet therapy
  • Obesity / drug therapy
  • Obesity / therapy*
  • Overweight / complications
  • Overweight / diet therapy
  • Overweight / drug therapy
  • Overweight / therapy*
  • Ovulation Induction*
  • Pennsylvania / epidemiology
  • Polycystic Ovary Syndrome / complications
  • Polycystic Ovary Syndrome / physiopathology*
  • Preconception Care*
  • Pregnancy
  • Pregnancy Rate
  • Prevalence


  • Anti-Obesity Agents
  • Fertility Agents, Female
  • Clomiphene

Associated data

  • ClinicalTrials.gov/NCT00704912