title: Natural conception: repeated predictions over time.
abstract: How can we predict chances of natural conception at various time points in couples diagnosed with unexplained subfertility?
  
  
  
  We developed a dynamic prediction model that can make repeated predictions over time for couples with unexplained subfertility that underwent a fertility workup at a fertility clinic.
  
  
  
  The most frequently used prediction model for natural conception (the 'Hunault model') estimates the probability of natural conception only once per couple, that is, after completion of the fertility workup. This model cannot be used for a second or third time for couples who wish to know their renewed chances after a certain period of expectant management.
  
  
  
  A prospective cohort studying the long-term follow-up of subfertile couples included in 38 centres in the Netherlands between January 2002 and February 2004. Couples with bilateral tubal occlusion, anovulation or a total motile sperm count <1 × 106were excluded.
  
  
  
  The primary endpoint was time to natural conception, leading to an ongoing pregnancy. Follow-up time was censored at the start of treatment or at the last date of contact. In developing the new dynamic prediction model, we used the same predictors as the Hunault model, i.e. female age, duration of subfertility, female subfertility being primary or secondary, sperm motility and referral status. The performance of the model was evaluated in terms of calibration and discrimination. Additionally, we assessed the utility of the model in terms of the variability of the calculated predictions.
  
  
  
  Of the 4999 couples in the cohort, 1053 (21%) women reached a natural conception leading to an ongoing pregnancy within a mean follow-up of 8 months (5th and 95th percentile: 1-21). Our newly developed dynamic prediction model estimated the median probability of conceiving in the first year after the completion of the fertility workup at 27%. For couples not yet pregnant after half a year, after one year and after one and a half years of expectant management, the median probability of conceiving over the next year was estimated at 20, 15 and 13%, respectively. The model performed fair in an internal validation. The prediction ranges were sufficiently broad to aid in counselling couples for at least two years after their fertility workup.
  
  
  
  The dynamic prediction model needs to be validated in an external population.
  
  
  
  This dynamic prediction model allows reassessment of natural conception chances after various periods of unsuccessful expectant management. This gives valuable information to counsel couples with unexplained subfertility that are seen for a fertility workup.
  
  
  
  This study was facilitated by grant 945/12/002 from ZonMW, The Netherlands Organization for Health Research and Development, The Hague, The Netherlands. No competing interests.
authors.affiliation: Academic Medical Center, Centre for Reproductive Medicine, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands r.vaneekelen@amc.uva.nl.|Department of Biostatistics and Research Support, Julius Center, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: van Eekelen
authors.affiliation: Academic Medical Center, Centre for Reproductive Medicine, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: Scholten
authors.affiliation: Academic Medical Center, Centre for Reproductive Medicine, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: R I
authors.initials: RI
authors.lastname: Tjon-Kon-Fat
authors.affiliation: Department of Obstetrics and Gynaecology, Jeroen Bosch Ziekenhuis, 's-Hertogenbosch, The Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: van der Steeg
authors.affiliation: Department of Obstetrics and Gynaecology, St. Elisabeth Ziekenhuis, Tilburg, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Steures
authors.affiliation: Department of Obstetrics and Gynaecology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Hompes
authors.affiliation: Academic Medical Center, Centre for Reproductive Medicine, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van Wely
authors.affiliation: Academic Medical Center, Centre for Reproductive Medicine, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: van der Veen
authors.affiliation: The Robinson Institute-School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia.
authors.forename: B W
authors.initials: BW
authors.lastname: Mol
authors.affiliation: Department of Biostatistics and Research Support, Julius Center, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Eijkemans
authors.affiliation: Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: E R
authors.initials: ER
authors.lastname: Te Velde
authors.affiliation: Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: van Geloven
mesh_terms: D000328:Adult; D000367:Age Factors; D005260:Female; D005306:Fertilization / Q000502:physiology*; D006801:Humans; D007246:Infertility / Q000503:physiopathology*; D008297:Male; D011247:Pregnancy; D018873:Pregnancy Rate; D011379:Prognosis; D055101:Semen Analysis; D013081:Sperm Motility / Q000502:physiology; D013997:Time Factors
keywords: dynamic prediction; expectant management; natural conception; prospective cohort; spontaneous pregnancy