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      Predicting personalized cumulative live birth rate after a complete in vitro fertilization cycle: an analysis of 32,306 treatment cycles in China

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          Abstract

          Background

          The cumulative live birth rate (CLBR) has been regarded as a key measure of in vitro fertilization (IVF) success after a complete treatment cycle. Women undergoing IVF face great psychological pressure and financial burden. A predictive model to estimate CLBR is needed in clinical practice for patient counselling and shaping expectations.

          Methods

          This retrospective study included 32,306 complete cycles derived from 29,023 couples undergoing IVF treatment from 2014 to 2020 at a university-affiliated fertility center in China. Three predictive models of CLBR were developed based on three phases of a complete cycle: pre-treatment, post-stimulation, and post-treatment. The non-linear relationship was treated with restricted cubic splines. Subjects from 2014 to 2018 were randomly divided into a training set and a test set at a ratio of 7:3 for model derivation and internal validation, while subjects from 2019 to 2020 were used for temporal validation.

          Results

          Predictors of pre-treatment model included female age (non-linear relationship), antral follicle count (non-linear relationship), body mass index, number of previous IVF attempts, number of previous embryo transfer failure, type of infertility, tubal factor, male factor, and scarred uterus. Predictors of post-stimulation model included female age (non-linear relationship), number of oocytes retrieved (non-linear relationship), number of previous IVF attempts, number of previous embryo transfer failure, type of infertility, scarred uterus, stimulation protocol, as well as endometrial thickness, progesterone and luteinizing hormone on trigger day. Predictors of post-treatment model included female age (non-linear relationship), number of oocytes retrieved (non-linear relationship), cumulative Day-3 embryos live-birth capacity (non-linear relationship), number of previous IVF attempts, scarred uterus, stimulation protocol, as well as endometrial thickness, progesterone and luteinizing hormone on trigger day. The C index of the three models were 0.7559, 0.7744, and 0.8270, respectively. All models were well calibrated ( p = 0.687, p = 0.468, p = 0.549). In internal validation, the C index of the three models were 0.7422, 0.7722, 0.8234, respectively; and the calibration P values were all greater than 0.05. In temporal validation, the C index were 0.7430, 0.7722, 0.8234 respectively; however, the calibration P values were less than 0.05.

          Conclusions

          This study provides three IVF models to predict CLBR according to information from different treatment stage, and these models have been converted into an online calculator ( https://h5.eheren.com/hcyc/pc/index.html#/home). Internal validation and temporal validation verified the good discrimination of the predictive models. However, temporal validation suggested low accuracy of the predictive models, which might be attributed to time-associated amelioration of IVF practice.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12958-024-01237-3.

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          Most cited references38

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          Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles.

          While live birth is the principal clinical outcome following in vitro fertilization (IVF) treatment, the number of eggs retrieved following ovarian stimulation is often used as a surrogate outcome in clinical practice and research. The aim of this study was to explore the association between egg number and live birth following IVF treatment and identify the number of eggs that would optimize the IVF outcome. Anonymized data on all IVF cycles performed in the UK from April 1991 to June 2008 were obtained from the Human Fertilization and Embryology Authority (HFEA). We analysed data from 400 135 IVF cycles. A logistic model was fitted to predict live birth using fractional polynomials to handle the number of eggs as a continuous independent variable. The prediction model, which was validated on a separate HFEA data set, allowed the estimation of the probability of live birth for a given number of eggs, stratified by age group. We produced a nomogram to predict the live birth rate (LBR) following IVF based on the number of eggs and the age of the female. The median number of eggs retrieved per cycle was 9 [inter-quartile range (IQR) 6-13]. The overall LBR was 21.3% per fresh IVF cycle. There was a strong association between the number of eggs and LBR; LBR rose with an increasing number of eggs up to ∼15, plateaued between 15 and 20 eggs and steadily declined beyond 20 eggs. During 2006-2007, the predicted LBR for women with 15 eggs retrieved in age groups 18-34, 35-37, 38-39 and 40 years and over was 40, 36, 27 and 16%, respectively. There was a steady increase in the LBR per egg retrieved over time since 1991. The relationship between the number of eggs and live birth, across all female age groups, suggests that the number of eggs in IVF is a robust surrogate outcome for clinical success. The results showed a non-linear relationship between the number of eggs and LBR following IVF treatment. The number of eggs to maximize the LBR is ∼15.
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            Multicenter Comparison of Machine Learning Methods and Conventional Regression for Predicting Clinical Deterioration on the Wards.

            Machine learning methods are flexible prediction algorithms that may be more accurate than conventional regression. We compared the accuracy of different techniques for detecting clinical deterioration on the wards in a large, multicenter database.
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              Cumulative live birth rate: time for a consensus?

              Traditionally, IVF success rates have been reported in terms of live birth per fresh cycle or embryo transfer. With the increasing use of embryo freezing and thawing it is essential that we report not only outcomes following fresh but also those after frozen embryo transfer as a complete measure of success of an IVF treatment. Most people agree that an individual's chance of having a baby following fresh and frozen embryo transfer should be described as cumulative live birth rate. However, views on the most appropriate parameters required to calculate such an outcome have been inconsistent. There is an additional dimension-time for all frozen embryos to be used up by a couple, which can influence the outcome. Given that cumulative live birth rate is generally perceived to be the preferred reporting system in IVF, it is time to have an international consensus on how this statistic is calculated, reported and interpreted by stakeholders across the world.
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                Author and article information

                Contributors
                495380513@qq.com
                nbliu@cmu.edu.cn
                wuqiongfang898@sina.com
                Journal
                Reprod Biol Endocrinol
                Reprod Biol Endocrinol
                Reproductive Biology and Endocrinology : RB&E
                BioMed Central (London )
                1477-7827
                7 June 2024
                7 June 2024
                2024
                : 22
                : 65
                Affiliations
                [1 ]Reproductive Medicine Center, Jiangxi Maternal and Child Health Hospital Affiliated to Nanchang Medical College, ( https://ror.org/01hbm5940) Nanchang, China
                [2 ]Jiangxi Key Laboratory of Reproductive Health, Nanchang, China
                [3 ]Department of Health Statistics, School of Public Health, China Medical University, ( https://ror.org/00v408z34) Shenyang, China
                [4 ]Columbia College of Art and Science, the George Washington University, ( https://ror.org/00y4zzh67) Washington, DC USA
                [5 ]Department of Child Health, Jiangxi Maternal and Child Health Hospital Affiliated to Nanchang Medical College, ( https://ror.org/01hbm5940) Nanchang, China
                [6 ]Department of Acupuncture, the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, ( https://ror.org/050d0fq97) Nanchang, China
                Article
                1237
                10.1186/s12958-024-01237-3
                11158004
                38849798
                e85302e9-0c96-4118-ac7c-3bb5131997f1
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 21 March 2024
                : 23 May 2024
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81960288
                Categories
                Research
                Custom metadata
                © BioMed Central Ltd., part of Springer Nature 2024

                Human biology
                in vitro fertilization,cumulative live birth rate,predictive model,restricted cubic splines

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