External validation of a dynamic prediction model for repeated predictions of natural conception over time

R van Eekelen (Corresponding Author), D J McLernon, M van Wely, M J Eijkemans, S Bhattacharya, F van der Veen, N van Geloven

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

STUDY QUESTION
How well does a previously developed dynamic prediction model perform in an external, geographical validation in terms of predicting the chances of natural conception at various points in time?

SUMMARY ANSWER
The dynamic prediction model performs well in an external validation on a Scottish cohort.

WHAT IS KNOWN ALREADY
Prediction models provide information that can aid evidence-based management of unexplained subfertile couples. We developed a dynamic prediction model for natural conception (van Eekelen model) that is able to update predictions of natural conception when couples return to their clinician after a period of unsuccessful expectant management. It is not known how well this model performs in an external population.

STUDY DESIGN, SIZE, DURATION
A record-linked registry study including the long-term follow-up of all couples who were considered unexplained subfertile following a fertility workup at a Scottish fertility clinic between 1998 and 2011. Couples with anovulation, uni/bilateral tubal occlusion, mild/severe endometriosis or impaired semen quality according to World Health Organization criteria were excluded.

PARTICIPANTS/MATERIALS, SETTING, METHODS
The endpoint was time to natural conception, leading to an ongoing pregnancy (defined as reaching a gestational age of at least 12 weeks). Follow-up was censored at the start of treatment, at the change of partner or at the end of study (31 March 2012). The performance of the van Eekelen model was evaluated in terms of calibration and discrimination at various points in time. Additionally, we assessed the clinical utility of the model in terms of the range of the calculated predictions.

MAIN RESULTS AND THE ROLE OF CHANCE
Of a total of 1203 couples with a median follow-up of 1 year and 3 months after the fertility workup, 398 (33%) couples conceived naturally leading to an ongoing pregnancy. Using the dynamic prediction model, the mean probability of natural conception over the course of the first year after the fertility workup was estimated at 25% (observed: 23%). After 0.5, 1 and 1.5 years of expectant management after the completion of the fertility workup, the average probability of conceiving naturally over the next year was estimated at 18% (observed: 15%), 14% (observed: 14%) and 12% (observed: 12%). Calibration plots showed good agreement between predicted chances and the observed fraction of ongoing pregnancy within risk groups. Discrimination was moderate with c statistics similar to those in the internal validation, ranging from 0.60 to 0.64. The range of predicted chances was sufficiently wide to distinguish between couples having a good and poor prognosis with a minimum of zero at all times and a maximum of 55% over the first year after the workup, which decreased to maxima of 43% after 0.5 years, 34% after 1 year and 29% after 1.5 years after the fertility workup.

LIMITATIONS, REASONS FOR CAUTION
The model slightly overestimated the chances of conception by ~2–3% points on group level in the first-year post-fertility workup and after 0.5 years of expectant management, respectively. This is likely attributable to the fact that the exact dates of completion of the fertility workup for couples were missing and had to be estimated.

WIDER IMPLICATIONS OF THE FINDINGS
The van Eekelen model is a valid and robust tool that is ready to use in clinical practice to counsel couples with unexplained subfertility on their individualized chances of natural conception at various points in time, notably when couples return to the clinic after a period of unsuccessful expectant management.

STUDY FUNDING/COMPETING INTEREST(S)
This work was supported by a Chief Scientist Office postdoctoral training fellowship in health services research and health of the public research (ref PDF/12/06). There are no conflicts of interest.
Original languageEnglish
Pages (from-to)2268-2275
Number of pages8
JournalHuman Reproduction
Volume33
Issue number12
Early online date25 Oct 2018
DOIs
Publication statusPublished - 1 Dec 2018

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Fertility
Pregnancy
Calibration
Anovulation
Tubal Sterilization
Conflict of Interest
Semen Analysis
Health Services Research
Endometriosis
Infertility
Gestational Age
Registries
Public Health
Research
Population

Keywords

  • natural conception
  • expectant management
  • prognosis
  • prediction model
  • dynamic prediction
  • retrospective cohort

Cite this

External validation of a dynamic prediction model for repeated predictions of natural conception over time. / van Eekelen, R (Corresponding Author); McLernon, D J; van Wely, M; Eijkemans, M J; Bhattacharya, S; van der Veen, F; van Geloven, N.

In: Human Reproduction, Vol. 33, No. 12, 01.12.2018, p. 2268-2275.

Research output: Contribution to journalArticle

van Eekelen, R ; McLernon, D J ; van Wely, M ; Eijkemans, M J ; Bhattacharya, S ; van der Veen, F ; van Geloven, N. / External validation of a dynamic prediction model for repeated predictions of natural conception over time. In: Human Reproduction. 2018 ; Vol. 33, No. 12. pp. 2268-2275.
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abstract = "STUDY QUESTIONHow well does a previously developed dynamic prediction model perform in an external, geographical validation in terms of predicting the chances of natural conception at various points in time?SUMMARY ANSWERThe dynamic prediction model performs well in an external validation on a Scottish cohort.WHAT IS KNOWN ALREADYPrediction models provide information that can aid evidence-based management of unexplained subfertile couples. We developed a dynamic prediction model for natural conception (van Eekelen model) that is able to update predictions of natural conception when couples return to their clinician after a period of unsuccessful expectant management. It is not known how well this model performs in an external population.STUDY DESIGN, SIZE, DURATIONA record-linked registry study including the long-term follow-up of all couples who were considered unexplained subfertile following a fertility workup at a Scottish fertility clinic between 1998 and 2011. Couples with anovulation, uni/bilateral tubal occlusion, mild/severe endometriosis or impaired semen quality according to World Health Organization criteria were excluded.PARTICIPANTS/MATERIALS, SETTING, METHODSThe endpoint was time to natural conception, leading to an ongoing pregnancy (defined as reaching a gestational age of at least 12 weeks). Follow-up was censored at the start of treatment, at the change of partner or at the end of study (31 March 2012). The performance of the van Eekelen model was evaluated in terms of calibration and discrimination at various points in time. Additionally, we assessed the clinical utility of the model in terms of the range of the calculated predictions.MAIN RESULTS AND THE ROLE OF CHANCEOf a total of 1203 couples with a median follow-up of 1 year and 3 months after the fertility workup, 398 (33{\%}) couples conceived naturally leading to an ongoing pregnancy. Using the dynamic prediction model, the mean probability of natural conception over the course of the first year after the fertility workup was estimated at 25{\%} (observed: 23{\%}). After 0.5, 1 and 1.5 years of expectant management after the completion of the fertility workup, the average probability of conceiving naturally over the next year was estimated at 18{\%} (observed: 15{\%}), 14{\%} (observed: 14{\%}) and 12{\%} (observed: 12{\%}). Calibration plots showed good agreement between predicted chances and the observed fraction of ongoing pregnancy within risk groups. Discrimination was moderate with c statistics similar to those in the internal validation, ranging from 0.60 to 0.64. The range of predicted chances was sufficiently wide to distinguish between couples having a good and poor prognosis with a minimum of zero at all times and a maximum of 55{\%} over the first year after the workup, which decreased to maxima of 43{\%} after 0.5 years, 34{\%} after 1 year and 29{\%} after 1.5 years after the fertility workup.LIMITATIONS, REASONS FOR CAUTIONThe model slightly overestimated the chances of conception by ~2–3{\%} points on group level in the first-year post-fertility workup and after 0.5 years of expectant management, respectively. This is likely attributable to the fact that the exact dates of completion of the fertility workup for couples were missing and had to be estimated.WIDER IMPLICATIONS OF THE FINDINGSThe van Eekelen model is a valid and robust tool that is ready to use in clinical practice to counsel couples with unexplained subfertility on their individualized chances of natural conception at various points in time, notably when couples return to the clinic after a period of unsuccessful expectant management.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by a Chief Scientist Office postdoctoral training fellowship in health services research and health of the public research (ref PDF/12/06). There are no conflicts of interest.",
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T1 - External validation of a dynamic prediction model for repeated predictions of natural conception over time

AU - van Eekelen, R

AU - McLernon, D J

AU - van Wely, M

AU - Eijkemans, M J

AU - Bhattacharya, S

AU - van der Veen, F

AU - van Geloven, N

N1 - This work was supported by a Chief Scientist Office postdoctoral training fellowship in health services research and health of the public research (ref PDF/12/06). There are no conflicts of interest.

PY - 2018/12/1

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N2 - STUDY QUESTIONHow well does a previously developed dynamic prediction model perform in an external, geographical validation in terms of predicting the chances of natural conception at various points in time?SUMMARY ANSWERThe dynamic prediction model performs well in an external validation on a Scottish cohort.WHAT IS KNOWN ALREADYPrediction models provide information that can aid evidence-based management of unexplained subfertile couples. We developed a dynamic prediction model for natural conception (van Eekelen model) that is able to update predictions of natural conception when couples return to their clinician after a period of unsuccessful expectant management. It is not known how well this model performs in an external population.STUDY DESIGN, SIZE, DURATIONA record-linked registry study including the long-term follow-up of all couples who were considered unexplained subfertile following a fertility workup at a Scottish fertility clinic between 1998 and 2011. Couples with anovulation, uni/bilateral tubal occlusion, mild/severe endometriosis or impaired semen quality according to World Health Organization criteria were excluded.PARTICIPANTS/MATERIALS, SETTING, METHODSThe endpoint was time to natural conception, leading to an ongoing pregnancy (defined as reaching a gestational age of at least 12 weeks). Follow-up was censored at the start of treatment, at the change of partner or at the end of study (31 March 2012). The performance of the van Eekelen model was evaluated in terms of calibration and discrimination at various points in time. Additionally, we assessed the clinical utility of the model in terms of the range of the calculated predictions.MAIN RESULTS AND THE ROLE OF CHANCEOf a total of 1203 couples with a median follow-up of 1 year and 3 months after the fertility workup, 398 (33%) couples conceived naturally leading to an ongoing pregnancy. Using the dynamic prediction model, the mean probability of natural conception over the course of the first year after the fertility workup was estimated at 25% (observed: 23%). After 0.5, 1 and 1.5 years of expectant management after the completion of the fertility workup, the average probability of conceiving naturally over the next year was estimated at 18% (observed: 15%), 14% (observed: 14%) and 12% (observed: 12%). Calibration plots showed good agreement between predicted chances and the observed fraction of ongoing pregnancy within risk groups. Discrimination was moderate with c statistics similar to those in the internal validation, ranging from 0.60 to 0.64. The range of predicted chances was sufficiently wide to distinguish between couples having a good and poor prognosis with a minimum of zero at all times and a maximum of 55% over the first year after the workup, which decreased to maxima of 43% after 0.5 years, 34% after 1 year and 29% after 1.5 years after the fertility workup.LIMITATIONS, REASONS FOR CAUTIONThe model slightly overestimated the chances of conception by ~2–3% points on group level in the first-year post-fertility workup and after 0.5 years of expectant management, respectively. This is likely attributable to the fact that the exact dates of completion of the fertility workup for couples were missing and had to be estimated.WIDER IMPLICATIONS OF THE FINDINGSThe van Eekelen model is a valid and robust tool that is ready to use in clinical practice to counsel couples with unexplained subfertility on their individualized chances of natural conception at various points in time, notably when couples return to the clinic after a period of unsuccessful expectant management.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by a Chief Scientist Office postdoctoral training fellowship in health services research and health of the public research (ref PDF/12/06). There are no conflicts of interest.

AB - STUDY QUESTIONHow well does a previously developed dynamic prediction model perform in an external, geographical validation in terms of predicting the chances of natural conception at various points in time?SUMMARY ANSWERThe dynamic prediction model performs well in an external validation on a Scottish cohort.WHAT IS KNOWN ALREADYPrediction models provide information that can aid evidence-based management of unexplained subfertile couples. We developed a dynamic prediction model for natural conception (van Eekelen model) that is able to update predictions of natural conception when couples return to their clinician after a period of unsuccessful expectant management. It is not known how well this model performs in an external population.STUDY DESIGN, SIZE, DURATIONA record-linked registry study including the long-term follow-up of all couples who were considered unexplained subfertile following a fertility workup at a Scottish fertility clinic between 1998 and 2011. Couples with anovulation, uni/bilateral tubal occlusion, mild/severe endometriosis or impaired semen quality according to World Health Organization criteria were excluded.PARTICIPANTS/MATERIALS, SETTING, METHODSThe endpoint was time to natural conception, leading to an ongoing pregnancy (defined as reaching a gestational age of at least 12 weeks). Follow-up was censored at the start of treatment, at the change of partner or at the end of study (31 March 2012). The performance of the van Eekelen model was evaluated in terms of calibration and discrimination at various points in time. Additionally, we assessed the clinical utility of the model in terms of the range of the calculated predictions.MAIN RESULTS AND THE ROLE OF CHANCEOf a total of 1203 couples with a median follow-up of 1 year and 3 months after the fertility workup, 398 (33%) couples conceived naturally leading to an ongoing pregnancy. Using the dynamic prediction model, the mean probability of natural conception over the course of the first year after the fertility workup was estimated at 25% (observed: 23%). After 0.5, 1 and 1.5 years of expectant management after the completion of the fertility workup, the average probability of conceiving naturally over the next year was estimated at 18% (observed: 15%), 14% (observed: 14%) and 12% (observed: 12%). Calibration plots showed good agreement between predicted chances and the observed fraction of ongoing pregnancy within risk groups. Discrimination was moderate with c statistics similar to those in the internal validation, ranging from 0.60 to 0.64. The range of predicted chances was sufficiently wide to distinguish between couples having a good and poor prognosis with a minimum of zero at all times and a maximum of 55% over the first year after the workup, which decreased to maxima of 43% after 0.5 years, 34% after 1 year and 29% after 1.5 years after the fertility workup.LIMITATIONS, REASONS FOR CAUTIONThe model slightly overestimated the chances of conception by ~2–3% points on group level in the first-year post-fertility workup and after 0.5 years of expectant management, respectively. This is likely attributable to the fact that the exact dates of completion of the fertility workup for couples were missing and had to be estimated.WIDER IMPLICATIONS OF THE FINDINGSThe van Eekelen model is a valid and robust tool that is ready to use in clinical practice to counsel couples with unexplained subfertility on their individualized chances of natural conception at various points in time, notably when couples return to the clinic after a period of unsuccessful expectant management.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by a Chief Scientist Office postdoctoral training fellowship in health services research and health of the public research (ref PDF/12/06). There are no conflicts of interest.

KW - natural conception

KW - expectant management

KW - prognosis

KW - prediction model

KW - dynamic prediction

KW - retrospective cohort

U2 - 10.1093/humrep/dey317

DO - 10.1093/humrep/dey317

M3 - Article

VL - 33

SP - 2268

EP - 2275

JO - Human Reproduction

JF - Human Reproduction

SN - 0268-1161

IS - 12

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