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

Richard Legro, William Dodson, Penny Margaret Kris-Etherton, Allen Kunselman, Christy M. Stetter, Nancy Williams, Carol Gnatuk, Stephanie Estes, Jennifer Anne Fleming, Kelly C. Allison, David B. Sarwer, Christos Coutifaris, Anuja Dokras

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)4048-4058
Number of pages11
JournalJournal of Clinical Endocrinology and Metabolism
Volume100
Issue number11
DOIs
StatePublished - Nov 1 2015

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Polycystic Ovary Syndrome
Oral Contraceptives
Randomized Controlled Trials
Life Style
Weight Loss
Ovulation
sibutramine
Live Birth
Infertility
Caloric Restriction
Clomiphene
Ethinyl Estradiol
Units of measurement
Ovulation Induction
Birth Rate
Contraceptive Agents
Meals
Acetates
Body Mass Index
Odds Ratio

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

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title = "Randomized controlled trial of preconception interventions in infertile women with polycystic ovary syndrome",
abstract = "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.",
author = "Richard Legro and William Dodson and Kris-Etherton, {Penny Margaret} and Allen Kunselman and Stetter, {Christy M.} and Nancy Williams and Carol Gnatuk and Stephanie Estes and Fleming, {Jennifer Anne} and Allison, {Kelly C.} and Sarwer, {David B.} and Christos Coutifaris and Anuja Dokras",
year = "2015",
month = "11",
day = "1",
doi = "10.1210/jc.2015-2778",
language = "English (US)",
volume = "100",
pages = "4048--4058",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "11",

}

TY - JOUR

T1 - Randomized controlled trial of preconception interventions in infertile women with polycystic ovary syndrome

AU - Legro, Richard

AU - Dodson, William

AU - Kris-Etherton, Penny Margaret

AU - Kunselman, Allen

AU - Stetter, Christy M.

AU - Williams, Nancy

AU - Gnatuk, Carol

AU - Estes, Stephanie

AU - Fleming, Jennifer Anne

AU - Allison, Kelly C.

AU - Sarwer, David B.

AU - Coutifaris, Christos

AU - Dokras, Anuja

PY - 2015/11/1

Y1 - 2015/11/1

N2 - 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.

AB - 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.

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