TY - JOUR
T1 - Randomized controlled trial of preconception interventions in infertile women with polycystic ovary syndrome
AU - Legro, Richard S.
AU - Dodson, William C.
AU - Kris-Etherton, Penny M.
AU - Kunselman, Allen R.
AU - Stetter, Christy M.
AU - Williams, Nancy I.
AU - Gnatuk, Carol L.
AU - Estes, Stephanie J.
AU - Fleming, Jennifer
AU - Allison, Kelly C.
AU - Sarwer, David B.
AU - Coutifaris, Christos
AU - Dokras, Anuja
N1 - Funding Information:
In addition to the authors, we acknowledge the outstanding leadership of the study coordinators Patsy Rawa (Penn State) and Karen Lecks (University of Pennsylvania). Amy Ciccarella (Penn State University) at the Clinical Research Center at Penn State University Park for analyzing the 3-day dietary records; Urs Leuenberger, MD, (Penn State College of Medicine) for interpreting electrocardiographs and providing cardiology guidance; Mardi Sawyer (Penn State College of Medicine) for help with DXA scans and analysis; and the nursing staff at the Clinical Research Center at Penn State Hershey for assistance with oral glucose tolerance and exercise testing. We also wish to acknowledge the collaboration with the Core Ligand Laboratory at the University of Virginia under the leadership of Dan Haisenleider, PhD (University of Virginia) for their expertise in running our assays. Other members of the research team were as follows: Penn State College of Medicine, Hershey: Christy Bartlebaugh; Sandy Eyer; Jamie Ober, RN; Barb Scheetz; Janis Moessner;, University of Pennsylvania: Kurt Barnhart, MD; Karen Lecks; Linda Martino, RN; R. Marunich; and Jacqueline Spitzer, MS. We also acknowledge and thank the Chair of the DSMB, Evan Myers (Duke University). Address all correspondence and requests for reprints to: Richard S. Legro, MD, Department of Obstetrics and Gynecology, Penn State College of Medicine, M.S. Hershey Medical Center, 500 University Drive, H103, Hershey PA, 17033. E-mail: rsl1@psu.edu. This study was registered in ClinicalTrials.gov as trial number NCT00704912. This work was supported by the Eunice Kennedy Shriver National Institutes of Child Health and Human Development (NICHD), National Center for Research Resources, and the National Center for Advancing Translational Sciences at the National Institutes of Health through Grants R01 HD056510 (to R.S.L.), UL1 TR000127 (Penn State Clinical and Translational Institute), and U54 HD29834 (UVA Core Ligand Assay Core of the Specialized Cooperative Centers Program in Reproduction of the NICHD). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Disclosure Summary: R.S.L. reports consulting fees from Euroscreen, Astra Zeneca, Clarus Therapeutics, Takeda, Kindex, and research funding from Ferring and Astra Zeneca; A.R.L. reports ownership of Merck stock; S.J.E. reports research funding from AbbVie; D.B.S. reports consulting fees from BAROnova, EnteroMedics, and Ethicon; C.C. is on the Medical Advisory Board of NORA Therapeutics; W.C.D., P.M.K.-E., C.M.S., N.I.W., C.L.G., J.F., K.C.A., and A.D. have nothing to disclose.
Publisher Copyright:
Copyright © 2015 by the Endocrine Society.
PY - 2015/11
Y1 - 2015/11
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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U2 - 10.1210/jc.2015-2778
DO - 10.1210/jc.2015-2778
M3 - Article
C2 - 26401593
AN - SCOPUS:84958674610
VL - 100
SP - 4048
EP - 4058
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 11
ER -
