R van Eekelen1,2, I Scholten3, R I Tjon-Kon-Fat3, J W van der Steeg4, P Steures5, P Hompes6, M van Wely3, F van der Veen3, B W Mol7, M J Eijkemans2, E R Te Velde8, N van Geloven9. 1. Academic Medical Center, Centre for Reproductive Medicine, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands r.vaneekelen@amc.uva.nl. 2. Department of Biostatistics and Research Support, Julius Center, University Medical Center Utrecht, Utrecht, The Netherlands. 3. Academic Medical Center, Centre for Reproductive Medicine, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. 4. Department of Obstetrics and Gynaecology, Jeroen Bosch Ziekenhuis, 's-Hertogenbosch, The Netherlands. 5. Department of Obstetrics and Gynaecology, St. Elisabeth Ziekenhuis, Tilburg, The Netherlands. 6. Department of Obstetrics and Gynaecology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. 7. The Robinson Institute-School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia. 8. Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands. 9. Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.
Abstract
STUDY QUESTION: How can we predict chances of natural conception at various time points in couples diagnosed with unexplained subfertility? SUMMARY ANSWER: 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. WHAT IS KNOWN ALREADY: 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. STUDY DESIGN, SIZE, DURATION: 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 × 106 were excluded. PARTICIPANTS/MATERIALS, SETTING, METHODS: 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. MAIN RESULTS AND THE ROLE OF CHANCE: 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. LIMITATIONS, REASONS FOR CAUTION: The dynamic prediction model needs to be validated in an external population. WIDER IMPLICATIONS OF THE FINDINGS: 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. STUDY FUNDING/COMPETING INTERESTS: 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.
STUDY QUESTION: How can we predict chances of natural conception at various time points in couples diagnosed with unexplained subfertility? SUMMARY ANSWER: 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. WHAT IS KNOWN ALREADY: 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. STUDY DESIGN, SIZE, DURATION: 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 × 106 were excluded. PARTICIPANTS/MATERIALS, SETTING, METHODS: 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. MAIN RESULTS AND THE ROLE OF CHANCE: 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. LIMITATIONS, REASONS FOR CAUTION: The dynamic prediction model needs to be validated in an external population. WIDER IMPLICATIONS OF THE FINDINGS: 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. STUDY FUNDING/COMPETING INTERESTS: 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: Rui Wang; Nora A Danhof; Raissa I Tjon-Kon-Fat; Marinus Jc Eijkemans; Patrick Mm Bossuyt; Monique H Mochtar; Fulco van der Veen; Siladitya Bhattacharya; Ben Willem J Mol; Madelon van Wely Journal: Cochrane Database Syst Rev Date: 2019-09-05
Authors: R van Eekelen; K Rosielle; N van Welie; K Dreyer; M van Wely; B W Mol; M J Eijkemans; V Mijatovic; N van Geloven Journal: Hum Reprod Open Date: 2020-11-17
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