Pregnancy Rate

BackgroundAccurate assessments of current and future fertility-including overall trends and changing population age structures across countries and regions-are essential to help plan for the profound social, economic, environmental, and geopolitical challenges that these changes will bring. Estimates and projections of fertility are necessary to inform policies involving resource and health-care needs, labour supply, education, gender equality, and family planning and support. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 produced up-to-date and comprehensive demographic assessments of key fertility indicators at global, regional, and national levels from 1950 to 2021 and forecast fertility metrics to 2100 based on a reference scenario and key policy-dependent alternative scenarios.MethodsTo estimate fertility indicators from 1950 to 2021, mixed-effects regression models and spatiotemporal Gaussian process regression were used to synthesise data from 8709 country-years of vital and sample registrations, 1455 surveys and censuses, and 150 other sources, and to generate age-specific fertility rates (ASFRs) for 5-year age groups from age 10 years to 54 years. ASFRs were summed across age groups to produce estimates of total fertility rate (TFR). Livebirths were calculated by multiplying ASFR and age-specific female population, then summing across ages 10-54 years. To forecast future fertility up to 2100, our Institute for Health Metrics and Evaluation (IHME) forecasting model was based on projections of completed cohort fertility at age 50 years (CCF50; the average number of children born over time to females from a specified birth cohort), which yields more stable and accurate measures of fertility than directly modelling TFR. CCF50 was modelled using an ensemble approach in which three sub-models (with two, three, and four covariates variously consisting of female educational attainment, contraceptive met need, population density in habitable areas, and under-5 mortality) were given equal weights, and analyses were conducted utilising the MR-BRT (meta-regression-Bayesian, regularised, trimmed) tool. To capture time-series trends in CCF50 not explained by these covariates, we used a first-order autoregressive model on the residual term. CCF50 as a proportion of each 5-year ASFR was predicted using a linear mixed-effects model with fixed-effects covariates (female educational attainment and contraceptive met need) and random intercepts for geographical regions. Projected TFRs were then computed for each calendar year as the sum of single-year ASFRs across age groups. The reference forecast is our estimate of the most likely fertility future given the model, past fertility, forecasts of covariates, and historical relationships between covariates and fertility. We additionally produced forecasts for multiple alternative scenarios in each location: the UN Sustainable Development Goal (SDG) for education is achieved by 2030; the contraceptive met need SDG is achieved by 2030; pro-natal policies are enacted to create supportive environments for those who give birth; and the previous three scenarios combined. Uncertainty from past data inputs and model estimation was propagated throughout analyses by taking 1000 draws for past and present fertility estimates and 500 draws for future forecasts from the estimated distribution for each metric, with 95% uncertainty intervals (UIs) given as the 2·5 and 97·5 percentiles of the draws. To evaluate the forecasting performance of our model and others, we computed skill values-a metric assessing gain in forecasting accuracy-by comparing predicted versus observed ASFRs from the past 15 years (2007-21). A positive skill metric indicates that the model being evaluated performs better than the baseline model (here, a simplified model holding 2007 values constant in the future), and a negative metric indicates that the evaluated model performs worse than baseline.FindingsDuring the period from 1950 to 2021, global TFR more than halved, from 4·84 (95% UI 4·63-5·06) to 2·23 (2·09-2·38). Global annual livebirths peaked in 2016 at 142 million (95% UI 137-147), declining to 129 million (121-138) in 2021. Fertility rates declined in all countries and territories since 1950, with TFR remaining above 2·1-canonically considered replacement-level fertility-in 94 (46·1%) countries and territories in 2021. This included 44 of 46 countries in sub-Saharan Africa, which was the super-region with the largest share of livebirths in 2021 (29·2% [28·7-29·6]). 47 countries and territories in which lowest estimated fertility between 1950 and 2021 was below replacement experienced one or more subsequent years with higher fertility; only three of these locations rebounded above replacement levels. Future fertility rates were projected to continue to decline worldwide, reaching a global TFR of 1·83 (1·59-2·08) in 2050 and 1·59 (1·25-1·96) in 2100 under the reference scenario. The number of countries and territories with fertility rates remaining above replacement was forecast to be 49 (24·0%) in 2050 and only six (2·9%) in 2100, with three of these six countries included in the 2021 World Bank-defined low-income group, all located in the GBD super-region of sub-Saharan Africa. The proportion of livebirths occurring in sub-Saharan Africa was forecast to increase to more than half of the world's livebirths in 2100, to 41·3% (39·6-43·1) in 2050 and 54·3% (47·1-59·5) in 2100. The share of livebirths was projected to decline between 2021 and 2100 in most of the six other super-regions-decreasing, for example, in south Asia from 24·8% (23·7-25·8) in 2021 to 16·7% (14·3-19·1) in 2050 and 7·1% (4·4-10·1) in 2100-but was forecast to increase modestly in the north Africa and Middle East and high-income super-regions. Forecast estimates for the alternative combined scenario suggest that meeting SDG targets for education and contraceptive met need, as well as implementing pro-natal policies, would result in global TFRs of 1·65 (1·40-1·92) in 2050 and 1·62 (1·35-1·95) in 2100. The forecasting skill metric values for the IHME model were positive across all age groups, indicating that the model is better than the constant prediction.InterpretationFertility is declining globally, with rates in more than half of all countries and territories in 2021 below replacement level. Trends since 2000 show considerable heterogeneity in the steepness of declines, and only a small number of countries experienced even a slight fertility rebound after their lowest observed rate, with none reaching replacement level. Additionally, the distribution of livebirths across the globe is shifting, with a greater proportion occurring in the lowest-income countries. Future fertility rates will continue to decline worldwide and will remain low even under successful implementation of pro-natal policies. These changes will have far-reaching economic and societal consequences due to ageing populations and declining workforces in higher-income countries, combined with an increasing share of livebirths among the already poorest regions of the world.FundingBill & Melinda Gates Foundation.

BackgroundEven though the total fertility rate (TFR) has decreased significantly over the past decades in many countries, it has remained stable in sub-Saharan African (SSA) countries. However, there is variation among the sub-regions and inhabitants of SSA. Therefore, this study aimed to conduct a meta-analysis of demographic and health surveys (DHS) to estimate the pooled level of TFR in SSA and to depict sub-regional and inhabitant differences.MethodsThe data source for this study was the standard Demographic and Health Survey datasets of 33 sub-Saharan African countries, accessed through www.meaasuredhs.com between 2010 and 2018. The point estimate of the total fertility rate with its corresponding standard error in each sub-Saharan African country was estimated using the DHS.rates R package. Using the point estimate of the TFR with the standard error of each country, the pooled estimate of the TFR was generated by the metan STATA command.ResultsThe study comprised 1,324,466 live births in total. The pooled estimate of sub-Saharan Africa's overall fertility rate was five children per woman (95% CI: 4.63-5.37). Consequently, the pooled estimate of total fertility for people living in urban and rural areas was 3.90 (95% CI: 3.60-4.21) and 5.82 (95% CI: 5.43-6.21) children per woman, respectively. In sub-group analysis, the pooled estimates of the TFR for the East African, Central African, Southern African, and West African regions, respectively, were 4.74, 5.59, 3.18, and 5.38 children per woman. Total fertility rates were greater in low-income nations (5.45), lower-middle-income countries (4.70), and high-middle-income countries (3.80).ConclusionsSSA has a relatively high total fertility rate. The regions of West and Central Africa have the highest overall fertility rate. The fertility rate is higher in countries with a large rural population and low income. Strategies should be developed to address this public health concern, especially in rural Central and Western Africa.

Study questionCan machine learning predict the number of oocytes retrieved from controlled ovarian hyperstimulation (COH)?Summary answerThree machine-learning models were successfully trained to predict the number of oocytes retrieved from COH.What is known alreadyA number of previous studies have identified and built predictive models on factors that influence the number of oocytes retrieved during COH. Many of these studies are, however, limited in the fact that they only consider a small number of variables in isolation.Study design, size, durationThis study was a retrospective analysis of a dataset of 11,286 cycles performed at a single centre in France between 2009 and 2020 with the aim of building a predictive model for the number of oocytes retrieved from ovarian stimulation. The analysis was carried out by a data analysis team external to the centre using the Substra framework. The Substra framework enabled the data analysis team to send computer code to run securely on the centre's on-premises server. In this way, a high level of data security was achieved as the data analysis team did not have direct access to the data, nor did the data leave the centre at any point during the study.Participants/materials, setting, methodsThe Light Gradient Boosting Machine algorithm was used to produce three predictive models: one that directly predicted the number of oocytes retrieved and two that predicted which of a set of bins provided by two clinicians the number of oocytes retrieved fell into. The resulting models were evaluated on a held-out test set and compared to linear and logistic regression baselines. In addition, the models themselves were analysed to identify the parameters that had the biggest impact on their predictions.Main results and the role of chanceOn average, the model that directly predicted the number of oocytes retrieved deviated from the ground truth by 4.21 oocytes. The model that predicted the first clinician's bins deviated by 0.73 bins whereas the model for the second clinician deviated by 0.62 bins. For all models, performance was best within the first and third quartiles of the target variable, with the model underpredicting extreme values of the target variable (no oocytes and large numbers of oocytes retrieved). Nevertheless, the erroneous predictions made for these extreme cases were still within the vicinity of the true value. Overall, all three models agreed on the importance of each feature which was estimated using Shapley Additive Explanation (SHAP) values. The feature with the highest mean absolute SHAP value (and thus the highest importance) was the antral follicle count, followed by basal AMH and FSH. Of the other hormonal features, basal TSH, LH, and testosterone levels were similarly important and baseline LH was the least important. The treatment characteristic with the highest SHAP value was the initial dose of gonadotropins.Limitations, reasons for cautionThe models produced in this study were trained on a cohort from a single centre. They should thus not be used in clinical practice until trained and evaluated on a larger cohort more representative of the general population.Wider implications of findingsThese predictive models for the number of oocytes retrieved from COH may be useful in clinical practice, assisting clinicians in optimizing COH protocols for individual patients. Our work also demonstrates the promise of using the Substra framework for allowing external researchers to provide clinically relevant insights on sensitive fertility data in a fully secure, trustworthy manner and opens a number of exciting avenues for accelerating future research.Study funding/competing interest(s)This study was funded by the French Public Bank of Investment as part of the Healthchain Consortium. T.Fe., C.He., J.C., C.J., C.-A.P., and C.Hi. are employed by Apricity. C.Hi. has received consulting fees and honoraria from Vitrolife, Merck Serono, Ferring, Cooper Surgical, Dibimed, Apricity, and Fairtility and travel support from Fairtility and Vitrolife, participates on an advisory board for Merck Serono, was the founder and organizer of the AI Fertility conference, has stock in Aria Fertility, TMRW, Fairtility, Apricity, and IVF Professionals, and received free equipment from Planar in exchange for first user feedback. C.J. has received a grant from BPI. J.C. has also received a grant from BPI, is a member of the Merck AI advisory board, and is a board member of Labelia Labs. C.He has a contract for medical writing of this manuscript by CHU Nantes and has received travel support from Apricity. A.R. haș received honoraria from Ferring and Organon. T.Fe. has received a grant from BPI.Trial registration numberN/A.

Freeze-drying (FD) is a promising method for achieving the long-term, low-cost, and safe preservation of mammalian sperm at room temperature (RT, 23-25°C). However, the birth rate of embryos fertilized with FD sperm is reduced to less than half compared to those fertilized with fresh sperm. Moreover, the underlying causes and potential solutions remain unclear. In this study, we investigated a rehydration process using FD sperm to determine its effects on sperm DNA damage. We also attempted to optimize this rehydration method to improve birth rates. We initially examined the effects of slowing water infiltration into mouse FD sperm using a high osmolarity or viscosity solution, but we found that this increased DNA damage and decreased birth rates. Next, to accelerate infiltration speed, we performed rehydration of FD sperm using ultrapure water heated up to as hot as 90°C. However, we found that the DNA damage of the FD sperm decreased as the temperature increased. The level of DNA damage in the male pronucleus at the zygote stage and of abnormal chromosome segregation (ACS) at the two-cell stage were also decreased at 37°C or 50°C. Finally, the birth rates of embryos derived from FD sperm also significantly improved when rehydration was performed using 50°C ultrapure water (37%) compared with the RT control (22%). Taken together, the results of this study demonstrate that the DNA of FD sperm can be damaged during the rehydration process and that rapid rehydration significantly improves the birth rate.