title: Identification and replication of prediction models for ovulation, pregnancy and live birth in infertile women with polycystic ovary syndrome.
abstract: OBJECTIVE
  Can we build and validate predictive models for ovulation and pregnancy outcomes in infertile women with polycystic ovary syndrome (PCOS)?
  
  
  CONCLUSIONS
  We were able to develop and validate a predictive model for pregnancy outcomes in women with PCOS using simple clinical and biochemical criteria particularly duration of attempting conception, which was the most consistent predictor among all considered factors for pregnancy outcomes.
  
  
  BACKGROUND
  Predictive models for ovulation and pregnancy outcomes in infertile women with polycystic ovary syndrome have been reported, but such models require validation.
  
  
  METHODS
  This is a secondary analysis of the data from the Pregnancy in Polycystic Ovary Syndrome I and II (PPCOS-I and -II) trials. Both trials were double-blind, randomized clinical trials that included 626 and 750 infertile women with PCOS, respectively. PPCOS-I participants were randomized to either clomiphene citrate (CC), metformin, or their combination, and PPCOS-II participants to either letrozole or CC for up to five treatment cycles.
  
  
  METHODS
  Linear logistic regression models were fitted using treatment, BMI, and other published variables as predictors of ovulation, conception, clinical pregnancy, and live birth as the outcome one at a time. We first evaluated previously reported significant predictors, and then constructed new prediction models. Receiver operating characteristic (ROC) curves were constructed and the area under the curves (AUCs) was calculated to compare performance using different models and data. Chi-square tests were used to examine the goodness-of-fit and prediction power of logistic regression model.
  
  
  RESULTS
  Predictive factors were similar between PPCOS-I and II, but the two participant samples differed statistically significantly but the differences were clinically minor on key baseline characteristics and hormone levels. Women in PPCOS-II had an overall more severe PCOS phenotype than women in PPCOS-I. The clinically minor but statistically significant differences may be due to the large sample sizes. Younger age, lower baseline free androgen index and insulin, shorter duration of attempting conception, and higher baseline sex hormone-binding globulin significantly predicted at least one pregnancy outcome. The ROC curves (with AUCs of 0.66-0.76) and calibration plots and chi-square tests indicated stable predictive power of the identified variables (P-values ≥0.07 for all goodness-of-fit and validation tests).
  
  
  CONCLUSIONS
  This is a secondary analysis. Although our primary objective was to confirm previously reported results and identify new predictors of ovulation and pregnancy outcomes among PPCOS-II participants, our approach is exploratory and warrants further replication.
  
  
  CONCLUSIONS
  We have largely confirmed the predictors that were identified in the PPCOS-I trial. However, we have also revealed new predictors, particularly the role of smoking. While a history of ever smoking was not a significant predictor for live birth, a closer look at current, quit, and never smoking revealed that current smoking was a significant risk factor.
  
  
  BACKGROUND
  The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Grants U10 HD27049, U10 HD38992, U10HD055925, U10 HD39005, U10 HD33172, U10 HD38998, U10 HD055936, U10 HD055942, and U10 HD055944; and U54-HD29834. Heilongjiang University of Chinese Medicine Grants 051277 and B201005. R.S.L. reports receiving consulting fees from Euroscreen, AstraZeneca, Clarus Therapeutics, and Takeda, and grant support from Ferring, Astra Zeneca, and Toba. K.R.H. reports receiving grant support from Roche Diagnostics and Ferring Pharmascience. G.C. reports receiving Honorarium and grant support from Abbvie Pharmaceuticals and Bayer Pharmaceuticals. M.P.D. holds equity from Advanced Reproductive Care Inc. and DS Biotech, receives fees from Advanced Reproductive Care Inc., Actamax, Auxogyn, ZSX Medical, Halt Medical, and Neomed, and receives grant support from Boehringer-Ingelheim, Abbott, and BioSante, Ferring Pharmaceuticals, and EMD Serono. H.Z. receives research support from the Chinese 1000-scholar plan. Others report no disclosures other than NIH grant support.
  
  
  BACKGROUND
  PPCOS-I and -II were respectively registered at Clinicaltrials.gov: NCT00719186 and NCT00719186.
authors.affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital and Heilongjiang University of Chinese Medicine, Harbin 150040, PR China Department of Biostatistics, Yale University School of Public Health, New Haven, CT 06520, USA.
authors.forename: Hongying
authors.initials: H
authors.lastname: Kuang
authors.affiliation: Department of Biostatistics, Yale University School of Public Health, New Haven, CT 06520, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Jin
authors.affiliation: Department of Obstetrics and Gynecology, University of Oklahoma College of Medicine, Oklahoma City, OK 73104, USA.
authors.forename: Karl R
authors.initials: KR
authors.lastname: Hansen
authors.affiliation: Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Diamond
authors.affiliation: Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Christos
authors.initials: C
authors.lastname: Coutifaris
authors.affiliation: Department of Obstetrics and Gynecology, University of Vermont, Burlington, VT 05405, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Casson
authors.affiliation: Department of Obstetrics and Gynecology, Shands Hospital, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Christman
authors.affiliation: Department of Obstetrics and Gynecology, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Ruben
authors.initials: R
authors.lastname: Alvero
authors.affiliation: Department of Biostatistics, Yale University School of Public Health, New Haven, CT 06520, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Obstetrics and Gynecology, University of Alabama Birmingham, Birmingham, AL, USA.
authors.forename: G Wright
authors.initials: GW
authors.lastname: Bates
authors.affiliation: Department of Obstetrics and Gynecology, Carolinas Medical Center, Charlotte, NC, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Usadi
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Lucidi
authors.affiliation: Department of Obstetrics and Gynecology, Stanford University Medical Center, Stanford, CA, USA.
authors.forename: Valerie
authors.initials: V
authors.lastname: Baker
authors.affiliation: Department of Obstetrics and Gynecology, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Nanette
authors.initials: N
authors.lastname: Santoro
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA.
authors.forename: Esther
authors.initials: E
authors.lastname: Eisenberg
authors.affiliation: Department of Obstetrics and Gynecology, Penn State College of Medicine, Hershey, PA 17033, USA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Legro
authors.affiliation: Department of Biostatistics, Yale University School of Public Health, New Haven, CT 06520, USA heping.zhang@yale.edu.
authors.forename: Heping
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000328:Adult; D005260:Female; D005306:Fertilization / Q000502:physiology*; D006801:Humans; D007247:Infertility, Female / Q000453:epidemiology* / Q000209:etiology; D050498:Live Birth / Q000453:epidemiology*; D008962:Models, Theoretical; D010060:Ovulation / Q000502:physiology*; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000453:epidemiology*; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic
keywords: calibration; conception; live birth; mathematical modeling; polycystic ovaries; prediction; pregnancy; receiver operating characteristic