M B Ratna1, S Bhattacharya2, B Abdulrahim3, D J McLernon1. 1. Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UK. 2. School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, AB25 2ZD, UK. 3. NHS Grampian, Aberdeen Fertility Centre, Aberdeen, UK.
Abstract
STUDY QUESTION: What are the best-quality clinical prediction models in IVF (including ICSI) treatment to inform clinicians and their patients of their chance of success? SUMMARY ANSWER: The review recommends the McLernon post-treatment model for predicting the cumulative chance of live birth over and up to six complete cycles of IVF. WHAT IS KNOWN ALREADY: Prediction models in IVF have not found widespread use in routine clinical practice. This could be due to their limited predictive accuracy and clinical utility. A previous systematic review of IVF prediction models, published a decade ago and which has never been updated, did not assess the methodological quality of existing models nor provided recommendations for the best-quality models for use in clinical practice. STUDY DESIGN, SIZE, DURATION: The electronic databases OVID MEDLINE, OVID EMBASE and Cochrane library were searched systematically for primary articles published from 1978 to January 2019 using search terms on the development and/or validation (internal and external) of models in predicting pregnancy or live birth. No language or any other restrictions were applied. PARTICIPANTS/MATERIALS, SETTING, METHODS: The PRISMA flowchart was used for the inclusion of studies after screening. All studies reporting on the development and/or validation of IVF prediction models were included. Articles reporting on women who had any treatment elements involving donor eggs or sperm and surrogacy were excluded. The CHARMS checklist was used to extract and critically appraise the methodological quality of the included articles. We evaluated models' performance by assessing their c-statistics and plots of calibration in studies and assessed correct reporting by calculating the percentage of the TRIPOD 22 checklist items met in each study. MAIN RESULTS AND THE ROLE OF CHANCE: We identified 33 publications reporting on 35 prediction models. Seventeen articles had been published since the last systematic review. The quality of models has improved over time with regard to clinical relevance, methodological rigour and utility. The percentage of TRIPOD score for all included studies ranged from 29 to 95%, and the c-statistics of all externally validated studies ranged between 0.55 and 0.77. Most of the models predicted the chance of pregnancy/live birth for a single fresh cycle. Six models aimed to predict the chance of pregnancy/live birth per individual treatment cycle, and three predicted more clinically relevant outcomes such as cumulative pregnancy/live birth. The McLernon (pre- and post-treatment) models predict the cumulative chance of live birth over multiple complete cycles of IVF per woman where a complete cycle includes all fresh and frozen embryo transfers from the same episode of ovarian stimulation. McLernon models were developed using national UK data and had the highest TRIPOD score, and the post-treatment model performed best on external validation. LIMITATIONS, REASONS FOR CAUTION: To assess the reporting quality of all included studies, we used the TRIPOD checklist, but many of the earlier IVF prediction models were developed and validated before the formal TRIPOD reporting was published in 2015. It should also be noted that two of the authors of this systematic review are authors of the McLernon model article. However, we feel we have conducted our review and made our recommendations using a fair and transparent systematic approach. WIDER IMPLICATIONS OF THE FINDINGS: This study provides a comprehensive picture of the evolving quality of IVF prediction models. Clinicians should use the most appropriate model to suit their patients' needs. We recommend the McLernon post-treatment model as a counselling tool to inform couples of their predicted chance of success over and up to six complete cycles. However, it requires further external validation to assess applicability in countries with different IVF practices and policies. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Elphinstone Scholarship Scheme and the Assisted Reproduction Unit, University of Aberdeen. Both D.J.M. and S.B. are authors of the McLernon model article and S.B. is Editor in Chief of Human Reproduction Open. They have completed and submitted the ICMJE forms for Disclosure of potential Conflicts of Interest. The other co-authors have no conflicts of interest to declare. REGISTRATION NUMBER: N/A.
STUDY QUESTION: What are the best-quality clinical prediction models in IVF (including ICSI) treatment to inform clinicians and their patients of their chance of success? SUMMARY ANSWER: The review recommends the McLernon post-treatment model for predicting the cumulative chance of live birth over and up to six complete cycles of IVF. WHAT IS KNOWN ALREADY: Prediction models in IVF have not found widespread use in routine clinical practice. This could be due to their limited predictive accuracy and clinical utility. A previous systematic review of IVF prediction models, published a decade ago and which has never been updated, did not assess the methodological quality of existing models nor provided recommendations for the best-quality models for use in clinical practice. STUDY DESIGN, SIZE, DURATION: The electronic databases OVID MEDLINE, OVID EMBASE and Cochrane library were searched systematically for primary articles published from 1978 to January 2019 using search terms on the development and/or validation (internal and external) of models in predicting pregnancy or live birth. No language or any other restrictions were applied. PARTICIPANTS/MATERIALS, SETTING, METHODS: The PRISMA flowchart was used for the inclusion of studies after screening. All studies reporting on the development and/or validation of IVF prediction models were included. Articles reporting on women who had any treatment elements involving donor eggs or sperm and surrogacy were excluded. The CHARMS checklist was used to extract and critically appraise the methodological quality of the included articles. We evaluated models' performance by assessing their c-statistics and plots of calibration in studies and assessed correct reporting by calculating the percentage of the TRIPOD 22 checklist items met in each study. MAIN RESULTS AND THE ROLE OF CHANCE: We identified 33 publications reporting on 35 prediction models. Seventeen articles had been published since the last systematic review. The quality of models has improved over time with regard to clinical relevance, methodological rigour and utility. The percentage of TRIPOD score for all included studies ranged from 29 to 95%, and the c-statistics of all externally validated studies ranged between 0.55 and 0.77. Most of the models predicted the chance of pregnancy/live birth for a single fresh cycle. Six models aimed to predict the chance of pregnancy/live birth per individual treatment cycle, and three predicted more clinically relevant outcomes such as cumulative pregnancy/live birth. The McLernon (pre- and post-treatment) models predict the cumulative chance of live birth over multiple complete cycles of IVF per woman where a complete cycle includes all fresh and frozen embryo transfers from the same episode of ovarian stimulation. McLernon models were developed using national UK data and had the highest TRIPOD score, and the post-treatment model performed best on external validation. LIMITATIONS, REASONS FOR CAUTION: To assess the reporting quality of all included studies, we used the TRIPOD checklist, but many of the earlier IVF prediction models were developed and validated before the formal TRIPOD reporting was published in 2015. It should also be noted that two of the authors of this systematic review are authors of the McLernon model article. However, we feel we have conducted our review and made our recommendations using a fair and transparent systematic approach. WIDER IMPLICATIONS OF THE FINDINGS: This study provides a comprehensive picture of the evolving quality of IVF prediction models. Clinicians should use the most appropriate model to suit their patients' needs. We recommend the McLernon post-treatment model as a counselling tool to inform couples of their predicted chance of success over and up to six complete cycles. However, it requires further external validation to assess applicability in countries with different IVF practices and policies. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Elphinstone Scholarship Scheme and the Assisted Reproduction Unit, University of Aberdeen. Both D.J.M. and S.B. are authors of the McLernon model article and S.B. is Editor in Chief of Human Reproduction Open. They have completed and submitted the ICMJE forms for Disclosure of potential Conflicts of Interest. The other co-authors have no conflicts of interest to declare. REGISTRATION NUMBER: N/A.